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Biomedical subjects

T Lee

Publications and source records attributed to T Lee.

At least 37 records · Page 2Linked to original sources
PubMed2003

Electrical characterization of metal-molecule-silicon junctions.

Direct assembly of molecules onto silicon surfaces is of particular interest for potential employment in hybrid organic-semiconductor devices. In the study we report here, aryl diazonium salts were used to assemble covalently bound molecular groups on a hydride-passivated, oxide-free n-type Si(111) surface. The reaction of 4-(trimethylsilylethynyl)benzenediazonium tetrafluoroborate generates a molecular layer of 4-(trimethylsilylethynyl)phenylene (TMS-EP) on the n++-Si(111) surface. The monolayer modifies the electrical properties of the interface and exhibits nonlinear current-voltage characteristics, as compared with the ohmic behavior observed from metal-n++-Si(111) junctions. The result of current-voltage measurements at variable temperatures (from 300 to 10 K) on samples made with the TMS-EP molecule does not show significant thermally-activated transport, indicating that tunneling is the dominant transport mechanism. The measured data is compared to a tunneling model.

Electric Conductivity↗
PubMed2002

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗
PubMed2002

Investigation of bovine bone by resonant ultrasound spectroscopy and transmission ultrasound.

The method of resonant ultrasonic spectroscopy (RUS) was evaluated for bovine bone and compared with the traditional wave transmission ultrasound method. In RUS, the resonance structure of a cubic or rectangular specimen is scanned. For some low-damping materials, a single measurement yields sufficient resonant frequencies to determine all of the anisotropic elastic constants. Bone has a high viscoelastic damping at ultrasonic frequency. Consequently, resonance peaks of a cubic specimen tend to overlap. Therefore, the usual RUS method must be modified for application to bone; even so, one cannot obtain all the elastic constants. Concurrent studies with transmission ultrasound were conducted. Results were used to generate a map of the elastic moduli vs position along the bone axis. Stiffness was greatest in the mid part of the bovine femur.

Animals↗
PubMed2002

Familial aggregation of Barrett's oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults.

BACKGROUND: Although familial clusters of Barrett's oesophagus and oesophageal adenocarcinoma have been reported, a familial predisposition to these diseases has not been systematically investigated. AIMS: To determine whether Barrett's oesophagus and oesophageal (or oesophagogastric junctional) adenocarcinoma aggregate in families. PATIENTS AND METHODS: A structured questionnaire eliciting details on reflux symptoms, exposure history, and family history was given to Caucasian case (n=58) subjects with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma, and to Caucasian control (n=106) subjects with symptomatic gastro-oesophageal reflux disease without Barrett's oesophagus. Reported diagnoses of family members were confirmed by review of medical records. RESULTS: The presence of a positive family history (that is, first or second degree relative with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma) was significantly higher among case subjects compared with controls (24% v 5%; p<0.005). Case subjects were more likely to be older (p<0.001) and male (74% v 43% male; p<0.0005) compared with control subjects. In a multivariate logistic regression analysis, family history was independently associated with the presence of Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma (odds ratio 12.23, 95% confidence interval 3.34-44.76) after adjusting for age, sex, and the presence of obesity 10 or more years prior to study enrollment. CONCLUSIONS: Individuals with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma are more likely to have a positive family history of Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma than individuals without Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma. A positive family history should be considered when making decisions about screening endoscopy in patients with symptoms of gastro-oesophageal reflux.

Adenocarcinoma↗
PubMed2002

A new top-loading venous bag provides vacuum-assisted venous drainage.

A new venous bag has been developed, prototyped, and tested. The new bag has its inlet, outlet purge, and infusion tubes extending upward from the top of the bag, and are threaded through, bonded to, and sealed within a flat rigid top plate. This design allows the bag to be hung from its top plate by its tubes. It also allows the bag to be: 1) dropped into or removed from its holder, as is done with existing hard-shell reservoirs so that its weight pulls it into the holder without the need for eyelets and hooks and 2) placed closer to the floor so that gravity drainage is facilitated. The V-Bag (VB) is easily sealed within an accompanying rigid housing. Once sealed, vacuum applied to the housing is transmitted across the flexible walls of the bag to the venous blood. Thus, vacuum-assisted venous drainage (VAVD) is obtained as it is with a hard-shell reservoir, but without any contact of air with the blood. Bench tests, using a circuit that simulated the venous side of the cardiopulmonary bypass (CPB) circuit, showed that applying suction to the housing increased venous flow, and the fractional increase in flow was not a function of the venous cannula, but of the level of vacuum applied. In the gravity drainage mode, the bubble counts at the outlet of the V-Bag compared to two other bags were lower at any pumping condition. When used in the VAVD mode, bubble counts were two orders of magnitude lower than when using kinetically assisted venous drainage (KAVD) with a centrifugal pump. Results obtained with the VB suggest its clinical usefulness.

Cardiopulmonary Bypass↗
PubMed2001

Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox.

High molecular weight homologues of gp91phox, the superoxide-generating subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, have been identified in human (h) and Caenorhabditis elegans (Ce), and are termed Duox for "dual oxidase" because they have both a peroxidase homology domain and a gp91phox domain. A topology model predicts that the enzyme will utilize cytosolic NADPH to generate reactive oxygen, but the function of the ecto peroxidase domain was unknown. Ce-Duox1 is expressed in hypodermal cells underlying the cuticle of larval animals. To investigate function, RNA interference (RNAi) was carried out in C. elegans. RNAi animals showed complex phenotypes similar to those described previously in mutations in collagen biosynthesis that are known to affect the cuticle, an extracellular matrix. Electron micrographs showed gross abnormalities in the cuticle of RNAi animals. In cuticle, collagen and other proteins are cross-linked via di- and trityrosine linkages, and these linkages were absent in RNAi animals. The expressed peroxidase domains of both Ce-Duox1 and h-Duox showed peroxidase activity and catalyzed cross-linking of free tyrosine ethyl ester. Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the stabilization of cuticular extracellular matrix.

Amino Acid Sequence↗
PubMed2001

Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type Ca(2+) channels.

T-type Ca(2+) currents have been proposed to be involved in the genesis of spike-and-wave discharges, a sign of absence seizures, but direct evidence in vivo to support this hypothesis has been lacking. To address this question, we generated a null mutation of the alpha(1G) subunit of T-type Ca(2+) channels. The thalamocortical relay neurons of the alpha(1G)-deficient mice lacked the burst mode firing of action potentials, whereas they showed the normal pattern of tonic mode firing. The alpha(1G)-deficient thalamus was specifically resistant to the generation of spike-and-wave discharges in response to GABA(B) receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by alpha(1G) T-type Ca(2+) channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway.

4-Butyrolactone↗
PubMed2001

Plant diversity enhances ecosystem responses to elevated CO2 and nitrogen deposition.

Human actions are causing declines in plant biodiversity, increases in atmospheric CO2 concentrations and increases in nitrogen deposition; however, the interactive effects of these factors on ecosystem processes are unknown. Reduced biodiversity has raised numerous concerns, including the possibility that ecosystem functioning may be affected negatively, which might be particularly important in the face of other global changes. Here we present results of a grassland field experiment in Minnesota, USA, that tests the hypothesis that plant diversity and composition influence the enhancement of biomass and carbon acquisition in ecosystems subjected to elevated atmospheric CO2 concentrations and nitrogen deposition. The study experimentally controlled plant diversity (1, 4, 9 or 16 species), soil nitrogen (unamended versus deposition of 4 g of nitrogen per m2 per yr) and atmospheric CO2 concentrations using free-air CO2 enrichment (ambient, 368 micromol mol-1, versus elevated, 560 micromol mol-1). We found that the enhanced biomass accumulation in response to elevated levels of CO2 or nitrogen, or their combination, is less in species-poor than in species-rich assemblages.

Atmosphere↗
PubMed2001

Modification of inhibitor binding sites in the cytochrome bf complex by directed mutagenesis of cytochrome b(6) in Synechococcus sp. PCC 7002.

The cytochrome bf complex, which links electron transfer from photosystem II to photosystem I in oxygenic photosynthesis, has not been amenable to site-directed mutagenesis in cyanobacteria. Using the cyanobacterium Synechococcus sp. PCC 7002, we have successfully modified the cytochrome b(6) subunit of the cytochrome bf complex. Single amino acid substitutions in cytochrome b(6) at the positions D148, A154, and S159 revealed altered binding of the quinol-oxidation inhibitors 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), myxothiazol, and stigmatellin. Cytochrome bf and mitochondrial-type cytochrome bc(1) complexes are closely related in structure and function but exhibit quite different inhibitor specificities. Cytochrome bf complexes are insensitive to myxothiazol and sensitive to DBMIB, whereas cytochrome bc(1) complexes are sensitive to myxothiazol and relatively insensitive to DBMIB. Measurements of flash-induced and steady-state electron transfer rates through the cytochrome bf complex revealed increased resistance to DBMIB in the mutants A154G and S159A, increased resistance to stigmatellin in A154G, and created sensitivity to myxothiazol in the mutant D148G. Therefore these mutations made the cytochrome bf complex more like the cytochrome bc(1) complex. This work demonstrates that cyanobacteria can be used as effective models to investigate structure-function relationships in the cytochrome bf complex.

Alleles↗
PubMed2001

Extreme damping in composite materials with negative-stiffness inclusions.

When a force deforms an elastic object, practical experience suggests that the resulting displacement will be in the same direction as the force. This property is known as positive stiffness. Less familiar is the concept of negative stiffness, where the deforming force and the resulting displacement are in opposite directions. (Negative stiffness is distinct from negative Poisson's ratio, which refers to the occurrence of lateral expansion upon stretching an object.) Negative stiffness can occur, for example, when the deforming object has stored (or is supplied with) energy. This property is usually unstable, but it has been shown theoretically that inclusions of negative stiffness can be stabilized within a positive-stiffness matrix. Here we describe the experimental realization of this composite approach by embedding negative-stiffness inclusions of ferroelastic vanadium dioxide in a pure tin matrix. The resulting composites exhibit extreme mechanical damping and large anomalies in stiffness, as a consequence of the high local strains that result from the inclusions deforming more than the composite as a whole. Moreover, for certain temperature ranges, the negative-stiffness inclusions are more effective than diamond inclusions for increasing the overall composite stiffness. We expect that such composites could be useful as high damping materials, as stiff structural elements or for actuator-type applications.

Journal Article↗
PubMed2001

Laparoscopic repositioning of a ventriculo-peritoneal catheter tip for a sterile abdominal cerebrospinal fluid (CSF) pseudocyst.

Abdominal cerebrospinal fluid (CSF) pseudocyst is an uncommon but well-described complication that is reported to occur in <1% of ventriculo-peritoneal (VP) shunts. Management options for pseudocysts include various types of shunt revisions, which recently have been conducted laparoscopically. We report the case of an 11-year-old girl in whom a sterile abdominal CSF pseudocyst was successfully fenestrated and the VP catheter repositioned using laparoscopy. This technique in the setting of a noninfected pseudocyst has proven to be safe, with results comparable to the conventional open technique. However, the long-term success rate is still unknown.

Abdomen↗
PubMed2001

Transcriptional activation of p21(WAF1/CIP1) by apicidin, a novel histone deacetylase inhibitor.

Apicidin [cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-l-2-amino-8-oxodecanoyl)], a novel histone deacetylase inhibitor, has been identified as an antiprotozoal and antiproliferative agent. In this study, we show apicidin induces transcriptional activation of p21(WAF1/CIP1) (p21) in human prostate carcinoma cells. Apicidin induces expression of p21 protein and mRNA and activation of p21 promoter-luciferase reporter constructs. Apicidin causes an accumulation of acetylated histones H3 and H4 in total cellular chromatin. Chromatin immunoprecipitation shows p21 promoter DNA is associated with hyperacetylated histones H3 and H4 after treatment with apicidin. Therefore, the data here demonstrate that apicidin activates p21 transcription associated with the acetylation of histones H3 and H4.

Acetylation↗
PubMed2001

Nucleotide sequence and structure of the mouse carbonic anhydrase III gene.

At least 14 distinct isozymes of carbonic anhydrase have been identified in mammals. These enzymes catalyze the hydration of carbon dioxide and are essential for regulation of cellular pH and carbon dioxide transport. Carbonic anhydrase III is highly expressed in certain tissues, including muscle and fat where it constitutes up to 25% of the soluble protein. We cloned a cDNA encoding mouse carbonic anhydrase III. This cDNA contains 1653 bp, consisting of 79 bp in the 5' UTR, a 780 bp open reading frame, and 794 bp of the 3' UTR, including two potential polyadenylation signals. Fluorescent in situ hybridization confirmed the existence of a single copy of the gene on chromosome 3. We then isolated the genomic DNA for mouse carbonic anhydrase III and analyzed its structure. The gene consists of seven exons and six introns which span 10.5 kb. The 5' flanking region of the genomic DNA is notable for a pyrimidine rich region consisting of two dinucleotide repeats containing 23 and 20 TC pairs separated by the same 15 bp spacer.

Amino Acid Sequence↗
PubMed2001

Differential regulation of three catalytic activities of platelet-activating factor (PAF)-dependent transacetylase.

We have previously established that PAF-dependent transacetylase (TA) purified to apparent homogeneity from rat kidney membranes and cytosol contains three separate catalytic activities, namely PAF lysophospholipid transacetylase (TAL), PAF sphingosine transacetylase (TAS), and PAF acetylhydrolase (AH). In the present investigation, we studied the biochemical factors and mechanism(s) that differentially regulate these three TA activities of the purified enzymes. We found that only the TAS activity of the TA purified from the membranes was stimulated by phosphatidyl-serine (PS) with optimal concentration of activation occurring at 25 microM. Other acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylinositol 4-phosphate (PIP), are partially effective, while diacylglycerol and free fatty acids had no effect on the TAS activity. PS exerted its effect on the TAS activity through the increases of both Km and Vmax. In addition, N-ethylmalimide (NEM) and dithiobis-(2-nitro-5-thiobenzoic acid) (DTNB) strongly inhibited the TAS activity and partially decreased the TAL and AH activities of the purified membrane enzyme in a dose-dependent manner. The addition of PS, but not by its substrate, sphingosine, could prevented the inhibition by NEM on the basal level of TAS. On the other hand, the inhibition of TAL by NEM and DTNB were partially protected by the substrate, lysoplasmalogens. Furthermore, PAF fully protects the inhibition of AH, partially protects the inhibition of TAL, and does not protect the inhibition of TAS by NEM. These results suggested that the three individual catalytic activities of TA have different dependencies on the thiol-containing residue(s) of the enzyme, i.e., cysteine. Furthermore, the nonresponsiveness of the purified cytosolic TAS to PS activation is consistent with our previous notions that membrane and cytosolic TA are posttranslationally distinct.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

enok encodes a Drosophila putative histone acetyltransferase required for mushroom body neuroblast proliferation.

Mushroom bodies in the Drosophila brain are centers for olfactory learning and memory. We have previously shown that the mushroom bodies comprise three types of neurons with distinct axonal projections. These three types of neurons are generated sequentially from common neuroblasts. We report here the identification of a gene that we have named enoki mushroom (enok), which when it is mutated gives rise to mushroom bodies with reduced axonal structures. enok encodes a putative histone acetyltransferase (HAT) of the MYST family, members of which have been implicated as important modulators of transcriptional activity. A single amino acid change in the zinc finger motif of the putative catalytic HAT domain gives the same phenotype as a null allele, and this finding indicates the importance of HAT activity to Enok's function. Further phenotypic analysis demonstrates that the mushroom body defect is due to an arrest in neuroblast proliferation rather than a failure of either cell fate switching or axon branching. Clonal analyses in the wing discs and the ovaries suggest that enok is essential for normal cell proliferation in some, but not all, tissues. Our results provide in vivo evidence for essential functions of a histone acetyltransferase in the construction of the Drosophila brain.

Acetyltransferases↗