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Biomedical subjects

Y Kang

Publications and source records attributed to Y Kang.

At least 145 records · Page 8Linked to original sources
PubMed1997

Role of calcium conductances on spike afterpotentials in rat trigeminal motoneurons.

Intracellular recordings were obtained from rat trigeminal motoneurons in slice preparations to investigate the role of calcium conductances in the depolarizing and hyperpolarizing spike afterpotential (ADP and mAHP, respectively). The mAHP was suppressed by bath application of 1 microM apamin, 2 mM Mn2+, and 2 mM Co2+, and also by intracellular injection of ethylene glycol-bis(b-aminoethylenether)-N,N,N',N'-tetraacetic acid (EGTA), suggesting that the potassium conductance generating the mAHP is activated by Ca2+ influx. Mn2+ (2 mM) or Cd2+ (500 microM) reduced the ADP, whereas the ADP amplitude was increased by raising extracellular Ca2+ concentration from 2 to 8 mM by bath application of Ba2+ (0.5-5 mM) and by intracellular injection of EGTA. This would suggest that Ca2+ itself is likely to be the charge carrier generating the ADP. Focal application of omega-conotoxin GVIA (10-30 microM) suppressed the mAHP and enhanced the ADP, whereas focal application of omega-agatoxin IVA (10-100 microM) reduced the ADP amplitude without apparent effects on the mAHP. We conclude that Ca2+ influx through omega-agatoxin IVA-sensitive calcium channels is at least in part responsible for the generation of the ADP and that Ca2+ influx through omega-conotoxin GVIA-sensitive calcium channels contributes to the generation of the mAHP. Because of the selective suppression of the ADP and mAHP by omega-agatoxin IVA and omega-conotoxin GVIA, respectively, it is suggested that both calcium channels are separated geometrically in rat trigeminal motoneurons.

Animals↗
PubMed1997

Magnetic resonance imaging of sequelae of temporal lobe herniation secondary to traumatic acute subdural hematoma: Kernohan's notch and posterior cerebral artery territory infarctions contralateral to the supratentorial lesion--case report.

A 16-year-old girl presented with left hemiparesis and right oculomotor nerve paresis due to temporal lobe herniation resulting from a traumatic acute subdural hematoma secondary to a head injury. Computed tomography revealed a subdural hematoma in the right frontotemporal regions and midline structures shifted to the left. She became comatose and underwent an emergency operation. The hemiparesis and newly manifested homonymous hemianopsia on the right side persisted after surgery. Postoperative magnetic resonance imaging showed Kernohan's notch in the cerebral peduncle and infarctions in the occipital lobe and posterolateral part of the thalamus on the left side, contralateral to the supratentorial lesion.

Adolescent↗
PubMed1997

[A clinicopathological analysis of keratoacanthoma in eye].

PURPOSE: To discuss clinic and histopathologic features of keratoacanthoma. The diagnosis and differential diagnosis were discussed. METHODS: The authors analyze clinical characteristics of keratoacanthoma which is testified by hisopathology. Clinically, the tumors developed rapidly. They appeared as a dome or nodule with a central keratin filled crater and elevated rolled margins. RESULTS: Histologically, they had a cup-differentiated squamous opithalium surrounding a central mass of keratin. The base was rather uniform. The lesions may extend into underlying stroma even orbicularis muscle. CONCLUSION: Keratoacanthoma is a specialized variant of pseudocarcinomatous hyperplasia. It has clinic and histopathologic characteristics and differs from other tumors.

Adult↗
PubMed1997

Hemodynamic effects of inhaled nitric oxide in four patients with severe liver disease and pulmonary hypertension.

Patients with moderate and severe pulmonary hypertension have a very high mortality rate when undergoing orthotopic liver transplantation. Because nitric oxide has been successful in reducing pulmonary artery pressures in certain patients with pulmonary hypertension, the efficacy of NO inhalation (40 and 80 ppm) in 4 patients with pulmonary hypertension associated with liver disease was determined. No clinically significant changes in pulmonary artery pressures or other hemodynamic parameters were observed using either concentration of NO. In conclusion, no pulmonary vasodilatory response from inhalation of NO in 4 patients with severe liver disease and pulmonary hypertension was found.

Adult↗
PubMed1996

Extracellular ATP induces formation of AP-1 complexes in astrocytes via P2 purinoceptors.

The transcription activator protein-1 (AP-1) complex is a heterodimer consisting of Fos and Jun family members. We found that extracellular ATP stimulated AP-1 DNA binding activity in cerebral cortical astrocyte cultures. This activity was maximal at 1 h and persisted for at least 3 h post-treatment. Shift-Western blotting indicated the presence of c-Fos in the AP-1 complexes. Stimulation of AP-1 binding by ATP was due to activation of P2 rather than P1 purinoceptors. The protein kinase C (PKC) inhibitor Ro 31-8220 markedly reduced P2 purinoceptor-mediated AP-1 induction. The induction of AP-1 complexes by ATP may contribute to changes in gene expression which underlie the trophic effects of extracellular ATP on astrocytes.

Adenosine Triphosphate↗
PubMed1996

Effect of acute and chronic intermittent hypoxia on DNA topoisomerase II alpha expression and mitomycin C-induced DNA damage and cytotoxicity in human colon cancer cells.

Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was investigated under aerobic, acute hypoxic (after 4 hr in 95% N2, 5% CO2 < 0.01% O2), and chronic intermittent hypoxic (after 4 hr hypoxia/day x 7 days) conditions. Acute hypoxia induced topo II alpha mRNA and protein, effects that were more pronounced in HT-29 cells. Chronic intermittent hypoxia caused a decrease in topo alpha mRNA and protein, changes that were again more pronounced in HT-29 cells. The observed changes in topo II alpha protein were associated with parallel changes in topo II activity under all conditions tested. Topo II beta mRNA was expressed at a very low level in both cell lines under aerobic and hypoxic conditions. Compared with cells under aerobic conditions, HT-29 cells were more sensitive to MMC under acute hypoxia but more resistant under chronic intermittent hypoxia. In contrast, the senstivity of HT-29R13 cells was unchanged under acute hypoxia, but the cells were more resistant under chronic intermittent hypoxia. Under all conditions tested, the degree of cytotoxicity corresponded to the frequency of MMC-induced DNA cross-links and topo II alpha protein levels and activity. Our results demonstrated that MMC cytotoxicity in hypoxic cells is highly dependent upon the type of hypoxia and the cell type. Hypoxia has significant effects on topo II alpha expression in HT-29 and HT-29R13 cells which correlate with MMC cytotoxicity.

Colonic Neoplasms↗
PubMed1996

Antitumor activity of S-(p-bromobenzyl)glutathione diesters in vitro: a structure-activity study.

S-(p-Bromobenzyl)glutathione is a competitive inhibitor of human glyoxalase I which is part of the cytosolic glyoxalase system. It may be delivered into the cystosol of cells by diesterification wherein it is deesterified by cytosolic nonspecific esterases. S-(p-Bromobenzyl)glutathione diesters had antitumor activity in vitro and in vivo. The inhibition of human leukemia 60 cell growth in vitro by a series of alkyl and cycloalkyl diesters of S-(p-bromobenzyl)glutathione was investigated. For n-alkyl diesters, the n-propyl diester was the most potent derivative with a median growth inhibitory concentration GC50 value of 7.77 +/- 0.01 microM (N = 18). The most potent derivative was S-(p-bromobenzyl)glutathione cyclopentyl diester which had a GC50 value of 4.23 +/- 0.01 microM (N = 21) and also had antitumor activity in vivo.

Antineoplastic Agents↗
PubMed1996

Antitumour activity of S-p-bromobenzylglutathione cyclopentyl diester in vitro and in vivo. Inhibition of glyoxalase I and induction of apoptosis.

The glyoxalase I inhibitor diester, S-p-bromobenzyl-glutathione cyclopentyl diester (BrBzGSHCp2), inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The median growth inhibitory concentration GC50 value of BrBzGSHCp2 was 4.23 +/- 0.001 microM (n = 21), and the median toxic concentration TC50 value was 8.86 +/- 0.01 microM (n = 21). BrBzGSHCp2 inhibited DNA synthesis in the third hr of incubation: the median inhibitory concentration IC50 value was 6.11 +/- 0.02 microM (n = 8). Incubation of HL60 cells with 10 microM BrBzGSHCp2 delivered the diester into cells: de-esterification of the diester there in lead to formation of the S-p-bromobenzylglutathione, inhibition of glyoxalase I activity in situ, increase in the methylglyoxal concentration after 1 hr, and induction of apoptosis after 6 hr. BrBzGSHCp2 (50-200 mg/kg) also inhibited the growth of murine adenocarcinoma 15A in vivo. Glyoxalase I inhibitor diesters may, therefore, inhibit tumour growth by inducing the accumulation of methylglyoxal in tumour cells, and induction of apoptosis.

Adenocarcinoma↗
PubMed1996

Role of c-myc in tamoxifen-induced apoptosis estrogen-independent breast cancer cells.

BACKGROUND: The antiestrogen tamoxifen (TAM) is effective in the treatment of estrogen receptor (ER)-positive as well as some ER-negative breast cancers. However, the precise mechanism of action of TAM, especially in estrogen-independent cells, remains unclear. Previous work by our laboratory has demonstrated that TAM induces the morphologic and biochemical changes that are characteristic of apoptosis in both ER-positive and ER-negative cells. PURPOSE: We compared the effect of TAM at a clinically achievable concentration on cell growth and apoptosis with the effect of TAM on c-myc (also known as C-MYC) messenger RNA (mRNA) and protein expression in ER-negative MDA-231 cells. METHODS: MDA-231 cells were treated for up to 72 hours with 1.0 microM TAM alone or in the presence of 50 microM c-myc antisense or nonsense oligonucleotides. c-myc mRNA expression was determined by northern blot analysis, protein expression by western blot analysis, cell growth inhibition counts, and DNA cleavage by agarose gel electrophoretic analysis. Differences between the mean values from different treatment groups were compared with the use of the two-sided Wilcoxon Ranksum test. RESULTS: TAM treatment for 72 hours increased c-myc mRNA five-fold (from a relative radiolabeled hybridization signal intensity of 17 +/- 4 up to 93 +/- 10; P<.05) and c-MYC protein threefold (from a relative immunofluorescence signal intensity of 28 +/- 7 up to 83+/-21; P< .05). The induction of c-myc by TAM was accompanied by internucleosomal DNA cleavage characteristic of apoptotic cell death. Addition of c-myc antisense oligonucleotide (5'CACGTTGAGGGGCAT-3') to MDA-231 cells resulted in a nearly twofold decrease of basal c-myc mRNA (P< .05) and a sevenfold decrease of basal c-Myc protein (P< .05) expression. Addition of c-myc antisense oligomer also antagonized the TAM-induced increase in c-myc mRNA (P< .05) and protein expression (P< .05) and inhibited TAM-induced cytostasis (P< .01) and apoptosis. In parallel experiments, addition of the nonsense oligomer had no effect on any of the measured parameters. CONCLUSIONS: These results indicate that the effects of TAM on ER-negative MDA-231 cells may be mediated through c-myc overexpression. c-myc may play a critical role in the growth and progression of MDA-231 breast cancer cells.

Antineoplastic Agents, Hormonal↗
PubMed1996

Ionized hypomagnesemia in patients undergoing orthotopic liver transplantation: a complication of citrate intoxication.

Using a new ion-selective electrode, plasma concentration of ionized magnesium was measured in nine adult patients undergoing orthotopic liver transplantation. Baseline plasma ionized magnesium (IMg2+) concentration (0.49 +/- 0.07 mmol/L) was slightly below normal values (0.55-0.66 mmol/L, 95% CI): Six patients had ionized hypomagnesemia and two of these had total hypomagnesemia. Ionized IMg2+ concentration progressively decreased during the dissection (0.45 +/- 0.07 mmol/L, p < 0.05) and anhepatic stage (0.38 +/- 0.07 mmol/L, p < 0.05) and returned toward baseline values by 2 hours after graft reperfusion. Plasma ionized calcium levels and acid-base status were maintained within normal limits during surgery. Serum citrate concentration increased during the dissection (0.58 +/- 0.60 mmol/L) and anhepatic stages (1.18 +/- 0.78 mmol/L), the result of transfusion of citrate-rich blood products in the absence of adequate hepatic function, and gradually returned toward baseline values after graft reperfusion. IMg2+ concentration inversely correlated with the plasma citrate concentration (r2 = 0.54). The results of this study demonstrate that ionized hypomagnesemia invariably occurs during liver transplantation and suggest that this derangement may be a clinical concern, because magnesium is an important cofactor for the maintenance of cardiovascular homeostasis. The data further suggest the clinical importance of supplementation with magnesium based on the monitoring of plasma IMg2+ concentration.

Analysis of Variance↗
PubMed1996

Altered endothelin homeostasis in patients undergoing liver transplantation.

The liver is a major site of synthesis, clearance, and actions of the powerful vasoactive peptide endothelin-1 (ET-1). We investigated the role of the liver in ET-1 homeostasis by comparing circulating and hepatic ET-1 levels and hepatic ET receptors in patients undergoing orthotopic liver transplantation (OLTx) for end-stage liver disease (ESLD) with those in patients undergoing liver resection for focal lesions with otherwise normal hepatic synthetic function. Central venous and radial arterial blood was drawn immediately after induction of anesthesia (point I), 10 minutes before beginning of resection or the anhepatic stage (point II), and 30 minutes after completion of resection or reperfusion of the grafted liver (point III). Portal and hepatic venous blood was drawn at points II and III. Plasma ET-1 levels were higher in ESLD patients than in resection patients. Plasma ET-1 levels rose both during resection and transplantation; the increase in ET-1 was more pronounced during transplantation. In ESLD patients, hepatic venous ET-1 was higher than portal venous ET-1, suggesting reduced clearance and/or enhanced synthesis of the peptide in the cirrhotic liver. Conversely, hepatic venous ET-1 was lower than portal venous ET-1 in resection patients at all time points and at point III in the ESLD patients. Hepatic concentration of ET-1 was greater and the capacity of the liver to catabolize ET-1 was reduced in ESLD patients as compared to the resection patients. Further, hepatic ET receptor density was higher in ESLD than in resection patients. These results suggest that the cirrhotic liver may contribute to elevated plasma ET-1 in ESLD. Considering its potent hemodynamic and metabolic effects in the liver, increased hepatic ET-1 and ET receptors and plasma ET-1 could play a role in the pathophysiology of liver disease and perioperative complications of OLTx.

Adult↗
PubMed1996

Morbidity and mortality in patients with coronary artery disease undergoing orthotopic liver transplantation.

Thirty-two patients with coronary artery disease who underwent liver transplantation between 1990 and 1994 were identified. Coronary artery disease was managed medically (n = 9), by angioplasty (n = 1), or surgically (n = 22) prior to liver transplantation. Two patients underwent simultaneous coronary artery bypass grafting and liver transplantation. Complete preoperative cardiac evaluation was performed in all patients. Perioperative and postoperative morbidity and mortality were retrospectively determined. Overall mortality was 50%, whereas morbidity was 81%. Follow-up was between 1 and 3 years after liver transplantation. Subgroup analysis revealed that medically managed patients had a 56% mortality and a 100% morbidity. The patient who underwent angioplasty survived without morbidity. One patient who underwent simultaneous coronary artery bypass grafting and liver transplantation died intraoperatively. The second patient survived but required pacemaker insertion and inotropic agents postoperatively. The 20 patients with prior coronary artery bypass grafting had a 50% mortality and 80% morbidity. Further, analysis by United Network for Organ Sharing functional status revealed a higher than expected mortality in all groups. The morbidity and mortality associated with liver transplantation is significantly increased in patients with coronary artery disease and is equally high in medically and surgically treated patients. By comparison, patients without coronary artery disease have a 3-year survival of 55.4% (status I) to 79.7% (status III and IV). The increased intraoperative and postoperative risk in patients with coronary artery disease undergoing liver transplantation should be considered when determining the candidacy of these patients as well as when providing informed consent.

Adult↗
PubMed1996

p-Glycoprotein expression as a predictor of breast cancer recurrence.

BACKGROUND: Many new prognostic factors for breast cancer have been described, and yet the ability to predict patient outcomes remains poor. Overexpression of p-glycoprotein (p-gp), the multidrug resistance efflux pump, confers a worse prognosis to patients with certain leukemias and other tumors. The purpose of this study was to analyze the potential usefulness of p-gp expression as a prognostic factor in patients with breast cancer. METHODS: Paraffin blocks were obtained from 55 previously untreated patients who underwent surgery between 1987 and 1988. To determine p-gp expression, tumor cell suspensions were incubated with the p-gp-specific C219 monoclonal antibody and analyzed using an indirect immunofluorescent flow cytometric assay. RESULTS: Twenty-four (44%) of the tumors were p-gp positive and 31 (56%) were p-gp negative. Among the p-gp positive patients, 65% had recurrence of their disease, whereas only 13% of the p-gp negative patients experienced recurrence (p = 0.0001). The 5-year disease-free rate for p-gp positive patients was 39% compared with 83% for p-gp negative patients (p = 0.0001). In univariate analysis examining 10 different variables, significant predictors of recurrence were p-gp, stage, and tumor size. Multivariate analysis using Cox Proportional Hazards regression showed that only p-gp and stage were significant independent predictors of recurrence (p = 0.0002). CONCLUSIONS: p-gp is frequently expressed in patients with untreated breast cancer, with p-gp-positive patients being at significantly greater risk for disease recurrence. p-gp appears to be a useful prognostic factor in breast cancer and could potentially help guide management.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis.

Methylglyoxal induced growth arrest in the G1 phase of the cell cycle and toxicity in human leukaemia 60 cells in vitro. Inhibition of DNA synthesis but not inhibition of RNA synthesis, protein synthesis or inhibition of glyceraldehyde-3-phosphate dehydrogenase activity correlated with cytotoxicity. Incubation of human leukaemia 60 cells with methylglyoxal led to the rapid accumulation of adducts of methylglyoxal with DNA, and a lower accumulation of methylglyoxal adducts with RNA and protein in the initial hour of culture; fragmentation of nuclear DNA characteristic of apoptosis developed in the second hour of culture. Methylglyoxal induced apoptosis in human leukaemia 60 cells but did not affect the growth and viability of concanavalin A-stimulated human peripheral lymphocytes in vitro. These effects confirm and further substantiate the anti-proliferative anti-tumour activity of methylglyoxal in vitro, which may mediate the anti-tumour activity of glyoxalase I inhibitors in vivo.

Apoptosis↗
PubMed1996

Identification and cloning of a novel type I serine/threonine kinase receptor of the TGF-beta/BMP superfamily in rat prostate.

A cDNA clone encoding a new member of the type I serine/threonine kinase receptors of the TGF-beta/BMP superfamily was isolated from a rat prostate cDNA library. The predicted sequence of the encoded protein is 493 amino acids with a molecular weight of 55 kDa. It contains a putative cysteine rich extracellular domain, a transmembrane domain, a conserved type I receptor GS domain and a cytoplasmic serine/threonine kinase domain. The kinase domain shares 80% homology with that of ALK-4 and ALK-5 whose ligands are activin and TGF-beta. Northern blot analysis revealed that this prostate serine/threonine kinase receptor I (PSKR-I) is highly expressed in rat dorsolateral prostate, coagulating gland (anterior prostate), cerebellum and adipose tissue.

Amino Acid Sequence↗
PubMed1996

Accuracy of college students' reports of parental handedness.

College students' reports of their parents' handedness were compared with data provided by the parents themselves. The students' reports of their parents' writing hand were highly accurate, the reports of their parents' general handedness somewhat less so. For the latter measure, the students were asked, ''What is your mother's (father's) handedness?'' and were given the choice ''left'',''either'', ''right'',and ''don't know''. Their answers were then compared with the investigators' classification based on the parents' answers to a 10-item hand-use questionnaire. For this measure, the accuracy of the students' reports was also found to be related to the students' own handedness.

Journal Article↗