Biomedical subjects

M J Lee

Publications and source records attributed to M J Lee.

At least 91 records · Page 5Linked to original sources

PubMed2000

Zinc induces the accumulation of hypoxia-inducible factor (HIF)-1alpha, but inhibits the nuclear translocation of HIF-1beta, causing HIF-1 inactivation.

The replacement of heme iron by cobalt or nickel in a putative oxygen sensor is supposed to reduce oxygen binding to the heme protein, resulting in HIF-1 activation and erythropoietin (EPO) induction. According to this hypothesis, zinc might be another example of a transition metal which is capable of stimulating EPO production. By substituting for heme iron, zinc protoporphyrin IX is produced, which has a known low oxygen affinity. However, it has been reported that zinc fails to induce EPO in normoxia, and that it suppresses EPO production in hypoxic cells. This unexpected effect of zinc on EPO production is not understood. In this study, we found that zinc induced the accumulation and nuclear translocation of hypoxia-inducible factor (HIF)-1alpha but inhibited the nuclear translocation of HIF-1beta, which inactivated HIF-1 and suppressed EPO mRNA induction in hypoxic cells.

Biological Transport↗

PubMed2000

Synthesis of 5-(4-alkoxy-[1,2,5]thiadiazol-3-yl)-3-methyl-1,2,3,4-tetrahydropyrimidi ne oxalate salts and their evaluation as muscarinic receptor agonists.

The synthesis and biological testing of 5-(4-alkoxy-[1,2,5]thiadiazol-3-yl)-3-methyl-1,2,3,4-tetrahydro pyrimidine oxalate salts 8 as muscarinic receptor agonists are described. The key intermediate 4 was obtained by modified Strecker reaction and cyclization of starting material 1. Subsequent alkoxy substitution, quaternization, and reduction afforded 7. For the sake of purity and stability of the final products 8, the 3-methyl-1,2,3,4-tetrahydropyrimidines were obtained as oxalic acid salts. All final compounds were examined in vitro for their binding affinities to the cloned human muscarinic receptor by the [3H]-NMS binding assay.

Alzheimer Disease↗

PubMed2000

Mechanisms of inhibition of carcinogenesis by tea.

Tea (Camellia sinensis) preparations have been shown to inhibit tumorigenesis at the initiation, promotion, and progression stages in different animal models. The anti-proliferative effects of tea polyphenols may be a key mechanism, especially in the NNK-induced lung tumorigenesis model with mice. Studies with cell lines have demonstrated that tea polyphenols inhibit cell proliferation and induce apoptosis. The effective concentrations used in these studies (20-100 microM) are usually higher than those observed in blood and tissues of humans and animals, which are in the low micromolar range. Glucuronide and sulfate conjugated and methylated catechins as well as ring fission products (due to intestinal microflora) have been observed in human plasma and urine. Purified green and black tea polyphenols inhibited the H-ras induced milogen-activated protein kinases, AP-1 activities, and the growth of 30.7b Ras 12 and BES21 cells. Among the catechins, both the galloyl structure on the B ring and the gallate moiety are important for the inhibition. Both (-)-epigallocatechin-3-gallate and theaflavin-3,3'-digallate inhibited the phosphorylation of c-jun and p44/42 (ERK 1/2). More mechanistic and human studies in these areas will help us to understand the possible inhibitory action of tea against carcinogenesis in humans.

Animals↗

PubMed2000

Mecamylamine prevents tolerance but enhances whole brain [3H]epibatidine binding in response to repeated nicotine administration in rats.

RATIONALE: Chronic administration of nicotine in rats results in upregulation of neuronal nicotinic receptors. Upregulation has been proposed to reflect receptor desensitization, which may underlie functional tolerance to nicotine's effects. However, evidence indicates that tolerance and upregulation do not always parallel each other, suggesting that either upregulation does not always reflect desensitization, or mechanisms other than receptor desensitization account for tolerance to nicotine. OBJECTIVES: The present studies examined tolerance to nicotine-induced antinociception and changes in receptor binding after two regimens of intermittent nicotine injections in rats. The role of receptor activation in upregulation and tolerance was also examined by co-administering nicotine with the non-competitive antagonist, mecamylamine. METHODS: Sprague-Dawley rats were administered a short (once-daily, s.c. for 6 days (0.35 mg/kg)) or long (twice-daily for 11 days (0.66 mg/kg)) series of injections and tolerance to nicotine-induced antinociception and [3H]epibatidine binding in whole brain were measured. RESULTS: The short series of injections resulted in tolerance to nicotine-induced antinociception, but failed to increase [3H]epibatidine binding. In contrast, the long series of injections resulted in both tolerance and increased receptor binding. Once-daily pairings of mecamylamine (1 mg/kg, s.c.) with nicotine (0.35 mg/kg) for 6 days blocked the development of tolerance, indicating receptor activation is necessary for tolerance to occur. Pairing mecamylamine with nicotine (0.66 mg/kg) twice daily for 11 days blocked tolerance but produced a greater increase in [3H]epibatidine binding than nicotine alone. CONCLUSIONS: A dissociation of tolerance from receptor upregulation was observed in the present study. The finding that receptor activation may be necessary for tolerance but not upregulation is discussed within the context of possible mechanisms controlling tolerance to nicotine.

Animals↗

PubMed2000

An arachnoid granulation in the straight sinus.

We report CT, MRI and angiographic findings of an arachnoid granulation in the straight sinus in a young man. Its density and signal intensity were isodense and isointense with cerebrospinal fluid on CT and MRI, respectively. The lesion appeared as a filling defect on MR venography and conventional angiography.

Adult↗

PubMed2000

Intra-articular regional migratory osteoporosis of the knee.

We report a case of intra-articular regional migratory osteoporosis of the knee in a 53-year-old man. The case demonstrates an unusual pattern of migration of the marrow edema within the knee joint. This phenomenon has received scant attention in the radiological literature.

Analgesics↗

PubMed2000

The C677T mutation in the methylene tetrahydrofolate reductase gene increases serum uric acid in elderly men.

A common mutation, C677T, in the methylene tetrahydrofolate reductase gene (MTHFR) reduces the activity of MTHFR and increases total homocysteine levels in plasma. Increased homocysteine levels are reportedly associated with high serum uric acid levels. The relationship between the MTHFR mutation and uric acid metabolism remains unclear, however. To investigate whether the C677T MTHFR mutation is a risk factor for hyperuricemia, we performed MTHFR genotyping and clinical laboratory determinations, including serum uric acid, in 271 elderly Japanese men (age range, 40-79 years; mean, 52.6 years). The mean uric acid levels for the C/C, C/T, and T/T genotypes were 5.67, 6.00, and 6.39 mg/dl, respectively (P = 0.012). The T/T genotype was more frequent in subjects with high uric acid levels than in those with low uric acid levels (P = 0.038). These findings suggest that the C677T MTHFR mutation contributed to higher uric acid levels in subjects enrolled in this study. In conclusion, the mutation of the MTHFR gene may be a risk factor for hyperuricemia in elderly men.

Adult↗

PubMed2000

Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia.

Previous studies have suggested that an abnormality in neuronal nicotinic acetylcholine receptor expression or function may be involved in the neuropathophysiology of schizophrenia. [(3)H]-nicotine and [(3)H]-epibatidine binding were compared in postmortem brain from control and schizophrenic subjects with varying smoking histories. In control subjects, increased receptor binding was seen in hippocampus, cortex, and caudate with increasing tobacco use. In contrast, schizophrenic smokers had reduced nicotinic receptor levels in these brain regions compared to control smokers. Chronic haloperidol and nicotine treatment, in the rat, was used to assess neuroleptic effects on receptor up-regulation by nicotine. A significant increase in cortical nicotinic receptors was seen in both nicotine treated as well as haloperidol and nicotine co-treated animals, suggesting that the abnormal regulation of high affinity neuronal nicotinic receptors in schizophrenics following nicotine use was not related to chronic neuroleptic treatment.

Aconitine↗

PubMed2000

Mathematical modelling of insect neuropeptide potencies. Are quantitatively predictive models possible?

The potencies of natural adipokinetic hormones and synthetic variants have been determined in Locusta migratoria using the lipid mobilisation assay in vivo, and/or the acetate uptake assay in vitro. These data are combinations of previously published and unpublished data (a total of sixty-nine analogues), and form data sets for the construction of mathematical models of the hormone potencies. The sequence variations of amino acids in both natural and artificial adipokinetic hormone analogues were described using continuous descriptor scales z(1)', z(2)', and z(3)', each previously published scale being derived from various properties of the amino acids. By means of these z'-scales and partial least squares regression we attempted to model the potencies in Locusta migratoria of adipokinetic hormones in the two assays. Correlations (r(2) values) between predicted and actual potencies of the different peptides were up to 0.73. We discuss the potential of the partial least squares method for formulating quantitative relationships between different hormone structures and their potencies, and describe how the procedure might be used in structure-activity prediction with the construction of an optimised peptide data set.

Amino Acid Sequence↗

PubMed2000

Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion.

Tea is a popular beverage consumed worldwide. The metabolic fate of its major constituents, catechins, however, is not well-known. In this study, two catechin metabolites were detected in the urine and plasma of human volunteers after ingestion of green tea. These metabolites were identified by LC/ESI-MS and NMR as (-)-5-(3',4', 5'-trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3', 4'-dihydroxyphenyl)-gamma-valerolactone (M6). The renal excretion of M4 and M6 had a 3 h lag time and peaked 7.5-13.5 h after ingestion of a single dose of green tea, while (-)-epigallocatechin (EGC) and (-)-epicatechin peaked at 2 h. M4 and M6 were two major tea metabolites with urinary cumulative excretions as high as 8-25 times the levels of EGC and (-)-epicatechin in some of our subjects, and accounted for 6-39% of the amounts of ingested EGC and (-)-epicatechin. Both the metabolites appeared to be produced by intestinal microorganisms, with EGC and (-)-epicatechin as the precursors of M4 and M6, respectively. Repeated ingestion of green tea produced a slight accumulative effect of the metabolites. They were also detected in the plasma, exhibiting kinetics similar to those of the urinary metabolites, and in the feces. Study on these metabolites may help us further understand the cancer chemopreventive actions and other beneficial effects of tea.

Adult↗

PubMed2000

Transfusion-dependent congenital dyserythropoietic anaemia with intraerythroblastic inclusions of a non-globin protein.

The congenital forms of dyserythropoiesis comprise a group of hereditary disorders characterized by ineffective erythropoiesis as the predominant mechanism of anaemia and morphologically abnormal erythroblasts. Up to now three major forms and four variants have been described. Group VII is characterized by dyserythropoiesis with intraerythroblastic precipitation of a non-globin protein. Here we described a case of dyserythropoietic anaemia presenting neonatally and requiring regular blood transfusions. Optical and electronic microscopy studies confirmed that this case was very similar to those in two previously reported transfusion-dependent patients with an unusual type of congenital dyserythropoietic anaemia.

Anemia, Dyserythropoietic, Congenital↗

PubMed2000

Expression of cyclin D1, cyclin E, cdk4 and loss of heterozygosity of 8p, 13q, 17p in hepatocellular carcinoma: comparison study of childhood and adult hepatocellular carcinoma.

AIMS/BACKGROUND: In hepatitis B virus-related hepatocellular carcinoma (HCC), at least 20-40 years of continuous necro-inflammation is necessary for the hepato-carcinogenesis to occur. However, HCC in childhood shows an unusually short latent period and rapid progression. In our previous report, mutation of c-met was found only in childhood HCC, but not in adult HCC. In order to determine the specific biological tumorous features of childhood HCC, a comparison study of childhood and adult HCC was performed. METHODS: Eighteen cases of HBV positive HCC (nine children and nine adults aged more than 40 years) were selected. The expression of G1 phase regulatory proteins (cyclin D1, cyclin E and cdk4) was studied using immunohistochemical methods. Loss of heterozygosity (LOH) on chromosomal arms 8p, 13q and 17p was analyzed. RESULTS: Cyclin D1 expression was significantly lower in childhood HCC than in adult HCC (cases of cyclin D1 expression under 3+: childhood 5/9 vs. adult 1/9, p=0.046). No difference in cyclin E and cdk4 expression was found between childhood and adult HCC. LOH frequency on 13q was relatively higher in childhood than in adult HCC (66.7% vs. 22.2%, p=0.058). LOH frequency on 8p and 17p was 44.4% and 33.3% in childhood HCC and 44.4% and 75% in adult HCC with no statistical significance between the two groups. CONCLUSION: Our data suggest that childhood HCC may be less dependent on cyclin D1 protein for tumor growth and progression than adult HCC, and that the LOH on 13q may be an important feature of childhood HCC.

Adolescent↗

PubMed2000

Cadmium blocks hypoxia-inducible factor (HIF)-1-mediated response to hypoxia by stimulating the proteasome-dependent degradation of HIF-1alpha.

Cadmium is a substantial industrial and environmental pollutant which seriously impairs erythropoiesis. Cd has been demonstrated to aggravate anemia by suppressing erythropoietin gene expression in anemic patients. As hypoxic induction of erythropoietin mRNA depends on a transcription factor, hypoxia-inducible factor 1 (HIF-1), we hypothesized that Cd suppresses the hypoxic activation of HIF-1. In hypoxic Hep3B cells, all mRNAs of various genes, which are known to be upregulated by HIF-1 activation under hypoxia, were suppressed by Cd in a dose-dependent manner. Cd inhibited the hypoxia-induced activity of luciferase in 293 cells which was transfected with a reporter plasmid carrying a hypoxia response element. By electrophoretic mobility gel shift assay, Cd inhibited the DNA-binding activity of HIF-1 in hypoxic Hep3B cells. Cd reduced the amount of HIF-1alpha protein in hypoxia, whereas it didn't affect HIF-1 alpha mRNA levels. Moreover, Cd inhibited HIF-1alpha accumulation induced by cobalt and desferrioxamine. Antioxidants and a proteasome inhibitor prevented the HIF-1alpha degradation caused by Cd. The possibility that oxidative stress mediates this action of Cd was examined. Cd didn't affect protein oxidation and reduced glutathione levels in hypoxic cells. These results indicate that Cd triggers a redox/proteasome-dependent degradation of HIF-1alpha protein, reducing HIF-1 activity and in turn suppressing the hypoxic induction of hypoxia-inducible genes.

Cadmium↗

PubMed2000

Effects of various implant materials on regeneration of calvarial defects in rats.

The purpose of the present study was to determine the best implant material, the best conditions to substitute absorbable membrane for non-absorbable membrane, and the factors influencing guided regeneration of critical size defects using experimental rats. An 8-mm circular transosseous calvarial bony defect was made and implant materials, such as demineralized freeze-dried bone (DFDB), absorbable membrane (BioMesh; Samyang Co., Seoul Korea), non-absorbable membrane (Millipore filter; Micro Filtration System, MA, USA) or a combination of these materials, was placed on the defect. As for the results of sequential time-based guided bone regeneration, histological, histochemical, immunohistochemical and histomorphometric aspects were observed, and a statistical comparative analysis was performed, with control group of a soft tissue flap. Bone formation was significantly enhanced when DFDB was retained within the defect with a protective absorbable membrane. Inframembranous DFDB-filling was required to prevent membrane collapse and to preserve spaces for bone regeneration. The absorbable membrane which was recommended to overcome the disadvantages of the non-absorbable membrane should remain intact for more than 5 weeks in order for it to be effective. The macrophages recruited by grafts were involved partly in decreasing bone regeneration via the sequential events of releasing fibronectin, and in chemotactic effect of the fibronectin to fibroblasts and collagen lay-down. Thus, the activity of new bone formation was dependent upon the physical barrier effect of the membrane, such as the preserving ability to secure spaces and the suppression ability of early infiltration of collagen and epithelium, inducible ability of inflammation by the implant material, and potential in guiding bone regeneration of the grafts.

Animals↗

PubMed2000

Early prenatal ultrasound diagnosis of cleidocranial dysplasia.

A woman was referred in the first trimester of her third pregnancy because of a family history of cleidocranial dysplasia. An ultrasound examination at 14 weeks 4 days revealed a fetus with appropriate biometric measurements. However, the clavicles were noted to be hypoplastic and the cranium appeared less well ossified than expected for gestational age, suggesting the diagnosis of cleidocranial dysplasia. On subsequent examination at 21 weeks, the findings were essentially unchanged. Induced vaginal delivery owing to decreased amniotic fluid volume occurred at 37 weeks, and a female weighing 3200 g was delivered. The infant had clinical and X-ray signs of cleidocranial dysplasia.

Adult↗

PubMed2000

Diagnostic accuracy of magnetic resonance cholangiopancreatography and ultrasound compared with direct cholangiography in the detection of choledocholithiasis.

AIM: To determine the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) and trans-abdominal ultrasound in the detection of choledocholithiasis, and to compare bile duct stone characteristics using endoscopic retrograde cholangiopancreatography (ERCP), MRCP and ultrasound. MATERIALS AND METHODS: Of 191 consecutive patients referred for diagnostic ERCP, choledocholithiasis was diagnosed in 34 patients using direct cholangiography. The latter took the form of ERCP (n = 29), intraoperative cholangiography (n = 3) or percutaneous transhepatic cholangiography (n = 2). All patients underwent MRCP and ultrasound examinations and their findings for choledocholitiasis were compared with those at direct cholangiography. Finally, in the 29 patients with choledocholithiasis diagnosed under ERCP, stone characteristics were compared across the three investigations of ERCP, MRCP and ultrasound. RESULTS: Compared with direct cholangiography, MRCP showed a sensitivity, specificity and diagnostic accuracy of 91%, 98% and 97%, respectively, in the diagnosis of choledocholithiasis. MRCP resulted in three false-negative and three false-positive findings, four of which occurred due to confusion with lesions at the ampulla. Ultrasound showed a sensitivity, specificity and diagnostic accuracy of 38%, 100% and 89%, respectively, in the diagnosis of choledocholithiasis. ERCP revealed a greater number of stones and these were more proximally distributed within the bile ducts when compared to MRCP. CONCLUSIONS: MRCP is highly accurate in the diagnosis of choloedocholithiasis and has the potential to replace diagnostic ERCP. MRCP underestimates the number of bile duct stones present.

Adult↗

PubMed2000

Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma.

Chlamydia pneumoniae is commonly detected in atherosclerotic plaque but the frequency of detection in non-cardiovascular (CV) tissues has not been well determined. In this study, archival autopsy tissue specimens from both CV and non-CV sites from 38 patients were tested by polymerase chain reaction and immunocytochemistry to detect C. pneumoniae. In addition, 33 surgical granuloma biopsy specimens were also tested. C. pneumoniae was detected most frequently in coronary artery tissue (34%) but was also detected in specimens from lung (13%), liver (10%), spleen (5%), bone marrow (10%), and lymph node (8%). The organism was detected in 3 of 33 granuloma specimens. These findings suggest that C. pneumoniae demonstrates a tropism for CV tissues and is either not widely distributed to non-CV tissues or does not persist chronically in those tissues after initial infection.

Arteries↗

PubMed2000

Genomic organization, expression, and chromosome localization of a third aurora-related kinase gene, Aie1.

We previously reported two novel testis-specific serine/threonine kinases, Aie1 (mouse) and AIE2 (human), that share high amino acid identities with the kinase domains of fly aurora and yeast Ipl1. Here, we report the entire intron-exon organization of the Aie1 gene and analyze the expression patterns of Aie1 mRNA during testis development. The mouse Aie1 gene spans approximately 14 kb and contains seven exons. The sequences of the exon-intron boundaries of the Aie1 gene conform to the consensus sequences (GT/AG) of the splicing donor and acceptor sites of most eukaryotic genes. Comparative genomic sequencing revealed that the gene structure is highly conserved between mouse Aie1 and human AIE2. However, much less homology was found in the sequence outside the kinase-coding domains. The Aie1 locus was mapped to mouse chromosome 7A2-A3 by fluorescent in situ hybridization. Northern blot analysis indicates that Aie1 mRNA likely is expressed at a low level on day 14 and reaches its plateau on day 21 in the developing postnatal testis. RNA in situ hybridization indicated that the expression of the Aie1 transcript was restricted to meiotically active germ cells, with the highest levels detected in spermatocytes at the late pachytene stage. These findings suggest that Aie1 plays a role in spermatogenesis.

Amino Acid Sequence↗