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Biomedical subjects

H S Hwang

Publications and source records attributed to H S Hwang.

34 records · Page 2Linked to original sources

Ibd1p, a possible spindle pole body associated protein, regulates nuclear division and bud separation in Saccharomyces cerevisiae.

The proper spatial and temporal coordination of mitosis and cytokinesis is essential for maintaining genomic integrity. We describe the identification and characterization of the Saccharomyces cerevisiae IBD1 gene, which encodes a novel protein that regulates the proper nuclear division and bud separation. IBD1 was identified by the limited homology to byr4, a dosage-dependent regulator of cytokinesis in Schizosaccharomyces pombe. IBD1 is not an essential gene, and the knock-out cells show no growth defects except for the reduced mating efficiency [1]. However, upon ectopic expression from an inducible promoter, IBD1 is lethal to the cell and leads to abnormal nuclear division and bud separation. In detail, approximately 90% of the IBD1 overexpressing cells arrest at large bud stages with dividing or divided nuclei. In some IBD1 overexpressing cells, spindle elongation and chromosome separation occur within the mother cell, leading to anucleated and binucleate daughter cells. The anucleated cell can not bud, but the binucleate cell proceeds through another cell cycle(s) to produce a cell with multiple nuclei and multiple buds. Observations of the F-actin and chitin rings in the IBD1 overexpressing cells reveal that these cells lose the polarity for bud site selection and growth or attain the hyper-polarity for growth. Consistent with the phenotypes, the IBD1 overexpressing cells contain a broad range of DNA content, from 2 to 4 N or more. A functional Ibd1p-GFP fusion protein localizes to a single dot at the nuclear DNA boundary in the divided nuclei or to double dots in dividing nuclei, suggesting its localization on the spindle pole body (SPB). The cross-species expressions of IBD1 in S. pombe and byr4 in S. cerevisiae cause defects in shape, implicating the presence of a conserved mechanism for the control of cytokinesis in eukaryotes. We propose that Ibd1p is an SPB associated protein that links proper nuclear division to cytokinesis and bud separation.

Cell Cycle Proteins↗

Effect of DW2282 on the induction of methemoglobinemia, hypoglycemia or WBC count and hematological changes.

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl] -4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induce methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it does produce.

Alanine Transaminase↗

On cultural similarities in attitudes toward eating of women students in Pennsylvania and South Korea.

This study compared attitudes toward eating among 226 women undergraduates at universities in Pennsylvania and South Korea. Analysis indicated that both groups (ns = 111 and 115, respectively) had similar percentages (21% and 18%, respectively) of respondents with scores suggesting symptomatology of eating disorders. Mean differences between groups on the Eating Attitudes Test-26 were not significant. Implications for research are discussed.

Adolescent↗

Synthesis and antitumor activity of 4-phenyl-1-arylsulfonyl imidazolidinones.

Novel 1-(1-benzoylindoline-5-sulfonyl)-4-phenyl-4,5-dihydroimidazolon es 3 synthesized show highly potent and broad cytotoxicities. Among them compound 3b (DW2143) exhibits much more potent cytotoxicities than doxorubicin and highly effective antitumor activities against murine (3LL, Colon 26) and human xenograft (NCI-H23, SW620) tumor models.

Animals↗

Comparative study of three phacotrabeculectomy procedures through a single incision.

The objective of this study is to evaluate and compare the effects of three combined phacoemulsification and trabeculectomy procedures procedures (phacotrabeculectomy) involving intraocular lens implantation through a single incision. Twenty-eight eyes of 28 patients suffering from chronic open angle glaucoma and chronic angle closure glaucoma were enrolled in this study. No-stitch phacotrabeculectomy (Group A), modified T-flap phacotrabeculectomy (Group B) and phacotrabeculectomy with sutures (Group C) were performed in 11, eight, and nine patients respectively, who were followed up for 6 months. At the end of that period, the mean reduction of intraocular pressure was 6.39 mm Hg; in group A, B and C, the reduction was 3.27, 4.87 and 11.55 mm Hg, respectively. The procedure followed in group C was therefore most effective, and there was a statistically significant difference between the groups (p < 0.05). The survival rate of blebs was also marked in group C. There were no apparent differences in terms of visual improvement, complications and number of medications between the groups. This study suggests that the choice of procedure should be determined by the desired degree of pressure reduction.

Aged↗

The effect of orthodontic treatment on centric discrepancy.

The purpose of this study is to investigate the effects of orthodontic treatment on centric discrepancy. Thirty-six orthodontic patients who had been treated with an edgewise appliance were selected for this study while 30 persons who had no history of orthodontic treatment were used as a control group. After recording centric relation using a leaf gauge, centric prematurity, and centric slide were compared using a SAM2 articulator and mandibular position indicator. Results indicated that the number of subjects with one prematurity was significantly greater in the control group (86.7%); however, the number of subjects with two or more prematurities was greater in the orthodontic treatment group (41.6%). The orthodontic treatment group showed more bilateral prematurities. There were no differences between the two groups with regard to the teeth involved in centric prematurities. Just considering the anatomic portion of teeth, centric prematurities were significantly associated with the buccal incline of the maxillary palatal cusp. There were no significant differences in the amount or direction of centric slide between the orthodontic and control groups. This study indicates that orthodontic treatment does not generally result in an increase in centric discrepancy.

Adult↗

Giant infantile hemangioendothelioma of the liver. Scintigraphic diagnosis.

Infantile hemangioendothelioma of the liver is benign mesenchymal tumor composed of anastomosing vascular channels lined with plump endothelial cells. It is a congenital lesion noted at birth or during the first 6 months of life. The authors report a large infantile hemangioendothelioma that was imaged with anatomical modalities and Tc-99m RBC scintigraphy. An early "blush" on Tc-99m RBC hepatic scintigraphy is a diagnostic feature of infantile hemangioendothelioma.

Erythrocytes↗

Dysfunction of insulin mediator protein kinase FA in lymphocytes of patients with NIDDM.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) had an impaired capability to activate exogenous ATP.Mg-dependent protein phosphatase in lymphocytes compared with nondiabetic subjects. More importantly, the impaired protein phosphatase activation in the lymphocytes of patients with NIDDM could be consistently and completely restored to normal by exogenous pure protein kinase FA (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in patients with NIDDM is due to a functional loss of kinase FA. By contrast, both NIDDM patients and nondiabetic subjects had similar levels of total cell proteins and spontaneously active protein phosphatase activity in their lymphocytes, indicating that the dysfunction of kinase FA in patients with NIDDM is very specific. Statistical analysis further revealed that the lymphocytes isolated from 21 nondiabetic subjects contained high levels of FA activity (148 +/- 22 mU/mg cell protein), whereas, the lymphocytes of 21 patients with NIDDM contained low levels of FA activity (50 +/- 22 mU/mg), indicating statistically significant differences in FA activity between diabetic patients and nondiabetic subjects. This is the first report providing initial evidence that patients with NIDDM may statistically have a common impairment in the protein phosphatase activation in their lymphocytes and that the molecular mechanism for this defect is due to a biochemical dysfunction of protein kinase FA, a biological mediator for both insulin and epidermal growth factor.

Adult↗

dNTP pool imbalance induced endonuclease: 5-fluorodeoxyuridine induced DNA double strand break in mouse FM3A cells and the mechanism of cell death.

The mechanism of intracellular deoxyribonucleotide triphosphates (dNTP) pool imbalance-induced cell death in mouse FM3A cells was studied. When the cells were treated with 1 microM 5-fluorodeoxyuridine (FdUrd), the imbalance of the cellular dNTP pool was induced. The imbalance was followed by DNA double stranded breaks and subsequent cell death. The endonuclease toward double stranded DNA has been found in a fraction of FdUrd treated cell lysate, and isolated using column chromatography. SDS-polyacrylamide gel electrophoresis showed a major protein species of approximate 45 kDa. The endonuclease was revealed, using electrophoretic separation in SDS-polyacrylamide gels containing DNA, by incubating the gels in buffer to remove SDS and to allow renaturation and enzyme activity.

Animals↗

Therapeutic embolization of post-cholecystectomy hepatic artery aneurysm.

A "sandwich" technique employing steel coils and gelfoam embolization was applied in two cases of hepatic artery aneurysms. Immediate cessation of the bleeding was evident clinically and the post-embolization angiogram showed occlusion of the vascular lesion. Cholecystectomy is one of the most common abdominal operations and it is generally well tolerated, particularly in young and middle-aged patients. Morbidity rates of 5% to 32% and mortality rates of 0.4% to 2.5% have been reported, depending on such factors as age, underlying illness, etc. (1-4). The most frequent complications of cholecystectomy are wound infection, abscess, ductal injury or ligation, and bleeding. This paper describes two cases of hepatic pseudoaneurysm following iatrogenic damage during cholecystectomy which was treated with transarterial embolization.

Aneurysm↗

Characterization of the anticancer activity of DW2282, a new anticancer agent.

DW2282 [(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl) indoline-5-sulfonyl]-4,5-dihydro-2-imidazolone].hydrochloride] was derived from diarylsulfonylurea and was identified as a prominent new anticancer agent. We examined the characteristics of DW2282 activity on the proliferation of human lung carcinoma cells, A549 and human leukemic cells, K562. DW2282 effectively inhibited cancer cell proliferation in vitro. Colony forming assay and viability tests demonstrated that DW2282 is a cytotoxic agent rather than a cytostatic agent. The isotope uptake test exhibited that DW2282 inhibited or inactivated protein synthesis. Also, under conditions which cause RNA or protein synthesis inhibition, by co-treatment with actinomycin D or cycloheximide, reduced the anticancer effects of DW2282. This means that the cytotoxicity of DW2282 depends partially on RNA or protein synthesis and proteins affected by DW2282 may inactivate or alter the process of the synthesis of another protein. DW2282 activity was highly diminished in the presence of colcemid, a metaphase spindle blocker. This result suggests that DW2282 may be related to the cell cycle. After exposure to DW2282, morphologically apoptotic cells appeared in A549 cells and fragmented DNA was detected in K562 cells. It demonstrated that apoptosis is one of the mechanisms by which DW2282 inhibits the proliferation of A549 and K562 cells.

Antineoplastic Agents↗

Momordins inhibit both AP-1 function and cell proliferation.

The activation of Jun/Fos is a crucial factor in transmitting the tumor promoting signal from the extracellular environment to nuclear transcription machinery. One of the final steps in signal transduction is the binding of Jun/Fos to the AP-1 site in order to express gene transcription. Utilizing this concept, we screened about 100 extracts of natural plants to search for a Jun-Fos function inhibitor. The methanol extract of Ampelopsis radix reduced Jun/Foc retardation remarkably. The active principles of the extract were isolated and purified by repeated column chromatography and their structures were identified as oleanolic acid glycosides known as momordin I, Id, and Ie. These compounds reduced the Jun/Fos-DNA interaction and their activities were quantitated with liquid scintillation counting of corresponding bands. Among them, momordin I had the strongest inhibitory activity, with an IC50 value of 22.8 micrograms/ml. The methanol extract and momordin I, Id and Ie also showed cell cytotoxicity against human cancer cell lines. As expected from a gel shift assay, momordin I showed the strongest cytotoxicity and its IC50 value was from 7.280 micrograms/ml to 16.05 micrograms/ml depending on the cell line. With these data, it may be concluded that the mechanism of anticancer activity of momordin I comes from its inhibitory effect on the protein-DNA interaction. The in vivo test was done only with the methanol extract. The extract showed measurable anticancer activity against murine colon cancer. The wet tumor weight reduction rate was 17.73% at 90 mg/kg dose. We suggest that the Jun/Fos-DNA interaction results in cell cytotoxicity.

Cell Division↗