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Biomedical subjects

D Y Yoon

Publications and source records attributed to D Y Yoon.

At least 19 recordsLinked to original sources

Detection and characterization of intracranial aneurysms with 16-channel multidetector row CT angiography: a prospective comparison of volume-rendered images and digital subtraction angiography.

BACKGROUND AND PURPOSE: The aim of our study was to compare multidetector row CT angiography (MDCTA) with digital subtraction angiography (DSA) in the detection and characterization of intracranial aneurysms. MATERIALS AND METHODS: In our blinded prospective study, 85 patients with suspected intracranial aneurysm (47 women, 38 men; age range, 19-83 years) underwent both 16-channel MDCTA and DSA. The MDCT angiograms were interpreted for the presence, location, size, ratio of the neck to the dome (N/D ratio), and lobularity of the aneurysms and relationship of the aneurysm with the adjacent arterial branches, by using volume-rendering techniques. MDCTA and DSA images (reference standard) were interpreted by 2 independent readers, and the results were compared. RESULTS: A total of 93 aneurysms were detected at DSA in 71 patients, whereas no aneurysms were detected in 14 patients. Compared with DSA, the overall sensitivity, specificity, and accuracy of MDCTA on a per-aneurysm basis were 92.5%, 93.3%, and 92.6%, respectively, for both independent readers. For aneurysms of <3 mm, however, MDCTA had a sensitivity of 74.1% for reader 1 and 77.8% for reader 2. There was excellent agreement between readers in the detection of aneurysms (kappa = 0.822). In addition, MDCTA was also accurate in determining N/D ratio of aneurysms, aneurysm lobularity, and adjacent arterial branches. CONCLUSION: MDCTA is accurate in the detection and characterization of intracranial aneurysms and can be used as a reliable alternative imaging technique to DSA in selected cases.

Adult↗

Multidetector-row CT angiography of cerebral vasospasm after aneurysmal subarachnoid hemorrhage: comparison of volume-rendered images and digital subtraction angiography.

BACKGROUND AND PURPOSE: Cerebral vasospasm remains a major problem in patients recovering after surgical treatment of cerebral aneurysms. The purpose of this study was to evaluate cerebral vasospasm at multidetector-row spiral CT angiography (MDCTA) compared with digital subtraction angiography (DSA) in patients with aneurysmal subarachnoid hemorrhages (SAHs). METHODS: Seventeen patients suspected of having vasospasm on clinical findings underwent both postoperative MDCTA and DSA. MDCTA was analyzed by using volume-rendered images as well as axial images. A total of 251 arterial segments were analyzed for vasospasm by using a 5-point grading system. The MDCTA results were then compared with findings on the corresponding DSA images. Sensitivity, specificity, and accuracy of MDCTA for detection of hemodynamically significant spasms were also calculated, with findings at DSA used as the reference standard. RESULTS: On DSA, 74 spasmatic segments were found among the 251 segments evaluated, and 40 segments with hemodynamically significant vasospasms were present. The overall agreement between MDCTA and DSA was 95.2%. We had 12 (4.8%) cases of disagreement between MDCTA and DSA. In 11 segments, the degree of stenosis was overestimated at MDCTA. Overall accuracy, sensitivity and specificity of MDCTA in the detection of hemodynamically significant vasospasm were 97.5%, 98.1%, and 98.0%, respectively, with positive and negative predictive values of 90.7% and 99.5%. CONCLUSION: MDCTA appears to be a reliable alternative imaging technique to DSA in the assessment of patients with cerebral vasospasm after aneurysmal SAH.

Adult↗

Benign breast diseases associated with cyclosporine therapy in renal transplant recipients.

PURPOSE: Our aim was to correlate the radiologic characteristics of cyclosporine-induced benign breast diseases with clinical and pathologic findings. MATERIALS AND METHODS: The clinical, mammographic, and ultrasonographic records of 33 female renal transplant recipients who received cyclosporine were retrospectively reviewed. Eleven patients had 46 breast masses on ultrasonography. We performed core needle biopsies on 20 masses and reviewed the pathologic findings. RESULTS: Among 33 female renal transplant recipients, 11 (33%) had 46 benign breast lesions detected on ultrasonography. We performed core needle biopsies on 20 of the 46 masses. On pathologic examination, 12 were fibroadenomas, 6 showed fibrocystic changes, and 2 revealed dense fibrosis. Regardless of the final pathologic diagnosis, more than half of the lesions revealed severe lymphatic and venular swellings. Among 11 patients with breast lesions on ultrasonography, 10/11 (91%) showed multiplicity, and 7/11 (64%) bilaterality. Mammographically, patients with breast lesions revealed heterogeneous or extremely dense breast patterns, and 8 of 11 patients, circumscribed masses. Twenty-two patients without breast lesions showed scattered fibroglandular densities (n = 7), or heterogeneously dense (n = 11) or extremely dense (n = 4) breast patterns, and 3 of 22 patients showed vague or asymmetric densities that needed further evaluation. CONCLUSION: The development of new breast lesions in patients after renal transplantation should suggest a diagnosis of cyclosporine-induced benign breast disease including fibroadenoma, fibrocystic changes, and dense fibrosis.

Adult↗

Enhanced IL-18 expression in common skin tumors.

Interleukin-18 (IL-18) has been found to have multiple effects upon various cells involved in inflammatory response. Recently we reported that B16 murine melanoma cells are able to produce IL-18, which is involved in the regulation of intracellular reactive oxygen intermediates (ROI) and Fas-ligand expression, indicating that IL-18 plays key role in the tumor activity of melanoma. In this study, we investigated the pattern of IL-18 expression in the human system. IL-18 production was tested by enzyme linked immunosorbent assay (ELISA) assay in various tumor cell lines, including Raji (Burkitt's lymphoma), IM-9 (B lymphoblast), Jurkat (acute T cell leukemia), SK-MES-1 (squamous cell carcinoma (SCC) cell line), SK-MEL-2, G-361, DM-4, and DX-3 (melanoma cell lines). ELISA tests showed that IL-18 was highly expressed in malignant skin tumors such as SK-MES-1, SK-MEL-2, G-361, DM-4, and DX-3 cell lines, thus suggesting that IL-18 production may be associated with the malignancy of skin tumors. Here, we report that enhanced IL-18 expression is positively correlated with malignant skin tumors such as SCC and melanoma, suggesting the importance role of IL-18 in malignancy of skin tumors. Taken together, expression of IL-18 by tumor cells in human skin tissue may provide an important clue to understand the pathogenesis of malignant skin tumors.

Basal Cell Carcinoma↗

Identification of genes differentially induced by hypoxia in pancreatic cancer cells.

A hypoxic microenvironment is characteristic of many solid tumors, including pancreatic cancer, the fifth leading cause of cancer death in the United States. Hypoxia causes the stabilization of the HIF-1 (hypoxia-inducible factor-1) transcription factor and the induction of many genes that promote angiogenesis, tumor growth, and metastasis. We performed representational difference analysis (RDA) using mRNA extracted from hypoxic and normoxic Capan-2, a human pancreatic cancer cell line. cDNAs corresponding to hypoxia-inducible genes were cloned and sequenced. We identified GPI/NLK/AMF (glucose phosphate isomerase/neuroleukin/autocrine motility factor) as a hypoxic inducible gene. In addition, hexokinase II and DEC1/Stra13, genes known to be hypoxia inducible in other systems, were found to be hypoxia inducible in our pancreatic cancer system. We thus identified three genes that are induced by hypoxia in a human pancreatic cancer, including GPI/NLK/AMF, which was not previously known to be hypoxia inducible in any other system. These genes may provide new targets for diagnosis and treatment of pancreatic cancer.

Basic Helix-Loop-Helix Proteins↗

Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18.

To understand modulation of a novel immune-related cytokine, interleukin-18, by human papillomavirus type (HPV) 16 oncogenes, HaCaT, normal keratinocyte cell line, and C-33A, HPV-negative cervical cancer cell line, were prepared to establish stable cell lines expressing E6, E6 mutant (E6m), E6E7, or E7 constitutively. Expressions of various HPV oncogene transcripts were identified by RT-PCR. Expression of HPV oncogene E6 was reversely correlated to the expression of interleukin-18, a novel pro-inflammatory cytokine. The expression of E6 in C-33A, independent of E6 splicing, resulted in decreased IL-18 expression and that of IL-18 was also significantly reduced in HaCaT cells expressing E6. The level of p53 was reduced in C-33A cells expressing E6 whereas not altered in HaCaT cells expressing E6, suggesting that E6 downregulated IL-18 expression via an independent pathway of p53 degradation in HaCaT cells which have a mutated p53 form. However, E7 did not affect IL-18 expression significantly in both C-33A and HaCaT cells. Cotransfection experiments showed that E6 oncogene did not inhibit the activities of IL-18 promoter P1 and P2, suggesting that E6 oncogene indirectly inhibited IL-18 expression. Taken together, E6, E6m and E6/E7 inhibited IL-18 expression with some variation, assuming that cells expressing E6 oncogene can evade immune surveillance by downregulating the expression of immune stimulating cytokine gene, IL-18, and inhibiting the cascade of downstream effects that follow activation of the IL-18 receptor.

Binding, Competitive↗

Both E6 and E7 oncoproteins of human papillomavirus 16 inhibit IL-18-induced IFN-gamma production in human peripheral blood mononuclear and NK cells.

Cervical carcinoma is the predominant cancer among malignancies in women throughout the world, and human papillomavirus (HPV) 16 is the most common agent linked to human cervical carcinoma. The present study was performed to investigate the mechanisms of immune escape in HPV-induced cervical cancer cells. The presence of HPV oncoproteins E6 and E7 in the extracellular fluids of HPV-containing cervical cancer cell lines SiHa and CaSki was demonstrated by ELISA. The effect of HPV 16 oncoproteins E6 and E7 on the production of IFN-gamma by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-gamma production in both primary PBMCs and the NK0 cell line. FACS analysis revealed that the viral oncoproteins reduced the binding of IL-18 to its cellular surface receptors on NK0 cells, whereas there was no effect of oncoproteins on IL-1 binding to its surface IL-1 receptors on D10S, a subclone of the murine Th cell D10.G4.1. In vitro pull-down assays also revealed that the viral oncoproteins and IL-18 bound to IL-18R alpha-chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-gamma production locally in HPV lesions through inhibition of IL-18 binding to its alpha-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis.

Adjuvants, Immunologic↗

Site-specific mutations in the mature form of human IL-18 with enhanced biological activity and decreased neutralization by IL-18 binding protein.

IL-18 can be considered a proinflammatory cytokine mediating disease as well as an immunostimulatory cytokine that is important for host defense against infection and cancer. The high-affinity, constitutively expressed, and circulating IL-18 binding protein (IL-18BP), which competes with cell surface receptors for IL-18 and neutralizes IL-18 activity, may act as a natural antiinflammatory as well as immunosuppressive molecule. In the present studies, the IL-18 precursor caspase-1 cleavage site was changed to a factor Xa site, and, after expression in Escherichia coli, mature IL-18 was generated by factor Xa cleavage. Mature IL-18 generated by factor Xa cleavage was fully active. Single point mutations in the mature IL-18 peptide were made, and the biological activities of the wild-type (WT) IL-18 were compared with those of the mutants. Mutants E42A and K89A exhibited 2-fold increased activity compared with WT IL-18. A double mutant, E42A plus K89A, exhibited 4-fold greater activity. Unexpectedly, IL-18BP failed to neutralize the double mutant E42A plus K89A compared with WT IL-18. The K89A mutant was intermediate in being neutralized by IL-18BP, whereas neutralization of the E42A mutant was comparable to that in the WT IL-18. The identification of E42 and K89 in the mature IL-18 peptide is consistent with previous modeling studies of IL-18 binding to IL-18BP and explains the unusually high affinity of IL-18BP for IL-18.

Cells, Cultured↗

Improvement of gene transfer to cervical cancer cell lines using non-viral agents.

Virus-like particles (VLPs) composed of recombinant capsid protein L1 and L2 of human papillomavirus type 16 were conjugated with polylysine (PL) and gene transfer was performed using VLP-PL conjugates to allow the expression of targeted gene. When HeLa cells were incubated with VLP-PL conjugate coupled with plasmid cytomegalovirus beta-galactosidase (pCMVbeta-gal), about 10% of cells were transfected and demonstrated beta-galactosidase activity. Hence chloramphenicol acetyltransferase activity was also expressed significantly in VLP-PL-plasmid simian virus 2 chloramphenicol acetyl transferase (pSV2CAT)-transfected cells, VLP-PL conjugate was tested whether it could transfer a tumor suppressor gene, pCMVp53, to HeLa cells and the exogenously provided p53 gene complexed to VLP-PL conjugate was detected from HeLa cells by polymerase chain reaction (PCR) analysis. Interestingly, additional increase of transfection efficiency was demonstrated in the presence of poloxamer 407 when C-33A cells were transfected with VLP-PL-pCMVbeta-gal complex. The result support the notion that VLP-PL conjugate may be a promising vector to transfer genetic materials into cancer cells and poloxamer 407 can be used for enhancing the transfection efficiency of VLP-PL conjugate.

Capsid↗

Pancreatic surgery.

Recent advances have been made in both laparoscopic and endoscopic techniques for diagnosing and treating pancreatic neoplasms. These advances are reviewed. In addition to the traditional methods of pancreatic resection (eg, standard Whipple and pylorus-preserving Whipple), several other techniques have been described and are discussed (eg, median pancreatectomy and extended pancreatectomy). The morbidity and mortality rates of pancreatic operations have diminished, but significant complications still occur (eg, delayed gastric emptying, pancreatic fistula, and biliary strictures). These are discussed. In managing acute and chronic pancreatitis, less invasive and more conservative approaches are being advocated.

Journal Article↗

Solid and papillary epithelial neoplasms of the pancreas: aggressive resection for cure.

Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women. We retrospectively reviewed our experience with pancreatic neoplasms from 1986 to the present and identified nine patients with SPENP. All nine patients were female with a mean age of 32 years (range 16-66). All patients presented with gastrointestinal complaints including pain, mass, dyspepsia, or bloating and were subsequently diagnosed with a tumor of the pancreas by CT scan. All patients underwent surgical resection. Two patients had tumors located in the head of the pancreas and underwent a pancreaticoduodenectomy. The remainder had tumors located in the tail of the pancreas and underwent distal pancreatectomy. Pathology demonstrated solid and papillary or solid and cystic pseudopapillary neoplasm of the pancreas. Three tumors were positive for both vimentin and alpha-1 antitrypsin on immunohistochemical studies, and three were positive for neuron-specific enolase. All nine patients underwent curative resection and are alive without any evidence of recurrence with a mean follow-up of 5.4 years. SPENP is considered to be a low-grade malignancy with an excellent prognosis. Prompt diagnosis and surgical resection can result in cure.

Adolescent↗

Observation of low molecular weight poly(methylsilsesquioxane)s by graphite plate laser desorption/ionization time-of-flight mass spectrometry.

Mass spectra of polystyrene and poly(methylsilsesquioxane)(PMSSQ) derived from methyltriethoxysilane(MTES) were obtained in the 100-1,000 Da range by laser desorption/ionization time-of-flight mass spectrometry using a graphite plate without a matrix. Clean mass spectra were obtained without interference from carbon clusters or other low molecular weight compounds. Initial reaction products derived from condensation of partially hydrolyzed MTES were observed. Upon 30 min of heating at 30 degrees C, the ethoxy groups were fully hydrolyzed to hydroxy groups. Many PMSSQ species consistent with predictable polymerization reaction pathways involving intermolecular condensation and intramolecular dehydration were observed. Thus, laser desorption/ionization time-of-flight mass spectrometry using a graphite plate, without added matrix materials, is shown to provide valuable information on low molecular weight polymer not available by MALDI-TOF-MS.

Journal Article↗

Effect of bioflavonoids extracted from the bark of Pinus maritima on proinflammatory cytokine interleukin-1 production in lipopolysaccharide-stimulated RAW 264.7.

Currently, bioflavonoids have been known to have strong antioxidant capacities, and a variety of efforts have been made to identify the utilities of bioflavonoids in treating various diseases based on their antioxidant capacities. The effects of bioflavonoids extracted from the bark of Pinus maritima Pycnogenol (PYC) on free radical formation, activation of redox sensitive transcription factors, as well as interleukin-1 beta (IL-1 beta) production were investigated in murine macrophage cell lines. PYC exerted strong scavenging activities against reactive oxygen species generated either by H(2)O(2) or PMA in RAW 264.7 and IC-21 cells, respectively. In situ ELISA, immunoblot analysis, and competitive RT-PCR demonstrated that PYC pretreatment of LPS-stimulated RAW 264.7 cells dose-dependently reduced both the production of IL-1 beta and its mRNA levels. Furthermore, in the same cells, PYC blocked the activation of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1), two major transcription factors centrally involved in IL-1 beta gene expression. When RAW 264.7 cells were stimulated with LPS, the inhibitor protein I kappa B largely disappeared from cytosolic fractions. However, pretreatment of the cells with PYC abolished the LPS-induced I kappa B degradation. These results suggest that PYC can inhibit the expression of the proinflammatory cytokine IL-1 by regulating redox-sensitive transcription factors. This study may support the possibility that bioflavonoids including PYC can be used as antiinflammatory and immunosuppressive drugs based on their radical scavenging activities.

Animals↗

Improvement of receptor-mediated gene delivery to HepG2 cells using an amphiphilic gelling agent.

Gene transfer was performed using asialo-oroso-mucoid-polylysine (ASOR-PL) conjugates to allow targeted expression of the gene in cells of hepatic origin. In a gel-electrophoretic analysis, the ASOR-PL conjugate produced a complete DNA retardation effect at the optimal ratio of 222:1 (ASOR-PL conjugate/pCMV beta-gal plasmid). The gene-transfer efficiency of the ASOR-PL conjugate was evaluated in HepG2 cells that express asialoglycoprotein receptor and NIH 3T3 cells that do not. The expression was assayed by 5-bromo-4-chloroindol-3-yl beta-D-galactopyranoside ('X-Gal') staining and Chlorophenol Red beta-D-galactopyranoside. When an expression vector for the tumour-suppressor gene p53, pCMVp53, complexed to ASOR-PL conjugate, was transfected into HepG2 cells, the exogenously provided p53 gene was detected in the HepG2 cells by PCR. To improve the efficiency of DNA delivery and expression of the therapeutic proteins poloxamer 407, a fusogenic peptide, influenza-virus haemagglutinin HA2 and chloroquine were individually incorporated into the system. The expression level of beta-galactosidase in HepG2 cells was increased by about four times by the presence of poloxamer 407, whereas the fusogenic peptide HA2 and chloroquine had no effects. When HepG2 cells were transfected with pCMVp53 in the presence of poloxamer 407, the mRNA of transfected p53 could be detected by reverse transcriptase PCR. The current findings open the possibility that a receptor-mediated gene-delivery system for hepatic gene therapy using ASOR-PL conjugate in combination with poloxamer 407 may be developed in the future.

3T3 Cells↗

Transrectal ultrasonography of distal ureteral calculi: comparison with intravenous urography.

In a prospective fashion, transrectal ultrasonography and intravenous urography were performed in 48 patients with distal ureteral calculi. We compared the ability of the two modalities to detect calculus and to determine the size of the calculus, the degree of obstruction, and the degree of hydroureter. In 11 cases (23%), the calculus was not seen at intravenous urography, while transrectal ultrasonography detected calculus in each patient. In 37 cases in which calculi were detected by both modalities, the average diameter of the calculus determined by ultrasonography was significantly larger (P < 0.05) than that obtained by plain radiography. Positive correlations were obtained in the assessment of degree of obstruction (correlation coefficient = 0.587, P < 0.05) and hydroureter (correlation coefficient = 0.794, P < 0.05) between the two techniques. Transrectal ultrasonography appears to be a useful adjunctive method to evaluate distal ureteral calculus, particularly if the results of intravenous urography are inconclusive.

Adult↗

Influence of instrument settings on flow signal and background noise in power Doppler US. An experimental study using a flow phantom with hyperechoic background.

OBJECTIVE: To determine the influence of various power Doppler instrument settings on intensities of flow signal and background noise in flow with a tissue-equivalent phantom. METHODS: Power Doppler images were obtained with changing wall filter level (low, medium, high, and maximum), pulse repetition frequency (PRF; 500, 700, 1000, 1500, 3000, and 6000 Hz), and Doppler gain (60%, 70%, 80%, 90%, and 100%) at different flow velocities (13.3, 26.5, and 49.8 cm/sec). To make a quantitative comparison of different settings, the authors measured the intensities of flow signal and background noise in obtained power Doppler images using the scanner and a computer program, calculated signal-to-noise difference (SND; intensity of flow signal--intensity of background noise), and evaluated the relation between SND and power Doppler settings. RESULTS: The intensities of flow signal and background noise were proportional to flow velocity and power Doppler gain but were inversely proportional to PRF and wall filter level. At constant wall filter level (medium), changes of PRF and Doppler gain to the same directions resulted in a high SND. At constant PRF (1000 Hz), changes of wall filter and Doppler gain to the same directions also resulted in a high SND. However, at constant Doppler gain (80%), a high SND was obtained with changing wall filter level and PRF to the opposite directions. CONCLUSIONS: Three Doppler instrument settings--wall filter level, pulse repetition frequency, and Doppler gain--have reciprocal influences on SND.

Blood Flow Velocity↗