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Biomedical subjects

T S Kim

Publications and source records attributed to T S Kim.

At least 55 records · Page 3Linked to original sources

Role of the cytosolic phospholipase A2-linked cascade in signaling by an oncogenic, constitutively active Ha-Ras isoform.

Activation of Ras signaling by growth factors has been associated with gene regulation and cell proliferation. Here we characterize the contributory role of cytosolic phospholipase A(2) in the oncogenic Ha-Ras(V12) signaling pathway leading to activation of c-fos serum response element (SRE) and transformation in Rat-2 fibroblasts. Using a c-fos SRE-luciferase reporter gene, we showed that the transactivation of SRE by Ha-Ras(V12) is mainly via a Rac-linked cascade, although the Raf-mitogen-activated protein kinase cascade is required for full activation. In addition, Ha-Ras(V12)-induced DNA synthesis was significantly attenuated by microinjection of recombinant Rac(N17), a dominant negative mutant of Rac1. To identify the mediators downstream of Rac in the Ha-Ras(V12) signaling, we investigated the involvement of cytosolic phospholipase A(2). Oncogenic Ha-Ras(V12)-induced SRE activation was significantly inhibited by either pretreatment with mepacrine, a phospholipase A(2) inhibitor, or cotransfection with the antisense oligonucleotide of cytosolic phospholipase A(2). We also found cytosolic phospholipase A(2) to be situated downstream of Ha-Ras(V12) in a signal pathway leading to transformation. Together, these results are indicative of mediatory roles of Rac and cytosolic phospholipase A(2) in the signaling pathway by which Ha-Ras(V12) transactivates c-fos SRE and transformation. Our findings point to cytosolic phospholipase A(2) as a novel potential target for suppressing oncogenic Ha-Ras(V12) signaling in the cell.

Animals↗

A cytotoxic secocycloartenoid from Abies koreana.

Two triterpenoids, 24-methylene-3,4-seco-cycloart-4(28)-en-3-oic acid (1) and 3-oxo-9beta-lanosta-7,22Z,24-trien-26,23-olide (6) were isolated from Abies koreana, together with beta-sitosterol (2), maltol (3), beta-sitosterol-O-beta-D-glucoside (4), and hexacosylferulate (5). The structures of the compounds were established based on the spectroscopic data. The cytotoxic activities of triterpenoids have been evaluated using the sulforhodamine B (SRB) method. Compound 1 showed moderate cytotoxicities against human lung carcinoma (A549), ovarian carcinoma (SK-OV-3), malignant melanoma (SK-MEL-2), and colon carcinoma (HCT-15) cell lines.

Abies↗

Fluorodeoxyglucose positron emission tomography for detection of recurrent or metastatic breast cancer.

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive imaging technique capable of identifying primary tumors and metastases with high sensitivity and accuracy. The aim of this study was to evaluate the diagnostic accuracy of whole-body FDG-PET imaging for the detection of recurrent or metastatic breast cancer after surgery. Whole-body FDG-PET imaging was performed on 27 patients with suspected recurrent breast carcinoma. PET images were evaluated qualitatively for each patient and lesion. FDG-PET scans showed that there were 61 reference sites of malignant or benign lesions in 27 patients. In a patient-based analysis, FDG-PET scans correctly identified 16 of 17 patients with recurrent or metastatic disease and 8 of 10 without recurrence, resulting in a sensitivity, specificity, and accuracy of 94%, 80%, and 89%, respectively. In a lesion-based analysis, FDG-PET scans correctly identified 46 of 48 lesion sites with recurrent or metastatic disease and 11 of 13 without recurrence. The overall sensitivity, specificity, and accuracy for all lesion sites were 96%, 85%, and 93%, respectively. FDG-PET scans revealed unsuspected recurrent or metastatic diseases in 8 of 27 (30%) of patients and 11 of 20 (55%) distant metastatic lesions. In 13 patients treatment was altered by the outcome of the PET scan. We concluded that whole-body FDG-PET scan is a useful diagnostic imaging modality for detecting recurrent or metastatic breast carcinoma in patients suspected of having recurrent disease after primary surgery.

Adult↗

Cervical dermal sinus associated with dermoid cyst.

We report a rare case of cervical dermal sinus associated with a dermoid cyst in a 10-month-old infant, who presented with a 1-month history of motor weakness of the right upper extremity. Magnetic resonance imaging showed an intradural extramedullary dermoid cyst extending from C3 to C4, which was connected with the skin dimple along the sinus tract. Total excision of the dermoid cyst and the sinus tract with C3-5 laminectomy resulted in good functional recovery.

Cervical Vertebrae↗

Radiologically confirmed de novo glioblastoma multiforme and hippocampal sclerosis associated with the first onset of nonconvulsive simple partial status epilepticus.

The authors report a case of an unusual progression of glioblastoma multiforme in the temporal lobe associated with the first onset of nonconvulsive simple partial status epilepticus (SPSE), a rare form of status epilepticus. The patient underwent a left temporal craniotomy and the tumor was removed. Concurrently, the hippocampus was removed as well. The pathological diagnosis of the tumor and the hippocampus were glioblastoma multiforme and hippocampal sclerosis. The patient's postoperative course was uneventful.

Brain Neoplasms↗

Inhibition of porcine reproductive and respiratory syndrome virus by interferon-gamma and recovery of virus replication with 2-aminopurine.

Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to a group of RNA viruses that establish persistent infections. A proposed strategy for evading immunity during persistent PRRSV infection is by preventing the induction of IFN activity in pigs and/or by blocking the activation of antiviral proteins in permissive cells. IFN-gamma mRNA expression was observed in the lymph nodes and lungs of pigs infected with wild-type PRRSV strain SDSU-23983. Pretreatment of MARC-145 cells with IFN-gamma inhibited wild-type (SDSU-23983 P6) and culture-adapted (SDSU-23983 P136) PRRS viruses in a dose-dependent manner and at relatively low concentrations. The effect of IFN-gamma on virus replication included reductions in the number of infected cells, virus yield, and RNA content in single cells. Virus replication was partially restored by the addition of 2-aminopurine (2-AP), an inhibitor of dsRNA inducible protein kinase (PKR). The addition of 2-AP also restored the viral RNA content per cell to near normal levels, suggesting that inhibition of viral RNA synthesis was through PKR. The principal difference between P6 and P136 isolates was the recovery of P136 replication with lower concentrations of 2-AP. Immunostaining with anti-PKR antibody showed a redistribution of PKR from the cytoplasm into nucleoli of infected cells.

2-Aminopurine↗

New lactone-containing metabolites from a marine-derived bacterium of the genus Streptomyces.

Six novel metabolites containing a lactone moiety as a common structural feature, along with the previously described (-)-blastmycinolactol, have been isolated from the cultivation broth of a bacterium of the genus Streptomyces isolated from marine sediment. On the basis of the results of combined spectroscopic analysis, the structures of the new compounds have been determined as butenolides and 3-hydroxy-gamma-butyrolactones.

Antifungal Agents↗

Inhibition of interleukin-12 production by auranofin, an anti-rheumatic gold compound, deviates CD4(+) T cells from the Th1 to the Th2 pathway.

1. Interleukin-12 (IL-12) may play a central role in the development and progression of rheumatoid arthritis by driving the immune response towards T helper 1 (Th1) type responses characterized by high IFN-gamma and low IL-4 production. In this study we investigated the effect of auranofin (AF), an anti-rheumatic gold compound, on IL-12 production in mouse macrophages and dendritic cells, and studied whether AF-mediated inhibition of IL-12 production could regulate a cytokine profile of antigen (Ag)-primed CD4(+) Th cells. 2. Treatment with AF significantly inhibited IL-12 production in lipopolysaccharide (LPS)-stimulated macrophages and also in CD40L-stimulated dendritic cells. AF-pretreated macrophages reduced their ability to induce IFN-gamma and increased the ability to induce IL-4 in Ag-primed CD4(+) T cells. AF did not influence the cell surface expression of the class II MHC molecule and the costimulatory molecules CD80 and CD86. 3. Addition of recombinant IL-12 to cultures of AF-pretreated macrophages and CD4(+) T cells restored IFN-gamma production in Ag-primed CD4(+) T cells. 4. The in vivo administration of AF resulted in the inhibition of IL-12 production by macrophages stimulated in vitro with LPS or heat-killed Listeria monocytogenes (HKL), leading to the inhibition of Th1 cytokine profile (decreased IFN-gamma and increased IL-4 production) in Ag-primed CD4(+) T cells. 5. These findings may explain some known effects of AF including anti-rheumatic effects and the inhibition of encephalitogenicity, and point to a possible therapeutic use of AF in the Th1-mediated immune diseases such as autoimmune diseases.

Animals↗

Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin-18.

Interferon-gamma (IFN-gamma) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) was known to strongly induce IFN-gamma production by T cells and natural killer (NK) cells. In order to determine whether injection with DNA encoding IL-18 can stimulate the resistance to Mycobacterium avium complex (MAC) infection, the mature IL-18 cDNA with kappa leader sequence was cloned under control of the cytomegalovirus (CMV) promoter (TcCMVIL-18) and its effect on MAC infection was investigated in genetically susceptible BALB/c mice. Injection with the TcCMVIL-18 DNA during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while injection with the TcCMV control DNA did not. Lung cells in mice injected with the TcCMVIL-18 DNA showed persistent production of IFN-gamma throughout the 8-week period. Furthermore, immunization with the TcCMVIL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than immunization with the TcCMV control vector. This work suggests that IL-18 DNA vaccination may be useful in the immunotherapeutic or immunoprotection approaches of infections by intracellular parasites such as mycobacteria.

Animals↗

Cnidicin, a coumarin, from the root of Angelica koreana, inhibits the degranulation of mast cell and the NO generation in RAW 264.7 cells.

Cnidicin (1) and five related coumarins were isolated from the root extract of Angelica koreana (Umbelliferae) as active principles responsible for the inhibitory effect on the degranulation process of cultured mast cells. Cnidicin (1) demonstrated a significant inhibition upon the release of beta-hexosaminidase from the cultured RBL-2H3 cells in a dose dependent manner (IC50 value, 25 microM) and upon the nitric oxide production from the activated RAW264.7 cells (IC50 value, 7.5 microM). In agreement with this, cnidicin inhibited the expression of nitric oxide synthase in RAW264.7 cells.

Animals↗

Inhibition of interleukin-12 production in lipopolysaccharide-activated mouse macrophages by hpyericin, an active component of Hypericum perforatum.

Hypericin, an active component of Hypericum perforatum, was evaluated for the regulation of interleukin-12 (IL-12) production in mouse macrophages. Hypericin significantly inhibited IL-12 production in lipopolysaccharide-activated macrophages in a dose-dependent manner (IC50 = 1.45 micrograms/ml). Furthermore, hypericin potently inhibited the activation of IL-12 gene promoter, suggesting that hypericin negatively regulated IL-12 production at the transcription level. These results may explain some known biological activities of hypericin including its anti-rheumatic effect.

Animals↗

Large cell neuroendocrine carcinoma of the lung: clinical, CT, and pathologic findings in 11 patients.

The purpose of this study was to describe the clinical, computed tomographic (CT), and pathologic findings of large cell neuroendocrine carcinoma (LCNEC) of the lung. CT and pathologic findings as well as clinical features of surgically proven LCNEC of the lung were reviewed retrospectively in 11 consecutive patients (eight men and three women; mean age, 63 years; range, 44-77 years). Chest CT showed peripheral mass or nodule (n = 8) and central mass with distal atelectasis (n = 3). Six tumors were accompanied by mediastinal (n = 3) and hilar (n = 3) lymph node enlargement at CT. On pathologic examination, all resected tumors showed necrosis of variable extent (mean: 38%, range; 10-70%). The areas of intrinsic lipoid pneumonia and tumor emboli in two patients appeared at CT as areas of ground-glass opacity surrounding the tumor. Mediastinal nodal metastases were seen in three (27%) patients. Pathologic staging of 11 patients was IB in six, IIA in one, IIB in one, IIIA in two, and IIIB in one. Follow-up data showed extrathoracic metastases in four patients at mean follow-up period of 15 months. One patient died of distant metastasis 5 months after the surgery. CT findings of LCNEC of the lung are nonspecific and similar to those of other non-small cell lung cancers and extrathoracic metastasis is seen in approximately one third of the patients with follow-up study.

Adult↗

Meningeal solitary fibrous tumor as an unusual cause of expohthalmos: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: We report an extremely rare case of a patient with meningeal solitary fibrous tumor with orbital involvement presenting as unilateral exophthalmos. This rare tumor should be considered in the differential diagnosis for aggressive dural-based lesions. CLINICAL PRESENTATION: A 54-year-old man presented with a protruded eyeball on the right side and left hemiparesis. Computed tomography and magnetic resonance imaging demonstrated a huge mass, markedly enhanced in and around the right anterior clinoid process, which extended to the orbit and middle cranial fossa. Cerebral angiography revealed a richly vascular tumor fed by branches of both the right external and internal carotid arteries. A presumptive diagnosis of meningioma or hemangiopericytoma was considered. INTERVENTION: The tumor was exposed through an orbitozygomatic approach. At surgery, the tumor was grossly firm to hard and had destroyed the dura, orbital roof, anterior clinoid process, temporal bone, and muscle. Histological analysis revealed that the tumor was composed of spindle-cell proliferation in a collagen-rich background, but it exhibited regional variations. The vascular network demonstrated irregular vascular lumina with a "hemangiopericytoma-like" pattern. Histological features included high cellularity and a high degree of pleomorphism. Immunohistochemical analysis of the tumor demonstrated diffuse positive staining for CD34 and vimentin. The tumor displayed no positive staining for cytokeratin, epithelial membrane antigen, glial fibrillary antigenic protein, S-100 protein, and factor XIII. CONCLUSION: Meningeal solitary fibrous tumor is considered a unique pathological entity. Wider use of immunohistochemical screening should enable analysis of the real incidence of these tumors; larger series and longer follow-up duration will allow conclusions to be drawn regarding treatment and prognosis. Differential diagnosis is discussed and the literature is reviewed.

Angiography, Digital Subtraction↗

Long-term results of guided tissue regeneration therapy with non-resorbable and bioabsorbable barriers. I. Class II furcations.

BACKGROUND: The aim of this 5-year follow-up study was to clinically and radiographically evaluate the long-term results after guided tissue regeneration (GTR) therapy of Class II furcation defects using non-resorbable and bioabsorbable barriers. METHODS: Nine pairs of contralateral Class II furcation defects were treated in 9 patients with advanced periodontitis. Within each patient, one defect received a non-resorbable (expanded polytetrafluoroethylene [ePTFE]; control, C) barrier and the other a bioabsorbable (polyglactin 910; test, T) barrier by random assignment. At baseline, 6, and 60 +/- 3 months after surgery, clinical parameters and standardized radiographs were obtained. Gain of bone density within furcation areas was assessed using subtraction radiography. RESULTS: Six and 60 months after GTR therapy, statistically significant (P <0.05) horizontal attachment (CAL-H) gain was observed in both groups (C6: 1.7 +/- 0.8 mm; C60: 1.6 +/- 1.2 mm; T6: 2.0 +/- 0.7 mm; T60: 2.2 +/- 0.9 mm). However, 1 furcation assessed as Class I six months after GTR therapy with a bioabsorbable barrier had progressed to Class III after 5 years, and in another patient, 5 years after placement of an ePTFE barrier, 1 furcation had lost all the CAL-H gain that had been observed at 6 months. Subtraction analysis revealed similar area gain in both groups 6 and 60 months postsurgically (C6: 0.3 +/- 0.5; C60 1.0 +/- 1.7; T6: 0.4 +/- 0.4; T60: 1.1 +/- 1.7). CONCLUSIONS: CAL-H gain achieved after GTR therapy in Class II furcations was stable after 5 years in 16 of 18 defects. The study failed to show a statistically significant difference in stability of CAL-H gain between control and test groups 5 years after GTR therapy.

Absorbable Implants↗

Radiographic defect depth and width for prognosis and description of periodontal healing of infrabony defects.

BACKGROUND: The aims of the present study were to evaluate 1) defect depth and width as a prognostic factor and 2) change in defect width as a describing parameter of periodontal healing in infrabony defects treated by regenerative therapy after 6 and 24 months. METHODS: In 24 patients with advanced periodontitis, 39 infrabony defects were treated by guided tissue regeneration (GTR) using expanded polytetrafluoroethylene (ePTFE) (n = 7) or bioabsorbable barriers (n = 32). Clinical parameters were assessed and 39 standardized radiographs (in triplicate) were taken before and 6 and 24 months after surgery. Using a computer-assisted analysis, the depth, width, and angle of the bony defects were measured. RESULTS: Statistically significant vertical clinical attachment gains (CAL-V: 3.15 +/- 1.63 mm to 3.31 +/- 1.65 mm; P<0.001) and bony fill (1.30 +/- 2.53 mm; P<0.01 to 1.54 +/- 2.70 mm; P<0.005) were observed 6 and 24 months postsurgically. In a multilevel regression analysis CAL-V gain was predicted by baseline CAL-V (P <0.0001), actual smoking (P <0.05), and age (P <0.1). Bony fill could be predicted by baseline height of the infrabony component (P<0.0001), gingival index at baseline (P<0.05), and actual smoking (P <0.01). In narrow (<26 degrees) and deep (> or = 3 mm) infrabony defects bony fill was more pronounced than in wide and shallow defects (P <0.05). CONCLUSIONS: Improvement achieved by guided tissue regeneration in infrabony defects can be maintained up to 24 months after surgery. Narrow and deep infrabony defects respond radiographically and to some extent clinically more favorably to GTR therapy than wide and shallow defects. However, depth of the infrabony component was a stronger prognostic parameter than defect angle. Actual smoking impairs the results of GTR therapy in infrabony defects.

Adult↗

Malignant thymic epithelial tumors: CT-pathologic correlation.

OBJECTIVE: The purpose of our study was to describe and compare the CT and pathologic findings of atypical thymoma and thymic carcinoma. MATERIALS AND METHODS: Twenty-seven consecutive patients (14 men, 13 women ranging in age from 22 to 77 years [mean age, 52 years]) with pathologically proven atypical thymoma (n = 9) and thymic carcinoma (n = 18) constituted the study population. The chest CT findings in each of the 27 patients were reviewed retrospectively in consensus by two chest radiologists. These findings were correlated with pathologic findings. RESULTS: The tumors were located in the anterior mediastinum, and most tumors had a lobulated margin (24/27, 89%). Atypical thymomas were significantly smaller (mean, 4.7 cm) than thymic carcinomas (mean, 7.2 cm) (p = 0.041) on CT. The findings of invasion of the great vessels, lymph node enlargement, extrathymic metastases, and phrenic nerve palsy were seen only in patients with thymic carcinoma. The frequencies of necrosis, intratumoral calcification, pleural effusion, pleural implants, pericardial effusion, and obliteration of the mediastinal fat plane were not significantly different between atypical thymomas and thymic carcinomas (p > 0.05). Various histologic subtypes were included in thymic carcinoma. The tumor necrosis and calcification seen on CT were confirmed at pathologic examination. CONCLUSION: When a large thymic tumor appears with invasion of the great vessels, lymph node enlargement, phrenic nerve palsy, or extrathymic metastases on CT, thymic carcinoma rather than atypical thymoma should be considered.

Adult↗

Oncocytoma of the spinal cord. Case report.

The authors report a case of oncocytoma arising from the spinal cord in a 40-year-old woman who presented with the complaints of gradual difficulty in walking. The excised tumor was exclusively composed of polygonal cells with abundant homogeneous eosinophilic cytoplasms. Electron microscopy study showed densely packed swollen mitochondria and frequent desmosomes. The histological and ultrastructural findings were consistent with a diagnosis of oncocytoma. To the authors' knowledge, this represents the first reported case of oncocytoma of the spinal cord.

Adenoma, Oxyphilic↗