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J H Kwon

Publications and source records attributed to J H Kwon.

34 records · Page 2Linked to original sources
PubMed1998

Beta-adrenergic and fibroblast growth factor receptors induce neuronal process outgrowth through different mechanisms.

The mechanisms that initiate and direct neuronal process formation remain poorly understood. We have recently described a neuronal progenitor cell line, AS583-8.E4.22 (AS583-8) which undergoes neurite formation in response to beta2-adrenergic and basic fibroblast growth factor (bFGF) receptor activation [Kwon, J.H. et al., (1996) Eur. J. Neurosci., 8, 2042-2055]. In the present study, a comparison of these responses revealed that isoproterenol (ISO), a beta-adrenergic receptor agonist, induces multiple, highly branched processes within 30 min while bFGF induces fewer, unbranched processes within 24 h. In contrast to the ISO response, bFGF induces mitogen-activated protein kinase activation and c-fos expression in the cell line and results in neurite outgrowth that is dependent on new mRNA and protein synthesis. Two-dimensional isoelectric focusing-sodium dodecyl sulphate-polyacrylamide gel electrophoresis of cytoskeletal preparations revealed different patterns following ISO vs. bFGF exposure suggesting selective changes in protein expression and/or post-translational modifications. Immunoblot analysis of these preparations for beta-tubulin, tyrosinated alpha-tubulin and acetylated alpha-tubulin also revealed different patterns following each type of treatment. Follow-up confocal microscopy revealed that following ISO, the distribution of tyrosinated tubulin extends to the distal ends of processes whereas acetylated alpha-tubulin is diminished within distal ends. This pattern has been reported to be associated with enhanced microtubule dynamics, a state in which process outgrowth is facilitated. In contrast, following bFGF treatment the distributions of tyrosinated and acetylated alpha-tubulin were identical, a state associated with a diminution of microtubule dynamics. These results, a different time course of neurite formation, dependency on new gene expression and differential expression and cellular distribution of major cytoskeleton proteins suggest that neurite outgrowth induced by ISO vs. bFGF is mediated by two distinct intracellular effector mechanisms in AS583-8 cells. In addition, studies, using the differential distribution of post-translational modified alpha-tubulins in neurites of primary neuronal cultures as marker for the two distinct processes of neurite formation suggest, that similar mechanisms are present in vivo. Therefore, the AS583-8 cell line provides a useful model to study these signalling mechanisms that couple neurotransmitter and growth factor receptor activation to the cytoskeletal changes that mediate neurite formation.

Animals↗
PubMed1997

Insulin activates Ras in the PC12 cell line.

To address whether Ras can be activated by insulin in the PC12 cell line, proteins interacting with insulin receptor and IRS-1 molecules and their tyrosine phosphorylation were analyzed by immunoblotting following immunoprecipitation with antibodies. Tyrosine phosphorylation of the insulin receptor and IRS-1 was increased by insulin. Grb2 and Ras-GAP appeared in the immunoprecipitates by anti-insulin receptor and anti-IRS-1 from insulin-treated cells. In addition, PI 3-kinase was activated by insulin treatment in this cell line and Grb2, Ras-GAP, and MAP kinase were coprecipitated with Ras from both insulin-treated and NGF-treated cells. Analysis of MAP kinases from insulin-treated cells revealed that insulin, like NGF, increased tyrosine phosphorylation. However, activation of the MAP kinase by NGF lasted longer than activation by insulin. These results indicate that Ras can be activated by insulin in the PC12 cell line and that Ras activation is neither an accurate nor a plausible method of discriminating signals between proliferation and differentiation.

Animals↗
PubMed1996

Beta-adrenergic receptor activation promotes process outgrowth in an embryonic rat basal forebrain cell line and in primary neurons.

A clonal cell line, AS583-8.E4.22, from the embryonic day 15 rat basal forebrain was established using retrovirus-mediated transduction of a temperature-sensitive mutant of the simian virus 40 (SV40) large tumour antigen. The cell line expresses cytoskeletal and neurotransmitter features indicative of neuronal commitment. In response to agents that increase intracellular cAMP, including forskolin and catecholamines, the cell line exhibits rapid process outgrowth and growth cone formation that does not require new gene expression or protein synthesis. The neurite outgrowth induced by catecholamines is mediated by beta 2-adrenergic receptors and is characterized by a rapid, reversible redistribution of filamentous actin. Neurons from primary cultures of embryonic day 15 basal forebrain were also found to respond to beta-adrenergic receptor agonists by enhancing growth cone formation. These results suggest that catecholamines provide cues that induce cytoskeletal rearrangements leading to neuronal process outgrowth and growth cone formation in the developing basal forebrain and possibly other neuronal progenitor cell populations. The neuronal basal forebrain cell line provides an ideal model to study the signalling mechanisms underlying the catecholamine-induced process outgrowth.

Adrenergic beta-Agonists↗
PubMed1996

Obsessive-compulsive and spectrum disorders: overview and quality of life issues.

Although obsessive-compulsive disorder (OCD) is among the most common of all psychiatric disorders, the diagnosis is frequently overlooked unless specific screening questions are asked by the treating physician. The obsessive thinking and compulsive behaviours that primarily characterize OCD can be found in other obsessive-compulsive "spectrum" disorders as well. These disorders affect a sizable percentage of the U.S. population and have thus become an increasing public health problem. Preliminary results from our comprehensive survey of OCD sufferers found significant impairments in quality of life and substantial costs associated with the morbidity and treatment of OCD. This is of particular interest to the primary care practitioner since these patients often present initially to primary care physicians, and early diagnosis and appropriate treatment can substantially improve outcome.

Adolescent↗
PubMed1993

Hypereosinophilic syndrome: imaging findings in patients with hepatic involvement.

OBJECTIVE: Hypereosinophilic syndrome (eosinophilia without demonstrable cause) commonly involves eosinophilic infiltration of the liver and spleen, but few reports have described the imaging findings. Accordingly, we reviewed the imaging findings in five patients with this syndrome in whom the liver was involved. MATERIALS AND METHODS: Five patients who had hypereosinophilic syndrome with hepatic involvement were included in the study. The diagnosis of hepatic involvement was based on pathologic proof in two patients and on imaging and laboratory findings in the other three. Histologic examination of the hepatic lesions showed extensive eosinophilic infiltration in two patients and centrilobular necrosis in one. All patients had chest radiography, barium studies of the gastrointestinal tract, abdominal CT, and sonography. Four patients had hepatosplenic scintigraphy. All patients were followed up for 4-24 months. RESULTS: All patients had mild to marked hepatomegaly with multiple focal lesions. Focal lesions were detected on sonograms in three patients, on CT scans in four, and on scintigrams in three. On sonograms, the lesions were usually small (less than 2 cm in diameter), sharply or poorly defined nodules with varied echogenicity scattered throughout the liver. The lesions were hypodense with poorly defined margins on CT scans and appeared as variably sized areas of decreased radionuclide uptake on scintigrams. For each patient, the number, size, and shape of the lesions varied considerably from one imaging study to another. On follow-up studies 2-6 months after treatment, the appearance of the liver was normal. Other radiologic findings included transient pulmonary infiltrates (two patients), mild cardiomegaly (one patient), and mild lymphadenopathy (three patients). CONCLUSION: Hypereosinophilic syndrome is a cause of focal hepatic lesions seen on sonograms, CT scans, or scintigrams. The lesions are characterized by the varied appearance on the different types of images and the disappearance of the lesions with treatment.

Adult↗
PubMed1992

Responses to the negative emotions of others by autistic, mentally retarded, and normal children.

Attention, facial affect, and behavioral responses to adults showing distress, fear, and discomfort were compared for autistic, mentally retarded, and normal children. The normal and mentally retarded children were very attentive to adults in all 3 situations. In contrast, many of the autistic children appeared to ignore or not notice the adults showing these negative affects. As a group, the autistic children looked at the adults less and were much more engaged in toy play than the other children during periods when an adult pretended to be hurt. The autistic children were also less attentive to adults showing fear, although their behavior was not different from the normal children. Few of the children in any group showed much facial affect in response to these situations. The results are discussed in terms of the importance of affect in the social learning experiences of the young child.

Affect↗
PubMed1991

High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma.

Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method.

Adolescent↗
PubMed1989

In vitro chemosensitivity of two Ewing's sarcoma cell lines: implication for autologous bone marrow transplantation.

Intensive chemotherapy requiring rescue with autologous bone marrow may be an encouraging mode of treatment for poor prognosis Ewing's sarcoma (ES). In vitro chemosensitivity test may be useful for establishing an effective purging condition. We studied the in vitro effects of a variety of chemotherapeutic agents on two established ES cell lines (ES-5838 and ES-A4573) and marrow colony-forming unit-granulocyte macrophage (CFU-GM). 4-Hydroperoxycyclophosphamide (4-HC), at 100 microM produced complete inhibition (greater than 5 log) of clonogenic growth of both ES cell lines and spared 6.9% of normal CFU-GM growth. Etoposide (VP-16), at 100 microM produced 3-3.5 log inhibition of ES cell lines and complete inhibition of CFU-GM growth. Adriamycin (ADR) and vincristine (VCR) were more cytotoxic to ES-5838 cells than ES-A4573 cells. ADR at 1 microM produced 99.7% inhibition of ES-5838 cells, 92.2% of ES-A4573 cells, and 86% inhibition of CFU-GM. VCR at 1 microM produced 98.6% inhibition of ES-5838 cells, only 43.7% of ES-A4573 cells, and 75% inhibition of CFU-GM growth. Addition of verapamil did not enhance VCR cytotoxicity of ES cell lines. These studies indicate that 4-HC may be a useful agent for purging metastatic ES cells from the bone marrow for autologous marrow transplantation.

Antineoplastic Agents↗
PubMed1989

In vitro chemopurification of neuroblastoma cells: comparison of 6-hydroxydopamine and ascorbic acid with 4-hydroperoxycyclophosphamide.

To develop an effective neuroblastoma (NB) purging condition, we have compared in vitro cytotoxicity of 6-hydroxydopamine (6-OHDA) and ascorbic acid, with 4-hydroperoxycyclophosphamide (4-HC) on three NB cell lines (SK-N-BE2, SMS-SAN, and LA-N-1) and also upon human hematopoietic stem cells. Our study included mixing NB cells with 20-fold excess of irradiated bone marrow buffy coat cells to simulate the borderline remission marrow. When NB cells were treated without marrow cells, all three NB cell lines were very sensitive to 6-OHDA; complete inhibition of SK-N-BE2 and SMS-SAN cells was achieved at 10 micrograms/ml, and greater than 4 log inhibition of LA-N-1 was observed at 100 micrograms/ml of 6-OHDA. Addition of marrow cells caused marked reduction of the 6-OHDA-induced cytotoxicity of NB cells, and under similar conditions, colony-forming units-granulocyte-macrophage (CFU-GM) growth was not inhibited significantly. In the absence of normal marrow cells, 60 minutes of treatment with 100 microM of 4-HC produced complete inhibition (greater than 4.5 log) of SK-N-BE2 and SMS-SAN cells, greater than 4 log inhibition of LA-N-1 cells, and 97% of CFU-GM. Addition of marrow cells reduced the cytotoxicity of 4-HC, and 100 microM of 4-HC produced 99.8% inhibition of LA-N-1 colony growth. Shortening incubation duration to 30 minutes resulted in further reduction of 4-HC cytotoxicity; 100 microM of 4-HC caused 98.3%, 45%, and 33% inhibition of LA-N-1 cells, marrow CFU-GM, and burst-forming units-erythrocytes (BFU-E), respectively. At 200 microM, complete inhibition (greater than 4 log) of LA-N-1 colony growth was noted, and 9.9% of CFU-GM and 9.3% of BFU-E growth was observed. These data favor the use of 4-HC for purging marrow of NB, cells in the clinical autologous marrow transplantation.

Antibodies, Monoclonal↗
PubMed1988

Anti-tumor efficacy of interleukin-2-activated killer cells in human neuroblastoma ex vivo.

We studied the ex vivo sensitivity of continuously cultured neuroblastoma cells from 3 different patients towards interleukin-2-induced cell-mediated cytotoxicity. A mean (+/- SD) target cell lysis (4 h 51Cr release) of 49 +/- 11, 46 +/- 8, and 32 +/- 11% in SMS-SAN, LA-N-1, and SK-N-BE2 cell lines, respectively, was achieved when neuroblastoma cells were co-cultured at an effector-to-target (E:T) ratio of 50:1 with peripheral blood mononuclear cells (PBMC) that had been preincubated for 4 days in the presence of recombinant interleukin-2 (rIL-2; 100 U/ml). Under identical conditions, 93 +/- 9% of Daudi cells (a standard target for rIL-2-activated killer cells) were lysed. Preincubation of rIL-2-induced PBMC cultures in the presence of irradiated neuroblastoma targets (LA-N-1, SK-N-BE2) resulted in a significant cytolytic augmentation. At E:T ratios of 50:1 and 10:1, day-4 rIL-2/LA-N-1-stimulated PBMC produced 69 +/- 7 and 41 +/- 11% lysis of LA-N-1 cells, as compared to 46 +/- 8 and 22 +/- (mean +/- SD) 7% lysis by untargeted PBMC that were preincubated with rIL-2 (100 U/ml) in the absence of LA-N-1 target cells (p less than 0.05). Co-incubation of rIL-2-induced PBMC preparations with irradiated LA-N-1 and SK-N-BE2 cells, respectively, did not significantly enhance the cytolytic activity against other neuroblastoma targets and the standard Daudi cell line (p greater than or equal to 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity, Immunologic↗
PubMed1988

Ewing's sarcoma: ex vivo sensitivity towards natural and lymphokine-activated killing.

We studied the ex vivo cell-mediated cytotoxicity of natural killer (NK) and lymphokine-activated killer (LAK) cells against continuously cultured Ewing's sarcoma cells from 3 different patients. Target cell lysis was measured in a 4-hour 51Cr radioisotope release assay. At an effector to target (E:T) ratio of 50:1, the mean (+/- 1 SD) cytolysis by fresh purified large granular lymphocytes (NK cells) was 20 +/- 8, 25 +/- 2, and 21 +/- 3% in Ewing's sarcoma cell lines 6647, 5838, and A4573, respectively. Under identical conditions, NK cells lysed 56 +/- 7% of K562 (a standard NK target), and 3 +/- 3% of Daudi (a standard NK-resistant LAK target). When compared to fresh unseparated peripheral blood mononuclear cells (PBMC), purified NK cells did not exhibit an enhanced cytotoxic reactivity against either Ewing's sarcoma target. In contrast, LAK cells (i.e., PBMC that were preincubated for 4 days in the presence of rIL-2) were highly cytotoxic against all three Ewing's sarcoma targets. LAK activity was dependent on the concentration of rIL-2 used in PBMC cultures. Optimum cell-mediated toxicity against the standard LAK target Daudi (99 +/- 10% cytolysis at 50:1 E:T ratio) was achieved at rIL-2 concentrations of 1,000 u/ml. LAK cells grown under these conditions were also effective against Ewing's sarcoma cells. At an E:T ratio of 50:1, 86 +/- 16, 85 +/- 16, and 67 +/- 13% inhibition was observed in 6647, 5838, and A4573 cells, respectively, as compared to 17 +/- 10, 19 +/- 15, and 29 +/- 11% cytolysis by fresh uninduced PBMC. In summary, our results suggest that rIL-2-induced LAK-type immune effector cells may be of some therapeutic value in the treatment of poor prognosis Ewing's sarcoma.

Cell Line↗
PubMed1987

Human bone marrow CFU-GM and BFU-E localized by light scatter cell sorting.

Flow cytometric separation was performed on the normal human bone marrow (BM) by using the low-angle (0 degrees) or high-angle (90 degrees) light scatter. Four distinct subpopulations of cells can be enriched from normal human BM and these fractions were subsequently evaluated for their morphological properties as well as their clonogenic capacity in various progenitor cell assays. Our results indicate that human erythroid and granulocyte-macrophage progenitor cells can be separated from BM low-density cells by cell sorting, and these cells show similar 0 degrees and 90 degrees light scatter properties to those observed with murine bone marrow studies. Flow cytometric analysis also suggests that the majority of sorted BFU-E and CFU-GM resides in the blast cell subset of human BM mononuclear cells.

Bone Marrow Cells↗
PubMed1987

Effects of low dose rate irradiation on human marrow hematopoietic and microenvironmental cells: sparing effect upon survival of stromal and leukemic cells.

The effects of different dose rates of in vitro irradiation on the proliferative capacity of marrow stromal, hematopoietic and leukemic colony-forming cells (CFC) are described. Marrow cell suspensions, HL-60 cells and trypsin-dispersed fibroblasts were irradiated at 5 or 45 cGy/min and then assayed for CFC. Irradiation at low (5 cGy/min) compared to high (45 cGy/min) dose rate showed a significant difference in survival of stromal and of HL-60 cells, but not of hematopoietic progenitors: the respective D0 values were 170 and 120 (p = 0.003) for marrow fibroblastic progenitors (CFU-F); 145 and 110 (p = 0.005) for passaged marrow fibroblasts (CFU-F); 170 and 140 (p = 0.045) for HL-60 cells; 85 and 85 for multipotential CFC (CFU-mix); 125 and 120 for erythroid progenitors (BFU-E); and 115 and 120 for granulomonopoietic progenitors (CFU-GM) (p = 0.5 for hematopoietic clonogenic cells). Marrow suspensions did not establish confluent stromal layers in long-term marrow cultures following irradiation with 600 cGy at 45 cGy/min, whereas after 840 cGy at 5 cGy/min confluent stromal layers were obtained. This indicates that low dose rate-sparing effect applies to all stromal cell progenitors. Confluent stromal layers derived from progenitors surviving irradiation sustained hematopoiesis as well as controls when co-cultured with fresh hematopoietic cells. Adherent layers in long-term marrow cultures irradiated after establishment with doses less than or equal to 1500 cGy at 5 or 45 cGy/min also showed normal hematopoietic supportive function when co-cultured with freshly isolated hematopoietic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1987

Preclinical assessment of purging with VP-16-213: key role for long-term marrow cultures.

An evaluation of the effects of VP-16 on normal human marrow cells and representative lymphoma-leukemia cell lines was performed to assess this agent's applicability to ex vivo marrow purging. Tumoricidal dose curves were defined using malignant lymphoid (SK-DHL2 and Reh) and myeloid (HL-60) cells admixed with a 20-fold excess of irradiated marrow cells to simulate a borderline remission marrow. One-hour treatments yielded ID50 of less than 5 mumol/L of VP-16 for clonogenic units from each cell line; rare-to-zero clonogenic units survived exposure to 50 to 100 mumol/L. CFU-Mix, BFU-E, and CFU-GM were equal in their sensitivity to VP-16 (ID50s25 to 30 mumol/L). Marrows treated with 75 mumol/L were completely depleted of these colony-forming cells but produced CFU-GM in one-stage long-term marrow cultures (LTMCs). This dose had little adverse effect on the proliferative capacity of marrow stromal progenitors, as measured by CFU-F (ID50 271 mumol/L) and by the unperturbed development of adherent layers in LTMCs. Furthermore, these stromal layers were able to support hematopoiesis as well as controls in co-culture experiments with autologous marrow cells (two-stage LTMCs). In conclusion, doses of VP-16 that cleanse marrow of lymphoma-leukemia cells spare hematopoietic and stromal progenitors as demonstrated by LTMCs. These data favor the use of VP-16 in the clinical autotransplant setting.

Bone Marrow↗
PubMedDate not supplied

Retroanastomotic hernia after gastrojejunostomy: US and CT findings with an emphasis on the whirl sign.

BACKGROUND: We reviewed ultrasound (US) and computed tomographic (CT) findings of retroanastomotic hernia and established whether such findings are characteristic of retroanastomotic hernia in patients who have undergone gastrojejunostomy. METHODS: During a recent 10-year period, we encountered 13 consecutive cases of retroanastomotic hernia. Of the patients involved, 11 underwent US, 10 underwent CT, and three underwent small bowel followthrough imaging. The US and CT scans were retrospectively reviewed to determine abnormal findings. Surgical proof was available in all cases. RESULTS: The efferent loop was herniated through the defect created behind the anastomosis in 10 cases, the efferent and afferent loops in two cases, and the afferent loop in one case. Retroanastomotic hernia was prospectively suggested in 12 of these 13 cases. Among the 10 cases of efferent loop herniation, US and CT signs of retroanastomotic hernia included whirling of mesenteric vessels, jejunal loops, and mesentery in the periumbilical abdomen (10 of 10); mural thickening of herniated bowel loops (six of 10); dilatation of herniated bowel loops (four of 10); decreased peristalsis of herniated bowel loops on US (three of nine); and decreased contrast enhancement of herniated bowel loops on CT (one of seven). In one case, US and CT signs of retroanastomotic hernia of the afferent loop included its dilatation and whirling of a short length of afferent loop behind the anastomosis. In two cases, US and CT signs of retroanastomotic hernia of the afferent and efferent loops included findings of afferent and efferent loop herniations. Three of 13 cases had reversible bowel ischemia, and one had bowel necrosis. CONCLUSION: Retroanastomotic hernia is an important condition, and the US and CT findings we have described might suggest its diagnosis.

Adult↗