PubMed Health⌕ Search

Biomedical subjects

J Kwon

Publications and source records attributed to J Kwon.

51 records · Page 3Linked to original sources
PubMed1994

Asbestos stimulates IL-8 production from human lung epithelial cells.

Studies have indicated that soluble products, including chemotactic factors, released by activated lung macrophages and fibroblasts are critical mediators in the pathogenesis of asbestos-induced pulmonary fibrosis. We provide evidence that mediators produced by lung epithelial cells in response to asbestos may also contribute to lung disease. In the present study, the carcinogenic and fibrogenic fibers, chrysotile and crocidolite asbestos, were shown to directly stimulate the human pulmonary type-II epithelial cell line, A549, and to a lesser degree primary human bronchial epithelial cells, to elicit the chemotactic cytokine IL-8 in the absence of endogenous stimuli such as IL-1 and TNF. That the membrane signaling events responsible for asbestos-induced IL-8 production are distinct from those responsible for IL-8 induction by cytokines was confirmed by using membrane-stabilizing agents and protein synthesis inhibitors. Stimulation was not observed with nonfibrogenic fibers, wollastonite and titanium dioxide, and was the direct result of asbestos-induced initiation of transcription. Asbestos failed to stimulate the release of TNF, IL-1 beta, or monocyte chemoattractant protein-1 in A549 or primary bronchial epithelial cells, indicating that cytokine secretion by asbestos is highly selective. However, a slight release of IL-1 alpha, probably preformed, was released in human bronchial epithelial cells. These data suggest that epithelial cells may, in addition to macrophages and fibroblasts, be an important effector cell in the immunopathogenesis of asbestos-associated diseases and in particular, in the neutrophilic infiltration that is commonly observed after asbestos exposure.

Asbestos, Serpentine↗
PubMed1994

Conditional immortalization of neuronal cells from postmitotic cultures and adult CNS.

To determine whether postmitotic neurons can be immortalized by oncogenic transduction, we used two approaches involving conditional expression of a temperature-sensitive SV40 large T antigen (Tts). Initially, Tts was introduced into E17 rat embryonal hippocampal cells that were then cultured at the non-permissive temperature to enrich for postmitotic pyramidal neurons, and subsequently cloned at the permissive temperature. One clonal line (HMR10-3) expressed neuron-specific proteins upon differentiation, was capable of generating action potentials, and formed synapses with primary rat neurons in co-culture. Replating of these postmitotic cells at the permissive temperature resulted in reversible loss of neurofilament expression. Conditionally immortalized cell lines were also generated from the brain of an adult mouse carrying an inducible Tts transgene. These lines proliferated in a T antigen-dependent manner and expressed neuron-specific proteins upon differentiation at the non-permissive temperature. These results suggest that postmitotic neurons can be induced to enter the cell cycle without losing their commitment to a neuronal lineage.

Animals↗
PubMed1994

Fetal hematopoietic alterations after maternal exposure to ethylene glycol monomethyl ether: prolymphoid cell targeting.

Ethylene glycol monomethyl ether (EGME), which is extensively used in the chemical industries, has been associated with hematologic disorders in both humans and experimental animals. EGME is metabolized to the active compound methoxy-acetic acid (MAA), which readily crosses the placenta and impairs fetal development. However, little is known about the effect of maternal EGME exposure on the development of fetal immunity. In the present report, in utero treatment with EGME was found to alter expression of murine thymocyte and liver fetal cell-surface markers. Pregnant mice were exposed to 100, 150, or 200 mg/kg EGME from gestational days (gd) 10 to 17 and offspring examined on gd 18. Significant thymic atrophy and cellular depletion were found in EGME-exposed fetal mice. Flow cytometric analysis indicated that EGME treatment resulted in decreased percentages of CD4+8+ thymocytes and increased percentages of CD4-8- thymocytes. In vitro exposure to MAA did not result in decreased thymocyte viability or proliferation. These data suggest that EGME, in addition to producing thymic hypocellularity, may inhibit thymocyte maturation. EGME also reduced the percentage of CD45+ leukocytic cells present in fetal liver, an alteration that appeared to be largely manifested by decreased numbers of CD45R+ and CD44dim prolymphoid cells. In vitro MAA exposure of fetal liver cells enriched for lymphoid precursors resulted in significant inhibition of proliferation. Reconstitution of irradiated hosts with gd 18 fetal liver cells from vehicle and EGME-exposed syngeneic donors demonstrated impaired ability of the EGME-treated fetal liver to repopulate the host spleen with B or T lymphocytes. These data suggest that EGME-induced immunosuppression may result from targeting of multiple hematopoietic compartments. Further, the present data indicate that fetal liver prolymphocytes may represent sensitive targets of EGME exposure.

Acetates↗
PubMed1993

Cloning and sequence analysis of the rat tumor necrosis factor-encoding genes.

We have isolated an approximately 22-kb TNF locus (encoding tumor necrosis factor) from a rat genomic library and sequenced the 7105-bp fragment that comprises the TNF-alpha and TNF-beta genes, including their flanking sequences. The two genes are tandemly arranged with TNF-beta 5' to TNF-alpha and separated by approximately 1.1 kb of intergenic space, and each gene consists of four exons and three introns, similar to those of the other species examined thus far. Comparison analysis showed that the rat TNF have high sequence homology with the mouse TNF (TNF-alpha, 86.5%; TNF-beta, 89.3%) and relatively low homology with the human, rabbit, and porcine TNF. The upstream sequence of rat TNF-alpha contains a number of sequence motifs implicated in the expression and regulation of eukaryotic genes, including binding sites for the transcription factors Sp-1, Ap-2, IFN.1 and NF-kappa B. The possible significance of potential regulatory sequence elements found in the rat TNF-alpha in the context of transcriptional regulatory mechanisms is discussed.

Amino Acid Sequence↗
PubMed1992

Role of protein kinase C activity in tumor necrosis factor-alpha gene expression. Involvement at the transcriptional level.

Primary rat astrocytes express TNF-alpha protein in response to various stimuli including a combined treatment with IFN-gamma and LPS, or IFN-gamma and IL-1 beta. This study was undertaken to further elucidate the mechanisms underlying TNF-alpha gene expression in the astrocyte, and to determine the intracellular signaling pathways involved in IFN-gamma/LPS and/or IFN-gamma/IL-1 beta induction of the TNF-alpha gene. We demonstrate that TNF-alpha mRNA is rapidly induced, and mRNA levels peak after 2 h of stimulation. De novo protein synthesis is not required for TNF-alpha expression because the inclusion of cycloheximide does not prevent expression of the gene and acts to superinduce TNF-alpha mRNA levels. IFN-gamma/LPS induces transcriptional activation of the TNF-alpha gene as assessed by nuclear run-on experiments. Cycloheximide acts to increase both transcription of the TNF-alpha gene and stability of TNF-alpha mRNA thereby resulting in increased TNF-alpha steady state mRNA levels. Two protein kinase C (PKC) inhibitors, H7 and staurosporine, abrogate IFN-gamma/LPS- and IFN-gamma/IL-1 beta-induced TNF-alpha expression in a dose-dependent manner. PKC activity is required for transcription of the TNF-alpha gene, and does not appear to be involved in TNF-alpha mRNA stabilization. Taken together, these data demonstrate that TNF-alpha gene expression in primary rat astrocytes is induced in a PKC-dependent manner.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Expression of neurotrophins and the low-affinity NGF receptor in septal and hippocampal reaggregate cultures: local physiologic effects of NGF synthesized in the septal region.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are members of a family of trophic factors designated the neurotrophins, each of which can bind to the low-affinity NGF receptor (LNGFR). To investigate the mechanisms that regulate the expression of the neurotrophins and the LNGFR in the developing brain, we grew cells from the embryonic mouse septum and hippocampus in reaggregating cell culture and compared neurotrophin and LNGFR expression in developing reaggregates with that seen in the developing septum and hippocampus in situ. NGF, BDNF, NT-3 and LNGFR were each expressed in septal and hippocampal reaggregates as well as the native septum and hippocampus. Additionally, the temporal expression profiles observed in reaggregates were generally similar to those seen in the respective brain regions in situ. In order to determine whether NGF can modulate neurotrophin or LNGFR expression, reaggregates were cultured in the continual presence of either exogenous NGF or anti-NGF antibodies. NGF-treated septal cultures expressed twice the level of LNGFR mRNA as was seen in untreated septal cultures; on the other hand, septal cultures grown in the presence of anti-NGF antibodies, to neutralize endogenously synthesized NGF, displayed a 3-fold decrease in LNGFR mRNA expression compared to untreated cultures. No effects of NGF or anti-NGF were observed on LNGFR expression in hippocampal reaggregates, or on neurotrophin mRNA expression in either reaggregate type. These results suggest that regulatory mechanisms intrinsic to the septal and hippocampal regions control neurotrophin and LNGFR expression. NGF is likely to be one of these regulatory cues since it acts locally in septal reaggregates to control the developmental expression of LNGFR mRNA. The possible roles of locally synthesized NGF and other neurotrophins in the development of septal neurons are discussed.

Aging↗
PubMed1990

Effect of combined substance use on laboratory markers of alcoholism.

This article examines the commonly used laboratory indicators of heavy alcohol use (elevated MCV, GGTP and AST values) in subgroups of drug-using and non-drug-using alcoholic men admitted to an inpatient alcoholism treatment program. A total of 380 consecutive admissions meeting DSM-III diagnostic criteria for alcohol use or dependence were studied. Of these subjects, 75% used both alcohol and drugs. The most frequently used drugs were marijuana, cocaine, amphetamines and tranquilizers. Overall, subjects who used drugs with alcohol had significantly lower MCV and GGTP values than subjects who used alcohol alone. More specifically, cocaine use was associated with lower MCV values, marijuana use with lower AST values and heroin use with higher AST and GGTP values. These differences between drug-using and non-drug-using alcoholics were significant even after controlling for variables that affect the laboratory values such as age, quantity, frequency and duration of alcohol consumption. These findings indicate that any study of laboratory markers of alcoholism needs to consider concomitant illicit drug use patterns.

Adult↗
PubMed1989

Aspergillosis of the paranasal sinuses--diagnostic significance of the computed tomography.

Aspergillosis of the paranasal sinuses appears to be relatively rare in occurrence, but there is a growing incidence of it in accordance with the increasing use of antibiotics, steroid hormones, anticancer drugs, and radiation therapy. We have seen 15 cases of aspergillosis of the paranasal sinuses in which computed tomography (CT) was helpful for diagnosis. The characteristic feature of CT findings was the intermixture of high and low density areas in the affected paranasal sinuses, apparently caused by increased X-ray absorption due to calcification. These findings indicate that CT is useful in the preoperative diagnosis of aspergillosis of the paranasal sinuses.

Adult↗
PubMedDate not supplied

Accuracy of the Bernoulli equation for estimation of pressure gradient across stenotic Blalock-Taussig shunts: an in vitro and numerical study.

Accurate assessment of the pressure gradient (PG) across a modified Blalock-Taussig (mBT) shunt is important in planning for staging to a cavopulmonary anastomosis for many patients with cyanotic congenital heart disease. The mBT shunt Doppler velocity has been used in the simplified echo Bernoulli equation to predict this PG with variable results. The purpose of this investigation is to provide analysis of the flow dynamics through stenotic mBT shunts and to assess the accuracy of Doppler techniques in determining PGs and the presence and location of stenosis. Three-dimensional models of mBT shunts were created, with and without stenosis. In vitro and computational fluid dynamic flow experiments were carried out. In vitro experiments demonstrated that the Doppler-measured PG underestimated catheter-measured PG in the mBT shunt with diffuse stenosis. In nonstenotic mBT and those that had outlet and inlet stenosis, the Doppler-measured PG showed underestimation of catheter PG at low PG and generally improved estimation at higher PG. In the mBT shunt model with inlet stenosis, there was slight overestimation at higher PG. Numerical simulations provide an "observation window" into events occurring in and around mBT shunts showing that the hemodynamics vary significantly. Changing hemodynamic processes are at work through stenotic mBT shunts causing variations in overestimation and underestimation of catheter-measured PG using the simplified echo Bernoulli equation. Our results have relevance to the assessment of patients with mBT shunts, helping to explain some of the discrepancies that investigators have found in the past.

Binomial Distribution↗
PubMedDate not supplied

Comorbid personality impairment in body dysmorphic disorder.

Personality impairment was evaluated in 17 body dysmorphic disorder (BDD) patients undergoing a treatment study of clomipramine versus desipramine. Semistructured interviews were administered using both categorical (Structured Clinical Interview for DSM [SCID II]) and dimensional (Dimensional Assessment of Personality Impairment [DAPI]) methods. Personality measures were also correlated with a range of clinical variables (severity of BDD and depressive symptoms, age, duration of illness, and response to treatment). A secondary aim of the study was to provide preliminary validation for the DAPI. Consistent with previous studies, BDD patients showed considerable personality pathology. By SCID II, patients met criteria for a mean of 2.53 personality disorder diagnoses; 87% of patients met criteria for at least 1 diagnosis and 53% for more than 1. Cluster C diagnoses were the most common. Mean scores for the DAPI were 2.63 (3 = mild impairment) to 6.41 (7 = severe impairment), averaging 5.26 (5 = moderate). With regard to the DAPI, the results provided preliminary evidence of good reliability and validity. Moreover, both personality measures were highly intercorrelated. Although SCID II diagnoses correlated with baseline depression (Hamilton Rating Scale for Depression [HRSD]) scores, there were few other significant correlations between personality and other clinical variables. Of note, however, treatment responders demonstrated less personality impairment than nonresponders. The finding that personality measures were highly intercorrelated but, on the whole, not well correlated with other clinical measures supports the distinct and dissociable nature of personality phenomena in BDD. Despite the small sample size, these results suggest that personality impairment appears to be significant factor in BDD and may even play a role in treatment response.

Adult↗
PubMedDate not supplied

Atypical ductal hyperplasia in stereotactic breast biopsies: enhanced accuracy of diagnosis with the mammotome.

There is little literature assessing the incidence of subsequent carcinoma in patients diagnosed with atypical ductal hyperplasia (ADH) by mammotome. We reviewed 216 stereotactic mammotome biopsies (SMBs) and compared the results to the 121 automated tru-cut biopsies (ATC) performed at our breast care center from June 1994 to July 1998. The median age in the mammotome series was 57 years, compared to 56 years in the ATC group. An increase in biopsies for microcalcifications (49% versus 41%) was noted in the SMB series. This was accompanied by an increase in the number of cases with a diagnosis of pure ductal carcinoma in situ (DCIS) (10% versus 4%). Compared to the tru-cut, in which 38% (3 of 8) of the cases diagnosed as atypical hyperplasia (AH) showed DCIS and/or invasive carcinoma on open biopsy, none of the cases diagnosed as AH on mammotome revealed carcinoma on open biopsy. ADH is more accurately diagnosed with SMB than by the ATC method and may not be an indication for subsequent open biopsy.

Adult↗