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Biomedical subjects

J H Won

Publications and source records attributed to J H Won.

At least 19 recordsLinked to original sources
PubMed2001

The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines.

A 2.4-kb truncated L-plastin promoter was inserted either 5' to the LacZ gene (Ad-Lp-LacZ) or 5' to the cytosine deaminase (CD) gene (Ad-Lp-CD) in a replication-incompetent adenoviral vector backbone. Infectivity and cytotoxicity experiments with the LacZ and CD vectors suggested that the L-plastin promoter-driven transcriptional units were expressed at much higher levels in explants of ovarian cancer cells from patients and in established ovarian or bladder cancer cell lines than they were in normal peritoneal mesothelial cells from surgical specimens, in organ cultures of normal ovarian cells, or in the established CCD minimal deviation fibroblast cell line. Control experiments showed that this difference was not attributable to the lack of infectivity of the normal peritoneal cells, the normal ovarian cells, or the minimal deviation CCD fibroblast cell line, because these cells showed expression of the LacZ reporter gene when exposed to the replication-incompetent adenoviral vector carrying the cytomegalovirus (CMV)-driven LacZ gene (Ad-CMV-LacZ). The Ovcar-5 and Skov-3 ovarian cancer cell lines exposed to the Ad-Lp-CD adenoviral vector were much more sensitive to the prodrug 5-fluorocytosine (5FC), which is converted from the 5FC prodrug into the toxic chemical 5-fluorouracil, than was the CCD minimal deviation fibroblast cell line after exposure to the same vector. A mouse xenograft model was used to show that the Ad-Lp-CD vector/5FC system could prevent engraftment of ovarian cancer cells in nude mice. Finally, injection of the Ad-Lp-CD vector into s.c. tumor nodules generated a greater reduction of the size of the tumor nodules than did injection of the Ad-CMV-LacZ vectors into tumor nodules. The Ad-Lp-CD vectors were as suppressive to tumor growth as the Ad-CMV-CD vectors. These results suggest that an adenoviral vector carrying the CD gene controlled by the L-plastin promoter (Ad-Lp-CD) may be of potential value for the i.p. therapy of ovarian cancer.

Adenoviridae↗
PubMed2001

Inhibitory effect on immunoglobulin E production in vivo and in vitro by Siegesbeckia glabrescens.

Elevated levels of immunoglobulin (Ig)E are associated with immediate-type allergic reactions. The effect of an aqueous extract of Siegesbeckia glabrescens (Compositae) whole plants (SGWP) on in vivo and in vitro IgE production was studied in mice. SGWP dose-dependently inhibited the active systemic anaphylaxis and serum IgE production induced by immunization with ovalbumin and Bordetella pertussis toxin absorbed to aluminium hydroxide gel. SGWP dose-dependently inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, SGWP also showed an inhibitory effect on IgE production. These results suggest that SGWP has an anti-allergic activity by inhibiting IgE production from B cells.

Anaphylaxis↗
PubMed2001

Effect of Alpinia oxyphylla fruit extract on compound 48/80-induced anaphylactic reactions.

The effect of the aqueous extract of Alpinia oxyphylla Miq. (Zingiberaceae) fruits (AOFE) on anaphylactic reaction was investigated. AOFE completely inhibited compound 48/80-induced systemic anaphylactic shock at dose of 1.0 g/kg. When AOFE was pretreated at concentrations ranging from 0.01 to 1.0 g/kg, the plasma histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. AOFE also inhibited the histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. The level of cAMP in RPMC, when AOFE was added, transiently and significantly increased about 4-fold compared with that of basal cells. These results indicate that AOFE may be beneficial in the treatment of non-specific anaphylactic reactions.

Alpinia↗
PubMed2001

A case of malignant proliferating trichilemmoma of the scalp with multiple metastases.

We report a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. The patient demonstrated a round mass in the right occipital area for 12 months and the lesion grew rapidly to assume 8 x 6.5 x 4 cm in diameter, with areas of superficial erosion and crusting within the recent 3 months. The entire lesion was removed with a wide surgical excision. It recurred on the neck area 4 months after excision and the lesion was removed with surgical resection again. There was evidence of multiple metastases on CNS and mediastinal lymph nodes after 6 months. The patient was treated with cisplatin and etoposide combination chemotherapy and a partial response was achieved.

Adult↗
PubMed2000

Thrombopoietin is synergistic with other cytokines for expansion of cord blood progenitor cells.

We investigated the effects of recombinant human thrombopoietin (TPO) in combination with various cytokines including erythropoietin (EPO), interleukin-3 (IL-3), interleukin-6 (IL-6), and stem cell factor (SCF) on megakaryopoiesis, and the expansion of CD34+CD41a+ cells from human cord blood CD34+ cells with these cytokines under serum-free conditions. Human cord blood CD34+ cells were cultured in Megacult (Stem Cell Technologies Inc. Vancouver, Canada) in the presence of recombinant growth factors. Colony-forming unit-megakaryocyte (CFU-M) colonies were counted on day 14. CD34+CD41a+ and CD34-CD41a+ cell expansion was analyzed using a serum-free liquid culture system for 7 days with recombinant growth factors. TPO alone had a concentration-dependent effect on megakaryocyte colony growth. At concentrations above 1 ng/ml, TPO supported significant CFU-Meg colony formation in a concentration-dependent manner. The combination of TPO plus other cytokines, including EPO, IL-3, and SCF, resulted in a synergistic enhancement of the number of CFU-Meg colonies, but IL-6 failed to enhance the effect of TPO. The number of CD41a+ cells increased after 7 days in liquid culture of human cord blood CD34+ cells with various cytokines (EPO, IL-3, IL-6, SCF) combined with TPO, but SCF plus TPO only resulted in a significant synergistic increment of CD34+CD41a+ cells compared with TPO alone. The results of the present study indicate that EPO, IL-3, and SCF can be synergistic with TPO to stimulate proliferation of CFU-Meg and suggest that SCF plus TPO can expand CD34+CD41a+ cells to effect the rapid recovery of platelets in patients following stem cell transplantation.

Antigens, CD34↗
PubMed2000

Myelomatous effusion with poor response to chemotherapy.

While pleural effusion in multiple myeloma is relatively infrequent, myelomatous pleural effusion is extremely rare. We experienced a 61-year-old woman with IgD-lambda multiple myeloma and pleural effusion. The diagnosis was made originally by pleural biopsy, pleural fluid cytology and immunoelectropheresis of pleural fluid. Transient improvement of the pleural effusion was observed after administration of combination chemotherapy of vincristine, melphalan, cyclophosphamide, prednisone (VMCP)/vincristine, cyclophosphamide, adriamycin, prednisone (VCAP). Two months later, myelomatous pleural effusion recurred and no response to salvage therapy was observed. We reviewed the clinical feature of this case and literature concerning myelomatous pleural effusion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus.

We investigated the effect of an aqueous extract of Cichorium intybus (CIAE) on mast cell-mediated immediate type allergic reactions. CIAE (0.1-1000 mg kg-1) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, CIAE inhibited compound 48/80-induced anaphylactic reaction 100% with the dose of 1000 mg kg-1. CIAE 1000 mg kg-1also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with CIAE at a concentration ranging from 0.1 to 1000 mg kg-1, the plasma histamine levels were reduced in a dose-dependent manner. CIAE (1-1000 microg ml-1) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when CIAE (1000 microg ml-1) was added, increased significantly compared with that of control cells. These results indicate that CIAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Anaphylaxis↗
PubMed1999

Ammonium-chloride-induced prostatic hypertrophy in vitro: urinary ammonia as a potential risk factor for benign prostatic hyperplasia.

To test the possibility that urinary ammonia could be a risk factor for benign prostatic hyperplasia (BPH), we explored the cellular effects of ammonium chloride (NH(4)Cl) on prostatic cancer cells used as an experimental model. Following treatment of human prostatic cancer DU-145 cells with the varying concentrations of NH(4)Cl for 3 days, cell growth was inhibited by approximately 50% at 5 mM NH(4)Cl and almost completely inhibited at 10 mM NH(4)Cl. However, the individual cell size in these treated cells became approximately 2-fold larger and cellular protein content was also up to 2.5-fold greater than in untreated cells. This protein increase appeared to result from the reduced protein degradation, verified by metabolic labeling with [(14)C]valine. Western blot analysis further suggested that such reduced protein turnover could in part be due to the inactivation of a lysosomal acid protease, cathepsin D. Taken together, these studies demonstrate NH(4)Cl-induced hypertrophy in prostatic cancer cells, as evidenced by the growth inhibition, cell enlargement, and cellular protein increase. Therefore, ammonia is not an inert metabolic product; instead, its chronic effects on the prostate may ultimately lead to significant cellular and biochemical alterations of the prostate such as BPH.

Ammonia↗
PubMed1999

A new in vivo microvascular preparation of the hamster ovary.

Ovarian function in the cycling female is intimately related to and dependent upon significant microvascular regulation and restructuring. To enable investigation of the microvascular determinants of ovarian function, we present an in vivo preparation of the golden hamster ovary. The preparation does not compromise the ovarian vascular supply. The viability and responsiveness of the preparation were confirmed by quantifying arteriolar responses to vasoactive agents in 17 hamsters. Small surface arterioles (mean diameter 15-16 microns) responded with statistically significant changes in diameter to adenosine and oxygen and showed significant, dose-dependent constriction in response to norepinephrine and the NO synthase inhibitor L-NAME. Other key findings included extremely high microvascular permeability that varied with the day of the estrous cycle and functionally significant architectural features of the utero-ovarian vascular network. Potential applications of the preparation include elucidation of the role of the microvasculature in follicular development and luteal regression, investigation of utero-ovarian crossregulation, and development of a model for the study of ovarian angiogenesis and vascular regression.

Animals↗
PubMed1998

Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a potential purging method for autologous transplantation.

Ad.CMV-CD is a replication incompetent adenoviral vector carrying a cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD) gene. The CD transcription unit in this vector catalyzes the deamination of the nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic drug 5-fluorouracil (5-FU). This adenoviral vector prodrug activation system has been proposed for use in selectively sensitizing breast cancer cells, which may contaminate collections of autologous stem cells products from breast cancer patients, to the toxic effects of 5-FC, without damaging the reconstitutive capability of the normal hematopoietic cells. This system could conceivably kill even the nondividing breast cancer cells, because the levels of 5-FU generated by this system are 10 to 30 times that associated with systemic administration of 5-FU. The incorporation of 5-FU into mRNA at these high levels is sufficient to disrupt mRNA processing and protein synthesis so that even nondividing cells die of protein starvation. To test if the CD adenoviral vector sensitizes breast cancer cells to 5-FC, we exposed primary explants of normal human mammary epithelial cells (HMECs) and the established breast cancer cell (BCC) lines MCF-7 and MDA-MB-453 to the Ad.CMV-CD for 90 minutes. This produced a 100-fold sensitization of these epithelial cells to the effects of 48 hours of exposure to 5-FC. We next tested the selectivity of this system for BCC. When peripheral blood mononuclear cells (PBMCs), collected from cancer patients during the recovery phase from conventional dose chemotherapy-induced myelosuppression, were exposed to the Ad.CMV-CD for 90 minutes in serum-free conditions, little or no detectable conversion of 5-FC into 5-FU was seen even after 48 hours of exposure to high doses of 5-FC. In contrast, 70% of 5-FC was converted into the cytotoxic agent 5-FU when MCF-7 breast cancer cells (BCCs) were exposed to the same Ad.CMV-CD vector followed by 5-FC for 48 hours. All of the BCC lines tested were shown to be sensitive to infection by adenoviral vectors when exposed to a recombinant adenoviral vector containing the reporter gene betagalactosidase (Ad.CMV-betagal). In contrast, less than 1% of the CD34-selected cells and their more immature subsets, such as the CD34+CD38- or CD34(+)CD33- subpopulations, were positive for infection by the Ad.CMV-betagal vector, as judged by fluorescence-activated cell sorting (FACS) analysis, when exposed to the adenoviral vector under conditions that did not commit the early hematopoietic precursor cells to maturation. When artificial mixtures of hematopoietic cells and BCCs were exposed for 90 minutes to the Ad.CMV-CD vector and to 5-FC for 10 days or more, a greater than 1 million fold reduction in the number of BCCs, as measured by colony-limiting dilution assays, was observed. To test if the conditions were damaging for the hematopoietic reconstituting cells, marrow cells collected from 5-FU-treated male donor mice were incubated with the cytosine deaminase adenoviral vector and then exposed to 5-FC either for 4 days in vitro before transplantation or for 14 days immediately after transplantation in vivo. There was no significant decrease in the reconstituting capability of the male marrow cells, as measured by their persistence in female irradiated recipients for up to 6 months after transplantation. These observations suggest that adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene followed by exposure to the nontoxic pro-drug 5-FC may be a potential strategy to selectively reduce the level of contaminating BCCs in collections of hematopoietic cells used for autografts in breast cancer patients.

Adenoviridae↗
PubMed1998

Phospholipase C-delta1 and oxytocin receptor signalling: evidence of its role as an effector.

Although the oxytocin receptor modulates intracellular Ca2+ ion levels in myometrium, the identities of signal molecules have not been clearly clarified. Our previous studies on oxytocin receptor signalling demonstrated that 80 kDa Ghalpha is a signal mediator [Baek, Kwon, Lee, Kim, Muralidhar and Im (1996) Biochem. J. 315, 739-744]. To elucidate the effector in the oxytocin receptor signalling pathway, we evaluated the oxytocin-mediated activation of phospholipase C (PLC) by using solubilized membranes from human myometrium and a three-component preparation containing the oxytocin receptor-Ghalpha-PLC-delta1 complex. PLC-delta1 activity in the three-component preparation, as well as PLC activity in solubilized membranes, was increased by oxytocin in the presence of Ca2+ and activated Ghalpha (GTP-bound Ghalpha). Furthermore the stimulated PLC-delta1 activity resulting from activation of Ghalpha via the oxytocin receptor was significantly attenuated by the selective oxytocin antagonist desGly-NH2d(CH2)5[Tyr(Me)2,Thr4]ornithine vasotocin or GDP. Consistent with these observations, co-immunoprecipitation and co-immunoadsorption of PLC-delta1 in the three-component preparation by anti-Gh7alpha antibody resulted in the PLC-delta1 being tightly coupled to activated Ghalpha on stimulation of the oxytocin receptor. These results indicate that PLC-delta1 is the effector for Ghalpha-mediated oxytocin receptor signalling.

Calcium↗
PubMed1998

A case of CMV disease of the jejunum in a patient with non-Hodgkin's lymphoma.

CMV infection may occur anywhere in the gastrointestinal tract. Among the small intestine, ileum is the most common site of CMV disease and infection of jejunum is a rare one in patients with CMV gastroenteritis. Although rare, the reason why the recognition of this diagnosis is important is that it cause the lethal hemorrhage and perforation of gastrointestinal tract when its diagnosis and treatment was delayed. Rapid diagnosis are able to using the immunohistochemical stain in shell vial culture of infected specimen or peripheral neutrophils preparation in viremic patients within 8 to 36 hours. The treatment of choice is antiviral agent or surgical resection. We experienced a case of CMV disease of jejunum in patient with non-Hodgkin's lymphoma who showed severe ulceration in jejunum and massive intestinal hemorrhage, and he survived after successful treatment with segmental resection of jejunum and intravenous ganciclovir.

Adult↗
PubMed1997

'Swiss cheese' lymphangiectasia in a case of solitary morphea profunda.

Reports of lymphangiectases that occur in lesions of morphea are rare. We describe a 24-year-old woman with a solitary morphea profunda associated with lymphangiectasia. Unlike previously reported cases, our case showed lymphatic dilatation resembling Swiss cheese and developed around a milium.

Adult↗
PubMed1997

A case of coagulation factor V deficiency complicated with intracranial hemorrhage.

Factor V deficiency is a relatively uncommon disorder, inherited as an autosomal recessive trait that manifests clinically only in individuals who inherit the defective gene from both parents. The hemorrhage of nasal and oral cavity and ecchymosis are common but intracranial hemorrhage is very rare. We experienced a 53 year old male patient with intracranial hemorrhage due to factor V deficiency. The laboratory tests showed prolongation of APTT and PT, normal bleeding time and normal thrombin time. The levels of the coagulation profiles on the patient revealed a significant decrease factor V, below 1% of normal range (60-140%). Other coagulation factors were normal. He was treated with fresh frozen plasma and completely recovered 3 weeks after treatment.

Cerebral Hemorrhage↗
PubMed1997

A case of lymphomatoid papulosis occurred simultaneously with Ki-1-positive anaplastic large cell lymphoma.

Lymphomatoid papulosis (LyP) is a chronic self-healing skin eruption that is clinically benign but histologically mimics a malignant lymphoma. However, lymphomatoid papulosis with anaplastic large cell lymphoma responds poorly to medical treatments, including chemotherapies. We experienced a 60-year-old male patient with lymphomatoid papulosis occurred simultaneously with relapsed Ki-1-positive anaplastic large cell lymphoma who was treated with salvage chemotherapy but, unfortunately, failed to be rescued. We report it with a review of the literature.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Mineral metabolism in plasma, urine and bone of periparturient cows fed anionic diets with different calcium and phosphorous contents.

The objective of this experiment was to evaluate the influences of Ca and P contents in an anionic diet on the mineral metabolism in plasma, urine and bone in periparturient diary cows. Fifteen multiparous Holstein-Friesian cows were divided into 3 dietary groups (5 cows/group) by dietary Ca and P contents and dietary cation-anion balance [(Na + K) - (Cl + S) mEq/kg DM]; diet 1 [low Ca (0.46%), low P (0.24%), cationic (+195.8 mEq/kg DM)]; diet 2 [low Ca (0.46%), low P (0.24%), anionic (-32.4 mEq/kg DM)]; and diet 3 [high Ca (0.93%), high P (0.60%), anionic (-41.0 mEq/kg DM)]. Cows were fed one of these 3 diets from approximately 4 weeks before the expected calving date to 5 days after calving. There was no outbreak of milk fever in any cows fed these 3 diets; however, plasma Ca levels at 1 and 2 days after calving tended to be higher in the cows fed diet 3 than those in the cows fed diets 1 or 2. Fractional urinary excretion of Ca in the cows fed diet 2 or 3 was higher than that in the cows fed diet 1. Fractional urinary excretion and plasma level of Pi were higher during the periparturient period in the cows fed diet 3 than those in the cows fed diets 1 or 2. There were no significant differences in plasma parathyroid hormone levels among the 3 groups. In the spongy substance of ilium at 5 days after calving, the Ca and Mg contents bone volume and trabecular thickness were the lowest, but not significant, in the cows fed diet 2. These data suggest that sufficient Ca and P contents in an anionic diet may be effective in maintaining plasma Ca and Pi levels of periparturient cows and further in preventing of potential bone damage brought about by increased urinary mineral excretion following the feeding of an anionic diet.

Animal Feed↗