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Biomedical subjects

K Wu

Publications and source records attributed to K Wu.

At least 199 records · Page 11Linked to original sources

[Malignant fibrous histiocytoma of kidney].

Malignant fibrous histiocytoma of kidney is one kind of rare tumor. About 20 cases have been reported abroad and 3 in this country. This kind of tumor is characterized by high malignancy and invasive growth. It is difficult to differentiate it from renal cancer by radiology. Fibroblasts stand in line as "storiform pattern" and touton giant cell can be seen under microscopy. The definite diagnosis can be made through immunohistochemistry.

Histiocytoma, Benign Fibrous↗

The cleavage and inactivation of plasminogen activator inhibitor type 1 by neutrophil elastase: the evaluation of its physiologic relevance in fibrinolysis.

The effect of the proteolytic cleavage of plasminogen activator inhibitor type 1 (PAI-1) by human neutrophil elastase (HNE) on fibrinolysis was investigated. HNE cleaved active PAI-1 and produced low molecular weight forms of inactive PAI-1, as previously reported. Latent PAI-1 was resistant to HNE treatment. Vitronectin (VN) partially protected the cleavage. NH2-terminal sequence analysis indicated that the cleavage site was Val355-Ser356 (P4-P3). The effects of PAI-1 cleavage by HNE on clot lysis was studied in a purified system. Clot lysis time without PAI-1 was 20.0 +/- 5.0 minutes and was prolonged to 86.7 +/- 2.9 minutes by 68 nmol/L of PAI-1. It was shortened when HNE (from 0.6 nmol/L to 80 nmol/L) was added and returned to the value obtained without PAI-1 by 80 nmol/L of HNE (20.0 +/- 5.8 minutes). However, in the absence of PAI-1, elastase did not enhance clot lysis at all. Euglobulin clot lysis time was also shortened after HNE treatment. The cleavage and inactivation of PAI-1 by HNE was shown to be a novel pathway to enhance fibrinolysis.

Amino Acid Sequence↗

The GA5 locus of Arabidopsis thaliana encodes a multifunctional gibberellin 20-oxidase: molecular cloning and functional expression.

The biosynthesis of gibberellins (GAs) after GA12-aldehyde involves a series of oxidative steps that lead to the formation of bioactive GAs. Previously, a cDNA clone encoding a GA 20-oxidase [gibberellin, 2-oxoglutarate:oxygen oxidoreductase (20-hydroxylating, oxidizing), EC 1.14.11.-] was isolated by immunoscreening a cDNA library from liquid endosperm of pumpkin (Cucurbita maxima L.) with antibodies against partially purified GA 20-oxidase. Here, we report isolation of a genomic clone for GA 20-oxidase from a genomic library of the long-day species Arabidopsis thaliana Heynh., strain Columbia, by using the pumpkin cDNA clone as a heterologous probe. This genomic clone contains a GA 20-oxidase gene that consists of three exons and two introns. The three exons are 1131-bp long and encode 377 amino acid residues. A cDNA clone corresponding to the putative GA 20-oxidase genomic sequence was constructed with the reverse transcription-PCR method, and the identity of the cDNA clone was confirmed by analyzing the capability of the fusion protein expressed in Escherichia coli to convert GA53 to GA44 and GA19 to GA20. The Arabidopsis GA 20-oxidase shares 55% identity and > 80% similarity with the pumpkin GA 20-oxidase at the derived amino acid level. Both GA 20-oxidases share high homology with other 2-oxoglutarate-dependent dioxygenases (2-ODDs), but the highest homology was found between the two GA 20-oxidases. Mapping results indicated tight linkage between the cloned GA 20-oxidase and the GA5 locus of Arabidopsis. The ga5 semidwarf mutant contains a G-->A point mutation that inserts a translational stop codon in the protein-coding sequence, thus confirming that the GA5 locus encodes GA 20-oxidase. Expression of the GA5 gene in Ara-bidopsis leaves was enhanced after plants were transferred from short to long days; it was reduced by GA4 treatment, suggesting end-product repression in the GA biosynthetic pathway.

Amino Acid Sequence↗

Synthesis and biological activity of 7-alkylidenecephems.

Several 7-alkylidenecephalosporins were synthesized and biologically evaluated as beta-lactamase inhibitors. The three beta-lactamase enzymes used in this study included two type C beta-lactamases, derived from Enterobacter cloacae P99 and E. cloacae SC12368, and one type A beta-lactamase, derived from Escherichia coli WC3310. Of the cephalosporins prepared, compound 7e, the sodium salt of 7-[(Z)-(2'-pyridyl)methylene]cephalosporanic acid sulfone, was found to have excellent inhibitory properties against both type C enzymes. Also, compound 7f, the sodium salt of 7-[(Z)-(tert-butoxycarbonyl)methylene]cephalosporanic acid sulfone showed high activity as an inhibitor of the type A enzyme. The inhibition kinetics of 7e were further explored. The IC50 value of 7e indicated that this compound was approximately 20-fold more active than tazobactam against the enzyme derived from E. cloacae P99 and 167-fold more active than tazobactam against the enzyme derived from E. cloacae SC12368. A plot of enzymatic activity vs incubation time with stoichiometric amounts of inhibitor reveals a rapid deactivation of the enzyme followed by an extremely slow reactivation. 7e exhibited a second-order rate constant of k3' = 5.3 x 10(6) L/mol.min, and a partition ratio of approximately 20:1 inhibitor:enzyme was determined for this inhibitor. After separation of excess inhibitor with Sephadex filtration, a rate constant of enzyme reactivation was measured at kreactiv = 1.0 x 10(-3) s-1. Following 24 h of incubation of enzyme with a large excess of inhibitor and sephadex filtration to remove excess inhibitor, the enzyme was able to recover only 43% of its original activity, indicating an irreversible component to the inhibition. Potential mechanisms of inhibition for both 7e and 7f are suggested.

Anti-Bacterial Agents↗

Deficiency of brain synaptic dystrophin in human Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterized by a defect in dystrophin, a high molecular weight protein that is located predominantly in muscle, but which has been detected in brain. Brain dystrophin has been localized to the synapse, in the postsynaptic density (PSD), and is absent in the mdx mouse, an animal model of human DMD. To define the potential pathogenic role of dystrophin deficiency in cognitive impairment, we examined the protein in human DMD brain. The 427-kd dystrophin was absent in the PSD from DMD brain, but was normally expressed in the brain from an age-matched control subject. Our findings indicate that dystrophin is deficient in human DMD cortical synapses and provide a potential pathogenic mechanism for cognitive impairment.

Brain Chemistry↗

Social aspects of malaria in Heping, Hainan.

This paper presents findings from a study conducted in Heping Town, Qiongzhong County, Hainan Province, China. The study, conducted in 1992, used qualitative as well as quantitative methods to gather social, cultural and behavioural data associated with the acquisition, transmission and prevention of malaria, and the diagnosis and treatment of disease. These methods included focus groups, key informant and other in-depth interviews, and observations, a household survey and tests of school children of knowledge of malaria. The study is among the first to our knowledge that has utilized this broad mix of methods for tropical disease research in China.

Adolescent↗

Rate of glucose entry into hepatic uridine diphosphoglucose by the direct pathway in fasted and fed states in normal humans.

We used the glucuronate (GlcUA) probe technique to measure the rate of glucose entry into hepatic uridine diphosphoglucose (UDP-glc) by the direct pathway, to quantify the rate of appearance (Ra) of hepatic UDP-glc, and to calculate hepatic glucose cycling in vivo in normal humans. The direct pathway contribution to UDP-glc as determined by the ratio of [1-d1]-GlcUA to plasma [LD1]-glucose enrichments was minor (15% to 20%) in normal men after an overnight fast. After 9 hours of refeeding with intravenous (IV) glucose or an oral liquid formula meal each at a rate of 7 mg carbohydrate/kg/min, the direct pathway increased to 66.3% +/- 6.7% and 61.6% +/- 6.0% (mean +/- SE), respectively. Plasma glucose concentrations remained below 7.8 mmol/L and could not account for most of the variability in direct pathway contribution. The dilution of labeled [L-D1]-galactose in excreted acetaminophen-GlcUA was used to measure Ra UDP-glc, on the assumption that labeled galactose passes through the liver during its assimilation. Ra UDP-glc was 1.1 +/- 0.1 mg/kg/min after an overnight fast and increased to 2.0 +/- 0.1 with i.v. glucose and 2.6 +/- 0.2 with the oral liquid mixed meal. By combining the fractional glucose contribution with the Ra of hepatic UDP-glc, the rate of direct glucose entry into hepatic UDP-glc was 0.2 mg/kg/min (fasted) and increased to 1.3 to 1.6 (fed). This represented approximately 18% to 21% of systemic glucose disposal or 19% to 23% of the administered carbohydrate load during i.v. or oral refeeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density.

Senile plaques, a hallmark of Alzheimer's disease (AD), contain amyloid beta-peptide (A beta), which is generated from the larger amyloid beta protein precursor (APP). In addition to APP, several APP-related proteins have been recently identified in different organisms, including Drosophila amyloid precursor protein-like protein (APPL). Deficiency of APPL causes behavioral deficits in Drosophila, implicating a role in brain function. Moreover, mouse and human cDNA clones encoding amyloid precursor-like proteins (APLP1 and APLP2) have been identified and exhibit extensive sequence similarity to the APPL and APP genes. To define the potential role of APLP in the mammalian brain, we sought to directly localize APLP1 within the complex cortical synaptic structure. We focused on the postsynaptic density (PSD), which appears to be central to synaptic function. We now report that the 90 kDa APLP1, the first known APLP, is localized to the PSD from rat and human cerebral cortex. APLP1 increased during cortical synaptic development, suggesting a role in synaptogenesis or synaptic maturation. In contrast, APP was predominantly expressed in the synaptic membrane fraction, but was barely detectable in the PSD, including different subcellular distributions of APP and APLP1. Our observations raise the possibility that APLP1, a homologue of APPL, which appears to be necessary for normal behavior in Drosophila, participates in brain synaptic function in mammals.

Amyloid beta-Protein Precursor↗

Live cell image segmentation.

A major requirement of an automated, real-time, computer vision-based cell tracking system is an efficient method for segmenting cell images. The usual segmentation algorithms proposed in the literature exhibit weak performance on live unstained cell images, which can be characterized as being of low contrast, intensity-variant, and unevenly illuminated. We propose a two-stage segmentation strategy which involves: 1) extracting an approximate region containing the cell and part of the background near the cell, and 2) segmenting the cell from the background within this region. The approach effectively reduces the influence of peripheral background intensities and texture on the extraction of a cell region. The experimental results show that this approach for segmenting cell images is both fast and robust.

Algorithms↗

Expression and distribution of messenger ribonucleic acids for growth hormone (GH) receptor and GH-binding protein in mice during pregnancy.

The GH-binding protein (GHBP) in rodents consists of a ligand-binding domain, which is identical to the extracellular portion of the GH receptor (GHR), and a hydrophilic carboxyl-terminal domain, in place of the transmembrane and intracellular domains of the GHR. The two proteins are encoded by separate messenger RNAs (mRNAs), which are believed to be derived from a single gene by alternative splicing. In the present study, we report the gestational profiles of mouse GHR (mGHR) and mGHBP mRNAs in adipose tissue, brain, heart, kidney, liver, lung, mammary gland, muscle, ovary, and pituitary and describe the ontogeny of both messages in the liver of late gestational fetuses and newborns. A ribonuclease protection assay was used to simultaneously detect the two transcripts with an antisense RNA probe complementary to the extracellular domain- and hydrophilic tail-encoding regions of the mRNAs. Levels of hepatic GHR and GHBP mRNAs increased with fetal age. In the maternal liver, the abundance of both messages increased during pregnancy, with GHR mRNA levels rising less than GHBP mRNA. Also, the ratio between the two messages in this tissue increased during pregnancy in favor of mGHBP mRNA. In maternal mammary tissue, however, expression levels of both transcripts decreased gradually throughout pregnancy starting on day 8 of gestation and declining further during lactation, reaching a minimum 7-fold reduction on day 6 of lactation relative to nonpregnant values. Although there were no pregnancy-related changes in the remaining tissues we examined, the ratio of the abundance of GHR mRNA to that of GHBP mRNA varied tissue specifically. In the maternal brain, heart, liver, and mammary gland, mGHBP mRNA levels were higher than mGHR mRNA levels. In the maternal muscle and adipose tissue, the abundance of the two mRNA species was comparable. These observations indicate a gestational, developmental, and tissue-specific regulation of the expression of mGHR and mGHBP species.

Animals↗

Growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids with alternative 5'-untranslated regions are differentially expressed in mouse liver and placenta.

Two 5'-untranslated regions (5'UTRs) with distinctly different sequences, designated 5'UTR L1 and 5'UTR L2, were obtained by amplification of complementary DNA from mouse liver and placenta with primers complementary to sequences from the hormone-binding domain common to GH receptor (GHR) and GH-binding protein (GHBP) messenger RNAs (mRNAs). The presence of an open reading frame in the 5'UTR L2 and the high GC content of this sequence suggest that mRNAs containing this 5'UTR may be translated with a lower efficiency than those containing 5'UTR L1. Expression studies showed that 5'UTR L1 and 5'UTR L2 are present in GHR and GHBP mRNAs in both tissues. However, the relative expression of the two 5'UTRs differs between liver and placenta and in liver from different physiological states. The different expression patterns of the L1 and L2 5'UTRs predict that the corresponding 5'-noncoding exons of the GHR/GHBP gene are associated with different regulatory elements. The expression patterns of the 5'UTRs also indicate that there is a linkage between the 5'UTR present in GHR/GHBP gene transcripts and the alternative splicing of these transcripts to yield either GHR or GHBP mRNAs. The 5'-noncoding exon used for transcription of the GHR/GHBP gene, therefore, may be involved in regulating both the ratio of GHR to GHBP transcripts and the efficiency of translation of these transcripts. Transcription from the different 5'-noncoding exons of the GHR/GHBP gene thus may be a critical element in the regulation of the expression of GHR and GHBP and thereby in the control of the responses of different tissues to GH.

Alternative Splicing↗

[A study on human behavior and socioeconomic factors affecting malaria transmission and control in Qiongzhong, Hainan].

This study was conducted in Heping District of Quiongzhong County, a hyperedemic mountainous area, in August-September 1992. The comparative surveys between the village and state-run farm, Li and Miao nationalities and Han nationality were carried out by using the sociological method together with the epidemiological methods. Gray relational analysis was conducted between the aforementioned 7 socioeconomic human behavioral factors and IFA rates. The result showed that their degrees of relation (r) were in the following order: (1) percentage of persons who had stayed in the mountain overnight (r = 0.8690); (2) percentage of bed net users (r = 0.7990); (3) percentage of households seeking medical service (r = 0.7990); (4) number of mosquito nets per person (r = 0.7867); (5) percentage of householders knowing malaria transmission route (r = 0.7798); (6) percentage of households with tile-roofed houses (r = 0.6767) and (7) income per capita (r = 0.6636). It indicates that staying in the mountain, using bed net and seeking medical service were three discriminating factors affecting local malaria transmission and control. Therefore, it is suggested that carrying out health education, changing the stay-in-mountain behavior, increasing the utilization of mosquito nets and reinforcing the primary health care should be taken as the fundamental measures for malaria control programme.

China↗

Catalytic properties of NAD(P)H:quinone acceptor oxidoreductase: study involving mouse, rat, human, and mouse-rat chimeric enzymes.

NAD(P):quinone acceptor oxidoreductase (quinone reductase) (DT-diaphorase, EC 1.6.99.2) is involved in the process of reductive activation of cytotoxic antitumor quinones and nitrobenzenes. In this study, we initially examined the relative abilities of mouse, rat, and human quinone reductases to reduce two prodrugs, CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] and EO9 [5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1- methyl-1H-indole-4,7-dione]. By using Escherichia coli-expressed quinone reductases and evaluating them under identical conditions, we confirmed previous finding showing that the human enzyme is not as effective as the rat enzyme in reducing CB 1954 and EO9, although the two enzymes have similar NAD(P)H-menadione reductase activities. Interestingly, although the amino acid sequence of mouse quinone reductase is more homologous to that of the rat enzyme, we found that the mouse enzyme behaves similarly to the human enzyme in its ability to reduce these compounds and to generate drug-induced DNA damage. To determine the region of quinone reductase that is responsible for the catalytic differences, two mouse-rat chimeric enzymes were generated. MR-P, a chimeric enzyme that has mouse amino-terminal and rat carboxy-terminal segments of quinone reductase, was shown to have catalytic properties resembling those of rat quinone reductase, and RM-P, a chimeric enzyme that has rat amino-terminal and mouse carboxyl-terminal segments of quinone reductase, was shown to have catalytic properties resembling those of mouse quinone reductase. In addition, MR-P and RM-P were found to be inhibited by flavones with Ki values similar to those for rat and mouse quinone reductases, respectively. Based on these results, we propose that the carboxyl-terminal portion of the enzyme plays an important role in the reduction of cytotoxic drugs and the binding of flavones.

Amino Acid Sequence↗

[Inhibition of ornithine decarboxylase activity and epidermal papilloma in mice by beta-carotene].

Anticarcinogenic action of beta-carotene was analyzed with determination of ornithine decarboxylase (ODC) activity induced by TPA and a two-stage model of skin papilloma-genesis in mice. Results showed increase of ODC activity induced by TPA could be significantly inhibited, onset of tumor postponed, and number of tumor foci decreased by beta-carotene. It suggested beta-carotene had an obvious chemoprophylactic effect on tumor.

9,10-Dimethyl-1,2-benzanthracene↗

[Changes of collagen distribution in extrapulmonary arteries of hypoxia-induced pulmonary hypertensive rat].

Changes of collagen distribution in extrapulmonary arteries induced by hypoxia and the effects of ligustrazine (ligus) and 764-3 were investigated. Histological study showed that hypoxia could induce an increase of the medial and adventitial thickness of the pulmonary arterial trunk. An increase of type I and type III collagen fibers in pulmonary arterial trunk, particularly the increase of type III collagen fibers in adventitia of the pulmonary trunk were revealed by picrosirius-polarization methods. Ligus partially prevented the increase of type I and III collagen fibers of pulmonary arterial trunk. Electron microscopy showed that both the medial smooth muscle and adventitial fibroblasts were hypertrophic and hyperplastic, and the surrounding collagen fibers were increased.

Altitude Sickness↗

[An improved technique for preserving the nipple sensation in McKissock reduction mammaplasty].

An improved technique for preserving the nipple sensation in McKissock's reduction mammaplasty is described. Altogether four patients (seven breasts) have been operated on, and the primary results are highly satisfactory. The advantages of this technique are as followings: 1) The fourth lateral cutaneous nerve of the thorax, which mainly innervates the nipple, is preserved. All the patients retain the tactile sensation and the erectile reaction of the nipple after mammaplasty. 2) The operation is so modified that the suture line is smooth and has less tension. 3) The procedure ensures that both breasts are symmetrical after the operation.

Adult↗