Biomedical subjects

Y K Kang

Publications and source records attributed to Y K Kang.

At least 55 records · Page 3Linked to original sources

PubMed1999

Viral genotypes and p53 expression in Epstein-Barr virus-associated primary malignant lymphomas of the intestines.

A small number (4% to 6%) of primary malignant lymphomas arising in the intestines express the EBV genome. However, in these tumors, the viral genotype and the role of tumor suppressor gene p53 have not been investigated. We sought to determine what genotype of EBV is frequently involved and whether the expression of p53 is related to these tumors. We used EBER-1 in situ hybridization and polymerase chain reactions (PCRs) for EBNA-1, EBNA-2A, and EBNA-2B to detect latent infection with EBV and to determine the genotype, respectively. In addition, we performed p53 PCR-SSCP (exons 5 through 9) and immunohistochemical analysis for p53. We found that EBV type B was present in 4 of 6 cases (67%); the genotype of the remaining cases could not be determined. The p53 PCR-SSCP indicated normal migration patterns in all malignant lymphomas, despite the fact that the tumor cells were strongly immunostained for p53 protein in 5 of the 6 cases. Thus, our study demonstrates that EBV-associated non-Hodgkin's lymphomas of the intestines in Korea are strongly related to the type B EBV and not to mutations of p53 gene. We suggest that EBV-associated intestinal lymphomas may arise through an interaction between the latent proteins of EBV and the wild-type p53 protein.

Adult↗

PubMed1999

A hybrid bovine beta-casein/bGH gene directs transgene expression to the lung and mammary gland of transgenic mice.

We investigated spatial and temporal expression of bGH controlled by two different sizes (1.8 kb and 15 kb) of 5'-flanking sequences of the bovine beta-casein in transgenic mice. In the 1.8-kb promoter-containing mice, bGH expression was specifically confined to lung and mammary gland at lactation. While mammary gland expression was highly variable depending on the lines, lung expression was relatively constant with a high level in most lines. Moreover, this dual-tissue specificity of bGH expression was consistently retained in all of the 15 kb-promoter-containing mice, although a low ectopic expression was sometimes detected in salivary gland or brain. During mammary gland development in the 1.8-kb promoter-containing mice was mammary gland expression first detected at lactation, following the bovine rather than murine pattern of beta-casein expression. In contrast, lung expression was almost constant regardless of mammary gland developmental state or sex. Therefore, it can be concluded that a combination of the bovine beta-casein promoter and bGH gene directs a distinct dual-tissue specific bGH expression with different regulatory mechanisms between mammary gland and lung and as little as 1.8-kb promoter is sufficient for the proper regulation of the bovine beta-casein gene in mammary gland.

Animals↗

PubMed1999

Clinicopathological analysis of 501 non-Hodgkin's lymphomas in Korea according to the revised European-American classification of lymphoid neoplasms.

AIMS: The clinical relevance of the Revised European-American Classification of Lymphoid Neoplasms (REAL) is still debated. To test the clinical validity of the REAL classification in Korea, where the incidence of T-cell lymphoma is higher, we investigated the clinicopathological features of non-Hodgkin's lymphoma (NHL) from Korea Cancer Center Hospital. METHODS AND RESULTS: Five hundred and one patients with NHL were reclassified according to the REAL classification and clinicopathologically analysed. Immunophenotypically, B-cell lymphoma accounted for 67.9% and T- and NK-cell type for 30.5%. Approximately 48.5% of cases were forms of diffuse large B-cell lymphoma (DLBCL), while only 5.4% were follicular lymphoma. Peripheral T-cell lymphoma unspecified (PTCL-U; 10.8%) and angiocentric lymphomas (11.8%) comprised the majority of T-cell lymphomas. Most of the angiocentric lymphomas presented with localized nasal/nasopharyngeal or tonsillar primaries. All peripheral T-cell lymphomas (PTCL) showed a significantly low overall survival compared to DLBCL (P = 0.02, log rank). Overall survival rates for DLBCL and PTCL-U were also significantly different (P = 0.0043, log rank), though for DLBCL and angiocentric lymphoma there was no significant difference (P = 0.2142, log rank). Angiocentric lymphoma, however, was characterized by a shorter median survival time than DLBCL (54 months vs. 96 months). Among DLBCL patients according to the REAL classification, overall survival was significantly better in nonimmunoblastic type (intermediate-grade, WF-F,G) as compared to large cell immunoblastic type (high-grade, WF-H) (log rank, P < 0.001). The morphological distinction of the immunoblastic and nonimmunoblastic among DLBCL of the REAL classification bears significant prognostic relevance worthy of further consideration. CONCLUSION: We conclude that lineage assignment (T vs. B) in the REAL classification is a clinically important distinction, but that it is necessary to subdivide the broad category of DLBCL.

Adolescent↗

PubMed1999

Reduction of morning stiffness and improvement in physical function in fibromyalgia syndrome patients treated sublingually with low doses of human interferon-alpha.

One hundred and twelve fibromyalgia syndrome (FMS) patients were randomized into one of four demographically similar groups (n = 28/group). Sequential primary FMS patient volunteers were to receive daily sublingual placebo or interferon-alpha (IFN-alpha) at 15, 50, or 150 IU. After a screening evaluation, analgesic or sedative hypnotic medications were withdrawn. Two weeks later, daily IFN-alpha or placebo was initiated with follow-up evaluations at 2-week intervals ending with week 6. One primary, three secondary, and seven tertiary variables were assessed. Study outcome was based on improvement in the tender point index (TPI). The TPI did not improve with any IFN-alpha dose. However, significant improvement was seen in morning stiffness and in physical function with the 50 IU IFN-alpha (p < 0.01). None of the other outcome means changed significantly and no adverse events were attributable to IFN-alpha therapy.

Administration, Sublingual↗

PubMed1999

Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.

A clinical study was designed to utilize flow cytometric immunophenotyping and chromium release from cultured tumor target cells to characterize peripheral blood mononuclear leukocyte (PBML) subpopulations and natural killer activity in healthy normal controls (n = 18) and in patients with fibromyalgia syndrome (FMS) at baseline (n = 124) and again after 6 weeks of treatment with low-doses of orally administered human interferon-alpha (IFN-alpha). Volunteer subjects discontinued all analgesic and sedative hypnotic medications for 2 weeks prior to the baseline phlebotomy. Laboratory measures included a complete blood count; a phenotypic analysis of PBML by flow cytometry; and in vitro natural killer (NK) cell activity. After baseline blood sample collection, the FMS patients were randomized to one of four parallel treatment groups (n = 28/group) to receive sublingual IFN-alpha (15 IU, 50 IU, 150 IU), or placebo every morning for 6 weeks. The tests were repeated at week 6 to evaluate treatment effects. At baseline, FMS patients exhibited fewer lymphocytes and more CD25+ T lymphocytes than did normal controls. By week 6, the main significant and consistent change was a decrease in the HLA-DR+ CD4+ subpopulation in the 15 IU and 150 IU treatment groups. These data do not support an immunologically dysfunctional PBML phenotype among patients with FMS as has been observed in the chronic fatigue syndrome.

Administration, Sublingual↗

PubMed1999

Adjuvant (cisplatin, etoposide, and 5-fluorouracil) chemotherapy after curative resection of gastric adenocarcinomas involving the esophagogastric junction.

Gastric adenocarcinomas involving the esophagogastric junction represent a particular therapeutic problem because they lie in the border area between two body cavities: the thorax and the abdomen. The prognosis of gastric adenocarcinomas involving esophagogastric junction is poor because there is widespread lymphatic metastasis, making curative resection difficult. Even in patients with localized disease who are potentially curable, the 5-year survival rate is approximately 20% with curative resection only, somewhat lower than for those with cancer elsewhere in the stomach. The authors conducted a pilot study to evaluate the safety and possible efficacy of adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil (PEF) after curative resection of gastric adenocarcinoma involving esophagogastric junction. Three cycles of adjuvant PEF chemotherapy with cisplatin (20 mg/m2/day intravenously on days 1-5), etoposide (100 mg/m2/day intravenously on days 1, 3, and 5), and 5-fluorouracil (800 mg/m2/day continuous intravenous infusion on days 1-5) were given every 3 weeks after curative resection of gastric adenocarcinoma involving the esophagogastric junction. Between November 1989 and June 1995, a total of 50 patients with postoperative stage II, IIIA, or IIIB disease entered this trial. In 14 of 50 patients (28%), the disease recurred during the follow-up of 4-83 months (median 26 months). Disease-free survival was 4-83+ months (median 48 months), and the actuarial 5-year disease-free survival rate was 48% (95% CI: 41% to 55%). Overall survival was 4-83+ months (median 62 months), and the actuarial 5-year survival rate was 54% (95% CI: 40% to 68%). The prognostic factor analysis showed that the postoperative N stage and the interval between surgery and chemotherapy affected disease-free survival and overall survival. The toxicities of PEF adjuvant chemotherapy were leukopenia, nausea/vomiting, and alopecia, but they were mostly mild and reversible except in one patient who died because of treatment-related sepsis. Adjuvant chemotherapy with three cycles of PEF regimen was well tolerated and seems to be a promising treatment for gastric adenocarcinoma involving the esophagopstric junction, in comparison with previous treatments. To define the efficacy of adjuvant PEF chemotherapy for gastric adenocarcinoma involving esophagogastric junction, prospective randomized trials are warranted.

Adenocarcinoma↗

PubMed1999

Positional preference of proline in alpha-helices.

Conformational free energy calculations have been carried out for proline-containing alanine-based pentadecapeptides with the sequence Ac-(Ala)n-Pro-(Ala)m-NHMe, where n + m = 14, to figure out the positional preference of proline in alpha-helices. The relative free energy of each peptide was calculated by subtracting the free energy of the extended conformation from that of the alpha-helical one, which is used here as a measure of preference. The highest propensity is found for the peptide with proline at the N-terminus (i.e., Ncap + 1 position), and the next propensities are found at Ncap, N' (Ncap - 1), and C' (Ccap + 1) positions. These computed results are reasonably consistent with the positional propensities estimated from X-ray structures of proteins. The breaking in hydrogen bonds around proline is found to play a role in destabilizing alpha-helical conformations, which, however, provides the favored hydration of the corresponding N-H and C=O groups. The highest preference of proline at the beginning of alpha-helix appears to be due to the favored electrostatic and nonbonded energies between two residues preceding proline and the intrinsic stability of alpha-helical conformation of the proline residue itself as well as no disturbance in hydrogen bonds of alpha-helix by proline. The average free energy change for the substitution of Ala by Pro in a alpha-helix is computed to be 4.6 kcal/mol, which is in good agreement with the experimental value of approximately 4 kcal/mol estimated for an oligopeptide dimer and proteins of barnase and T4 lysozyme.

Peptides↗

PubMed1999

Conformational study of Ac-Xaa-Pro-NHMe dipeptides: proline puckering and trans/cis imide bond.

The conformational study on 20 Ac-Xaa-Pro-NHMe dipeptides has been carried out using an empirical potential function ECEPP/3 in order to investigate the factors responsible for the preference of proline puckering of the peptides with the trans or cis imide bond preceding the proline. The general conformational preference for down- and up-puckered dipeptides is calculated as trans-down > trans-up > cis-down > cis-up, which is reasonably in accord with that estimated by analyzing X-ray structures of proteins and the result for the single proline residue. The overestimated occurrence of trans-down conformations of proline seems to be caused by excluding long-range interactions that short dipeptides cannot have. The average computed occurrence of dipeptides with cis imide bonds is about 3%, somewhat lower than the value calculated for Ac-Pro-NHMe, which is close to experimental estimates obtained from X-ray structures of proteins. In particular, the interaction of the aromatic side chain of Xaa residue with the proline ring appears not to be strong enough to stabilize the stacked conformations of small dipeptides with cis imide bonds. The propensity to adopt trans or cis imide bond and to form secondary structures of Xaa-Pro sequences is discussed and compared with results obtained from X-ray structures of proteins.

Dipeptides↗

PubMed1999

Intrapulmonary and gastric teratoma : report of two cases.

The lung and stomach are very unusual sites for teratoma. The histologic findings of intrapulmonary and gastric teratomas are not different from those arising in usual sites, such as the ovary or testis. However, preoperative diagnosis is sometimes difficult to make partly because of unusual location. We report here two cases of teratoma, one intrapulmonary teratoma and the other gastric. The intrapulmonary teratoma in our study had an endobronchial tumor growth, which rules out mediastinal teratoma. Meanwhile gastric teratomas usually present as a submucosal tumor and most cases are reported in infancy and childhood. Gastric teratoma in this study occurred in a 27-year-old man. To the best of our knowledge, this case of intrapulmonary teratoma is the eighth and the gastric teratoma is the first to be reported in Korea.

Adult↗

PubMed1999

Mutation of p53 and K-ras, and loss of heterozygosity of APC in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor in liver; however, the carcinogenic mechanism of ICC is poorly understood. To analyze the molecular carcinogenesis of ICC, we examined the alterations of the p53, APC, and K-ras genes in 40 surgically resected ICC cases. The single-strand conformation polymorphism/sequencing revealed a p53 mutation in 12 cases (30%). An immunohistochemical overexpression of the p53 gene was detected in 10 cases (25%). The PCR/RFLP showed loss of heterozygosity of APC in 4 of 17 informative cases (23.5%). And the PCR/RFLP assay of K-ras codon 12 revealed the mutation in nine cases (22.5%). Twenty-one cases (52.5%) showed an alteration of at least one of the examined genes, and six (15%) carried an abnormality in more than two genes. The analysis of the clinicopathologic findings disclosed a significant relationship between the genetic alteration and gross type of the tumor: the p53 mutation was prominent in the ICC of mass-forming type, and K-ras mutation occurred more frequently in the ICC of periductal extension type (p < 0.05). These data suggest that each of the examined genes is involved in the development of ICC and that the p53 and K-ras mutation may play a role in the tumor growth pattern.

Adult↗

PubMed1998

Cellular resistance to adriamycin conferred by enhanced Rb expression is associated with increased MDR1 expression.

In order to investigate if the enhanced expression of Rb confers increased cellular resistance to adriamycin, we made Rb stable transfectants from colon carcinoma cells, SW620. Rb stable transfectants exhibited 5- to 10-fold more resistance to adriamycin than the control cells. To study the correlation between enhanced Rb expression and MDR1 expression, products of the Rb gene and the MDR1 gene in Rb stable transfectants were measured by Western blot analysis. These Rb transfectants showed increased MDR1 expression. Transient transfection of the MDR1 promoter-CAT reporter gene and the Rb gene demonstrated that Rb up-regulated MDR1 promoter activity in SW620 cells. Rb may, at least partly, contribute to a role in protecting cells from carcinogen exposure by up-regulating the MDR1 gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Prolactin-inducible enhancer activity of the first intron of the bovine beta-casein gene.

We have analyzed the regulatory roles of the first intron (intron-1) of the bovine beta-casein gene in the bovine beta-casein/CAT expression system using a mouse mammary epithelial cell line, HC11. After a combined treatment of HC11 cells with insulin, dexamethasone and prolactin, the induced expression of p beta c1.8/+ICAT vector including 2 kb intron-1 and 1.8 kb promoter was greatly increased to 23.5 folds, while that of p beta ca.8CAT basic vector with 1.8 kb promoter only, was 6.5. A classical enhancer activity was shown in the 2 kb intron fragment from the experiment in which the orientation and the position of the intron-1 on the vectors were changed. The enhancer activity was largely dependent on the lactogenic hormones, especially prolactin. A stepwise reduction of the inducibility in the 5' to 3' deletion analysis of the intron-1 indicates the existence of several functional elements in the region. In particular, an internal fragment (+1071 to +1490) was important for the prolactin-dependent enhancing activity of the intron-1. These results suggest that several elements in the intron-1 of the bovine beta-casein gene cooperatively interact not only with each other but also with its promoter for hormonal induction.

Animals↗

PubMed1998

Synthesis and antibacterial activities of new carbapenems having a proline reverse amide moiety at the C-2 position.

The synthesis of new 1 beta-methylcarbapenems (1a-l) having a proline reverse amide moiety at the C-2 position and their in vitro antibacterial activities are described. The compounds were evaluated by the Mueller-Hinton agar dilution method and compared with meropenem as control. Aliphatic amides (1a-h) are found to show greater antibacterial activity than aromatic amides (1i-l). Moreover, C-2 free amino compound (1m) reveals greater activity than any other amide compounds (1a-l).

Anti-Infective Agents↗

PubMed1998

p53 mutation and overexpression in hepatocellular carcinoma and dysplastic nodules in the liver.

In hepatocarcinogenesis, both de novo and multistep pathways have been suggested and in the latter a dysplastic nodule is the proposed precancerous lesion. In this study, we tried to ascertain whether or not the p53 gene is altered in low-grade/high-grade dysplastic nodules (LDN/HDN) and to determine the role of p53 alteration in multistep hepatocarcinogenesis. Eight hepatocellular carcinomas (HCCs), 9 HDNs, 17 LDNs and 25 cirrhotic nodules (LCs) were examined by polymerase chain reaction-single strand conformation polymorphism/direct sequencing and immunohistochemical staining for p53. Four of the 8 HCCs (50%) revealed p53 overexpression and 2 (25%) had missense mutations. Four of the 9 HDNs (44%) showed weak and/or focal p53 overexpression but none had mutation in the exons examined. Neither p53 overexpression nor mutation was found in 17 LDNs and 25 LCs. These results suggest that p53 mutation might be an unusual event in precancerous lesions of multistep hepatocarcinogenesis (DN-HCC sequence) and may play a less crucial part than in colorectal carcinogenesis.

Aged↗

PubMed1998

Transcription activation via enhanced preinitiation complex assembly in a human cell-free system lacking TAFIIs.

In contrast to previous findings in cell-free systems reconstituted with partially purified metazoan factors, we demonstrate dramatic activation of transcription in a TBP-dependent but TAFII-independent manner in HeLa nuclear extracts immunodepleted of TBP and major TAFIIs. Single-round transcription assays reveal that TAFII-independent activation is manifested at the level of productive preinitiation complex formation and that TAFIIs actually impair functional preinitiation complex assembly in a core promoter-specific manner. Furthermore, TAFIIs appear to elevate absolute levels of transcription under multiple-round transcription conditions, presumably by facilitating secondary initiation events. Finally, human coactivator activities related to those in yeast RNA polymerase II/mediator complexes appear to function in unfractionated HeLa nuclear extracts.

Cell Extracts↗

PubMed1998

Mesenchymal chondrosarcoma of the hyoid bone: a case report.

Mesenchymal chondrosarcoma is a rare tumor that is distinctly different from classic chondrosarcoma. The prognosis of this tumor is poor, with a high incidence of locoregional and distant metastases. It shows a predilection for the head and neck, however mesenchymal chondrosarcoma of hyoid bone has rarely been reported. We experienced a case of mesenchymal chondrosarcoma of the hyoid bone in a 39-year-old woman. She underwent excision of the tumor by right hemihyoidectomy. Histologically, a combination of cellular zones composed of undifferentiated small cells and chondroid zones typically presented a bimorphic appearance. CD99 (DN16) immunohistochemical stain demonstrated that all undifferentiated small cells had strong reactivity with a distinct membranous pattern. There was microscopic tumor extension to the resection margin of the hyoid bone, however, no evidence of reccurence is noted at follow-up of 4 months with neck CT.

Adult↗

PubMed1998

CDK4 down-regulation induced by paclitaxel is associated with G1 arrest in gastric cancer cells.

Paclitaxel induces a cell cycle block at G2-M phase by preventing the depolymerization of microtubules and induces p53-independent apoptosis in many cancer cells. We observed that gastric cancer cells treated with paclitaxel have shown a cyclin-dependent kinase (CDK)4 down-regulation. This paclitaxel-induced CDK4 down-regulation resulted in a cell cycle arrest at G1-S phase. To confirm this observation, we prepared stable transfectants that overexpressed CDK4 and analyzed the cell cycle progression. Ectopic expression of CDK4 in SNU cells resulted in a release of paclitaxel-induced G1 arrest. The release of G1 arrest by enforced expression of CDK4 seems to make the cells more sensitive to paclitaxel-induced apoptosis. From this finding, we could then suggest that paclitaxel treatment induces both G1-S and G2-M blocks in the cell cycle progression of gastric cancer cells.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization.

Acquired resistance to paclitaxel can be mediated by P-glycoprotein or by alterations involving tubulin. We report two paclitaxel-resistant sublines derived from 1A9 human ovarian carcinoma cells. Single-step paclitaxel selection with verapamil yielded two clones that are resistant to paclitaxel and collaterally sensitive to vinblastine. The resistant sublines are not paclitaxel-dependent, and resistance remained stable after 3 years of drug-free culture. All cell lines accumulate [3H]paclitaxel equally, and no MDR-1 mRNA was detected by polymerase chain reaction following reverse transcription. Total tubulin content is similar, but the polymerized fraction increased in parental but not in resistant cells following the paclitaxel addition. Purified tubulin from parental cells demonstrated paclitaxel-driven increased polymerization, in contrast to resistant cell tubulin, which did not polymerize under identical conditions. In contrast, epothilone B, an agent to which the resistant cells retained sensitivity, increased assembly. Comparable expression of beta-tubulin isotypes was found in parental and resistant cells, with predominant expression of the M40 and beta2 isotypes. Sequence analysis demonstrated acquired mutations in the M40 isotype at nucleotide 810 (T --> G; Phe270 --> Val) in 1A9PTX10 cells and nucleotide 1092 (G --> A; Ala364 --> Thr) in 1A9PTX22 cells. These results identify residues beta270 and beta364 as important modulators of paclitaxel's interaction with tubulin.

Antineoplastic Agents, Phytogenic↗