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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 487 records · Page 27Linked to original sources
PubMed2000

Cyclosporine impairs the guanylyl cyclase activity of the natriuretic peptide receptor in the glomerulus.

In order to elucidate the involvement of the atrial natriuretic peptide (ANP) and its receptor (natriuretic peptide receptor; NPR) system in cyclosporine-induced nephrotoxicity, we investigated the cyclosporine A (CsA)-induced changes in characteristics of the NPR/guanylyl cyclase system in the glomerulus and inner medulla of the rat kidney. CsA was administered intramuscularly to rats for 2 weeks (CsA group). Particulate guanylyl cyclase activity was measured in glomerular and inner medullary membranes. For receptor characteristics, quantitative in vitro receptor autoradiography was performed. The guanylyl cyclase activity in the glomerulus from the CsA group was attenuated compared with that from the control. However, the activity in the inner medulla was not affected by CsA treatment. Direct application of CsA to normal glomerular membrane completely abolished the ANP-induced guanylyl cyclase activation. Binding studies, using(125)I-ANP, revealed that B(max)was decreased in the CsA group, while K(d)was not affected in the glomerulus. However, in the inner medulla, neither B(max)nor K(d)was affected by CsA treatment. CsA did not displace the(125)I-ANP bindings to NPRs in the normal rat kidney. Local tissue ANP as well as plasma ANP concentration in both groups was not significantly different. These results indicate that CsA impairs the guanylyl cyclase activity mainly in the glomerulus by the decrease in NPR population and/or by direct inhibition, suggesting that the ANP/NPR system might be involved in CsA-induced nephrotoxicity.

Animals↗
PubMed2000

New aspects of integrin signaling in cancer.

Members of the integrin family of cell adhesion receptors influence several important aspects of cancer cell behavior, including motility and invasiveness, cell growth, and cell survival. Engagement of integrins with extracellular matrix (ECM) proteins can activate members of the Rho-family of small GTPases; conversely, Rho- and Ras-family proteins can influence the ability of integrins to bind their ligands. These events impinge on the control of cell motility, and ultimately on invasive and metastatic behavior. Integrin engagement with ECM also has important effects on cell survival, particularly for cells of epithelial origin. In some cases, specific integrins have selective effects on the efficiency of signal transduction in cell survival pathways.

Animals↗
PubMed2000

Characterization of the pcbE gene encoding 2-hydroxypenta-2,4-dienoate hydratase in Pseudomonas sp. DJ-12.

Nucleotide sequence extending 2,3-dihydroxybiphenyl 1,2-dioxygenase gene (pcbC) and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase gene (pcbD) of Pseudomonas sp. DJ-12 was previously analyzed and the two genes were present in the order of pcbD-pcbC preceded by a promoter from Pseudomonas sp. DJ-12. In this study, a 3.8-kb nucleotide sequence located downstream of the pcbC gene was analyzed to have three open reading frames (ORFs) that are designated as orf1, pcbE and orf2 genes. All of the ORFs were preceded by each ribosome-binding sequence of 5-GGAXA-3 (X=G or A). However, no promoter-like sequence and transcription terminator sequence were found in the analyzed region, downstream of pcbC gene. Therefore, the gene cluster appeared to be present in the order of pcbD-pcbC-orf1-pcbE-orf2 as an operon, which is unique organization characterized so far in biphenyl- and PCB-degrading bacteria. The orf1 gene was composed of 1,224 base pairs which can encode a polypeptide of molecular weight 44,950 containing 405 amino acid residues. A deduced amino acid sequence of the orf1 gene product exhibited 21-33% identity with those of indole dioxygenase and phenol hydroxylase components. The pcbE gene was composed of 783 base pairs encoding 2-hydroxypenta-2,4-dienoate hydratase involved in the 4-chlorobiphenyl catabolism. The orf2 gene was composed of 1,017 base pairs encoding a polypeptide of molecular weight 37,378 containing 338 amino acid residues. A deduced amino acid sequence of the orf2 gene product exhibited 31% identity with that of a nitrilotriacetate monooxygenase component.

Amino Acid Sequence↗
PubMed2000

Epidural naloxone reduces pruritus and nausea without affecting analgesia by epidural morphine in bupivacaine.

PURPOSE: To determine whether epidural naloxone preserved analgesia while minimizing side effects caused by epidural morphine. METHODS: Eighty patients undergoing combined epidural and general anesthesia for hysterectomy were randomly assigned to one of four groups. All received 2 mg epidural morphine bolus one hour before the end of surgery and a continuous epidural infusion was started containing 4 mg morphine in 100 ml bupivacaine 0.125% with either no naloxone (Group 1, n = 20), 0.083 microg x kg(-1) x hr(-1) of naloxone (Group 2, n = 20), 0.125 microg x kg(-1) x hr(-1) of naloxone (Group 3, n = 20) or 0.167 microg x kg(-1) x hr(-1) of naloxone (Group 4, n = 20). Analgesia and side effects were evaluated by blinded observers. RESULTS: The combination of epidural morphine and bupivacaine provided good analgesia. Eight hours after the end of surgery, the pain score in the group receiving the highest dose of naloxone was lower than in the control group (VAS 1.2 vs. 2.0, P<0.05) but there was less pruritus in the high-dose naloxone group (itching score 1.3 vs. 1.9, P<0.05). Pain scores were no different in any of the naloxone groups from the control group. Itching was less in both of the higher dose naloxone groups (P<0.05 at 8, 16, and 32 hours). The incidence of vomiting in the control group was 40% vs. 5% for high dose naloxone group (P<0.05). CONCLUSIONS: Epidural naloxone reduced morphine-induced side effects in dose-dependent fashion without reversal of the analgesic effect.

Adult↗
PubMed2000

Dosimetry of rhenium-188 diethylene triamine penta-acetic acid for endovascular intra-balloon brachytherapy after coronary angioplasty.

To examine the possibility of using rhenium-188 diethylene triamine penta-acetic acid (DTPA) for endovascular intra-balloon brachytherapy after angioplasty, dose distribution around the balloon was calculated and validated by film dosimetry. Medical internal radiation dosimetry (MIRD) was calculated assuming that the balloon had ruptured and that the contents had been released into the systemic circulation. 188Re-perrhenate eluate from the 188W/188Re generator was concentrated using an ion column and used to label DTPA. The dose distribution around the angioplasty balloon (20 mm length, 3 mm diameter cylinder) was estimated by Monte Carlo simulation using the EGS4 code. The time required for 17.6 Gy to be absorbed at 1 mm from the balloon's surface following application of 3700 MBq/ml of 188Re was found to be 278 s. Fifty percent of the energy was deposited in the first millimetre of the vessel wall from the balloon's surface. The calculated radiation absorbed dose agreed with that measured by film dosimetry, which was performed using a water phantom, with errors ranging from 9.4% to 17%. Upon balloon rupture the total amount of 188Re-DTPA was presumed to enter the systemic circulation. The resulting radiation absorbed dose was calculated using the MIRDOSE3 program and residence times obtained from dogs and amounted to 0.0056 mGy/MBq to the whole body and 4.56 mGy/MBq to the urinary bladder. The absorbed dose of 188Re-DTPA to the whole body was one-tenth of that of 188Re-perrhenate. A window-based program was developed to calculate the exposure time and the radiation dose absorbed as a function of the 188Re concentration and the arbitrary distance from the balloon to the surrounding tissues. We conclude that 188Re-DTPA is easy to prepare, safe to use and suitable for intra-balloon brachytherapy after coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed2000

Metabolism of chloramphenicol succinate in human bone marrow.

OBJECTIVE/METHODS: The metabolism of chloramphenicol succinate (CAPS) by human bone marrow was studied in vitro using 75 marrow samples. Whole marrow samples were incubated with CAPS with or without reduced nicotinamide adenine dinucleotide phosphate for 1, 2 and 3 h at 37 degrees C. Ficoll-paque-separated marrow mononuclear cells and erythrocytes were similarly incubated. After precipitation and centrifugation, clear supernatant was analysed for the presence of metabolites using high-performance liquid chromatography. RESULTS: Only one metabolite was detected when CAPS was incubated for 3 h with whole marrow from 72 donors. Its retention time (RT 10.9 min) corresponded to chloramphenicol (CAP). When CAPS was incubated with samples of whole marrow, marrow mononuclear cells, marrow erythrocytes, marrow plasma and peripheral blood from one donor who had taken Traditional Chinese Medicine (TCM), three metabolite peaks were detected within 15 min to 1 h. The RT of two of these peaks corresponded to CAP and nitroso-CAP (RT 14.9 min), but one peak remained unidentified. These peaks were not detected in the control samples incubated without CAPS. Blood samples collected after 3 months and 6 months to reconfirm metabolic activity yielded no such metabolite peaks when incubated with CAPS for 1-3 h. Therefore induction of enzyme activity by TCM was suspected. Three metabolite peaks with the same RTs were also detected when CAPS was incubated for 3 h with whole marrow from two other donors. CONCLUSION: These studies demonstrated that CAPS may be metabolised to CAP and occasionally other metabolites in human bone marrow. This novel observation is particularly important because the bone marrow is known to be a target organ for chloramphenicol toxicity.

Bone Marrow↗
PubMed2000

Analysis of single-nucleotide polymorphisms in the interleukin-4 receptor gene for association with inflammatory bowel disease.

Genetic linkage analysis in families with multiple cases of inflammatory bowel disease (IBD) has mapped a gene which confers susceptibility to IBD to the pericentromeric region of chromosome 16 (IBD1). The linked region includes the interleukin(IL)-4 receptor gene (IL4R). Since IL-4 regulation and expression are abnormal in IBD, the IL4R gene is thus both a positional and functional candidate for IBD1. We screened the gene for single-nucleotide polymorphisms (SNPs) by fluorescent chemical cleavage analysis, and tested a subset of known and novel SNPs for allelic association with IBD in 355 families, which included 435 cases of Crohn's disease and 329 cases of ulcerative colitis. No association was observed between a haplotype of four SNPs (val50ile, gln576arg, A3044G, G3289A) and either the Crohn's disease or ulcerative colitis phenotypes using the transmission disequilibrium test. There was also no evidence for association when the four markers were analyzed individually. The results indicate that these variants are not significant genetic determinants of IBD, and that the IL4R gene is unlikely to be IBD1. Linkage disequilibrium analyses showed that the val50ile and gln576arg variants are in complete equilibrium with each other, although they are separated by only about 21 kilobases of genomic DNA. This suggests that a very dense SNP map may be required to exclude or detect disease associations with some candidate genes.

Alleles↗
PubMed2000

The cyanobacterial origin and vertical transmission of the plastid tRNA(Leu) group-I intron.

We have surveyed the distribution and reconstructed the phylogeny of the group-I intron that is positioned in the anticodon loop of the tRNA(Leu) gene in cyanobacteria and several plastid genomes. Southern-blot and PCR analyses showed that the tRNA(Leu) intron is found in all 330 land plants that were examined. The intron was also found, and sequenced, in all but one of nine charophycean algae examined. Conversely, PCR analyses showed that the tRNA(Leu) group-I intron is absent from the red, cryptophyte and haptophyte algae, although it is present in three members of the heterokont lineage. Phylogenetic analyses of the intron indicate that it was present in the cyanobacterial ancestor of the three primary plastid lineages, the Rhodophyta, Chlorophyta, and Glaucocystophyta. Its present-day distribution in plastids is consistent with a history of strictly vertical transmission, with no losses in land plants, several losses among green algae, and nearly pervasive loss in the Rhodophyta and its secondary derivatives.

Anticodon↗
PubMed2000

Inhibition of apamin-sensitive K+ current by hypoxia in adult rat adrenal chromaffin cells.

The effect of hypoxia on small-conductance Ca(2+)-activated K+ current was investigated in a study of adult rat adrenomedullary chromaffin cells (AMCs), which were maintained in short-term culture. The nystatin-perforated, whole-cell patchclamp technique was used to study the effect of hypoxia with minimum perturbation of the intracellular milieu. Under voltage-clamp conditions, acute hypoxia (P(O2) approximately equal to 25 mmHg) suppressed the whole-cell outward currents of more than half the AMCs (24/46). This suppression was eliminated after application of apamin (400 nM), a selective inhibitor of small-conductance Ca(2+)-activated K+ current (I(SK)(Ca)) (n=5), suggesting that an apamin-sensitive component of whole-cell currents is suppressed during hypoxia. In contrast to I(SK)(Ca), Ca2+ current (I(Ca)) (n=10) was not affected by hypoxia. Finally, under current-clamp conditions, hypoxia reversibly depolarized the resting membrane potential of adult AMCs (34/40). Apamin, however, eliminated the hypoxia-induced depolarization (400 nM) (7/8), suggesting that hypoxic depolarization is related to the suppression of I(SK(Ca). From the above results, we conclude that adult AMCs are sensitive to hypoxia, and that I(SK)(Ca) contributes to the hypoxia-induced suppression of whole-cell outward current and depolarization of the resting membrane potential in adult AMCs.

Adrenal Medulla↗
PubMed2000

A ganglion cyst causing lumbar radiculopathy in a baseball pitcher: a case report.

This report describes a case of a professional baseball pitcher who developed acute left lumbar radicular symptoms after a baseball game and was subsequently sidelined for the rest of the season. Physical examination revealed depressed reflexes in the left posterior tibialis and left medial hamstring muscles, mild weakness in the left extensor hallucis longus, and positive dural tension signs. Magnetic resonance imaging demonstrated an ovoid mass at the L4-L5 level, causing compression of the dura. Surgical resection of the mass resulted in resolution of his symptoms. Pathology revealed that the mass was a ganglion cyst. A ganglion cyst is a rare cause of lumbar radiculopathy and should be considered in the differential diagnosis if a patient with lumbar radiculopathy fails to respond to conservative treatment.

Adult↗
PubMed2000

Theoretical studies of the response of a protein structure to cavity-creating mutations.

We have investigated the response of a protein structure to cavity-creating mutations by molecular dynamics (MD) simulations for the wild-type and the five mutants of phage T4 lysozyme. Essential dynamics (ED) analysis and the methods for calculating different components of local interaction energies are used to examine the structural and energetic characteristics associated with the mutations. In agreement with the x-ray results, it is found that the structural changes due to the replacements of a bulky side chain such as Leu or Phe with Ala within the hydrophobic core can be characterized as slight adjustments rather than substantial reorganization of the protein. The relative stability of different mutant structures can be related with the extent of structural readjustments in response to the mutation. The destabilization of the mutant Leu-->Ala proteins relative to the wild-type is closely related with the loss of van der Waals contacts due to the cavity-creating mutations.

Amino Acid Substitution↗
PubMed2000

Serodiagnosis of amoebiasis using a recombinant protein fragment of the 29 kDa surface antigen of Entamoeba histolytica.

To develop an improved serodiagnostic test for amoebiasis, we performed a detailed analysis of the immunodominant epitopes of the 29 kDa surface antigen and evaluated its sensitivity and specificity. Enzyme-linked immunosorbent assay (ELISA) based on the fragment containing the immunodominant epitope was evaluated further and compared with full-length recombinant 29 kDa protein. Specificity and sensitivity of the two ELISAs were assessed using 55 human sera of parasitic protozoa infection cases (25 amoebiasis, 20 giardiasis and 10 toxoplasmosis sera) and 10 healthy control sera. The immunodominant epitope of the 29 kDa antigen is localised only in the N-terminus 14-54 amino acid residues. The sensitivities of the two ELISAs were very high, 92 and 96%, respectively. The specificity of the fragment was 100%, whereas the specificity of the full-length 29 kDa protein was 86.6%. These results indicate that the fragment containing the immunodominant epitope of the 29 kDa protein can be used to accurately serodiagnose amoebiasis without cross-reactivity from other parasites.

Amebiasis↗