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Biomedical subjects

K W Kim

Publications and source records attributed to K W Kim.

At least 109 records · Page 6Linked to original sources
PubMed2000

Cadmium induces caspase-mediated cell death: suppression by Bcl-2.

Apoptosis is a process of active cell death and is characterized by activation of caspases, DNA fragmentation, and biochemical and morphological changes. To better understand apoptosis, we have characterized the dose- and time-dependent toxic effects of cadmium in Rat-1 fibroblasts. Staining of cells with phosphatidylserine (PS)-annexin V, Hoechst 33258 or Rhodamine 123 and Tunel assays showed that incubating cells with 10 microM cadmium induced a form of cell death exhibiting typical characteristics of apoptosis, including cell shrinkage, externalization of PS, loss of mitochondria membrane potential, nuclear condensation and DNA fragmentation. Expression of Bcl-2 or CrmA each suppressed cadmium-induced cell death although Bcl-2 was somewhat more effective than CrmA. In vitro assay of caspase activity carried out using poly(ADP-ribose) polymerase (PARP) as a substrate as well as intracellular caspase assays using a fluorigenic caspase-3 substrate confirmed that caspase-3 is activated in Rat-1 cells undergoing cadmium-induced apoptosis. Both Asp-Glu-Val-Asp-aldehyde (DEVD-cho) and Tyr-Val-Ala-Asp-chloromethylketone (YVAD-cmk), selective inhibitors of caspase-3 and caspase-1, respectively, suppressed significantly cadmium-induced cell death. However, the nonselective caspase inhibitor, z-Val-Ala-Asp-floromethylketone (zVAD-fmk), was the most efficacious agent, almost completely blocking cadmium-induced cell death. Taken together, these results demonstrate that as in other forms of apoptosis, caspases play a central role in cadmium-induced cell death.

Animals↗
PubMed2000

Synovial cyst of the transverse ligament of the atlas in a patient with os odontoideum and atlantoaxial instability.

STUDY DESIGN: A case report and review of the literature. OBJECTIVE: To describe the diagnosis and successful treatment of a synovial cyst arising from the transverse ligament in a patient with os odontoideum and atlantoaxial instability. SUMMARY OF BACKGROUND DATA: Synovial cysts arising from the transverse ligament of the atlas are extremely rare. Development of a synovial cyst is thought to be attributable to degenerative changes of the C1-C2 facet joints or to microtrauma. Direct excision of the cyst is the only treatment cited in previous reports. METHODS: A synovial cyst arising from the transverse ligament of the atlas in a 45-year-old man with os odontoideum and atlantoaxial instability was treated surgically with posterior atlantoaxial fusion alone. The magnetic resonance images, surgical treatment, and related literature are reviewed. RESULTS: Preoperative magnetic resonance images of the cervical spine showed a large cystic mass located ventral to the cord arising at the level of the transverse ligament of the atlas: the mass was of low signal intensity on T1-weighted images, was of high signal intensity on T2-weighted images, and was enhanced marginally with gadolinium-DTPA on T1-weighted images. Spontaneous regression of the cyst was identified on the follow-up magnetic resonance images taken 3 months after C1-C2 posterior wiring and fusion. CONCLUSIONS: A patient with a synovial cyst arising at the C1-C2 junction ventrally at the level of the transverse ligament showed spontaneous regression of the lesion after C1-C2 posterior wiring and fusion.

Atlanto-Axial Joint↗
PubMed2000

The effect of age on cyclooxygenase-2 gene expression: NF-kappaB activation and IkappaBalpha degradation.

Increased oxidative stress resulting in the activation of NF-kappaB is thought to play a crucial role in the expression of the cyclooxygenase-2 (COX-2), which is the key enzyme in proinflammatory prostanoid synthesis. In the current study, we investigated whether the aging process affects the status of the redox-sensitive NF-kappaB in rat kidney, and how this age-related modulation is related to COX-2 gene expression and COX-derived reactive oxygen species (ROS). We found that the aging process strongly enhanced the activation of NF-kappaB and its DNA-binding activity with an increased ROS status. Accompanied with the change in the NF-kappaB activity was a decreased IkappaBalpha as confirmed by the increased nuclear p65 protein. Thus, these data strongly indicated that the aging process increases NF-kappaB activity by downregulating IkappaBalpha. A closer examination further revealed that age-related oxidative status correlated with the increased COX-derived prostanoid biosynthetic process is mediated by the increased NF-kappaB-regulated COX activity. This increase in NF-kappaB activity was accompanied by the increased COX-2 mRNA and protein levels. Based on these data, we concluded that the age-related increase in redox-sensitive NF-kappaB translocation and binding activities are associated with increased ROS, and further that this transactivation was modulated by the age-related decrease of IkappaBalpha.

Aging↗
PubMed2000

Human hepatitis B virus X protein is a possible mediator of hypoxia-induced angiogenesis in hepatocarcinogenesis.

The hepatitis B virus (HBV)-encoded transcriptional activator HBV-X protein (HBx) was known to be involved in hepatocarcinogenesis. Hepatocarcinogenesis generally included an active angiogenesis that was mainly considered to be due to a local hypoxia in liver tissues. However, the exact mechanisms of HBx-induced hepatocarcinogenesis were poorly understood. In this study, we examined the role of HBx in the increased angiogenesis and the possible regulating mechanisms of HBx by hypoxia. We demonstrated that HBx stimulated the transcription of vascular endothelial growth factor (VEGF), a potent angiogenic factor, in HBx-stable transfectants. HBx-induced angiogenesis was confirmed by in vivo tumor angiogenesis assay, resulting in that the HBx transfectants increased the formation of new blood vessels compared to the control transfectants. Then, we demonstrated that the expression of HBx was enhanced after incubating HBV-infected hepatoma cells under hypoxia. Moreover, the activity of HBV enhancer 1 (Enh1) was increased when hepatoma cells transfected with the reporter plasmid containing HBV Enh1 were exposed to hypoxic conditions. These results strongly suggest that HBx may play a critical role in the hypoxia-induced angiogenesis through transcriptional activation of VEGF during hepatocarcinogenesis.

Cell Hypoxia↗
PubMed2000

Sphingosine 1-phosphate stimulates tyrosine phosphorylation of focal adhesion kinase and chemotactic motility of endothelial cells via the G(i) protein-linked phospholipase C pathway.

We have previously shown that sphingosine 1-phosphate (S1P) stimulates motility of human umbilical vein endothelial cells (HUVECs) (O.-H. Lee et al., Biochem. Biophys. Res. Commun. 264, 743-750, 1999). To investigate the molecular mechanisms by which S1P stimulates HUVEC motility, we examined tyrosine phosphorylation of p125 focal adhesion kinase (p125(FAK)) which is important for cell migration. S1P induces a rapid increase in tyrosine phosphorylation of p125(FAK). Compared with other structurally related lipid metabolites such as sphingosine, C2-ceramide, and lysophosphatidic acid, S1P uniquely stimulated p125(FAK) tyrosine phosphorylation and migration of HUVECs. The effect of S1P on p125(FAK) tyrosine phosphorylation was markedly reduced by treatment with pertussis toxin or U73122, a phospholipase C (PLC) inhibitor. As a downstream signal of PLC, p125(FAK) tyrosine phosphorylation in response to S1P was totally blocked by depletion of the intracellular calcium pool. However, protein kinase C (PKC) inhibitor had no effect on the response to S1P. Finally, chemotaxis assays revealed that inhibition of PLC but not PKC significantly abrogated S1P-stimulated HUVEC migration. These results suggest that the G(i)-coupled receptor-mediated PLC-Ca(2+) signaling pathway may be importantly involved in S1P-stimulated focal adhesion formation and migration of endothelial cells.

Cell Adhesion Molecules↗
PubMed2000

Role of cytosolic phospholipase A(2) as a downstream mediator of Rac in the signaling pathway to JNK stimulation.

Rac is an important regulatory molecule implicated in c-jun N-terminal kinase (JNK) activation in response to stress and cytokines. However, the signaling events that mediate the activation of JNK by Rac are not yet well characterized. To broaden our understanding of downstream mediators that link Rac signals to the JNK pathway, we investigated whether cytosolic phospholipase A(2) (cPLA(2)) is involved in Rac activation of JNK. In this report we demonstrate that either co-transfection with antisense cPLA(2) oligonucleotide or pretreatment with arachidonyltrifluoromethyl ketone (AACOCF3), a potent and specific inhibitor of cPLA(2), inhibits Rac-mediated JNK activation, implying a potential role of cPLA(2) in Rac-signaling to JNK activation. In accordance with this observation, we demonstrate that the addition of exogenous arachidonic acid (AA), a principal product of Rac-activated cPLA(2), or leukotrienes, products of 5-lipoxygenase (5-LO) of AA, caused a specific stimulation of JNK. Together, our findings suggest that cPLA(2) mediates, at least partly, the signaling cascade by which Rac stimulates JNK.

Animals↗
PubMed2000

Clinicopathologic correlation of p53 protein overexpression in adenoma and carcinoma of the ampulla of Vater.

It has been well documented that ampullary carcinoma arises from a precancerous lesion, but there have been few studies concerning changes at the molecular level during the adenoma-carcinoma sequence. In this study, p53 overexpression during the progression of carcinoma was compared and the relation between p53 expression and prognosis was analyzed. Ninety-four cases of adenocarcinoma of the ampulla of Vater were reviewed histopathologically and examined for overexpression of p53 protein using the DO-7 (mouse monoclonal; DAKO, Glostrup, Denmark) antibody. The correlation of p53 overexpression with the existence of adenoma, clinical stage, histologic grade, and overall survival was investigated. The proportion of p53-positive cases among normal mucosa, adenoma, early stage carcinoma (I and II), advanced stage carcinoma (III and IV), and metastatic lesion was 0% (0/94), 14.3% (6/42), 32.3% (20/62), 53.1% (17/32), and 63.3% (19/30), respectively. The existence of adenoma or histologic grade of carcinoma did not correlate with p53 overexpression. The carcinoma having adenomatous component was more common in early stages (54.8% in stages I and II, 25% in stages III and IV; p = 0. 006) and in well-differentiated carcinoma (p = 0.001). The existence of adenoma or p53 overexpression did not independently correlate with prognosis. In contrast, the p53 overexpressed group without adenoma showed a worse prognosis than the remaining patients (p = 0. 0006) and this trend was still demonstrable when the groups were compared stage by stage. In ampullary carcinoma, p53 abnormality occurs during malignant transformation from the adenoma and continues during the tumor progression in carcinoma. The clinical prognosis of de novo carcinomas with p53 overexpression was worse than that of the remaining patients.

Adenoma↗
PubMed2000

No association between presenilin 1 (PS1) intronic polymorphism and sporadic Alzheimer's disease in Koreans.

To investigate the possible involvement of an intronic polymorphism in the presenilin 1 (PS1) gene and its interactions with the aplolipoprotein E (APOE) or alpha-1 antichymotrypsin (ACT) polymorphisms in the manifestation of AD, we analyzed the PS1, APOE and ACT genotypes of 100 sporadic AD patients and 199 normal elderly controls in Koreans. The genotypic (chi2= 0.92, df = 2, P > 0.1) and allelic (chi2 = 0.01, df = 1, P > 0.1) frequencies of the PS1 polymorphism in the late- and early-onset sporadic AD patients did not differ from those in the controls. And the occurrence of the APOE epsilon4 allele and ACT A allele did not influence the distribution of the PS1 intronic polymorphism. The PS1 intronic polymorphism didn't influence the age-at-onset of AD (F = 0.02, df = 2, P > 0.1). In conclusion, the PS1 intronic polymorphism did not modify the risk for sporadic AD, neither independently nor synergistically with the APOE epsilon4 allele or ACT A allele, in Koreans.

Age of Onset↗
PubMed2000

Distribution of plasma-membrane Ca2+ pump in mandibular condyles from growing and adult rabbits.

Chondrocytes may control the mineralization of the extracellular matrix of condylar cartilage by several mechanisms including the release of microvesicles involved in the initial nucleation, the creation or modification of the local matrix to help propagate or restrict mineralization, and the regulation of the ionic environment at the calcifying foci within the matrix. The plasma membrane Ca2+-Mg2+ ATPase (Ca2+ pump) is known to play a part in the vectorial efflux of calcium in a variety of cells including chondrocytes. The purpose here was to study the distribution of Ca2+-pump protein in mandibular condyles from growing and adult rabbits, and compare the expression of that protein in progressively differentiating chondrocytes whose final stage is associated with a mineralized extracellular matrix. Ca2+-pump antigen was identified immunohistochemically in six growing and six adult rabbit mandibular condyles with a Ca2+ pump-specific monoclonal antibody. The presence of Ca2+-pump antigen was established in hypertrophic chondrocytes, and in osteoblasts and osteoclasts of subchondral bone. Slot-blot analysis of nitrocellulose-immobilized chondrocyte homogenates showed that the amount of Ca2+ pump in growing cartilage was more than twice that in adult cartilage (p < 0.05). The demonstration of Ca2+-pump antigen in the hypertrophic chondrocytes of growing rabbit condyles is consistent with a role for the plasma-membrane Ca2+ pump in the calcification of mandibular condylar cartilage.

Animals↗
PubMed2000

Procyanidins in crataegus extract evoke endothelium-dependent vasorelaxation in rat aorta.

The extract of Crataegus, a mixture of flavonoids and procyanidins extracted from hawthorn, Crataegus oxyacantha, L. and C. monogyna Jacq., relaxed vascular tone or increased production of cyclic GMP in the rat aorta, but flavonoid components of Crataegus extract, hyperoside, rutin and vitexin, did not affect the vascular tone. The aim of the present study was to characterize the endothelium-dependent relaxation elicited by procyanidins fractionated from Crataegus extract in isolated rat aorta. Procyanidins caused endothelium-dependent relaxation which was associated with the production of cyclic GMP. Both responses to these procyanidins were inhibited by methylene blue or N(G)-nitro-L-arginine, but not by indomethacin. Relaxation in response to procyanidins was not affected by atropine, diphenhydramine, [D-Pro2,D-Trp7,9]substance P, propranolol, nifedipine, verapamil and glibenclamide, but were markedly reduced by tetraethylammonium. These findings showed that procyanidins in Crataegus extract may be responsible for the endothelium-dependent nitric oxide-mediated relaxation in isolated rat aorta, possibly via activation of tetraethylammonium-sensitive K+ channels.

Animals↗
PubMed2000

The inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in chronic myelogenous leukemic K562 cells.

In this study, the downstream signaling of Bcr-Abl tyrosine kinase responsible for apoptosis resistance was investigated. DNA fragmentation, a hallmark of apoptosis, was observed after 2 days of herbimycin A treatment with a peak on 3 day. During the apoptosis induced by the treatment of herbimycin A, stress-activated protein kinase (SAPK) and p38 kinase were activated time- and dose-dependently, while extracellular signal-regulated kinase (ERK) was inhibited. However, apoptosis was induced by the treatment of PD98059, a specific inhibitor of MEK (MAPK or ERK kinase), not by the treatment of sorbitol, a strong activator of SAPK and p38 kinase. Although K562 cells were very resistant to sorbitol-induced apoptosis, DNA fragmentation was induced rapidly in Jurkat, HL-60 and U937 cells after exposure to sorbitol, despite that these apoptosis-sensitive cells have similar or lower activities of JNK/SAPK and p38 kinase compared with K562 cells after treatment of sorbitol. K562 cells had a much higher basal activity of ERK/MAPK than other apoptosis-sensitive cell lines, which were very susceptible to apoptosis induced by low dose of PD98059 compared with K562 cells. In HL-60 cells, sorbitol-induced apoptosis was prevented by the treatment of phorbol myristate 13-acetate (PMA), which activates the ERK/MAPK pathway, and this was blocked by PD98059. From these results, it could be suggested that the inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in K562 cells.

Apoptosis↗
PubMed2000

Voltage-dependent K(+) currents in spiral prominence epithelial cells of rat cochlea.

It has been suggested that spiral prominence is associated with ion transport, but the characterization of ion channels has not been explored so far. We studied the electrical properties and ion conductances of the spiral prominence epithelial cells (SPECs), which are epithelial cells covering the luminal side of spiral prominence, in the upper turn of neonatal rat cochlea using a whole-cell variant patch clamp technique. The cell capacitance was 16.3+/-2.1 pF (n=33) and the resting membrane potential was -68. 9+/-2.5 mV (n=14) in perilymph-like bath solution. It was found that those SPECs possess a large voltage-activated, outwardly rectifying K(+) current and a small inwardly rectifying K(+) current. The outward K(+) current was activated by depolarizing pulses more positive than -30 mV, and sensitive to tetraethylammonium chloride (20 mM), 4-aminopyridine (10 mM), but not to Ba(2+) (0.5 mM). Tail current analysis revealed that it was primarily K(+)-selective. The time course of activation was well fitted by an exponential function raised to second power. The small inwardly rectifying K(+) current was sensitive to Ba(2+) (0.5 mM), and the Ba(2+)-sensitive current was K(+)-selective. In cell-attached or inside-out patch recordings, no discernible K(+) channel currents were found in the apical membrane of SPECs. Based on these results, we conclude that SPECs have two types of voltage-dependent K(+) currents, which are most likely located in the basolateral membrane.

Animals↗
PubMed2000

Renal and pulmonary lymphangioleiomyomatosis: a case report.

Lymphangioleiomyomatosis (LAM) is a rare disease that most commonly involves the lung. However, extrapulmonary lymphangioleiomyomatosis rarely occurs with or without subsequent involvement of the lung. We report a case of incidentally found renal and pulmonary lymphangioleiomyomatosis in a patient who had no stigmata of tuberous sclerosis.

Female↗
PubMed2000

The mechanism of nitric oxide and/or superoxide cytotoxicity in endothelial cells.

We examined the mechanism of nitric oxide (NO) and/or superoxide (O2-)-induced cytotoxicity and the importance of thiols in endothelial cells by treating the cells with superoxide dismutase (SOD), catalase (CAT) and hemoglobin (Hb). Pyrogallol, a O2 generator and precursor of hydrogen peroxide (H2O2), had potent cytotoxic effects on the endothelial cells, but this effect was completely abolished by SOD/CAT. Hb, a NO scavenger, protected the endothelial cells from sodium nitroprusside-induced cytotoxicity. The cytotoxic effect of 3-morpholinosydnonimine (SIN-1), which is thought to form peroxynitrite (ONOO-) as a simultaneous O2- and NO generator, was completely blocked by SOD/CAT or Hb. On the other hand, pretreatment of endothelial cells with diethylmaleate, a glutathione depleter, aggravated the cytotoxicity induced by SIN-1, which was prevented by addition of exogenous glutathione and/or SOD/CAT. These data suggest that the cytotoxicity induced by NO, O2- and ONOO- can be blocked by glutathione, and that this is an important cellular protective mechanism against these reactive oxygen species.

Animals↗
PubMed2000

Hypotonic swelling increases L-type calcium current in smooth muscle cells of the human stomach.

The purpose of the present study was to characterize the Ca2+ channels in smooth muscle cells from human stomach and to examine the effects of osmotic swelling on the channel activity. Ca2+ channel current with either Ca2+ or Ba2+ as charge carrier was recorded from freshly isolated smooth muscle cells using the conventional whole-cell patch clamp technique. The degree of cell swelling as a result of hypotonic challenge was monitored using a video image analysis system. The changes in intracellular Ca2+ concentration ([Ca2+]i) were measured by microfluorimetry. The pharmacological and voltage activation profile suggests a typical dihydropyridine-sensitive L-type Ca2+ current. Cell swelling, induced by hypotonic challenge, enhanced the amplitude of currents through L-type Ca2+ channels without significant effects on steady-state voltage dependency. After treatment with the L-type Ca2+ channel agonist Bay K 8644 (0.1-2 microM), no further significant increase in calcium channel current or corresponding [Ca2+]i transients were provoked by the swelling. The above results demonstrated that the presence of L-type Ca2+ current in smooth muscle cells of the human stomach and the augmentation of the current are closely associated with the volume increase resulting from hypotonic swelling.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

Identification of cis-acting promoter elements that support expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) in v-src transformed Madin-Darby canine kidney cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) expressed in tumor cells is believed to be important for the pericellular degradation of extracellular matrices during invasion and metastasis. To analyze the mechanism by which MT1-MMP becomes expressed in cancer cells, we assessed the MT1-MMP promoter region for the presence of cis-acting promoter elements that support transcription in transformed cells. Our tumor model consisted of Madin-Darby canine kidney (MDCK) cells transformed by v-src (src4 cells). MT1-MMP mRNA was only faintly detected in parental cells but was strongly expressed in the src4 cells. In parallel, src4 cells invaded into collagen gels, whereas MDCK cells did not. When MDCK and src4 cells were transiently transfected with a plasmid containing of -3000 to -99 nt from the upstream region of the MT1-MMP gene, the promoter activity was 2.6-fold higher in src4 cells than in MDCK cells. Furthermore, the region between -399 and -356 nt was found to contain the src4-specific enhancer element(s). Tandem Sp1 binding sites were also found to be essential in promoting transcription. An Egr-1 site that partially overlaps with the Sp1 sites was found to cooperate with the src4-specific enhancer and to also contribute weakly to the basal promoter activity. The presence of transcription factors that bind to the src4-specific enhancer site was detected by mobility-shift assays in src4 cell nuclear extracts but only weakly in MDCK extracts. Thus, we have identified a novel enhancer element that acts specifically in the transformed cells to enhance MT1-MMP expression.

Animals↗
PubMed2000

Active properties of the urinary bladder: in vitro comparative studies between adult and neonatal rats.

OBJECTIVE: To determine, using in vitro comparative studies, developmental aspects associated with the active properties of the urinary bladder in neonatal and adult rats. MATERIALS AND METHODS: Urinary bladders were removed from neonatal (1-3 days old) and adult (15 weeks old) male Sprague-Dawley rats. Anterior longitudinal muscle strips were obtained from each group and isometric tensions recorded. Nerve-mediated contractions elicited by electrical field stimulation (0.8 ms pulse) or carbachol-induced contractile responses in neonatal and adult bladder strips were compared. Contractile tensions were normalized using the wet weight of the bladder strip or by using the percentage contraction induced by 60 mmol/L KCl. RESULTS: Nerve-mediated contractile responses showed that the muscarinic component predominated in the neonatal rat bladder, which contrasted with the predominant purinergic components in adult bladder. The pattern of spontaneous activity and carbachol-induced contraction differed in the two groups. Small spontaneous contractions in the basal state occurred in adult bladder strips, while short-lived large spontaneous contractions were present in neonatal strips. The amplitude of carbachol-induced contractions generated in the neonatal bladder was larger than that in the adult bladder. In addition, the time to achieve peak contraction elicited by carbachol (5 micromol/L) was shorter in the neonatal bladder. Repetitive carbachol applications induced an attenuation of the contractile response (desensitization), but the neonatal bladder was more resistant to desensitization than the adult bladder. CONCLUSIONS: These results show that nerve-mediated or agonist-induced contractile patterns, and spontaneous activity, in the neonatal bladder differ from those of the adult bladder in rats. The results suggest that in addition to neural immaturity, there are functional differences between the bladders of adult and neonatal rats.

Adenosine Triphosphate↗