Although it has been suggested that kinesin family member 14 (KIF14) has oncogenic potential in various cancers, including hepatocellular carcinoma (HCC), the molecular mechanism of this potential remains unknown. We aimed to elucidate the role of KIF14 in hepatocarcinogenesis by knocking down KIF14 in HCC cells that overexpressed KIF14. After KIF14 knockdown, changes in tumor cell growth, cell cycle and cytokinesis were examined. We also examined cell cycle regulatory molecules and upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown of KIF14 resulted in suppression of cell proliferation and failure of cytokinesis, whereas KIF14 overexpression increased cell proliferation. In KIF14-silenced cells, the levels of cyclins E1, D1 and B1 were profoundly decreased compared with control cells. Of the cyclin-dependent kinase inhibitors, the p27Kip1 protein level specifically increased after KIF14 knockdown. The increase in p27Kip1 was not due to elevation of its mRNA level, but was due to inhibition of the proteasome-dependent degradation pathway. To explore the pathway upstream of this event, we measured the levels of SCF complex molecules, including Skp1, Skp2, Cul1, Roc1 and Cks1. The levels of Skp2 and its cofactor Cks1 decreased in the KIF14 knockdown cells where p27Kip1 accumulated. Overexpression of Skp2 in the KIF14 knockdown cells attenuated the failure of cytokinesis. On the basis of these results, we postulate that KIF14 knockdown downregulates the expression of Skp2 and Cks1, which target p27Kip1 for degradation by the 26S proteasome, leading to accumulation of p27Kip1. The downregulation of Skp2 and Cks1 also resulted in cytokinesis failure, which may inhibit tumor growth. To the best of our knowledge, this is the first report that has identified the molecular target and oncogenic effect of KIF14 in HCC.
Carcinoma, Hepatocellular/*metabolism ; Cyclin-Dependent Kinase Inhibitor p27/genetics/*metabolism ; Cyclins/genetics/metabolism ; *Cytokinesis ; Gene Silencing ; Hep G2 Cells ; Humans ; Kinesin/genetics/*metabolism ; Liver Neoplasms/*metabolism ; Oncogene Proteins/genetics/*metabolism ; Proteasome Endopeptidase Complex/metabolism ; RNA, Messenger/genetics/metabolism ; S-Phase Kinase-Associated Proteins/genetics/metabolism ; *Ubiquitination

BACKGROUND: It is regarded that contemporary Korean diet, the combination of carbohydrates-based Korean traditional diet and the Western eating patterns, increases the vulnerability to chronic diseases such as coronary vascular disease, diabetes mellitus, and hypertension. Therefore, there is a rising interest in carbohydrate sources with low glycemic index; many researches have proven the medical benefits of low glycemic index diet. Barley has recently drawn attention and various benefits of barley, such as improvements of obesity and bowel function, have been suggested. It seems that the beta-glucan, a content of barley helps to lower blood sugar level. This study aimed to evaluate the advantages of barley consumption compared to wheat consumption in blood sugar and blood lipid profile levels. METHODS: Twenty-four healthy Korea University students were randomly assigned to two groups: 12 of barley bread consumption group (treatment group) and 12 of wheat bread consumption group (control group). Both groups took bread on an empty stomach and the changes of their blood sugar and lipid levels were measured, compared, and analyzed every hour for four hours. RESULTS: The blood sugar level one hour later in the barley bread consumption group was statistically low. In addition, the area under curve of the barley bread intake group was found to be statistically smaller. However, the blood lipid profiles between the two groups did not show meaningful difference. CONCLUSION: This study suggests that the consumption of food containing barley could bring various medical benefits to one's health by lowering blood sugar.
Area Under Curve ; Blood Glucose ; Bread ; Chronic Disease ; Diabetes Mellitus ; Diet ; Eating ; Glycemic Index ; Hordeum ; Humans ; Hypertension ; Korea ; Lipid Metabolism ; Obesity ; Stomach ; Triticum ; Vascular Diseases

Molecular mechanism of lung carcinogenesis and its aggressive nature is still largely elusive. To uncover the biomarkers related with tumorigenesis and behavior of lung cancer, we screened novel differentially expressed genes (DEG) in A549 lung cancer cell line by comparison with CCD-25Lu, normal pulmonary epithelial cell line, using annealing control primer(ACP)- based GeneFishing system. Of the DEGs, over-expression of leucyl-tRNA synthetase 1 (LARS1) was prominent and this up-regulation was confirmed by immunoblotting and real-time quantitative RT-PCR analysis. In addition to A549 cell line, primary lung cancer tissues also expressed higher level of LARS1 mRNA than their normal counter tissues. To explore the oncogenic potential of LARS1 over-expression in lung cancer, we knocked-down LARS1 by treating siRNA and observed the tumor behavior. LARS1 knock-down cells showed reduced ability to migrate through transwell membrane and to form colonies in both soft agar and culture plate. Taken together, these findings suggest that LARS1 may play roles in migration and growth of lung cancer cells, which suggest its potential implication in lung tumorigenesis.
Base Sequence ; Blotting, Western ; Cell Line, Tumor ; *Cell Movement ; DNA Primers ; Humans ; Leucine-tRNA Ligase/genetics/*metabolism ; Lung Neoplasms/*enzymology/pathology ; *RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction

Invasive aspergillosis is the most common Aspergillus fumigatus infection in immunocompromised patients. Although the treatment of the invasive aspergillosis has been mostly relied on antifungal agents, there still exists the need for more effective therapy. To develop cellular immunotherapy specific for Aspergillus fumigatus, we generated specific T cells using dendritic cells (DCs) pulsed with an Aspergillus fumigatus derived recombinant protein in vitro and examined their functions. The f16. p2+3 region containing the conserved region of Asp f16 gene was cloned from Aspergillus fumigatus and the recombinant protein was produced in E. coli. IFN-gamma secretion from the T cells stimulated with recombinant f16. p2+3 (rf16. p2+3) was measured by enzyme linked immunospot (ELISPOT) assay and the cytolytic activity of the stimulated T cells by 51Cr release assay. The number of IFN-gamma secreting cells were significantly increased in the peripheral blood mononuclear cells (PBMCs) stimulated with the rf16. p2+3 pulsed DCs (31+/-12 spots/10(4) cells), compared to that of PBMCs directly stimulated with rf16. p2+3 (83+/-15 spots/10(6) cells). IFN-gamma ELISPOT assay using purified CD4+ or CD8+ as responder cells showed that CD4+ T cells (43 spots/10(4) cells) mainly produced IFN-gamma compared with CD8+ T cells (7 spots/10(4) cells). Furthermore, helper T cells specific for rf16. p2+3 could be efficiently generated by the stimulation with DCs for two weeks. However, cytotoxic T lymphocyte activity was not induced. Our results suggest that the rf16. p2+3 protein could be used for the generation of helper T cells in vitro.
Antifungal Agents ; Aspergillosis ; Aspergillus fumigatus* ; Aspergillus* ; Clone Cells ; Dendritic Cells* ; Enzyme-Linked Immunospot Assay ; Immunocompromised Host ; Immunotherapy ; Lymphocytes ; T-Lymphocytes* ; T-Lymphocytes, Helper-Inducer ; Viperidae*

BACKGROUND: Acromegaly occurs by excessive secretion of growth hormone and more than 99% of cases are caused by a growth hormone-secreting pituitary adenoma. Pituitary adenomas expressing multiple immunoreactivities are common. We assumed that the pituitary adenomas which is immunochemically detected growth hormone and prolactin are responsible for it and reviewed 28 patients with acromagaly to determine the correlation between serum hormonal level and immunocytochemical finding. METHODS: Twenty-eight patients with acromegaly who underwent surgery of pituitary adenoma in Samsung Medical Center from October 1998 to may 2001 were included. Baseline hormonal evaluations and several endocine tests were performed. Immunocytochemical stain was done. RESULTS: According to the extent of hormonal stain, the adenoma was divided into two groups. The adenoma showing immunoreactivity over 50% to growth hormone was 100%, to prolactin was 71.4% and to FSH was 25.0%. The extent of other hormonal stain was less than 20%. There were no significant differences in age, sex, the ratio of macroadenoma and microadenoma, the basal serum GH level, serum IGF-1 level, and the response to TRH, somatostatin and bromocriptine suppression test between the two groups divided by the the extent of prolactin stain. But the serum prolactin level was 55.0+/-63.4 ng/mL, and 19.9+/-12.2 ng/mL each in two groups which was siginificantly increased in the adenoma showing immunoreactivity over 50% to prolactin. CONCLUSION: Acromegaly patients with higher expression of prolactin on immunocytochemical studies showed higher serum prolactin levels and patients with hyperprolactinemia showed higher serum IGF-1.
Acromegaly* ; Adenoma ; Bromocriptine ; Growth Hormone ; Growth Hormone-Secreting Pituitary Adenoma ; Humans ; Hyperprolactinemia ; Insulin-Like Growth Factor I ; Pituitary Neoplasms* ; Prolactin* ; Somatostatin

BACKGROUND: Craniopharyngioma is a suprasellar or intrasellar epithelial neoplasm that occurs in both children and adults. It accounts for 1.2 to 3 % of intracranial tumors with an incidence of 0.5 to 2 cases per one million populations each year. Recently, it has been postulated that it may have two pathogenetically separate subtypes, which are adamantinous and papillary craniopharyngioma, and that their clinical features may be different. However, there are some disagreements in this postulation. Therefore, we studied 22 consecutive patients with craniopharyngioma to evaluate the differences in clinical features and MRI findings between two subtypes. METHODS: We studied 22 patients with histologically proven craniopharyngioma after surgery at Samsung Medical center from 1995 to 1999. Thirteen patients were male, and nine patients were female. The average age was 30 years, with a range from 1 to 58 years. We divided 22 patients into two histopathologically separate subtypes; adamantinous and papillary subtypes. We compared the clinical features and MRI findings of two subtypes by reviewing medical records. RESULTS: Out of 22 patients with craniopharyngioma, 19 patients had an adamantinous subtype and 3 patients had a papillary subtype. The adamantinous subtype occurred frequently in the fifth decade and below twenty years, while the papillary subtype occurred predominantly in forth and fifth decades. The adamantinous subtype located in suprasellar or intrasellar portion as well as extrasellar portion, while the papillary subtype was restricted to the suprasellar location. The average tumor size of the adamantinous subtype was 3.7 cm, with a range from 1.4 to 6.0 cm, which was larger than that of the papillary subtype (average size 1.8 cm with a range from 1.5 to 2.3 cm, p< 0.05). The adamantinous subtype was predominantly cystic, while the papillary subtype was predominantly solid (p< 0.05). There were no significant differences in the preoperative clinical features and the postoperative complications between two subtypes. CONCLUSION: The adamantinous subtype had two peaks of occurrence in the fifth decade and below twenty years, while the papillary subtype occurred predominantly in forth and fifth decades. The adamantinous subtype was larger and had cystic portion, while the papillary subtype was smaller and had solid portion. The preoperative clinical features and the postoperative complications between two subtypes seemed not to be different.
Adult ; Child ; Craniopharyngioma* ; Female ; Humans ; Incidence ; Magnetic Resonance Imaging* ; Male ; Medical Records ; Neoplasms, Glandular and Epithelial ; Postoperative Complications

T-cell lymphoma is heterogeneous with respect to clinical presentation, course, and morphology, but it is rarely associated with sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Syndrome). We report a case of T-cell lymphoma with Rosai-Dorfman Syndrome like feature in a 31-years-old woman who presented severe non-immune hemolytic anemia and massive retroperitoneal and cervical lymphadenopathy. Her cervical lymph node biopsy revealed histiocytic infiltration showing erythrophagocytosis without marked fibrosis in the capsular and pericapsular areas and distension of sinusoids. After 6 cycles of CHOP (Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) chemotherapy, cervical and retroperitoneal lymphadenopathy was completely disappeared and according to the resolution of lymphadenopathy hemolytic anemia was also improved.
Anemia, Hemolytic ; Biopsy ; Doxorubicin ; Drug Therapy ; Female ; Fibrosis ; Histiocytosis, Sinus ; Humans ; Lymph Nodes ; Lymphatic Diseases ; Lymphoma, T-Cell* ; T-Lymphocytes* ; Vincristine

OBJECTIVES: The beta3 adrenergic receptor(beta3 -AR) may play an important role in the regulation of energy expenditure and lipolysis. A mutation of the beta3 - AR gene(Trp64Arg) has been reported to be associated with early onset of non-insulin dependent diabetes mellitus(NIDDM), obesity and syndrome X which are related with insulin resistance. It is well known that Korean NIDDM patients, in contrast to Caucasians, are mainly non-obese and have experienced severe weight loss during the course of disease. We studied the frequency of the mutation in Korean NIDDM patients and non-diabetics control and evaluated the clinical characteristics of Korean obese NIDDM patients. We investigated the frequency of the mutation in NIDDM patients and clinical characteristics of the patients with the mutation in order to elucidate the significance of the mutation in the pathogenesis of NIDDM in Koreans. METHODS: We studied 401 NIDDM patients and 99 controls. The NIDDM patients were divided into two groups, non-obese group and obese group, according to their body mass index at diagnosis of the disease. The Trp64Arg mutation was detected by the PCR/RFLP method using restriction enzyme Mva I. RESULTS: The Trp64Arg allele frequency(16M) of NIDDM did not differ from that(16%) of controls. Although the mutant allele frequency was not different between non-obese and obese group both in NIDDM patients and controls, the frequency of patient with the mutant allele was significantly higher in obese NIDDM patients than in non-obese NIDDM patients(38.5% vs. 26.9%, P=0.04). However, no significant differences were found in clinical and laboratory findings between the NIDDM patients with the mutant allele and those without the mutant allele. CONCLUSION: These data suggest that beta3 -AR mutation might be associated with Korean obese NIDDM, and other factors might also be associated with the development of obesity and insulin resistance in NIDDM patients.
Alleles ; Body Mass Index ; Diabetes Mellitus, Type 2* ; Diagnosis ; Energy Metabolism ; Gene Frequency ; Humans ; Insulin Resistance ; Lipolysis ; Obesity ; Receptors, Adrenergic* ; Weight Loss

Down's syndrome (trisomy 21) has been frequently associated with thyroid disease, mainly subclinical hypothyroidism (12.5-32.5%). The occurrence of Downs syndrome in conjunction with hyperthyroidism is rare (0.6-2.5%). The mechanism that Down's syndrome was frequently associated with autoimmune thyroid disease is not clear, but T cell maturation defects and overexpression of chromosome 21 products in Down's syndrome have been suggested. A 19-year-old female was transferred because of generalized weakness. She was born to a 42-year-old mother, She had been suffered from heat intolerance, weight loss, palpitation, dyspnea on exertion and neck swelling and had intermittently taken some medication since her age 9. She had mental retardation (IQ 41) and underdeveloprnent. Exophthalmos, upward-outward slant of palpabral fissures, epicanthal folds, lowset ears, and large, protruding, fissured tongue were identified. Short fifth middle phalanges, clinodactyly and small-sized interventricular septal defect were also detected. Thyroid gland was diffusely enlarged four times the normal size, firm in consistency and had a bruit. Serum T concentration was 7.8ug/dL, T2 306ng/dL, and TSH 0.01ulU/mL. She was positive for thyroid autoantibodies (antimicosomal antibody 1,867 IU/mL, antithyroglobulin antibody 106 IU/mL, and TBII 79.6%). Twenty-four hours radioactive iodine uptake was 64%. Chromosomal analysis with T cell culture stimulated by phytohemagglutinin revealed 47XX, 21 trisomy. Pituitary hormones except TSH were fully stimulated by combined pituitary stimulation. She was finally diagnosed as Down's syndrome with Graves' disease and controlled with use of methimazole.
Adult ; Autoantibodies ; Cell Culture Techniques ; Chromosomes, Human, Pair 21 ; Down Syndrome* ; Dyspnea ; Ear ; Exophthalmos ; Female ; Graves Disease* ; Hot Temperature ; Humans ; Hyperthyroidism ; Hypothyroidism ; Intellectual Disability ; Iodine ; Methimazole ; Mothers ; Neck ; Pituitary Hormones ; Thyroid Diseases ; Thyroid Gland ; Tongue, Fissured ; Trisomy ; Weight Loss ; Young Adult

BACKGROUND: Overt hypothyroidism is well-known cause of secondary hyperlipidemia and atherosclerosis. However, there have been dissenting reports of abnormalities in serum lipid concentrations in patients with subclinical hypothyroidism (SH). Recently, it has been reported that serum Lp (a) concentration, an independent risk factor of atherosclerosis, was increased in patients with SH. Therefore, we analyzed serum Lp (a) and other lipid concentrations to investigate whether they are increased in patients with SH and the correlation between serum Lp (a) and TSH concentrations. METHODS: We undertook this study in 53 patients with SH (TSH > 6 uiU/ml) and 197 age-and sex-matched healthy control subjects, They had no abnormalities in liver function, BUN, creatinine, fasting blood glucose, urinalysis, and past medical histories. Serum T3, T4, and TSH concentrations were measured by RIA using commercial kits. Serum concentrations of Lp (a), total cholesterol, triglyceride (TG), and HDL cholesterol (HDL-C) were measured by rate nephelometry and enzyme assay, respectively. RESULTS: There were no significant differences of serum Lp (a), total cholesterol, LDL cholesterol, TG, and HDL-C concentrations in 53 patients with SH and 197 control subjects (25.6+-3.8mg/dL vs. 25.4+-1.5mg/dL ; 204.0+-4.2mg/dL vs. 204.0+-2.4mg/dL ; 127.0+-3.9mg/dL vs. 125.0+-2.3 mg/dL ; 133.0+-8.5mg/dL vs. 130.0+-6.0mg/dL ; 50.0+-1.5mg/dL vs. 53.0+-0.9mg/dL). There was no correlation between Lp (a) and TSH concentrations in SH (r=0.12, p>0.05). CONCLUSION: Serum Lp (a) concentration as well as total cholesterol, LDL cholesterol, and TG was not increased in patients with SH. There was no correlation between serum Lp (a) and TSH levels in subclinical hypothyroidism.
Atherosclerosis ; Blood Glucose ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Creatinine ; Dissent and Disputes ; Enzyme Assays ; Fasting ; Humans ; Hyperlipidemias ; Hypothyroidism* ; Lipoprotein(a)* ; Lipoproteins* ; Liver ; Nephelometry and Turbidimetry ; Risk Factors ; Triglycerides ; Urinalysis