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Biomedical subjects

K Yu

Publications and source records attributed to K Yu.

At least 145 records · Page 8Linked to original sources
PubMed1993

Visually guided attention is neutralized when informative cues are visible but unperceived.

The ability to voluntarily shift the focus of visual attention away from the focus of gaze was investigated in a novel paradigm designed to elaborate the stages of processing underlying this ability. A basic experimental method used to investigate guided visual attention involves measuring response times to targets presented at positions of which the observer has been informed by an orienting cue. Binocular rivalry was utilized to dissociate presentation of the orienting cue from visual awareness of that cue. The findings indicated that when an informative cue was presented to an eye during the dominance phase, thus reaching visual awareness, manual response times were significantly affected by cue validity. In contrast, when the same cue was presented to an eye during suppression, and thus was not seen by observers, response times were not influenced by cue validity. We conclude that to guide attention, neural signals registering informative visual cues must be processed at stages lying beyond the site of rivalry suppression. Implications for investigating the neural basis of visual attention are discussed.

Attention↗
PubMed1993

The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann-Pick disease type C.

Niemann-Pick disease type C (NP-C) is a neurovisceral lipidosis characterized by defective intracellular trafficking of cholesterol and lysosomal accumulation of unesterified cholesterol, believed to be an offending metabolite. We studied the effect of cholesterol-lowering agents on hepatic and plasma cholesterol levels in NP-C by randomly assigning 25 patients with NP-C to one of five treatment regimens containing different combinations of cholestyramine, lovastatin, nicotinic acid, or dimethyl sulfoxide (DMSO). Unesterified cholesterol content was measured in liver biopsies before and after 4 months' treatment. All drug regimens except DMSO alone reduced hepatic and plasma cholesterol levels. Toxicity was limited and did not prevent any patient from completing the study. The combination of cholestyramine, lovastatin, and nicotinic acid lowered cholesterol levels in liver and blood with minimal side effects. A controlled clinical study will be necessary to determine if this regimen influences the rate of neurologic progression.

Adolescent↗
PubMed1992

Regulation of the cellular stress response by reactive electrophiles. The role of covalent binding and cellular thiols in transcriptional activation of the 70-kilodalton heat shock protein gene by nephrotoxic cysteine conjugates.

The cytotoxicity of nephrotoxic cysteine conjugates (NCC) in the renal epithelial cell line, LLC-PK1, is due to the covalent binding of a reactive electrophilic metabolite produced from NCC metabolism by cysteine conjugate beta-lyase. Covalent binding of NCC-derived reactive metabolites leads to a cascade of events including depletion of cellular non-protein sulfhydryls, increased cytosolic free calcium, and lipid peroxidation, which is ultimately responsible for cell death. We have used this model to investigate the signalling mechanism(s) through which reactive electrophiles increase synthesis of the 70-kD heat shock protein (HSP70). NCC treatment resulted in increased HSP70 synthesis as well as time- and dose-dependent increases in hsp70 mRNA in LLC-PK1 cells. The induction of hsp70 mRNA was blocked by actinomycin D, and nuclear run-on experiments showed that the hsp70 gene was transcriptionally activated. Inhibition of protein synthesis did not block the increase in hsp70 mRNA or transcriptional activation of the hsp70 gene suggesting that induction occurs due to activation of existing transcription factors. Inhibiting the covalent binding with a beta-lyase inhibitor, aminooxyacetic acid, blocked the increase in hsp70 mRNA. Agents which do not alter binding but do prevent toxicity by blocking the rise in cytosolic free calcium and lipid peroxidation were not effective inhibitors of hsp70 mRNA accumulation. However, the thiol reducing agent, dithiothreitol, inhibited induction of hsp70 mRNA by NCC. The data suggest that covalent binding and alterations in cellular non-protein thiols serve as signals for activation of pre-existing transcription factors which increase hsp70 gene expression. It is proposed that reactive electrophiles may have a primary effect on protein conformation resulting in activation of the hsp70 gene.

Aminooxyacetic Acid↗
PubMed1992

Transcriptional regulation of the thrombomodulin gene.

The transcriptional start sites of the endogenous human thrombomodulin (TM) gene and transiently expressed TM promoter/CAT gene constructs were defined by nuclease S1 mapping which showed two closely spaced sites at +1 and +6, respectively. Transient expression and in vitro transcription assays of 5' and internal deletion mutants of the TM promoter/CAT gene constructs reveal that the region from -72 to -29 exhibits a positive acting domain which is essential for transcriptional activity, whereas the region from -373 to -225 possesses two positive acting subdomains, -343 to -277 and -245 to -225, which together augment transcriptional activity by about 40%. Electrophoretic mobility shift assays with a duplex oligonucleotide corresponding to -72 to -29 and DNase I footprinting experiments show two specific interaction products which individually or cooperatively protect the DNA sequence from about -60 to -30. These components are essential for TM gene transcription since affinity fractionation of nuclear extracts with a duplex oligonucleotide corresponding to -72 to -29 depletes the above interaction products and specifically inhibits in vitro transcription activity of the promoter, whereas addition of the eluted components specifically restores in vitro transcription activity of the promoter. Electrophoretic mobility shift assays with duplex oligonucleotides corresponding to -294 to -215, as well as -373 to -295 and DNase I footprinting experiments show two specific interaction products which individually bind to the two subdomains but not -72 to -29 and protect the coding and noncoding strands from -245 to -225, and the noncoding strand from -337 to -314, respectively. Transient expression studies reveal that the TM promoter construct starting at -51 and including the TATA box is responsive to TNF only in cell lines exhibiting sensitivity of the endogenous receptor gene to cytokine, whereas other promoter constructs possessing a TATA box sequence are insensitive to TNF in all cell types. Based upon the above data, the regulatory events involved in TNF-dependent transcriptional regulation of the TM gene can be defined with the experimental tools and conceptual framework developed by the present investigation.

Animals↗
PubMed1992

Activation of the growth arrest and DNA damage-inducible gene gadd 153 by nephrotoxic cysteine conjugates and dithiothreitol.

The cellular and biochemical events which transduce chemical insults into signals for increased expression of the stress-responsive gene gadd 153 were investigated using nephrotoxic cysteine conjugates. In LLC-PK1 cells, cysteine conjugate toxicity is initiated by covalent binding, but depletion of cellular thiols, an increase in cytosolic free calcium, and lipid peroxidation couple the binding to cell death (Chen, Q., Jones, T. W., Brown, P. C., and Stevens, J. L. (1990) J. Biol. Chem. 265, 21603-21611; Chen, Q., Jones, T. W., and Stevens, J. L. (1991) Toxicologist 11, 101, 1991). Three different toxic cysteine conjugates induced gadd 153 mRNA. With S-(1,2-dichlorovinyl)-L-cysteine (DCVC), the induction was both concentration and time-dependent. Preventing the metabolism of DCVC and covalent binding of DCVC-derived reactive metabolites to cellular macromolecules with the beta-lyase inhibitor (aminooxy)acetic acid blocked the induction. However, buffering free calcium with a cell permeable calcium chelator or blocking lipid peroxidation with an antioxidant did not affect the induction of gadd 153 mRNA by DCVC even though these treatments inhibit toxicity. These data suggest that covalent binding of reactive metabolites to cellular macromolecules may serve as a primary signal for the induction of gadd 153 mRNA by nephrotoxic cysteine conjugates. Interestingly, the sulfhydryl agent dithiothreitol, which was nontoxic and prevented the toxicity of DCVC, also induced an increase in gadd 153 mRNA. When both dithiothreitol and DCVC were added to cells, there were no inhibitory or additive effects on expression. Therefore, cellular thiol-disulfide status may also play a role in gadd 153 induction.

Aminooxyacetic Acid↗
PubMed1992

Thrombomodulin gene regulation by cAMP and retinoic acid in F9 embryonal carcinoma cells.

Thrombomodulin (TM) expression was investigated during differentiation of F9 embryonal carcinoma cells into primitive or parietal endoderm. Exposure of F9 cells to retinoic acid (RA) triggers differentiation into primitive endoderm and induces the appearance of barely detectable amounts of TM mRNA, whereas treatment with dibutyryl cAMP plus theophylline (CT) augments the levels of TM mRNA to a 4-fold greater extent than RA. Exposure of F9 cells to RA plus CT initiates differentiation into parietal endoderm and synergistically increases the levels of TM mRNA by 10- to 12-fold compared with CT. The time-dependent establishment of cooperativity between RA and CT appears to be secondary to RA-induced differentiation to primitive endoderm. The above alterations in TM mRNA levels occur by a transcriptional mechanism as judged by nuclear run-on experiments. Transient gene expression experiments show that the human TM promoter is transactivated by coexpression of the human RA receptor beta. Thus, the mechanism of induction of TM expression in F9 cells undergoing differentiation to parietal endoderm appears to be similar, but not identical, to that noted for other late response genes.

Animals↗
PubMed1992

Do recognizable figures enjoy an advantage in binocular rivalry?

Five experiments examined whether recognizable stimuli predominate in binocular rivalry. It was found that a face predominated more than did a pattern equated for spatial frequency, luminance, and contrast; an objective reaction time procedure confirmed predominance of the face. The face was still liable to fragmentation as stimulus size increased. Observers tracked exclusive dominance of a picture of a camouflaged figure (a Dalmatian dog) prior to and then following discovery of the figure's presence; control observers received the same protocol with a scrambled version of the dog stimulus. Compared with control results, predominance of the dog picture was higher even before observers knew of the camouflaged figure. Inversion of the dog figure reduced its predominance. Binocular rivalry is sensitive to object-related, configural properties of a stimulus.

Attention↗
PubMed1992

[Umbilical and maternal amino acid concentrations in appropriate and small for gestational age infants].

Serum amino acid concentrations were determined in 63 pregnant women and their infants at delivery. Samples were obtained from 47 appropriate for gestational age infants (AGA) and 16 small for gestational age infants (SGA). The SGA group had significantly lower concentrations of total amino acid, compared with those of AGA, in both the umbilical and maternal blood. The essential amino acids of the cord, such as isoleucine and threonine, and maternal essential amino acids like threonine and arginine in the SGA group were lower than those in the AGA group. In contrast, nonessential amino acid concentrations, such as alanine, proline and aspartic acid were significantly higher in the umbilical blood of the SGA infants, while there were no differences in the maternal blood of both AGA and SGA groups. There was a positive relationship between maternal and umbilical total amino acid concentrations in the AGA group, but no relationship exists in the SGA group.

Amino Acids↗
PubMed1991

Altered expression of HLA antigens and CD16 Fc receptors on leukocytes of alcoholic subjects and uremic patients.

The possible influences of ethanol and its metabolic product acetate on the surface expression of HLA class I and class II antigens and CD16 Fc receptors were examined. Fluorescent-labeled monoclonal antibodies and flow cytometry were used to measure these antigens on leukocytes from reference controls, subjects admitted for alcohol detoxification, uremic patients undergoing hemodialysis using Cu-prophan dialyzers and fluids containing 4 to 37 mM acetate, and uremic patients that were not hemodialyzed. In comparison to the controls, the mean intensity of staining for class I antigens was not changed significantly on lymphocytes or monocytes from alcoholics but was depressed on cells from eight of 12 uremic patients. Interferon-gamma above 5 units/ml was detected in less than 15% of plasma samples from controls, uremic patients or alcoholics on admission but was detected in four of eight samples from alcoholics at discharge (2-4 days after admission). The intensity of staining for class II antigens was depressed by more than 50% on lymphocytes from alcoholics and uremic patients. The expression of HLA class I and class II antigens was depressed whether uremic patients were hemodialyzed or not. The percentage of lymphocytes expressing CD16 was depressed in three of seven alcoholics and five of seven hemodialyzed patients. In contrast, the percentage of monocytes expressing CD16 was increased in six of seven hemodialyzed patients and three of five uremic patients not undergoing hemodialysis suggesting activation of monocytes in these patients. Plasma levels of beta 2-microglobulin were elevated by 61% in alcoholics, 50-fold in hemodialyzed patients, and 26-fold in nonhemodialyzed uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[A case of sarcoid granulomatous interstitial nephritis improved by steroid therapy].

We report a case of sarcoid granulomatous tubulointerstitial nephritis diagnosed by renal biopsy. A 60-year-old man presented with productive cough, and exertional dyspnea of 3 months duration. A chest X-ray film revealed diffuse reticulonodular infiltrates in both lung fields. A transbronchial lung biopsy specimen showed inflammation of the alveolar septum associated with non-caseating granulomas. The patient also had tubular proteinuria and glucosuria. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in both lungs and kidneys. Renal function tests revealed tubular dysfunction. Tubulointerstitial nephropathy was suspected. A renal biopsy specimen exhibited tubulointerstitial nephritis associated with numerous non-caseating granulomas, similar to the findings of the lung biopsy specimen. No glomerular abnormalities were evident. Later, a scalene node biopsy confirmed the diagnosis of sarcoidosis. Prednisolone therapy yielded a favorable outcome for both the renal and pulmonary involvement. During the corticosteroid therapy, measurement of the urinary beta-2-microglobulin concentration proved a valuable monitoring tool for assessing the recovery of the tubular impairment.

Humans↗
PubMed1990

Genetics of 51D-52A, a region containing several maternal-effect genes and two maternal-specific transcripts in Drosophila.

Two genomic clones exhibiting a maternal-specific pattern of expression map to cytological region 52A. To elucidate the function of these clones we have undertaken a mutagenesis of the cytological region 51D-52A. This paper presents the results of this screen and the preliminary analysis of female-sterile and lethal mutations isolated. A total of twelve complementation groups have been identified, four of which are defined exclusively by female-sterile alleles. Only one visible mutation was isolated, a recessive temperature-sensitive allele of Thickened-arista (Tarts). Several of the seven lethal loci display an embryonic lethal phase. Three of the four female-sterile loci affect chorion structure with one resulting in underamplification of the chorion genes, and two (possibly three) of the four female-steriles affect nuclear division/DNA replication. Thus it appears that this is a "developmentally important" region, possibly representing a clustering of genes involved in either DNA replication or nuclear division.

Alleles↗
PubMed1989

Some of the signals for 3'-end formation in transcription of the Saccharomyces cerevisiae Ty-D15 element are immediately downstream of the initiation site.

Fragments from the Ty-D15 element of Saccharomyces cerevisiae were assayed for the ability to direct 3'-end formation for RNA initiated by the GAL1 promoter. The delta, the direct repeat at each end of the element, was capable of forming 3' ends at two sites, an inefficient upstream site and an efficient downstream site near the end of the delta. Different sequences were required for 3'-end formation at these sites. For the efficient site, all transcripts had 3' ends in the delta and no downstream transcription was detected, which suggested that these sequences terminate transcription. Surprisingly, the delta region downstream of the initiation site for Ty RNA comprised part of this major site and terminated more than 50% of the transcripts that read into it. Sequences necessary for the efficient site were localized to two small regions. Both regions were upstream of the 3' end and contained similarities to a tripartite consensus sequence that has been proposed as a terminator element. Sequences near the position of the 3' end could also affect termination; a short G + C-rich sequence inserted just downstream changed an efficient terminator to an inefficient one. Initiation in the delta had no effect on the efficiency or positions or termination in that delta. A new initiation site was seen when the same delta terminated transcription, but transcriptional interference did not occur, since the amount of initiation was not decreased.

Avian Leukosis Virus↗
PubMed1989

A region internal to the coding sequences is essential for transcription of the yeast Ty-D15 element.

The major transcript of the yeast transposable element Ty1 has its 5' end in one delta and the 3' end in the opposite delta, the direct repeats of about 335 base pairs (bp) at each end of the element. The transcriptional initiation signals of the Ty-D15 element that give rise to this transcript were found to have a number of unusual characteristics. The 5' delta by itself, which contained the initiation site for Ty transcription, gave no detectable transcription. A region internal to the transcript in a translated part of the element and about 140 bp downstream of the 5' delta was essential for initiation of the major Ty transcript. This internal activating region (IAR) had several interesting properties. When the portion of the delta upstream of the initiation site was replaced with DNA fragments that did not by themselves act as promoters, initiation directed by the IAR still occurred at about the same position, 200 to 400 bp upstream of the IAR. If fragments containing the IAR were inverted, transcription could still occur. When 468 or 636 bp was inserted between the delta and the IAR, initiations occurred near the normal delta initiation site and in the inserted DNA. Therefore, the location and properties of transcription signals for Ty-D15 differ considerably from those expected for a yeast gene transcribed by RNA polymerase II.

Cloning, Molecular↗
PubMed1985

Iatrogenic arteriovenous fistula of the internal mammary artery. Transcatheter intravascular coil occlusion.

We encountered a case of right internal mammary artery to innominate vein fistula following subclavian vein catheterization and the projection of the coil spring was projected after transcatheter intravascular coil occlusion. We were worried about both distal thromboembolism from small thrombi forming on a portion of the coil spring and stenosis of the subclavian artery. However, there was no evidence of thromboembolism of the distal artery, and good patency of the right subclavian artery was shown by an angiogram performed six months later. The patient has been receiving heparin therapy during hemodialysis, which should help prevent thromboembolism of the distal artery.

Adult↗