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Biomedical subjects

J S Yu

Publications and source records attributed to J S Yu.

At least 19 recordsLinked to original sources
PubMed1999

PAK2 is cleaved and activated during hyperosmotic shock-induced apoptosis via a caspase-dependent mechanism: evidence for the involvement of oxidative stress.

Hyperosmotic shock elicits a stress response in mammalian cells and can lead to apoptotic cell death. In the present study, we report that hyperosmotic shock can induce activation of a 36 kDa kinase detected by an in-gel kinase assay in several cell types, including mouse Balb/c 3T3 fibroblasts, and human Hep 3B and A431 cells. This 36 kDa kinase can be recognized by an antibody against the C-terminal region of a family of p21Cdc42/Rac-activated kinases (PAKs) on immunoblot. Further studies with this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 demonstrate that hyperosmotic shock can induce cleavage of PAK2 to generate a 36 kDa C-terminal catalytic fragment in cells. The cleavage and activation of PAK2 was found to be closely associated with both DNA fragmentation and activation of an ICE/CED-3 family cysteine protease termed caspase-3 in hyperosmotically shocked cells. Furthermore, pretreating the cells with two caspase inhibitors (Ac-DEVD-cho and Ac-YVAD-cmk) could inhibit both cleavage/activation of PAK2 and DNA fragmentation induced by hyperosmotic shock. Moreover, all these hyperosmotic shock-induced changes (i.e., activation of caspase-3, cleavage/activation of PAK2, and DNA fragmentation) in cells could be blocked by antioxidants such as ascorbic acid (vitamine C), alpha-tocopherol (vitamine E), dithiothreitol, beta-mercaptoethanol, and glutathione. Taken together, our results show that PAK2 is cleaved and activated via a caspase-dependent mechanism during hyperosmotic shock-induced apoptosis and suggest the involvement of antioxidant-preventable oxidative stress in inducing this process.

3T3 Cells↗
PubMed1999

Villous adenoma of the bile ducts: a case report and a review of the reported cases in Korea.

Villous adenomas are benign epithelial lesions with malignant potential which can occur at any site in the gastrointestinal tract. They are usually encountered in the rectum and colon, less frequently in the small bowel and very rarely in the biliary trees. Nine cases of bile duct villous adenomas have been reported in the literature. However, 4 cases of bile duct villous adenomas have been reported in the Korean literature. Recently, we experienced a case of villous adenoma in the common hepatic duct in a 77-year-old man presenting with obstructive jaundice in which preoperative histologic diagnosis of villous adenoma played a critical role in managing this patient. Herein, we present a case report of bile duct villous adenoma and a review of the reported cases in Korea to help define and manage this rare disease entity in the bile ducts. In addition, confusing nomenclature of bile duct adenomas is discussed.

Adenoma, Villous↗
PubMed1998

Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells.

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and can also lead to apoptotic cell death. In this report, we show that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be dramatically activated during the early stages of UV irradiation-triggered apoptosis of A431 cells. Immunoblot analysis revealed that this 36-kDa MBP kinase could be recognized by an antibody against the C-terminal regions of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as studying tools, we further demonstrated that UV irradiation caused cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment and a 30-kDa N-terminal fragment in A431 cells. The appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in A431 cells upon UV irradiation. In addition, UV irradiation also led to activation of CPP32/caspase-3, but not ICH-1L/caspase-2 and ICE/caspase-1, in A431 cells and the kinetics of activation of CPP32/caspase-3 appeared to correlate well with that of DNA fragmentation and of cleavage/activation of PAK2, respectively. Moreover, blockage of activation of CPP32/caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors for caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could significantly attenuate the extent of cleavage/activation of PAK2 induced by UV irradiation. Collectively, the results demonstrate that cleavage and activation of PAK2 can be induced during the early stages of UV irradiation-triggered apoptosis and indicate the involvement of CPP32/caspase-3 in this process.

Amino Acid Sequence↗
PubMed1998

Identification of the regulatory autophosphorylation site of autophosphorylation-dependent protein kinase (auto-kinase). Evidence that auto-kinase belongs to a member of the p21-activated kinase family.

Autophosphorylation-dependent protein kinase (auto-kinase) was identified from pig brain and liver on the basis of its unique autophosphorylation/activation property [Yang, Fong, Yu and Liu (1987) J. Biol. Chem. 262, 7034-7040; Yang, Chang and Soderling (1987) J. Biol. Chem. 262, 9421-9427]. Its substrate consensus sequence motif was determined as being -R-X-(X)-S*/T*-X3-S/T-. To characterize auto-kinase further, we partly sequenced the kinase purified from pig liver. The N-terminal sequence (VDGGAKTSDKQKKKAXMTDE) and two internal peptide sequences (EKLRTIV and LQNPEK/ILTP/FI) of auto-kinase were obtained. These sequences identify auto-kinase as a C-terminal catalytic fragment of p21-activated protein kinase 2 (PAK2 or gamma-PAK) lacking its N-terminal regulatory region. Auto-kinase can be recognized by an antibody raised against the C-terminal peptide of human PAK2 by immunoblotting. Furthermore the autophosphorylation site sequence of auto-kinase was successfully predicted on the basis of its substrate consensus sequence motif and the known PAK2 sequence, and was further demonstrated to be RST(P)MVGTPYWMAPEVVTR by phosphoamino acid analysis, manual Edman degradation and phosphopeptide mapping via the help of phosphorylation site analysis of a synthetic peptide corresponding to the sequence of PAK2 from residues 396 to 418. During the activation process, auto-kinase autophosphorylates mainly on a single threonine residue Thr402 (according to the sequence numbering of human PAK2). In addition, a phospho-specific antibody against a synthetic phosphopeptide containing this identified sequence was generated and shown to be able to differentially recognize the activated auto-kinase autophosphorylated at Thr402 but not the non-phosphorylated/inactive auto-kinase. Immunoblot analysis with this phospho-specific antibody further revealed that the change in phosphorylation level of Thr402 of auto-kinase was well correlated with the activity change of the kinase during both autophosphorylation/activation and protein phosphatase-mediated dephosphorylation/inactivation processes. Taken together, our results identify Thr402 as the regulatory autophosphorylation site of auto-kinase, which is a C-terminal catalytic fragment of PAK2.

Amino Acid Sequence↗
PubMed1998

Sulfoglucuronosyl glycolipids as putative antigens for autoimmune inner ear disease.

Autoimmune inner ear disease is diagnosed based on clinical history of fluctuating but progressive sensorineural hearing loss (SNHL) with or without vestibular symptoms occurring over weeks to months. An initial response to steroids or immunosuppressive drugs usually reverses the hearing loss. In search of specific diagnostic and therapeutic markers for autoimmune inner ear diseases, we investigated serum anti-glycolipid antibody activities in these patients by two different methods, HPTLC-immunoblotting and ELISA. We found that 37 out of 74 patients of clinically diagnosed autoimmune inner ear disease (30 of sensorineural hearing loss (SNHL) (group I), 14 of vestibular symptoms only (group II), 30 of Menieres symptoms (with both hearing loss and vestibular symptoms) (group III)) showed positive anti-sulfoglucuronosyl lactosaminyl paragloboside (SGLPG) antibody titers (p < 0.001). On the other hand, anti-sulfoglucuronosyl paragloboside (SGPG) titers were not elevated in these conditions. In contrast, only 3 out of 56 pathological control and 2 out of 28 healthy volunteers had measurable anti-SGLPG antibody titers. We further analyzed the localization of SGLPG in the auditory pathway and found that the antigens existed exclusively in inner ear and the eighth nerve, but not in pons, cerebellum, nor cerebrum. We conclude that the anti-SGLPG antibody represents a novel diagnostic marker for autoimmune inner ear disease and may participate in the pathogenesis of this disease.

Autoantibodies↗
PubMed1998

Heat shock stress induces cleavage and activation of PAK2 in apoptotic cells.

Heat shock induces a stress response in mammalian cells and can also lead to apoptotic cell death. Here we report that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be drastically activated in several cell types by heat shock. Immunoblot analysis revealed that this 36-kDa MBP kinase can be recognized by an antibody against the C-terminal region of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as tools, we further demonstrated that heat shock can induce cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment in mouse Balb/c 3T3 and human Hep 3B cells. The kinetic profile of appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in these cells induced by heat shock. In addition, the heat shock-induced cleavage and activation of PAK2 was found to be closely associated with both DNA fragmentation and activation of an ICE/CED-3 family cysteine protease termed caspase-3 in heat shock-treated Hep 3B cells. Moreover, blockage of the activation of caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors of caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could substantially diminish the extent of heat shock-induced cleavage/activation of PAK2. Overall, our results point out that PAK2 is cleaved and activated during the heat shock-induced apoptotic cell death process and suggest that caspase-3 is involved in this process.

3T3 Cells↗
PubMed1998

Activation of protein phosphatase 2A by the Fe2+/ascorbate system.

Freshly isolated protein phosphatase 2A (PP2A) was highly active as to the dephosphorylation of protein substrates, but lost most of its spontaneous activity on prolonged storage, and was converted to a latent form requiring Mn2+ or Co2+ ions for activity. In this report, we show that the latent form of PP2A can be activated by the Fe2+/ascorbate system. Activation of the phosphatase required both Fe2+ ions and ascorbate, and the level of activation was dependent on the concentrations of both Fe2+ ions and ascorbate. Both the holoenzyme and catalytic subunit of phosphatase 2A could be activated by the Fe2+/ascorbate system, indicating that direct modulation of the catalytic subunit of the phosphatase by the Fe2+/ascorbate system may cause this activation. Several common divalent metal ions, including Ca2+, Mg2+, Cu2+, Zn2+, and Ni2+ ions, cannot cooperate with ascorbate to activate the phosphatase. Dithiothreitol, a SH-containing reducing agent, could replace ascorbate in the Fe2+/ascorbate system to activate the phosphatase, whereas H2O2, a strong oxidizer, significantly diminished the phosphatase activation by the Fe2+/ascorbate system. The results indicate that iron ions stabilized in the +2 state by reducing agents can activate the phosphatase. Overall, the present study provides initial biochemical evidence suggesting that Fe2+ could be a biologically important metal ion cofactor responsible for PP2A activation.

Animals↗
PubMed1998

Osteochondral defect of the glenoid fossa: cross-sectional imaging features.

PURPOSE: To evaluate the cross-sectional imaging features of osteochondral defects (OCDs) of the glenoid fossa and to elicit a more detailed analysis of the trauma, if any, that may cause this injury. MATERIALS AND METHODS: Eight patients (seven male patients, one female patient; age range, 15-42 years; mean age, 27 years) with an OCD in the glenoid fossa were identified. Conventional computed tomography (CT), CT arthrography, or magnetic resonance (MR) imaging was performed. Surgical correlation was available in six patients. RESULTS: Six patients had a history of anterior dislocation or subluxation, one patient had an acromioclavicular joint separation, and one patient had chronic pain. Seven patients had anterior labral tears, and four had a redundant capsular insertion. A glenoid OCD appeared as either a multiloculated cyst in the subchondral bone mimicking a subchondral cyst (six patients) or a single osteochondral fragment (two patients). The lesion ranged from 8 mm to 2.0 cm in diameter. Three patients had an intraarticular body. Surgery confirmed an OCD in six of six patients. CONCLUSION: A glenoid OCD occurs most often as a result of acute trauma and has a high association with instability, labral tear, and intraarticular bodies.

Adolescent↗
PubMed1998

Acute cholecystitis: comparison of MR cholangiography and US.

PURPOSE: To evaluate the clinical usefulness of magnetic resonance (MR) cholangiography in the assessment of acute cholecystitis by comparing the diagnostic accuracy of MR cholangiography with that of ultrasonography (US). MATERIALS AND METHODS: Thirty-five patients with symptoms of acute cholecystitis underwent both US and MR cholangiography before cholecystectomy, which helped confirm acute cholecystitis. Two reviewers evaluated US and MR cholangiographic images for evidence of calculi and gallbladder wall thickening and compared these findings with surgical findings. RESULTS: MR cholangiography depicted all 21 (100%) calculi and one false-positive calculus in the cystic duct and gallbladder neck, but US depicted only one (14%) of seven cystic duct calculi and 12 (86%) of 14 gallbladder neck calculi. In the diagnosis of cystic duct obstruction, MR cholangiography had a sensitivity of 100%, a specificity of 93%, and an accuracy of 97%. US had a sensitivity of 62%, a specificity of 100%, and an accuracy of 77%. In the diagnosis of gallbladder wall thickening, MR cholangiography had a sensitivity of 69%, a specificity of 83%, and an accuracy of 71%. US had a sensitivity of 96%, a specificity of 83%, and an accuracy of 94%. CONCLUSION: In the assessment of acute cholecystitis, US is superior to MR cholangiography in the evaluation of gallbladder wall thickening. However, MR cholangiography is superior to US in the depiction of cystic duct and gallbladder neck calculi at the evaluation of cystic duct obstruction.

Acute Disease↗
PubMed1998

MR imaging during arterial portography for assessment of hepatocellular carcinoma: comparison with CT during arterial portography.

OBJECTIVE: The purpose of this study was to document the usefulness of MR imaging during arterial portography (MRAP) versus CT during arterial portography (CTAP) in the diagnosis and assessment of hepatocellular carcinoma. SUBJECTS AND METHODS: In addition to static T1- and T2-weighted MR imaging, MRAP was performed immediately after hepatic angiography through contrast material injection into intraarterially placed catheters (superior mesenteric or splenic artery) in 21 patients with nodular hepatocellular carcinoma. CTAP was performed afterward for each patient. The sensitivity and specificity of MRAP for lesion detection and the differential diagnosis of hepatocellular carcinoma were compared with the sensitivity and specificity of CTAP. RESULTS: MRAP revealed more perfusion defects (n = 56) than did CTAP (n = 46). The sensitivity for detection of hepatocellular carcinoma was higher for MRAP (94%) than for CTAP (83%); however, the difference was not statistically significant (p > .05). More hepatocellular nodules with unknown malignant potential were revealed on MRAP (n = 7) than on CTAP (n = 2). For the differential diagnosis of perfusion defects commonly revealed by both techniques, more benign lesions and pseudolesions (n = 14) were shown on MRAP through the combined interpretation with static images than on unenhanced and contrast-enhanced CTAP (n = 11). CONCLUSION: Because of its high sensitivity and its ability to enable radiologists to differentiate benign from malignant conditions, MRAP may have merit compared with CTAP in the assessment of hepatocellular carcinoma.

Adult↗
PubMed1998

Hepatic cavernous hemangioma: sonographic patterns and speed of contrast enhancement on multiphase dynamic MR imaging.

OBJECTIVE: Our purpose was to investigate a correlation between the speed of contrast enhancement in patients with hepatic cavernous hemangioma revealed by dynamic MR imaging and the internal echo pattern revealed by sonography. MATERIALS AND METHODS: Forty-five patients underwent multiphase IV contrast-enhanced dynamic MR imaging that revealed 71 hepatic cavernous hemangiomas less than 4 cm in diameter; the MR findings were compared with the sonographic findings in these patients. On MR imaging, the hemangiomas were classified as rapid-, intermediate-, and slow-enhancing. We classified sonographic features as hypoechoic, iso- or mixed-echoic, and hyperechoic according to the relative echogenicity seen between lesions and the surrounding hepatic parenchyma. Sonographic patterns and MR imaging findings of individual lesions were then compared. RESULTS: Rapid-enhancing hemangiomas revealed on dynamic MR imaging tended to be hypoechoic on sonography (18/24, 75%; p = .0143), and lesions that were slow-enhancing on MR imaging tended to be hyperechoic (26/29, 90%; p < .0001). Hypoechoic lesions on sonography tended to be rapid-enhancing on dynamic MR imaging (18/18, 100%). Likewise, hyperechoic lesions on sonography tended to be slow-enhancing on MR imaging (26/33, 79%; p = .0009). CONCLUSION: In most patients with hepatic cavernous hemangiomas, we found that the speed of contrast enhancement on multiphase dynamic MR imaging enabled us to predict the echo pattern in sonography and vice versa.

Contrast Media↗
PubMed1998

Diabetic foot and neuroarthropathy: magnetic resonance imaging evaluation.

Neuropathic osteoarthropathy occurs commonly in patients with long-standing diabetes mellitus and is one of the leading causes of debilitating complications of the foot. In this article, the pathologic and radiologic features of neuropathic joint disease are reviewed, with an emphasis on MRI.

Diabetic Foot↗
PubMed1997

Selective interaction of protein kinase FA/glycogen synthase kinase-3alpha with membrane phospholipids.

Previously we reported that the activity of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) can be detected in several brain membrane fractions. In this report, we examined whether kinase FA/GSK-3alpha can directly interact with membrane phospholipids by using anti-kinase FA/GSK-3alpha antibody as a more specific studying tool. It was found that kinase FA/GSK-3alpha can associate with NaOH-extracted brain membranes and selectively interact with several kinds of reconstituted phospholipid vesicles including phosphatidic acid (PA), phosphatidyl ethanolamine (PE), phosphatidyl inositol (PI), and phosphatidyl serine (PS) vesicles. Increasing ionic strength in the reaction could disrupt the interaction between kinase FA/GSK-3alpha and PA, PI, or PE vesicles but had no effect on the interaction between kinase FA/GSK-3alpha and PS vesicles, indicating that both ionic and non-ionic interactions are involved in this process, respectively. Moreover, both kinase activity and protease sensitivity of kinase FA/GSK-3alpha can be affected profoundly by these phospholipid vesicles and different forms of the kinase can be produced when it binds to distinct types of phospholipid vesicles. Taken together, the results demonstrate a direct interaction of kinase FA/GSK-3alpha with membrane phospholipids and suggest that membrane phospholipids may be directly involved in regulating kinase FA/GSK-3alpha activity.

Animals↗
PubMed1997

Gene therapy for metastatic brain tumors by vaccination with granulocyte-macrophage colony-stimulating factor-transduced tumor cells.

We have developed an ex vivo gene therapy paradigm for the treatment of brain tumors using granulocyte-macrophage colony-stimulating factor (GM-CSF). Murine B16 melanoma cells were infected with MFG recombinant retrovirus containing the mouse GM-CSF cDNA. Subcutaneous vaccination of syngeneic mice with irradiated GM-CSF-secreting B16 melanoma cells was capable of completely protecting animals against subsequent intracranial B16 tumor inoculation, with up to 5 x 10(3) cells. Histologic evaluation revealed the presence of neutrophils, eosinophils, and lymphocytes, including CD4+, CD8+, and CD45R+ cells, in the intracerebral inoculation site, peaking 4 days after intracranial inoculation. In contrast, nonvaccinated animals or animals vaccinated with irradiated, nontransduced B16 cells succumbed to intracranial tumor within 3 weeks after inoculation. Treatment of established intracranial B16 melanoma tumors with subcutaneous injection of irradiated GM-CSF-secreting B16 cells significantly delayed death, as compared to injection of irradiated nontransduced B16 cells or no treatment. In addition, treatment of established intracerebral GL261 gliomas by vaccination with irradiated GM-CSF-secreting B16 cells mixed with irradiated, transduced, or nontransduced GL261 cells also extended survival. These B16/GL261 co-vaccinations also improved outcome and, in some cases, induced immunological memory that protected survivors from subsequent intracranial challenge with GL261 tumor cells. These findings indicate that peripheral vaccination with irradiated tumor cells in the presence of GM-CSF-producing cells can initiate a potent antitumor immune response against intracranial neoplasms.

Animals↗