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Biomedical subjects

W J Kim

Publications and source records attributed to W J Kim.

At least 91 records · Page 5Linked to original sources
PubMed1995

Multidrug resistance-associated protein-mediated multidrug resistance modulated by cyclosporin A in a human bladder cancer cell line.

A doxorubicin-resistant subline (5637/DR5.5) from human bladder cancer cells (5637) was induced by stepwise increase in the doxorubicin concentration. 5637/DR5.5 cells were cross-resistant to vinblastine and etoposide but not to mitomycin C and cisplatin. We analyzed the mdr1, MRP (multidrug resistance-associated protein), and DNA topoisomerase II gene expression using the reverse transcription polymerase chain reaction assay (RT-PCR) and investigated possible differences in the accumulation and efflux of radiolabeled daunorubicin. 5637/DR5.5 cells do not express the mdr1 gene, but the expression levels of MRP are markedly higher than in drug-sensitive 5637 cells. The intracellular accumulation of radiolabeled daunorubicin was markedly decreased in the 5637/DR5.5 cells in comparison with the parent cells. This reduced drug accumulation was associated with an enhanced drug efflux, but was reversed when cells were incubated with cyclosporin A. Cyclosporin A at the concentration of 5 microM caused 3.4-fold enhancement of daunorubicin-sensitivity in the 5637/DR5.5 cells. On the other hand, there was no difference in DNA-topoisomerase II activity between the parent and resistant cells. The resistance of the 5637/DR5.5 cells is therefore associated with an enhanced drug efflux mediated by the MRP gene overexpression, as distinct from P-glycoprotein, and is modulated by cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

A clinical study of chronic headaches: clinical characteristics and depressive trends in migraine & tension-type headaches.

BACKGROUND & OBJECTIVES: Chronic headache is commonly encountered in the neurology outpatient clinic and it is often associated with depression. In Korea, however, chronic headache has not yet been systematically investigated. We conducted this study to investigate this clinical characteristics and level of depression in patients who presented migraine, tension-type headache, or transformed migraine. METHOD: Among those with chronic headache during the period from January 1, 1994 through December 31, 1994, 131 patients were diagnosed to have either migraine, tension-type headache (by IHS classification), or transformed migraine: migraine in 60 patients, tension-type headache in 49 patients, and transformed migraine in 22 patients. Beck Depression Inventory (BDI) was performed in 116 of the 131 patients. RESULTS & CONCLUSION: There was no significant difference in the age of onset, duration of headache, and family history among the three groups. However, patients with migraine had a more severe, unilateral, and throbbing characteristic pain than those with a tension-type headache. The mean BDI scores in the transformed migraine and the tension-type headache patients were significantly higher than those of migraine, but the level of depression did not correlate with the patient's age, duration, character, severity, and frequency of headache. These findings suggest that migraine, tension-type headache and transformed migraine may be considered clinically distinct entities in viewing their different clinical characteristics and level of depression.

Adolescent↗
PubMed1995

Expression of yeast O6-methylguanine-DNA methyltransferase (MGMT) gene.

We cloned the full genomic DNA of yeast (Saccharomyces cerevisiae) O6-methylguanine-DNA methyltransferase (MGMT) gene and examined its expression. The expression of yeast MGMT gene is decreased when cells reach stationary phase and cannot be induced by the pretreatment with alkylating agents, methylmethanesulfonate (MMS) or N-methyl-N'-nitroso-N-nitrosoguanidine (MNNG). The transcription initiation site was determined by primer extension analysis. This analysis showed that the authentic start codon is the ATG at position +32 from transcription initiation site.

Amino Acid Sequence↗
PubMed1995

Comparison of multidrug resistance gene expression levels with malignant potentials and influence of chemotherapy in urothelial cancers.

BACKGROUND: We sought to determine how often P-glycoprotein is involved in the drug-resistance of urothelial cancer, and whether MDR1 gene expression is correlated with tumor grade, invasiveness, or metastasis. METHODS: Forty-two tumor specimens and two normal bladder mucosal samples obtained from 34 urothelial cancer patients were analyzed. Reverse-transcription and polymerase chain reaction were conducted. MDR1 mRNA levels were determined by measuring the relative ratio of the MDR1 to beta-2-microglobulin (b2 m) mRNA specific PCR products. RESULTS: The MDR1/b2 m in two normal urothelial samples were 0.044 and 0.045. For untreated primary tumors, levels of MDR1 gene expression in 46% tumor samples were less than that of normal urothelium, while 27% showed expression levels with a MDR1/b2 m ratio more than 0.1. There was no statistical correlation between MDR1 mRNA level and tumor grade, stage, or metastatic status. There was higher MDR1 gene expression in two lymph node metastasis specimens and almost equal expressions in two more. There was no significant difference in the mean MDR1/b2 m ratio between postchemotherapy and untreated tumors. A remarkable elevation of the MDR1 mRNA level (15 times greater than prechemotherapy) was found in one tumor; mRNA levels of the multidrug resistance-associated protein (MRP) gene, glutathione S-transferase pi (GST-pi) gene or DNA topoisomerase II (topo II) gene did not increase. CONCLUSIONS: It is still unclear whether the MDR1 gene expression in urothelial tumor cells is inducible by the current combination chemotherapy regimens. RT-PCR quantitation is useful for determining the expression level of MDR1 gene in urothelial cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Molecular modeling of RNA polymerase II mutations onto DNA polymerase I.

Genetic and molecular analysis in Drosophila melanogaster identifies eight suppressor mutations in the second largest subunit of RNA polymerase II. The suppressor mutations fall into two classes: five are strong, result from the same serine to cysteine amino acid residue substitution and rescue one conditional lethal allele in the largest subunit of RNA polymerase II; three are mild, result from a change in the same methionine residue to either isoleucine or valine, are located seven amino acid residues away from the strong suppressors and rescue two conditional lethal alleles in the largest subunit. Sequence analysis of the three regions around these mutations demonstrates that they are located within highly conserved domains but fails to explain the observed genetic interactions. One of the conditional lethal alleles maps within a region previously reported to share sequence similarity to Escherichia coli DNA polymerase I. As the gross structure of RNA polymerase II and DNA polymerase I is similar, even though their primary sequence is not, we predict that more similarities exist but may be too highly divergent to be detected by normal homology searches. We identify the most similar regions between each of the three conserved domains of RNA polymerase II, identified as functionally important because of the mutations we isolated, and DNA polymerase I. Molecular modeling these regions of RNA polymerase II onto the tertiary structure of DNA polymerase I predicts that all lie adjacent to the DNA binding cleft in positions such that they could interact with the phosphate backbone of DNA. This juxtaposition of mutations in the two largest subunits of RNA polymerase II suggest a mechanism for their genetic interactions.

Amino Acid Sequence↗
PubMed1994

A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase.

Autophosphorylated growth factor receptors provide binding sites for the src homology 2 domains of intracellular signaling molecules. In response to epidermal growth factor (EGF), the activated EGF receptor binds to a complex containing the signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos, leading to activation of the Ras signaling pathway. We have investigated whether the platelet-derived growth factor (PDGF) receptor binds GRB2-Sos. In contrast with the EGF receptor, the GRB2 does not bind to the PDGF receptor directly. Instead, PDGF stimulation induces the formation of a complex containing GRB2; 70-, 80-, and 110-kDa tyrosine-phosphorylated proteins; and the PDGF receptor. Moreover, GRB2 binds directly to the 70-kDa protein but not to the PDGF receptor. Using a panel of PDGF beta-receptor mutants with altered tyrosine phosphorylation sites, we identified Tyr-1009 in the PDGF receptor as required for GRB2 binding. Binding is inhibited by a phosphopeptide containing a YXNX motif. The protein tyrosine phosphatase Syp/PTP1D/SHPTP2/PTP2C is approximately 70 kDa, binds to the PDGF receptor via Tyr-1009, and contains several YXNX sequences. We found that the 70-kDa protein that binds to the PDGF receptor and to GRB2 comigrates with Syp and is recognized by anti-Syp antibodies. Furthermore, both GRB2 and Sos coimmunoprecipitate with Syp from lysates of PDGF-stimulated cells, and GRB2 binds directly to tyrosine-phosphorylated Syp in vitro. These results indicate that GRB2 interacts with different growth factor receptors by different mechanisms and the cytoplasmic phosphotyrosine phosphatase Syp acts as an adapter between the PDGF receptor and the GRB2-Sos complex.

3T3 Cells↗
PubMed1994

Impairement of endothelium-dependent relaxation in chronic two-kidney, one clip hypertensive rats.

OBJECTIVES: Hypertension is commonly associated with an endothelial dysfunction that may contribute to the rise in blood pressure. Little information has been available so far on the role of endothelium-derived nitric oxide(EDNO) in renin-dependent, 2-kidney, 1 clip(2KIC) hypertension. The present study was aimed to determine a role for EDNO in the development and maintenance of 2KIC hypertension. METHODS: The effects of blocking synthesis or supplementation with precursor of EDNO on the development of hypertension were determined in 2KIC rats. Vascular responses to acetylcholine, nitroprusside, atrial natriuretic peptide and nifedipine were examined in 7- and 12-week hypertensive 2KIC rats. RESULTS: NG-nitro-L-arginine-methyl ester caused a sustained increase of blood pressure in normal rats, while it was only partially associated with a more pronounced increase of blood pressure in the developmental phase of hypertension in 2KIC rats. In 7-week and 12-week hypertensive rats, phenylephrine-induced contraction of the isolated thoracic aortic rings was more sensitive compared with control. Their acetylcholine-induced relaxation was attenuated while the responses to nitroprusside or atrial natriuretic peptide were unaltered. Although their blood pressure did not differ between 7-week and 12-week hypertensive groups, the attenuation in the acetylcholine-induced relaxation was more prominent in the latter with a longer duration of hypertension. Indomethacin did not affect the attenuated relaxation to acetylcholine. The relaxation response to nifedipine was more pronounced in 2KIC rats. CONCLUSION: These results indicate that ENDO has little influence of the 2KIC hypertension, at least during its developmental phase, which is associated with an activated reninangiotensin system. The chronic stage of 2KIC hypertension, however, is associated with an endothelial dysfunction which may contribute to the enhanced vasoconstriction and sustained high blood pressure.

Acetylcholine↗
PubMed1993

Diagnosis of tuberculous meningitis by detection of immunoglobulin G antibodies to purified protein derivative and lipoarabinomannan antigen in cerebrospinal fluid.

Enzyme-linked immunosorbent assay of immunoglobulin G (IgG) activity in cerebrospinal fluid (CSF) and sera was conducted prospectively in 27 patients with tuberculous meningitis (TBM) by using purified protein derivative (PPD) and lipoarabinomannan (LAM) antigens, from January 1989 to August 1990. 29 patients with aseptic meningitis and 49 patients with non-inflammatory neurological illnesses served as controls. All patients had a computed tomography (CT) scan of the head before a lumbar puncture. The IgG antibodies to the antigens were significantly elevated in TBM, and the reactivity was more frequently positive in the CSF than in the sera, suggesting a local synthesis of IgG in the central nervous system (CNS). The sensitivity and the specificity for the diagnosis of TBM were 59.2% and 93.9% for PPD antigen, and 85.2% and 95.9% for LAM antigen, respectively. Assay of IgG reactivity to LAM antigen was clinically very useful for the early diagnosis of TBM and was superior to PPD for detecting the serological evidence of TBM.

Adolescent↗
PubMed1993

The action of diazepam in the isolated rat detrusor muscle.

Diazepam is one of the benzodiazepines, a group of drugs that depresses the central nervous system. It also inhibits the contractility of smooth muscles in the periphery, but the mechanism of this inhibitory action has not been clarified. Our study was undertaken to investigate the effect of diazepam on the contractility of the detrusor muscle. Detrusor muscle strips isolated from rat urinary bladder were examined by isometric myography. Diazepam, as well as baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, reduced the electric field stimulation-induced contractions; delta-aminovaleric acid, a GABAB receptor antagonist, completely antagonized the inhibitory effect of baclofen, but not the inhibitory action of diazepam. Diazepam reduced the basal tone of detrusor muscle concentration dependently, and this inhibitory action was not affected by tetrodotoxin. Diazepam suppressed the contractile responses to bethanechol, adenosine triphosphate and potassium chloride. Diazepam diminished the calcium-induced recovery of tension in calcium-free PSS. A23187, a calcium ionophore, partially recovered the basal tone which had been reduced by diazepam in normal physiologic salt solution (PSS). The loss of tension in calcium free PSS containing diazepam could not be recovered by addition of A23187. On the other hand, the loss of tension in calcium-free PSS containing 3,4,5-trimethoxybenzoic acid 8(diethylamino)octyl ester (TMB-8), an inhibitor of intracellular calcium release, was considerably recovered by addition of A23187. Based on these results, it is suggested that diazepam inhibits the contractility of detrusor muscle acting directly on the smooth muscle cell, which is unrelated to the activation of GABA receptors. Its inhibitory action appears to be mediated through interference with the influx of extracellular calcium.

Adenosine Triphosphate↗
PubMed1993

Long-term results of myopic epikeratoplasty.

Twenty-three eyes of 20 patients who had had myopic epikeratoplasty were evaluated and the mean 21-month postoperative results (range: 12 to 47 months) tabulated. Average preoperative myopia was -16.7 diopters (D) spherical equivalent (range: -10 to -33 D), and average postoperative refractive correction was 13 D. Of 22 eyes, 17 eyes (77%) were within 4 D of emmetropia. Preoperative visual acuities without correction were between 2/200 and 20/100 (average = 2/40); postoperative acuities were between 2/200 and 20/20 (average = 20/40). Average preoperative best corrected visual acuity was 20/30. Best corrected visual acuities were unchanged or improved in 82% of cases. Re-epithelialization was complete within an average of seven days (range: three to 16 days) postoperatively except in one case in which the lenticule was removed because re-epithelialization did not occur. Five cases showed progressive loss of lenticular power.

Adolescent↗
PubMed1993

Is an abnormal Doppler umbilical artery waveform ratio a risk factor for poor perinatal outcome in the non-small for gestational age fetus?

To determine if abnormal umbilical artery velocimetry is associated with a higher rate of perinatal morbidity in pregnancies in which the outcome is not manifested by a small for gestational age (SGA) fetus, perinatal outcome was compared according to the results of Doppler umbilical artery velocimetry. Doppler study was performed in 328 singleton pregnancies with non-SGA fetuses within 7 days of delivery. The prevalence of abnormal Doppler studies was 10%. Patients with abnormal umbilical artery velocimetry had a significantly higher rate of complications, including cesarean section for fetal distress, preterm delivery, low Apgar scores, congenital anomalies, admission to the neonatal intensive care unit, and perinatal death, than patients with a normal umbilical artery velocimetry. Ten perinatal deaths were associated with major congenital anomalies. Moreover, in the absence of congenital anomalies patients with abnormal Doppler results also had a significantly higher incidence of adverse perinatal outcome compared with patients with normal umbilical artery velocimetry. Our data suggest that even the non-SGA fetus with an abnormal Doppler umbilical artery waveform ratio is at increased risk for poor perinatal outcome.

Adult↗
PubMed1993

Actions of potassium channel openers in rat detrusor urinae.

This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration-dependently. P 1060, RP 49356 and BRL 38227 suppressed the maximal responses to bethanechol and shifted the concentration-response curves of bethanechol-induced contraction to the right. RP 49356 and BRL 38227 reduced the contraction by low (20 mM) concentration of potassium. P 1060, however, diminished the high (80 mM) and low (20 mM) concentration of potassium-induced contraction. Glibenclamide, an inhibitor of ATP-dependent potassium channel, antagonized the suppressive action of P 1060, RP 49356 and BRL 38227 on the basal tone. Apamin or procaine did not antagonize it significantly. Based on these results, it is suggested that the relaxation of detrusor muscle strip caused by P 1060, RP 49356 and BRL 38227 may predominantly involve opening of the same potassium channel, i.e., the ATP-dependent potassium channel.

Animals↗
PubMed1992

Identification and characterization of an alpha-mannosidase from Trypanosoma cruzi.

In this report we describe the first purification and characterization of the acid alpha-mannosidase from the human parasite Trypanosoma cruzi. The purified enzyme exhibited a native mol. wt of 240,000 Da and is apparently composed of four identical subunits of mol. wt 58,000 Da. Each of the four subunits contains one N-linked high-mannose-type oligosaccharide. The alpha-mannosidase exhibited a pH optimum of 3.5 and a pI of 5.9. This low pH optimum and the ability of swainsonine to inhibit its activity suggest that the alpha-mannosidase is a lysosomal enzyme. Antibodies against the T.cruzi enzyme did not react with mammalian lysosomal alpha-mannosidase and, conversely, antibody against a rat lysosomal alpha-mannosidase did not react with the T.cruzi enzyme. Thus, the T.cruzi enzyme appears to be distinct from its mammalian counterpart.

Acid Phosphatase↗
PubMed1992

Characteristics of adopted juvenile delinquents.

There have been many reports describing the uniqueness of adopted children and adolescents' delinquent behaviors in terms of both their delinquent characteristics and courts' treatment of them. A total of 43 adopted juveniles, 32 extrafamilial (1.0%) and 11 intrafamilial (0.3%) adoptions were initially identified out of 3,280 juvenile delinquents. The adopted subjects were then compared with the demographically matched and offense matched nonadopted subjects. The family variables, such as marital and employment status of parents, were significantly different. However, there were only a few discernible trends, and in general there were no significant differences between the adopted and nonadopted juveniles in terms of their offense characteristics and dispositions.

Adolescent↗
PubMed1992

Unilateral congenital ocular motor apraxia: a case report.

Congenital ocular motor apraxia (COA), first described by Cogan in 1953, is a rare disorder which shows characteristic defects of the horizontal voluntary saccades, and compensatory head thrust. Until now, most cases have showed a presumably congenital origin, bilaterality, and a tendency to various stages of recovery with aging. But the cause and mechanism of COA are not completely known. Occasionally, it combines with other neurologic abnormalities and metabolic diseases such as Gaucher's disease exhibit similar clinical characteristics to COA. We recently experienced a case of a 3-year-old girl who showed the clinical features of unilateral congenital ocular motor apraxia.

Apraxias↗
PubMed1991

Separation reaction of psychiatrically hospitalized children: a pilot study.

This paper reports on the development of the Children's Separation Rating Scale (CSRS), its initial reliability and validity, and clinical/research utility with psychiatrically hospitalized children. The CSRS appears to be a reliable and valid instrument, and useful in distinguishing children's separation reaction from their general psychopathology. Findings from this pilot study support the notion that inpatient treatment programs should address the developmental needs and abilities of the various age groups and the particular deficits reflected in their psychopathology.

Adolescent↗
PubMed1991

Psychiatric aspects of epileptic children and adolescents.

Epilepsy is the most prevalent neurological disorder of childhood and adolescence and a very heterogenous disease with a diverse course of illness. It may be a benign disease for the majority of children and adolescents, who recover spontaneously or are managed well medically; however, a sizeable group of children and adolescents with epilepsy, at least one-third, do manifest various difficulties--seizure control, academic, emotional, behavioral, and family problems. As a group, they have a much higher rate of psychiatric disorder than healthy children and children with other chronic illnesses. This review is undertaken to summarize the literature on epilepsy in children and adolescents, especially with respect to epidemiology, developmental and psychiatric problems, and psychiatric treatment issues.

Adolescent↗