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Biomedical subjects

Y K Hong

Publications and source records attributed to Y K Hong.

36 records · Page 2Linked to original sources
PubMed1999

Inhibition of human malignant glioma growth in vivo by human recombinant plasminogen kringles 1-3.

Human malignant gliomas are highly vascularized and aggressive tumors. Angiogenesis inhibitors have been shown to induce regression of a variety of primary and metastatic tumors in vivo. However, their usefulness in treating brain tumors is not well understood. Angiostatin, a multiple kringle (1-4 of 5)-containing fragment of plasminogen, is one of the highly effective natural cryptic angiogenesis inhibitors. In our study, the therapeutic efficacy of non-glycosylated and small molecular size recombinant kringles 1-3 (rPK1-3) was examined in the treatment of brain tumors generated by stereotactic intracerebral implantation of U-87 human glioma cells in nude mice. Mice bearing tumors 7 days post-implant were treated daily with rPK1-3 (100 mg/kg) s.c. for 21 days. Treated animals showed suppressed brain tumor growth by greater than 71.2% along with a 3-fold increase of apoptotic index and suppressed vascularization by 78.9%, without any observable signs of toxicity. Analysis of bFGF and VEGF expression in the tumors of treated animals using immuno-histochemical methods showed near complete absence of growth factors. Our results indicate that the non-glycosylated, small molecular size rPK1-3 is an efficient tumoristatic agent for the treatment of intracranial human glioma xenografts in mice and might provide new strategies for the treatment of brain tumors.

Animals↗
PubMed1999

A new structure for the murine Xist gene and its relationship to chromosome choice/counting during X-chromosome inactivation.

In this report, we present structural data for the murine Xist gene. The data presented in this paper demonstrate that the murine Xist transcript is at least 17.4 kb, not 14.3 kb as previously reported. The new structure of the murine Xist gene described herein has seven exons, not six. Exon VII encodes an additional 3.1 kb of information at the 3' end. Exon VII contains seven possible sites for polyadenylation; four of these sites are located in the newly discovered 3' end. Consequently, it is possible that several distinct transcripts may be produced through differential polyadenylation of a primary transcript. Alternative use of polyadenylation signals could result in size changes for exon VII. Two major species of Xist are detectable by Northern analysis, consistent with differential polyadenylation. In this paper, we propose a model for the role of the Xist 3' end in the process of X-chromosome counting and choice during embryonic development.

3' Untranslated Regions↗
PubMed1999

Differential expression of MMAC/PTEN in glioblastoma multiforme: relationship to localization and prognosis.

MMAC/PTEN, a tumor suppressor gene located on chromosome 10q, has recently been shown to act as a phosphatidylinositol 3,4,5-triphosphate phosphatase and to modulate cell growth and apoptosis. Somatic mutations of MMAC/PTEN have been reported in a number of human cancers, especially in glioblastoma multiforme (GBM), although the number of identified mutations (approximately 10-35%) is significantly lower than the frequency of LOH affecting the MMAC/PTEN locus in the specimens (approximately 75-95%). To further investigate the possible alterations that may affect MMAC/PTEN, we examined the expression of the gene by reverse transcription-PCR in a series of gliomas. A significant difference (P < 0.001) was observed between the expression of MMAC/PTEN in GBMs versus lower grades of gliomas, thus mimicking the difference in allelic deletion associated with the locus in these tumors. Furthermore, Kaplan-Meier survival plots, adjusted for age and tumor grade, showed a significantly better prognosis for patients whose tumors expressed high levels of MMAC/PTEN. Additionally, immunostaining of GBMs revealed little or no MMAC/PTEN expression in about two-thirds of the tumors, whereas the other approximately one-third of tumors had significantly higher levels of expression. However, in about two-thirds of the high-expressing specimens, a heterogeneous pattern of expression was observed, indicating that certain cells within the tumor failed to express MMAC/PTEN. The combination of these results suggest that, in addition to molecular alterations affecting the gene, altered expression of MMAC/PTEN may play a significant role in the progression of GBM and patient outcome.

Biomarkers, Tumor↗
PubMed1999

Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas.

The MET protooncogene encodes a transmembrane tyrosine kinase identified as the receptor of a polypeptide known as hepatocyte growth factor/scatter factor. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the tyrosine kinase domain of the MET gene (exon 15-19) in 75 primary liver cancers. Three missense mutations were detected exclusively in 10 childhood hepatocellular carcinomas (HCCs), while no mutations were detected in 16 adult HCCs, 21 cholangiocarcinomas, or 28 hepatoblastomas. The extremely short incubation period from hepatitis B virus infection to the genesis of childhood HCC as compared with the adult HCC suggests that there may be an additional mechanism that accelerates the carcinogenesis of childhood HCC. Our results indicate that mutations of the tyrosine kinase domain of the MET gene may be involved in the acceleration of the carcinogenesis in childhood HCC.

Adolescent↗
PubMed1999

Single base discrimination of CENP-B repeats on mouse and human Chromosomes with PNA-FISH.

The satellite repeat structure of the mammalian centromere contains the CENP-B protein binding site. Using the peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH), we show by direct PNA-DNA binding that all detectable CENP-B sites in a mammalian genome might have the same sequence. Two species-specific PNA 17-mers, pMm and pMc, were identified from CENP-B binding sites of Mus musculus and M. caroli, respectively. Fluorescence in situ hybridization confirmed that pMc hybridized to M. caroli centromeres only; however, pMm cross-hybridized to M. musculus and human centromeres. By using a series of CENP-B PNA 17-mers containing 1, 2, 3, 5, and 7 base-pair mismatches to their DNA counterparts, we further demonstrate that PNA-FISH can discriminate between two CENP-B DNA sequences that differ by a single base-pair in mouse and human centromeres, suggesting the degree of conservation of CENP-B sequences throughout the genome. In comparison with DNA oligonucleotides, PNA oligomers demonstrate the higher sequence specificity, improved stability, reproducibility, and lower background. Therefore, PNA oligomers have significant advantages over DNA oligonucleotide probes in analyzing microsatellites in a genome.

Animals↗
PubMed1998

Perioperative specific management of blood volume loss in craniosynostosis surgery.

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.

Blood Loss, Surgical↗
PubMed1998

Differentially expressed gene products in glioblastoma cells suppressed for tumorigenicity.

The loss of large segments or an entire copy of chromosome 10 is the most common genetic alteration in human glioblastomas. To address the biological and molecular consequences of this chromosomal alteration, we transferred a human chromosome 10 into a glioma cell clone devoid of an intact copy. The hybrid cells exhibited an altered cellular morphology, a decreased saturation density, and a suppression of both anchorage-independent growth and tumor formation in nude mice. The hybrids also expressed the recently identified candidate tumor suppressor gene MMAC1/PTEN. To further identify gene products that may be involved in glioma progression, a subtractive hybridization was performed between the human glioblastoma cells and the phenotypically suppressed hybrid cells to identify differentially expressed gene products. Sixty-one clones were identified, with nine clones being preferentially expressed in the hybrid cells. Four cDNA clones represented markers of differentiation in glial cells. Two cDNA clones shared homology with platelet derived growth factor-alpha and the insulin receptor, respectively, both genes previously implicated in glioma progression. A novel gene product that was expressed predominantly in the brain, but which did not map to chromosome 10, was also identified. This clone contained an element that was also present in three additional clones, two of which also exhibited differential expression. Consequently, the presence of a functional copy of chromosome 10 in the glioma cells results in differential expression of a number of gene products, including novel genes as well as those associated with glial cell differentiation.

Blotting, Northern↗
PubMed1996

Post-exercise response of ventricular ejection fraction after total repair of congenital heart disease with left to right shunt.

A radioisotope first pass study was done on patients over a period of 1 to 15 years (average 4.6 years) after repair for ventricular septal defect or arterial septal defect with a left to right shunt. The age of the patients ranged from 6 to 32 years (average 14.2 year) at the time of the study. The total work of exercise and the right and left ventricular ejection fraction(EF) were evaluated at rest and after exercise. The results were compared with the preoperative hemodynamic findings and with the age of patient at the time of the operation. 1) When the total work of exercise was divided with the maximal exercise capacity of the normal individual corresponding to the patients' height and body surface area (the percentage of total work), it were very low with the average of 40% of normal. There was no sexual difference, but the percentage of total work of exercise had significant correlation with the patients' age at the time of operation (r = -0.52, p < 0.01) and post-exercise left ventricular ejection fraction (LVEF)(r = -0.39, p < 0.05). 2) LVEF at rest had some correlation with the preoperative mean pulmonary arterial pressure (r = -0.29, p = 0.05), but showed no relationship with Qp/Qs or Rp/Rs ratios. The right ventricular ejection fraction (RVEF) at rest had no relations with the preoperative hemodynamic findings with maximal workload. 3) The post-exercise RVEF showed linear correlation with the preoperative Rp/Rs ratio (r = -0.49, p < 0.005), and mean pulmonary arterial pressure (r = -0.37, p < 0.05). The post-exercise LVEF had no significant correlation with any preoperative hemodynamic factors. 4) When greater than 5% increase in ventricular EF after exercise is considered normal, the group with the normal right and left ventricular responses (n = 11) showed normal preoperative Rp/Rs ratio (7.6 +/- 4.1). In the group with normal left, but abnormal right ventricular response (n = 9) and the group with abnormal biventricular response (n = 11), both demonstrated incremental increase in Rp/Rs ratio (20.1 +/- 11.3, 26.3 +/- 19.8 respectively). Normal right, but abnormal left ventricular reaction (n = 2) was noted in patients with residual aortic valvular insufficiency and residual ventricular septal defect. In conclusion, post-operative ventricular response was much more sensitive and informative than that of ventricular function at rest and to detect subclinical cardiac dysfunction. Post-exercise RVEF was closely correlated with preoperative pulmonary vascular hemodynamics, while post-exercise LVEF seemed to be a major determinant of working capacity after repair.

Adolescent↗
PubMed1985

Central retinal artery occlusion following transfemoral cerebral angiography.

Whereas most ocular complications following cerebral angiography are benign and transient, central retinal artery occlusion following cerebral angiography produces severe permanent visual deficits in nearly 40% of patients. Physicians ordering and performing cerebral angiography should be aware of this complication, since immediate attention to patients with visual disturbance from central retinal artery occlusion may save useful vision. All previously reported cases of central retinal artery occlusion following cerebral angiography have occurred after direct percutaneous carotid angiography. We report a case of central retinal artery occlusion following transfemoral cerebral angiography using a #5 French catheter and meglumine iothalamate (Conray-60) contrast.

Arterial Occlusive Diseases↗
PubMedDate not supplied

The use of high-resolution computed tomography in the evaluation of pulmonary hemodynamics in patients with congenital heart disease: in pulmonary vessels larger than 1 mm in diameter.

High-resolution computed tomography (HRCT) was carried out in 36 patients with congenital left-to-right shunt disease and 10 normal control subjects to assess the feasibility of CT in the evaluation of pulmonary hemodynamics. The patients had a left-to-right or a bidirectional shunt and the hemodynamic data obtained by cardiac catheterization in these patients were compared to the information obtained by CT imaging. The pulmonary/systemic blood flow (Q(p)/Q(s)) ratio and pulmonic/systemic resistance (R(p)/R(s)) ratio had a significant correlation with the pulmonary artery/bronchus (PA/Br) ratio (r = 0.54 and r = -0.37, respectively) and pulmonary vein/bronchus (PV/Br) ratio (r = 0.66 and r = -0.66, respectively), and the R(p)/R(s) and mean PA pressure also showed a significant correlation with the PA/PV ratio (r = 0.53 and r = -0.61, respectively) in the mid-lung field when accompanying bronchi were 4. 0-5.9 mm in diameter. There was no correlation between the hemodynamic data and the size of the central and hilar PA or with the rate of PA tapering. With HRCT, it is possible to evaluate pulmonary hemodynamics in patients with congenital heart disease with a left-to-right or bidirectional shunt, particularly R(p)/R(s) and mean PA pressure, which have been very difficult to obtain noninvasively. The small-sized pulmonary vessel/Br ratio or the small-sized PA/PV ratio could offer very useful information, but the dimension of the central PA provided the least useful information.

Adolescent↗
PubMedDate not supplied

Experience with pineal region tumors.

The results are reported of a retrospective review of the presentation and outcome of 43 pineal region tumors treated from 1982 to 1996, including 20 identified tumors: 5 germinomas, 8 teratomas, 2 embryonal carcinomas, 1 endodermal sinus tumor, 2 pineocytomas and 2 pineoblastomas. Of the 43 tumors reviewed, 36 were located in the pineal region, 5 in the suprasellar, and 2 in both the pineal and suprasellar regions. Twenty patients underwent surgical resection: total in 6 and partial in 10, while only a biopsy was taken in 4 cases. Fifteen patients were managed on the basis of serum CSF tumor markers and radiation response. Twenty-three patients with germinomas received radiotherapy (RT) and had a 5-year survival rate of 87%. Fifteen patients with non-germinomatous germ cell tumors received RT and chemotherapy following direct surgery, and 5 died (mortality rate of 33.3%). The overall survival rate of the 43 patients with pineal tumors was 79.1% (34/43) and the death rate was 20.9% (9/43). It is now recognized that the wide variety of tumor types found in the pineal region necessitates different modes of treatment, and improved microsurgical and stereotactic surgical techniques have made mortality and morbidity rates acceptably low. Because the radiation response and CSF cytology are not enough to determine optimum treatment, a tissue diagnosis should be obtained in all patients.

Adolescent↗
PubMedDate not supplied

CT findings of pulmonary tuberculosis presenting as segmental consolidation.

PURPOSE: The purpose of our study was to determine specific CT findings of tuberculous pneumonia presenting as segmental or lobar consolidation along with a pathologic review of specimens with similar radiographic patterns. METHOD: CT findings of 45 cases of proven tuberculous pneumonia and 21 proven nontuberculous pneumonia were compared. Pathologic findings of five surgically resected tuberculous pneumonia cases were also investigated. The presence of fluid bronchogram (linear, branching shadow of fluid attenuation) and inner low attenuation/cavitation in the area of consolidation, luminal dilatation, and wall thickening of proximal bronchi were the main points sought on CT scan. In addition, the presence of bronchogenic dissemination, lymph node enlargement, and pleural lesions was also checked for in the unaffected area of both lungs. RESULTS: The following bronchial changes were seen in the tuberculous pneumonia and nontuberculous pneumonia groups, respectively: fluid bronchogram in 68.9 and 23.8% (p < 0.05), bronchial luminal dilatation in 60.0 and 23.8% (p < 0.05), and bronchial wall thickening of the proximal airway leading to the area of consolidation in 52.8 and 7% (p < 0.05). Bronchogenic dissemination outside the consolidation appeared in 88.9 and 52.4% (p < 0.05), respectively. In the tuberculous pneumonia group, lymph node enlargement and pleural reaction were seen in 55.6 and 35.6%, respectively, but in 42.9 and 57.1% in the nontuberculous pneumonia group (p > 0.05). Histologically, tuberculous pneumonia showed either bronchioles containing inflammatory exudates and submucosal granuloma or alveoli containing aggregates of alveolar macrophages or cellular debris. CONCLUSION: Fluid bronchogram in the area of homogeneous consolidation, bronchial luminal dilatation, and bronchial wall thickening of the proximal airway were the bronchial changes more significantly prominent in the tuberculous pneumonia group. We suspect that these findings may represent tuberculous bronchitis in small airways.

Bronchoalveolar Lavage Fluid↗
PubMedDate not supplied

Efficacy of MRI in complicated congenital heart disease with visceral heterotaxy syndrome.

PURPOSE: The authors' goal was to assess the diagnostic accuracy and clinical effect of MRI compared with echocardiography and catheterization in the evaluation of cardiac defects with situs ambiguous. METHOD: Twenty-two patients with visceral heterotaxy syndrome were included. RESULTS: Because situs determined by the relation between the pulmonary artery and bronchi showed most predominantly a tendency toward lateralization, this was regarded as the standard reference of situs determination. For the purpose of this study, patients were classified as having right isomerism (n = 13) or left isomerism groups (n = 9). MRI has several advantages compared with echocardiography or cardiac angiography for examining patients with situs ambiguous. (1) The bronchial, pulmonary arterial, and splenic situs can be readily determined, and discrepancies (n = 2) can be assessed easily. (2) Venoatrial connections are adequately imaged. In particular, all types of total and partial anomalous pulmonary venous return are delineated, regardless of whether restrictions of pulmonary blood flow or pulmonary venous obstructions are involved (n = 4). The courses of vertical veins were easily identified, and the prearterial position was revealed in only one of seven right isomerisms with total anomalous pulmonary venous return. The drain pattern of the hepatic vein can be visualized using three-dimensional spatial information and is useful for total cavopulmonary connection design. (3) Associated complicated cardiac anomalies, particularly the size or peripheral stenosis of the pulmonary arteries, may be evaluated, and this information is useful for palliative shunt operations. CONCLUSION: Because of its wide field of view and imaging, which is not restricted by associated anomalies, a thorough understanding of the cardiovascular anatomy of the situs ambiguous can be achieved using MRI, which is of considerable value in the surgical correction of this complicated anomaly. MRI can obviate or facilitate catheterization in these critically ill patients.

Abnormalities, Multiple↗
PubMedDate not supplied

High-resolution computed tomography in patients with bronchial asthma: correlation with clinical features, pulmonary functions and bronchial hyperresponsiveness.

The high-resolution computed tomography (HRCT) studies for bronchial asthma (BA) have revealed abnormal radiologic findings such as bronchial wall thickening, bronchiectasis, emphysema and mosaic pattern of lung attenuation. But the clinical significance of these findings are not yet clarified. In this study, we quantified the bronchial wall thickness and evaluated HRCT features in 57 BA subjects (338 bronchi) who had precipitating factors of irreversible airway remodeling, 19 COPD subjects (70 bronchi) and 10 healthy subjects (23 bronchi). Then we correlated HRCT findings with the clinical features, pulmonary functions and methacholine PC20 (PC20M) and studied their clinical significance. The bronchial wall for BA was about 1.48 mm thicker than that for COPD and about 2.34 mm thicker than for healthy controls (p < 0.0001, respectively). But the individual mean ratio of bronchial wall thickness to luminal diameter (BWT/LD) in asthmatics did not correlate with the clinical features, lung functions and PC20M. Abnormal HRCT findings, such as bronchiectasis (17.5%), emphysema (5.3%) and mosaic pattern of lung attenuation (17.5%) were found in BA. These findings were more common in BA with moderate to severe airflow limitation (FEV1 < 80%, p < 0.05) and patients with these changes had a more prolonged history of asthma (p < 0.05). PC20M was higher in BA with these abnormal changes (p < 0.001) but these patients' FEV1 (p < 0.05), FEF25-75 (p < 0.05) and specific airway conductance (p < 0.05) were lower than those having BA without such findings. In this study we showed that the bronchial wall was more significantly thickened in BA but that it did not correlate well with the clinical features, lung functions and PC20M. Additionally, patients having BA with abnormal airway and air space HRCT findings had a prolonged history of asthmatic symptoms, loss of lung functions and decreased bronchial hyperresponsiveness. These results suggested the possibility that HRCT can be used for the differentiation of BA from COPD or healthy controls. Furthermore, patients having BA with abnormal HRCT changes demonstrate poor lung function and less hyperreactive bronchi than those without. We concluded that HRCT may be useful for the prognosis and treatment of bronchial asthma cases who have the precipitating factors of irreversible airway remodelling.

Adult↗
PubMedDate not supplied

The inhibitory effect of adenovirus-mediated p16INK4a gene transfer on the proliferation of lung cancer cell line.

Abnormalities in the p16INK4a tumor suppressor gene are found in many lung cancer cell lines and primary lung cancer tissue. To examine its tumor suppressor function and potential adequacy in cancer gene replacement therapy, wild-type p16INK4a gene was inserted in an adenovirus derived gene delivery system and introduced into lung cancer cell lines (NCI-H441 and NCI-H157) that did not express p16INK4a. Western blot assay and immunocytochemistry demonstrated production of wild-type p16 protein in these cell lines. The biological function of exogenous p16 protein was confirmed by the inhibition of pRB phosphorylation. The expression of exogenous p16 protein via recombinant adenovirus significantly inhibited cancer cell growth and colony formation in vitro of NSCLC that can not express endogenous p16. The flow cytometric analysis showed these results correlated with G1 cell cycle arrest. These observations suggest the value of adenovirally-mediated p16INK4a gene replacement therapy for lung cancer.

Adenoviridae↗