Search PubMed⌕ Search

Biomedical subjects

M J Lee

Publications and source records attributed to M J Lee.

At least 163 records · Page 9Linked to original sources
PubMed1999

Correlation of changes in natural killer cell activity and glutathione S-transferase placental form positive hepatocytes in diethylnitrosamine-induced rat hepatocarcinogenesis.

To evaluate the induction of preneoplastic hepatic foci in relation to natural killer cell (NK) activity, we sequentially analyzed glutathione S-transferase placental form positive (GST-P+) hepatocytes and NK activity during diethylnitrosamine (DEN) and phenobarbital (PB)-induced hepatocarcinogenesis in Sprague-Dawley rats. Previous studies have shown that NK activity can modulate the carcinogenic process induced by chemical carcinogens. Newborn females were initially given a single intraperitoneal injection of 15 mg DEN/kg and three weeks later, they were treated with 500 ppm phenobarbital (PB). From week 3, PB was administered in drinking water for 9 weeks. Interim and terminal sacrifices were performed at weeks 12, 15 and 30. GST-P+ hepatocytes increased with age in DEN-treated rats, especially in the population of more than two GST-P+ hepatocytes. The NK activity of DEN-treated rats did not significantly differ from that of control rats until week 12, but it progressively decreased from week 15 to 30. These results indicate that changes of NK activity inversely correlated with the induction of preneoplastic hepatic foci. This strong correlation of decreased NK activity with enhanced induction of GST-P+ foci suggests that NK activity is important in the early progression of hepatocarcinogenesis in rats.

Animals↗
PubMed1999

Mercury concentrations in scalp hair as an environmental contamination index from foods in Korea.

Relationships have been established between the mercury (Hg) levels in human scalp hair and environmental or dietary mercury exposures. The average value of total mercury (THg) in scalp hair of male residents in Seoul city was 1.66 +/- 1.10 ppm (+/- SD) and for methylmercury (MeHg) was 1.02 +/- 0.72 ppm (61% of total Hg). For females, THg was 1.06 +/- 0.46 ppm and MeHg was 0.51 +/- 0.27 ppm (48.8% of total Hg). The levels of Hg in scalp hair of male subjects were significantly different according to their occupations and age groups, but in females such variation was not detectable. The Hg levels in fishing village residents were significantly higher than those of Seoul residents. The concentrations of both THg and MeHg of residents in Korean fishing villages were similar to those of residents in fishing villages of other countries. Correlation between THg and MeHg contents in scalp hair was statistically highly significant.

Adolescent↗
PubMed1999

123I-metaiodobenzylguanidine scans in phaeochromocytoma diagnosis: current clinical practice and relationship to biochemical screening.

The use in practice of 123I-metaiodobenzylguanidine (MIBG) scans in phaeochromocytoma diagnosis in a teaching hospital over an eight-year period is reported. MIBG scans were performed in 43 patients and the clinical context is reviewed and reported in 42 of these. A paraganglioma and five phaeochromocytomas were found in the MIBG series. There were no false negative MIBG scans. CT was performed in 61.9%, abdominal ultrasound in 45.3% and MRI in 7.1% of the patients. Urinary catecholamines and metanephrines are considered the best screening tests for phaeochromocytoma and false positive biochemistry values were associated with MIBG scans in 35% of the cases. Despite published limitations on its sensitivity, MIBG scans were the only modality used in 21.4%; 25% of the scans were performed for clinical reasons when the biochemical screen was within the reference range. MIBG is superior to CT and MRI for the localisation of suspected recurrence after surgery and is also useful for the detection of extra adrenal tumours and metastases.

3-Iodobenzylguanidine↗
PubMed1999

Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans.

The objective of this Phase I/II study was to assess the potential for green tea to be used as a colorectal cancer chemopreventive agent. This study measured the dose-related biological effects of administration of a single dose of green tea on the rectal mucosa of normal volunteers. Volunteers were admitted to the Robert Wood Johnson Medical School Clinical Research Center for 24 h. Baseline blood and rectal biopsy samples were obtained before the volunteers drank 0.6, 1.2, or 1.8 g of green tea solids dissolved in warm water. Blood samples were taken 2, 4, 8, and 24 h after the tea administration. Rectal biopsies were obtained at 4, 8, and 24 h. Prostaglandin E2 (PGE2) levels were analyzed by ELISA. Tea polyphenol levels in the blood, urine, and rectal tissue were measured by high-performance liquid chromatography using a Coulochem electrode array detection system. Statistical comparisons were made using ANOVA. Decreased levels of PGE2 in rectal mucosa were observed at 4 and 8 h after consumption of green tea. There was no correlation between inhibition of PGE2 and tissue or plasma levels of tea polyphenols. Ten of 14 subjects demonstrated a response to green tea, as evidenced by at least a 50% inhibition of PGE2 levels at 4 h. We conclude that green tea constituents have biological activity in inhibiting PGE2 synthesis. Given the 71% "response rate," we believe these data support the study of green tea as a colorectal chemopreventive agent in more long-term Phase II trials.

Administration, Oral↗
PubMed1999

Prenatal diagnosis of a Japanese family at risk for Tay-Sachs disease. Application of a fluorescent competitive allele-specific polymerase chain reaction (PCR) method.

Tay-Sachs disease (TSD) is caused by mutation of the HEXA gene, which results in a deficiency of the alpha-subunit of hexosaminidase A. The major mutation in Japanese TSD is a G-to-T transversion at the 3'-splice site of intron 5. We established a fluorescent competitive allele-specific polymerase chain reaction (FCAS-PCR) method for detection of the mutation and applied it to prenatal diagnosis of a Japanese TSD family. FCAS-PCR distinguished the wild and mutant alleles clearly, with broad ranges in the amount of template DNA, the dNTP concentration, the MgCl2 concentration and the number of PCR cycles. After obtaining ethics committee approval and informed consent from the parents in the index family, chorionic villus sampling was performed. FCAS-PCR analysis using chorionic villus DNA disclosed that the fetus was homozygous for the mutation. To confirm the diagnosis, direct sequencing analysis of the genomic PCR fragment was performed, and showed the same results as those of the FCAS-PCR analysis. FCAS-PCR proved to be helpful for carrier screening and prenatal diagnosis in TSD families in the Japanese population. It would also be a useful DNA-diagnostic method for many other inherited disorders.

Adult↗
PubMed1999

C677T mutation of the methylenetetrahydrofolate reductase gene among the Korean infants in Seoul city.

The missense mutation, C677T (Ala--->Val), in the methylenetetrahydrofolate reductase (MTHFR) gene, is related to hyperhomocysteinemia and is regarded as a risk factor for coronary artery disease and neural tube defects. The prevalence of this mutation was reported to differ among various ethnic groups, but there are few reports concerning Asian populations. We have investigated the frequencies of C677T mutation in 124 Korean infants (residents in Seoul city, Korea) and 115 Japanese adults (residents in Kobe city, Japan), and compared them with the reported data from other ethnic groups. The frequencies of the three genotypes in Koreans were as follows: C/C (wild homozygosity) 0.27, C/T (heterozygosity) 0.66, T/T (mutated homozygosity) 0.07, while those in Japanese were as follows: C/C 0.44, C/T 0.40, T/T 0.16. There was a marked difference in the genotype frequencies between the two populations (chi-square = 16.67, P = 0.0002), even though they are closely related in genetic background. The high C/T genotype frequency led to significant deviation from Hardy-Weinberg equilibrium (chi-square = 17.35, P = 0.00003). Deviation from Hardy-Weinberg equilibrium has not been found in any other ethnic groups. The high frequency of C/T genotype may offer Koreans a selective advantage.

Adult↗
PubMed1999

Human salivary tea catechin levels and catechin esterase activities: implication in human cancer prevention studies.

Because of the possible application of tea in the prevention of oral and esophageal cancers, the salivary levels of tea catechins were determined in six human volunteers after drinking tea. Saliva samples were collected after thoroughly rinsing the mouth with water. After drinking green tea preparations equivalent to two to three cups of tea, peak saliva levels of (-)-epigallocatechin (EGC; 11.7-43.9 microg/ml), EGC-3-gallate (EGCG; 4.8-22 microg/ml), and (-)-epicatechin (EC; 1.8-7.5 microg/ml) were observed after a few minutes. These levels were 2 orders of magnitude higher than those in the plasma. The elimination half-life (t(1/2)) of the salivary catechins was 10-20 min, much shorter than that of the plasma. Holding a tea solution in the mouth for a few minutes without swallowing produced even higher salivary catechin levels, but taking tea solids in capsules resulted in no detectable salivary catechin level. Holding an EGCG solution in the mouth resulted in EGCG and EGC in the saliva and, subsequently, EGC in the urine. The results suggest that EGCG was converted to EGC in the oral cavity, and both catechins were absorbed through the oral mucosa. A catechin esterase activity that converts EGCG to EGC was found in the saliva. The enzyme was likely of human origin, but the activity was not inhibited by common human esterase inhibitor. The present results suggest that slowly drinking tea is a very effective way of delivering rather high concentrations of catechins to the oral cavity and then the esophagus.

Absorption↗
PubMed1999

Location of the primary motor cortex in schizencephaly.

BACKGROUND AND PURPOSE: Functional reorganization of the brain can result from congenital brain disorders as well as from brain infarction. The purpose of our study was to use functional MR imaging to determine whether reorganization of brain function occurs in patients with schizencephaly. METHODS: Four patients with schizencephaly (three right-handed, one ambidextrous) presented with seizures. Associated lesions included agenesis of the corpus callosum (n = 1) and absence of the septum pellucidum (n = 1). Functional MR imaging was performed in each patient using a single-section fast low-angle shot (FLASH) blood oxygen level-dependent (BOLD) technique at 1.5 T in a standard head coil. The motor cortex was initially identified on an axial T1-weighted anatomic image. Thirty consecutive images were obtained during a motor task consisting of repetitive finger-to-thumb opposition. The percentage of change in increased signal intensity was calculated for the primary motor area. An ipsilateral activation index was used to compare the affected with the unaffected hemisphere. RESULTS: The percentage of change in increased signal intensity in the area of activation ranged from 4.8% +/- 0.9 to 9.2% +/- 1.2 (mean, 5.6% +/- 1.5). The ipsilateral activation index in the affected hemisphere was 0.00 to 0.38, whereas that in the unaffected hemisphere was 15.4 to infinity. The difference in the ipsilateral activation index between each hemisphere was considered significant. CONCLUSION: Our results showed increased activation in the unaffected hemisphere in patients with schizencephaly, which may reflect functional reorganization of the motor area in patients with this congenital disorder.

Adolescent↗
PubMed1998

Maternal or paternal exposure to radiation increases susceptibility to the induction of glutathione S-transferase-positive hepatic foci in offspring rats.

Experiments were conducted to determine whether gamma-ray-induced genetic damage in parental rats can lead to the development of cancer in their offspring rats using glutathione S-transferase-positive (GST-P+) hepatic foci with or without the addition of diethylnitrosamine (DEN), a carcinogen. A single 1 Gy whole-body exposure of gamma-rays was given to pregnant rats at day 14 and during postnatal week 3, DEN was intraperitoneally injected twice in 1 week. Female pups from irradiated maternal and paternal rats were also used. Twelve weeks after birth, the rats were sacrificed. GST-P+ foci in animals subjected only to radiation were not different to those of normal control pups, but the incidence of GST-P+ foci was 2.4 times higher in pups treated with DEN alone at 3 weeks after birth than in those irradiated after the onset of pregnancy. In DEN-combined groups, irradiation of post-pregnant or maternal and paternal rats with gamma-rays before mating significantly increased both the incidence and area of GST-P+ foci when compared to those of rats treated with DEN alone. The proliferating cell nuclear antigen (PCNA) labeling index was significantly higher in the offspring of rats subjected to radiation alone or radiation combined with DEN than in normal control pups. Using a rat-liver model, the results of this study indicate that although the dose did not induce phenotypic malformation, exposure to radiation during the embryonic or pre-embryonic stage increases susceptibility to carcinogens.

Animals↗
PubMed1998

Overexpression of cyclin D1 and cdk4 in tumorigenesis of sporadic hepatoblastomas.

Abnormality of the cyclin D1/cdk4/p16INK4a/pRb pathway during tumorigenesis has recently been reported. Hepatoblastoma is a rare malignant liver tumor of childhood, but underlying abnormalities of cell-cycle regulating protein remain to be elucidated. The expression of cyclin D1, cdk4, p16 and retinoblastoma gene product (pRb) was studied by immunohistochemistry in 17 paraffin-embedded tissues consisting of both tumor and corresponding non-neoplastic tissues. Tumor tissues showed overexpression of cyclin D1 (13/17, 76%) and cdk4 (15/17, 88%). Eleven cases showed co-overexpression of both cyclin D1 and cdk4. No abnormal p16 or pRb expression was noted. In the group with a high score (+4) for cyclin D1 expression, a positive correlation with tumor recurrence was noted (P = 0.043). These data suggest that overexpressed cyclin D1 and cdk4 protein might play an important role in the tumorigenesis of hepatoblastoma and that in the group with high cyclin D1 expression, tumor recurrence may be more frequent.

Adolescent↗
PubMed1998

Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5.

We previously reported the isolation of a 2.5 Mb tumor-suppressing subchromosomal transferable fragment (STF) from 11p15.5 and the identification of nine known genes and four novel genes within this STF. We now report the isolation of a fifth novel cDNA, tumor-suppressing STF cDNA 5, designated TSSC5, located within the STF. TSSC5 encodes a predicted protein of 424 amino acids. Sequence analysis suggests that TSSC5 is a membrane protein with 10 transmembrane segments, and it is located between two imprinted genes, p57KIP2 and TSSC3. Northern blot hybridization revealed a 1.6-kb transcript in multiple adult tissues and in fetal liver and kidney, consistent with a potential role in embryonal tumors. We also found that TSSC5 is imprinted with preferential expression from the maternal chromosome. Reverse transcription-PCR analysis of TSSC5 revealed frequent occurrence of aberrant RNA splicing, which deleted exons 4, 5, and 6 in Wilms' tumors. Mutational analysis of TSSC5 by direct DNA sequencing of exons revealed a base substitution of G1120A in a Wilms' tumor, matched normal kidney, and the patient's mother, changed Arg at codon 309 to Gln. The G1120A substitution thus represents either a rare polymorphism or a tumor-predisposing mutation, because the mutant allele was of maternal origin and preferentially expressed in the patient's tissue. A second base substitution, C892T, was found in a lung cancer, changing Ser at codon 233 to Phe. This substitution was absent from the matched normal tissue and thus represented a somatic mutation. We also found loss of heterozygosity in the lung cancer, suggesting that TSSC5 may be a conventional tumor suppressor gene in the adult human lung and an imprinted tumor suppressor gene in the fetal kidney.

Adult↗
PubMed1998

Lysophosphatidic acid stimulates the G-protein-coupled receptor EDG-1 as a low affinity agonist.

EDG-1, an inducible G-protein-coupled receptor from vascular endothelial cells, is a high affinity receptor for sphingosine 1-phosphate (SPP) (Lee, M-J., van Brocklyn, J. R., Thangada, S., Liu, C. H., Hand, A. R., Menzeleev, R., Spiegel, S., and Hla, T. (1998) Science 279, 1552-1555). In this study, we show that lysophosphatidic acid (LPA), a platelet-derived bioactive lipid structurally related to SPP, is an agonist for EDG-1. LPA binds to EDG-1 receptor with an apparent Kd of 2.3 microM. In addition, LPA binding to EDG-1 induces receptor phosphorylation, mitogen-activated protein kinase activation, as well as Rho-dependent morphogenesis and P-cadherin expression. These data suggest that LPA is a low-affinity agonist for EDG-1. Activation of the endothelial receptor EDG-1 by platelet-derived lipids LPA and SPP may be important in thrombosis and angiogenesis, conditions in which critical platelet-endothelial interactions occur.

Cell Differentiation↗
PubMed1998

Tumor promoting effect of N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (a nitrosated Maillard reaction product) in benzo(a)pyrene-initiated mouse skin carcinogenesis.

N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (NO-HNTA) is a product generated in a model browning system in the presence of sodium nitrite. The chemical structure of this compound has been confirmed by UV, mass, nuclear magnetic resonance and infrared spectroscopy in our study. Twenty weeks, twice weekly, topical application of NO-HNTA at the concentration of 10, 50 and 250 mumol to mice previously initiated with benzo(a)pyrene (B[a]P) increased their tumor formation by 3.2-, 4.6- and 5.8-fold respectively. Application of the same amount of NO-HNTA not only caused significant induction of hyperplasia but also the activity of epidermal ornithine decarboxylase (ODC). Treatment of mouse skin with various amounts of NO-HNTA (10, 50 and 250 mumol) caused production of hydrogen peroxide by 1.38-, 1.95- and 3.26-fold respectively, and induction myeloperoxidase (MPO) by 24-, 63- and 102-fold. These results indicate that the formation of NO-HNTA or its derivatives derived from the reaction of tyrosine and glucose in the presence of sodium nitrite has the potential as a tumor promoter.

Animals↗
PubMed1998

Detection of threonine structural changes upon formation of the M-intermediate of bacteriorhodopsin: evidence for assignment to Thr-89.

The behavior of threonine residues in the bacteriorhodopsin (bR) photocycle has been investigated by Fourier transform infrared difference spectroscopy. L-Threonine labeled at the hydroxyl group with 18O (L-[3-(18)O]threonine) was incorporated into bR and the bR-->M FTIR difference spectra measured. Bands are assigned to threonine vibrational modes on the basis of 18O induced isotope frequency shifts and normal mode calculations. In the 3500 cm-1 region, a negative band is assigned to the OH stretch of threonine. In the 1125 cm-1 region, a negative band is assigned to a mixed CH3 rock/CO stretch mode. The frequency of both these bands indicates the presence of at least one hydrogen bonded threonine hydroxyl group in light adapted bR which undergoes a change in structure by formation of the M intermediate. Spectral changes induced by the substitution Thr-89-->Asn but not Thr-46-->Asn or Asp-96-->Asn are consistent with the assignment of these bands to Thr-89. These results along with another related study on the mutant Thr-89-->Asn indicate that the active site of bR includes Thr-89 and that its interaction with the retinylidene Schiff base and Asp-85 may play an important role in regulating the color of bacteriorhodopsin and the transfer of a proton to the Schiff base.

Bacteriorhodopsins↗
PubMed1998

Prodrugs of nitroxyl and nitrosobenzene as cascade latentiated inhibitors of aldehyde dehydrogenase.

The prototypic aromatic C-nitroso compound, nitrosobenzene (NB), was shown previously to mimic the effect of nitroxyl (HN=O), the putative active metabolite of cyanamide, in inhibiting aldehyde dehydrogenase (AlDH). To minimize the toxicity of NB in vivo, pro-prodrug forms of NB, which were designed to be bioactivated either by an esterase intrinsic to AlDH or the mixed function oxidase enzymes of liver microsomes, were prepared. Accordingly, the prodrug N-benzenesulfonyl-N-phenylhydroxylamine (3) was further latentiated by conversion to its O-acetyl (1a), O-methoxycarbonyl (1b), O-ethoxycarbonyl (1c), and O-methyl (2) derivatives. Similarly, pro-prodrug forms of nitroxyl were prepared by derivatization of the hydroxylamino moiety of methanesulfohydroxamic acid with N, O-bis-acetyl (7a), N,O-bis-methoxycarbonyl (7b), N, O-bis-ethoxycarbonyl (7c), and N-methoxycarbonyl-O-methyl (7d) groups. It was expected that the bioactivation of these prodrugs would initiate a cascade of nonenzymatic reactions leading to the ultimate liberation of NB or nitroxyl, thereby inhibiting AlDH. Indeed, the ester pro-prodrugs of both series were highly active in inhibiting yeast AlDH in vitro with IC50 values ranging from 21 to 64 microM. However, only 7d significantly raised ethanol-derived blood acetaldehyde levels when administered to rats, a reflection of the inhibition of hepatic mitochondrial AlDH-2.

Acetaldehyde↗
PubMed1998

Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival.

Sphingosine-1-phosphate (SPP), a bioactive lipid, acts both intracellularly and extracellularly to cause pleiotropic biological responses. Recently, we identified SPP as a ligand for the G protein-coupled receptor Edg-1 (Lee, M.-J., J.R. Van Brocklyn, S. Thangada, C.H. Liu, A.R. Hand, R. Menzeleev, S. Spiegel, and T. Hla. 1998. Science. 279:1552-1555). Edg-1 binds SPP with remarkable specificity as only sphinganine-1-phosphate displaced radiolabeled SPP, while other sphingolipids did not. Binding of SPP to Edg-1 resulted in inhibition of forskolin-stimulated cAMP accumulation, in a pertussis toxin-sensitive manner. In contrast, two well-characterized biological responses of SPP, mitogenesis and prevention of apoptosis, were clearly unrelated to binding to Edg-1 and correlated with intracellular uptake. SPP also stimulated signal transduction pathways, including calcium mobilization, activation of phospholipase D, and tyrosine phosphorylation of p125(FAK), independently of edg-1 expression. Moreover, DNA synthesis in Swiss 3T3 fibroblasts was significantly and specifically increased by microinjection of SPP. Finally, SPP suppresses apoptosis of HL-60 and pheochromocytoma PC12 cells, which do not have specific SPP binding or expression of Edg-1 mRNA. Conversely, sphinganine-1-phosphate, which binds to and signals via Edg-1, does not have any significant cytoprotective effect. Thus, SPP is a prototype for a novel class of lipid mediators that act both extracellularly as ligands for cell surface receptors and intracellularly as second messengers.

3T3 Cells↗