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Biomedical subjects

Y Moon

Publications and source records attributed to Y Moon.

At least 19 recordsLinked to original sources
PubMed2004

Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox.

Macrophages, T cells, and B cells of the immune system are central targets of deoxynivalenol (DON) and other trichothecenes-mycotoxins that can be immunostimulatory or immunosuppressive depending on dose, exposure frequency and timing of functional immune assay. Notably, low dose trichothecene exposure transcriptionally and post-transcriptionally upregulates expression of cytokines, chemokines and inflammatory genes with concurrent immune stimulation, whereas high dose exposure promotes leukocyte apoptosis with concomitant immune suppression. DON and other trichothecenes, via a mechanism known as the ribotoxic stress response, bind to ribosomes and rapidly activate mitogen-activated protein kinases (MAPKs). The latter are important transducers of downstream signaling events related to immune response and apoptosis. Using cloned macrophages, our laboratory has identified two critical upstream transducers of DON-induced MAPK activation. One transducer is double-stranded RNA-(dsRNA)-activated protein kinase (PKR), a widely-expressed serine/theonine protein kinase that can be activated by dsRNA, interferon, and other agents. The second transducer is hematopoetic cell kinase (Hck), a non-receptor associated Src family kinase. Inhibitors and gene silencing studies have revealed that Hck and PKR play roles in DON induced gene expression and apoptosis. Future studies should focus on the molecular linkages between these kinases and trichothecene toxicity.

Adjuvants, Immunologic↗
PubMed2001

[Chemoradiotherapy and salvage surgery in a patient with advanced esophageal cancer].

We report a case of advanced esophageal cancer, which was treated by chemoradiotherapy combined with surgical treatment. Moreover, 14 advanced esophageal cancer patients treated by chemoradiotherapy are discussed. The chemoradiotherapy showed beneficial control of the tumor; however, it sometimes leads to esophageal stenosis and ulcer. We conclude that additional salvage surgery is needed for such complications.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Regulation of the fatty acid synthase promoter by insulin.

Expression of critical enzymes in fatty acid and fat biosynthesis is tightly controlled by nutritional and hormonal stimuli. The expression of fatty acid synthase, which catalyzes all reactions for synthesis of palmitate from acetyl-CoA and malonyl-CoA, and of mitochondrial glycerol-3-phosphate acyltransferase, which catalyzes the first acylation step in glycerophospholipid synthesis, is decreased to an undetectable level during fasting. Food intake, especially a high carbohydrate, fat-free diet after fasting, causes a dramatic increase in the transcription of these genes. Insulin secretion is increased during feeding and has a positive effect on expression. By using adipocytes in culture and transgenic mice that express the reporter gene driven by the fatty acid synthase promoter, the cis-acting sequence that mediates insulin regulation of the fatty acid synthase promoter was defined. Upstream stimulatory factors (USF) that bind to the -65 E-box are required for insulin-mediated transcriptional activation of the fatty acid symthase gene. Sterol regulatory element binding protein (SREBP)-1 may be also involved in induction of these genes during feeding. Using specific inhibitors and expressing various signaling molecules, we found that insulin regulation of the fatty acid synthase promoter is mediated by the phosphatidylinositol (PI)3-kinase signaling pathway and that protein kinase B/akt is a downstream effector.

Animals↗
PubMed2000

Enhanced radiation killing by 5-fluorouracil of biliary tract cancer cell lines.

Despite the frequent clinical use of 5-fluorouracil (5-FU) in combination with radiotherapy for patients with biliary tract cancers, data remain scarce concerning specifically the influence of 5-FU on the sensitivity of these cancer cells to radiation. The present study was carried out to evaluate the effects of concomitant treatment with 5-FU on radiation-induced cell killing in two established human biliary tract cancer cell lines (Mz-ChA-2 and SK-ChA-1 cells). These lines were chosen as we have previously shown that SK-ChA-1 cells are significantly more resistant to both radiation and 5-FU than Mz-ChA-2 cells. Clonogenic survival was employed as the end-point for cell killing. Administration of 5-FU at LD50 doses to each cell line significantly enhanced radiation-induced cell killing. The enhancement ratio (ER) was obtained by dividing the radiation dose required to decrease the cell survival fraction to 37% (D0) by the dose to decrease cell survival to the same level when the cells were also treated with 5-FU. The ER in each of the cell lines was greater when they were incubated with 5-FU after radiation rather than prior to radiation. Longer exposure times with 5-FU resulted in enhanced radiation killing. The ER was significantly higher in the radioresistant cell line than in the radiosensitive line. These findings suggest that therapy with radiation and 5-FU may be of value as components of multidisciplinary treatment for biliary tract cancer. Protracted low dose exposure to 5-FU may prove to be most efficacious in enhancing the effects of radiation therapy.

Biliary Tract Neoplasms↗
PubMed1999

Hematopoietic and reproductive toxicity of 2-bromopropane, a recently introduced substitute for chlorofluorocarbons.

2-Bromopropane and hydrochlorofluorocarbons (HCFCs), whose toxicity has scarcely been known, have recently been introduced as main substitutes for chlorofluorocarbons (CFCs). A major corporation in Korea replaced CFCs with 2-bromopropane and this actually led 23 Korean workers to be the world's first 2-bromopropane intoxication victims. Out of 25 female workers in the tactile switch assembling section, 17 (68%) were diagnosed as having ovarian failure. Two affected female workers showed marked pancytopenia with markedly hypoplastic marrow. In the same section, two out of eight male workers showed azoospermia and four some degree of oligospermia. The above toxicity of 2-bromopropane was reproduced in experimental animal studies. Recently, health effects of HCFC 123, including toxic hepatitis, have been reported by several authors. The principle of replacement of toxic substances with non-toxic or less toxic chemicals is important in risk management, but substances still poorly known should not be confused with non-toxic or less toxic substances. Measures aimed at reducing exposure to chemicals with known toxicity rather than using new unknown alternatives may be a rational and effective approach to risk management.

Animals↗
PubMed1999

Evaluation of exposure to ethylene glycol monoethyl ether acetates and their possible haematological effects on shipyard painters.

OBJECTIVES: To evaluate exposure to mixed solvents containing ethylene glycol monoethyl ether acetate (EGEEA) in shipyard painters, to determine if EGEEA is toxic to the bone marrow. METHODS: An industrial hygiene survey was performed to identify exposure to EGEEA of two groups of shipyard painters, a low exposure group (n = 30) and a high exposure group (n = 27). Urinary ethoxyacetic acid and methyl hippuric acid as well as haemoglobin, packed cell volume, red cell indices, total and differential white blood cell counts (WBCs), and platelet count for the shipyard painters and the control subjects were measured. RESULTS: The mean (range) exposure concentration (ppm) to EGEEA in the high and low exposure groups were 3.03 (not detectable to 18.27), 1.76 (not detectable to 8.12), respectively. The concentrations of methyl hippuric acid and ethoxyacetic acid in the high exposure group were significantly higher than those in the control group. The mean WBCs in the high exposure group were significantly lower than in the control group, and a significant proportion, six (11%) of the 57 painters, were leucopenic; none of the controls were affected. CONCLUSION: The high rate of possible haematological effects among shipyard painters and a hygienic evaluation of their working environment in the present study suggests that EGEEA might be toxic to bone marrow.

Adult↗
PubMed1999

Special medical examination program reform proposal in Korea.

We are at a time when reform in the special medical examination program in keeping with the changing times is desperately needed because the common perception of workers, employers, and medical examination facilities is "special medical examination is merely ritualistic and unproductive." Therefore, we have tried to set forth the basic structure for reforming the special medical examination program by taking a close look at the management status of the current program and analyzing its problems. The specifics of the special medical examination program reform proposal consist of three parts such as the types, health evaluation based on occupational medicine, and the interval, subject selection, items and procedure. Pre-placement medical examination and non-periodic medical examinations-as-necessary are introduced newly. Health evaluation based on occupational medicine consists of classification of health status, evaluation of work suitability, and post-examination measure. Details regarding the medical examination interval, subject selection, items and procedure were changed.

Government↗
PubMed1999

Killing effects of 5-fluorouracil on human biliary tract cancer cell lines.

Data concerning the cellular sensitivity of human biliary tract cancer cell lines to 5-FU are scarce. The purpose of the present study was to evaluate the cellular sensitivity of Mz-ChA-2 (derived from gall bladder cancer) and SK-ChA-1 (derived from bile duct cancer) to 5-FU. The clonogenic capacity of these lines after pulse (1 h) or continuous (168 h) administration of various 5-FU concentrations (0.1-100 microg/ml) was evaluated in exponentially growing cells as well as in those that had reached the plateau phase. In both cell lines, exponentially growing cells were 1.8-times more susceptible to 5-FU than those in plateau phase. However, when cells in the same growth phase were compared, Mz-ChA-2 cells were 10 times more sensitive to the drug than SK-ChA-1 cells. Regardless of the growth phase or cell line, increasing the duration of exposure to 5-FU decreased the proportion of surviving cells. Even at a non-cytocidal dosage, exposing the cells for three doubling times markedly decreased the number of viable cells remaining after treatment.

Antimetabolites, Antineoplastic↗
PubMed1999

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers.

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.

Adult↗
PubMed1997

Cloning and characterization of the 5' flanking region of human ATP-citrate lyase gene.

Two phage clones, lambda hgACL21 and lambda hgACL28, harboring the 5' flanking region of human ATP-citrate lyase (ACL) gene were identified by screening about 1.5 X 10(6) recombinant plaques from the lambdaEMBL3-human placental genomic DNA library. The 5' flanking region of ACL had the CAAT box on -92 bp from the transcription initiation site (+1), however, the TATA box was not found. The primer extension and rapid amplification of cDNA end showed that mRNA is transcribed at a thymine extending 12 bp upstream of the reported cDNA end. The sequences of 5' flanking region in 1.5 kb size of human ACL showed 60% homology with those of rat; however, no homology was found in the exon 1 and intron 1 region. Several consensus sequences, including four Sp1 binding sites, were found in the 5' flanking region of this gene. The promoter activity was assayed by transfecting the 3' or 5' deletion clones of ACL-chloramphenicol acetyl transferase (CAT) plasmid into PLC/PRF5 cells. The clone that contains the part of the first intron sequences from -659 to +440 bp showed the highest CAT activity in the transient transfection assay. High promoter activities were maintained until the transcription initiation site was removed. It is suggested that the sequences from -213 to +12 which contain three Sp1-binding sequences, CAAT box, and the transcription initiation site were necessary as a mean of for exerting the basal promoter activity of ACL gene.

ATP Citrate (pro-S)-Lyase↗
PubMed1996

Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology.

PURPOSE: To evaluate outcomes and identify prognostic factors in allogeneic bone marrow transplantation in patients with end-stage lymphoma. PATIENTS AND METHODS: Data were retrospectively analyzed of 64 patients (42 men and 22 women) 18 to 48 years of age with recurrent or refractory lymphoma who underwent allogeneic bone marrow transplantation from matched sibling donors (or in 1 case from a one antigen-mismatched relative) between May 1981 and July 1994. RESULTS: Twelve patients survived free of disease. They were 8 of 15 with low-grade lymphoma (disease-free survival at 2 years 59% +/- 13%); 3 of 25 with lymphoblastic lymphoma (disease-free survival 17% +/- 8%); and 1 of 10 with diffuse small non-cleaved cell lymphoma (disease-free (10% +/- 9%). Survival and disease-free survival of patients with low-grade lymphoma were significantly superior compared to any other subgroup of patients (P <0.01). Only 2 patients with low-grade lymphoma had disease progression (9% +/- 9% actuarial risk at 2 years) as opposed to 5 of 15 with intermediate-grade lymphoma (39% +/- 14%), 9 of 25 with lymphoblastic lymphoma (28% +/- 9%), and 8 of 10 (80% +/- 13%) with diffuse small non-cleaved lymphoma. The actuarial risk for disease progression was significantly lower for patients with low-grade lymphoma than for any other histologic subgroup (P <0.02). It was significantly higher for those with diffuse small non-cleaved cell lymphoma than for other histologic subgroups (P < or = 0.003). CONCLUSIONS: Allogeneic bone marrow transplantation is an effective procedure in patients with refractory low-grade lymphoma. It results in long-term remissions and should be considered in younger patients with recurrent disease who have a matched sibling donor. The late recurrence in 1 patient indicates the necessity of continued follow-up. A small fraction of patients with end-stage intermediate- and high-grade lymphoma can obtain prolonged disease-free survival, but recurrence and regimen-related toxicity remain major problems. The results could be improved by the development of conditioning regimens with less toxicity and by the use of bone marrow transplantation earlier in the course of the disease.

Adolescent↗
PubMed1996

In situ hybridization studies of cytomegalovirus and Epstein-Barr virus in reactive histiocytic hyperplasia with hemophagocytosis.

We studied 14 adult patients presenting with fever and cytopenia of the peripheral blood and histiocytic hyperplasia with hemophagocytosis (HHH) in the bone marrow regarding an association of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) by using in situ hybridization (ISH) and also evaluated the clinical and laboratory findings according to the encountered organisms. ISH using a CMV RNA probe demonstrated infected cells in 6 out of 14 cases (43%), and ISH using an EBV EBER RNA probe demonstrated infected nuclei in 5 out of the same 14 cases (36%) of HHH. No cases showed a positive reaction with both probes. Three cases showed a negative reaction with both probes. The mean age of all patients was 29 years; and that of the CMV-positive patients was 27 years and that of the EBV-positive patients was 36 years. Organomegaly was found in 3 out of 6 CMV-positive patients (1 hepatomegaly, 1 splenomegaly, 1 hepatosplenomegaly), and 4 out of 5 EBV-positive patients (lymphadenopathy in all 4 cases, hepatosplenomegaly in 2 cases). One of the CMV-positive case had acute myeloblastic leukemia, and 2 EBV-positive cases had underlying malignancy (1 Hodgkin's disease, 1 non-Hodgkin's lymphoma). Seven out of the 14 HHH cases (50%) died within several months after diagnosis. Nucleic acid hybridization methods can be used for the routine examination of the association of CMV or EBV.

Adult↗
PubMed1996

Hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane.

OBJECTIVES: The purpose of this study was to describe hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane. METHODS: Detailed medical and occupational histories were taken and thorough physical examinations with clinical laboratory tests were done for 33 workers (8 men and 25 women). Previous and present exposure was investigated in detail by industrial hygienists. RESULTS: Of the 25 female workers, 16 were shown to have secondary amenorrhea with high follicle-stimulating hormone levels, normal prolactin levels, and hot flashes. A total of eight workers with amenorrhea concurrently showed findings of pancytopenia. Among eight male workers, two showed azoospermia and another four showed some degree of oligospermia (normal > 20 million. ml-1) or reduced sperm motility (normal > 50%). The bone marrow effects and the testis or ovarian failure was shown to be the main health hazards in this workplace. Except for the cleaning solution containing 97.4% 2-bromopropane, no other known physical or chemical agents could be identified as responsible for the gonadal and bone marrow effects, including ionizing radiation, lead, ethylene glycol ether and its acetates, benzene, and dibromochloropropane. CONCLUSIONS: No previous studies have reported human toxicity for 2-bromopropane, but the results of this study lead to the tentative conclusion that the causal agent for the gonadal and bone marrow effects among the workers might be 2-bromopropane.

Adult↗
PubMed1995

Hormonal and nutritional control of the fatty acid synthase promoter in transgenic mice.

To study the molecular basis of tissue-specific and hormonally regulated expression of the fatty acid synthase (FAS) gene in vivo, we generated lines of transgenic mice carrying 2.1 kilobases of the 5'-flanking region (-2100 to +67) of the rat FAS gene fused to a chloramphenicol acetyltransferase (CAT) reporter gene. This reporter gene construct was strongly expressed in tissues that normally express high levels of FAS mRNA, which include liver and white adipose tissues. In contrast, CAT reporter activity was not detected in appreciable levels in lung, heart, kidney, and muscle tissues, which do not normally show significant levels of FAS activity. The relative levels of the CAT mRNA driven by the rat FAS promoter in various tissues of the transgenic animals approximated those of the endogenous mouse FAS mRNA. We also examined the hormonal and nutritional regulation of the FAS(2.1)-CAT reporter gene in transgenic mice. CAT activity was increased in both liver and white adipose tissue when fasted animals were refed a high carbohydrate, fat-free diet. These changes in CAT activity and CAT mRNA levels occurred in parallel to the changes in endogenous mouse FAS mRNA levels. On the other hand, fasting/refeeding did not change CAT activity appreciably in other tissues, such as muscle and brown adipose tissue. Administration of dibutyryl cAMP at the start of refeeding prevented an increase in CAT activity in liver. However, the cAMP effect was tissue-specific as cAMP treatment did not bring about change in CAT activity in adipose tissue. Next, to examine the effect of insulin, we made the transgenic mice insulin-deficient by streptozotocin treatment. Insulin treatment of the streptozotocin-diabetic mice increased both the CAT activity and CAT mRNA levels driven by the rat FAS promoter in liver and white adipose tissue. These changes in CAT expression by insulin paralleled those in endogenous FAS mRNA levels. Administration of glucocorticoids increased CAT activity in all tissues examined: liver, white and brown adipose tissues, lung, heart, and spleen. Overall, the first 2.1 kilobases of the 5'-flanking region of the rat FAS gene appear to contain sequence elements necessary to confer tissue-specific and hormonally regulated expression characteristic of the endogenous FAS gene.

Adipose Tissue↗
PubMed1994

Nitrous oxide: sensory, motor, associative, and behavioral tolerance effects in classical conditioning of the rabbit nictitating membrane response.

Experiment 1, of a series of six experiments with the rabbit nictitating membrane response (NMR) preparation, revealed that nitrous oxide (0%, 33%, 67%) impaired acquisition of conditioned responses (CRs). Subsequent experiments indicated that nitrous oxide (N2O) had no reliable effects upon nonassociative processes (Experiment 2); impaired unconditioned response (UR) amplitude (Experiment 3); attenuated tone-conditioned stimulus (CS) intensity (Experiment 4); decremented tone-induced reflex modification of the unconditioned NMR (Experiment 5); and demonstrated no reliable evidence of behavioral tolerance (Experiment 6). It was concluded that N2O's impairment of CR acquisition was attributable to its attenuation of the intensity of tone CSs and shock USs and/or UR amplitude. These findings are consistent with the behavioral laws of conditioning: the attenuation of the intensive sensory properties of the CS and US and/or UR components of conditioning affect their ability to enter into the establishment of CS-CR connections and, therefore, the development of associative learning.

Acoustic Stimulation↗