Biomedical subjects

Y Wu

Publications and source records attributed to Y Wu.

At least 1,027 records · Page 57Linked to original sources

PubMed1994

Altered angiotensin-II receptors in human hepatocellular and hepatic metastatic colon cancers.

OBJECTIVE: To characterize angiotensin-II receptor density and affinity in normal and cirrhotic livers and in hepatocellular and metastatic colorectal cancer. SUMMARY BACKGROUND DATA: Several studies have indicated a possible beneficial effect of angiotensin-II as a biologic response modifier in the treatment of hepatic or metastatic colon cancer. This is based on evidence that angiotensin-II will cause a selective increase in arterial vasoconstriction in normal liver compared with tumor. METHODS: Human hepatoma (5), metastatic colon (10), or cirrhotic (3) liver was obtained. Non-tumor-bearing regions served as normal liver. Angiotensin-II receptor binding was determined on membranes with 125I-angiotensin-II and in situ studies were performed using the biotin-avidin detection system. RESULTS: Angiotensin-II receptor density was markedly down-regulated in tumor compared with normal or cirrhotic liver. CONCLUSIONS: A loss of angiotensin-II receptors occurs on the neovasculature of hepatic tumors.

Adult↗

PubMed1994

Systemic and portal prostacyclin and thromboxane response to hemorrhage in portal hypertension.

Prostacyclin (PGI2) and thromboxane (Tx-A2) levels increase in hemorrhagic shock. Prostanoids have been implicated as mediators of the systemic and splanchnic hyperemia characteristic of portal hypertension (PHT). We hypothesized that prostanoid pharmacokinetics could be altered during shock in PHT and mediate the poor tolerance of PHT animals to hemorrhage. Hemodynamics and PGI2 and Tx-A2 levels were determined in portal, systemic venous, and arterial vascular beds at baseline and following hemorrhage and resuscitation. Portal and systemic PGI2 levels were elevated at baseline in PHT animals, with no change in resting Tx-A2. Following hemorrhage, PGI2 and Tx-A2 levels increased in normal animals, but were unchanged in PHT. Portal hypertension PGI2 production was elevated at rest, while Tx-A2 levels were diminished. There is a diminished prostanoid response to hemorrhage in PHT animals compared to normal. This abnormality in prostanoid pharmacokinetics may contribute to the abnormal response to hemorrhage in PHT.

Animals↗

PubMed1994

Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation.

The let-60 ras gene of Caenorhabditis elegans is one of the key players in a signal transduction pathway that controls the choice between vulval and epidermal differentiation in response to extracellular signals. To identify components acting downstream of let-60 ras in the vulval signaling pathway, we have identified a reduction-of-function mutation in the sur-1 gene that completely suppresses the multivulva phenotype of a hyperactive let-60 ras mutation. About 10% of animals homozygous for the sur-1 mutation also display a specific and intriguing vulval cell lineage defect. In addition, the sur-1 mutation results in a cold-sensitive egg-laying defective phenotype and a partial larval lethal phenotype. We have cloned the sur-1 gene by DNA-mediated transformation and have shown that it encodes a protein similar in overall structure to mammalian MAP kinases (ERKs). The functional homology between Sur-1 MAP kinase and mammalian MAP kinases was also demonstrated by the ability of a rat ERK2 kinase to rescue the sur-1 mutant phenotypes. Genetic double-mutant analyses place sur-1 downstream of let-60 ras but upstream of lin-1 in the vulval signaling pathway. Our results provide further evidence for the extreme conservation of Ras-mediated signaling pathway between worms and humans and for the function of MAP kinases in cell signaling processes that control cell differentiation and animal development.

ATP-Binding Cassette Transporters↗

PubMed1994

Computerized detection of clustered microcalcifications in digital mammograms using a shift-invariant artificial neural network.

A computer-aided diagnosis (CAD) scheme has been developed in our laboratory for the detection of clustered microcalcifications in digital mammograms. In this study, we apply a shift-invariant neural network to eliminate false-positive detections reported by the CAD scheme. The shift-invariant neural network is a multilayer back-propagation neural network with local, shift-invariant interconnections. The advantage of the shift-invariant neural network is that the result of the network is not dependent on the locations of the clustered microcalcifications in the input layer. The neural network is trained to detect each individual microcalcification in a given region of interest (ROI) reported by the CAD scheme. A ROI is classified as a positive ROI if the total number of microcalcifications detected in the ROI is greater than a certain number. The performance of the shift-invariant neural network was evaluated by means of a jackknife (or holdout) method and ROC analysis using a database of 168 ROIs, as reported by the CAD scheme when applied to 34 mammograms. The analysis yielded an average area under the ROC curve (Az) of 0.91. Approximately 55% of false-positive ROIs were eliminated without any loss of the true-positive ROIs. The result is considerably better than that obtained in our previous study using a conventional three-layer, feed-forward neural network. The effect of the network structure on the performance of the shift-invariant neural network is also studied.

Biophysical Phenomena↗

PubMed1994

Neutralization sensitivity of human immunodeficiency virus type 1 is determined in part by the cell in which the virus is propagated.

Neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) vary widely and have not been reproducibly associated with prognosis or disease progression. We have found that both low-passage clinical isolates and laboratory-adapted strains of HIV-1 have different sensitivities to neutralization by the same antiserum, depending on the host cell in which the viral stock is prepared. One such isolate (VL069) grown in H9 cells was neutralized by 20 human sera at a geometric mean titer of 1:2,047; this same isolate prepared in peripheral blood mononuclear cell (PBMC) culture was neutralized at a mean titer of < 1:10 by the same sera. Adsorption and mixing experiments indicated that neither antibody to H9 cell components nor blocking by excess viral antigen was responsible for the differences observed. This host cell effect is rapidly reversible upon passage of the virus from PBMCs to H9 cells and back into PBMCs. In contrast, the neutralization characteristics remained remarkably stable over extended culture in PBMCs. Two laboratory strains and five clinical isolates were evaluated in expanded studies of this phenomenon. While the neutralization characteristics of most of the strains studied were affected by the host cell in which the strain was propagated, two of the strains (one clinical isolate and one laboratory strain) appeared antigenically unaffected by their cell of origin. Host cell effect was also evident in neutralization by monoclonal antibodies directed against the CD4-binding region and the V2, V3, and gp41 regions. Possible mechanisms for this host cell effect include (i) mutation during passaging; (ii) selection in different host cells of different subpopulations of the (uncloned) viral stock; and (iii) cell-specific posttranslational modifications. To explore these possibilities, the V3 through V5 region of gp120 was sequenced in preparations made by passing VL069 into H9 cells and into PBMCs; HIVMN grown in CEM-SS cells and in PBMCs was also sequenced. In both cases, a few amino acid changes outside the V3 region were found. Studies are currently under way to assess the significance of these changes.

Adaptation, Biological↗

PubMed1994

Identification of the putative RNA polymerase of Cryphonectria hypovirus in a solubilized replication complex.

Hypovirulence of the pathogenic fungus Cryphonectria parasitica, caused by the unencapsidated viral double-stranded RNA of Cryphonectria hypovirus (CHV1), provides a means for biological control of chestnut blight. We report here the isolation of a replication complex of the virus solubilized from host membranes. The conserved regions of the putative RNA polymerase encoded by strain CHV1-713 were cloned and expressed, and the recombinant protein was purified and used to produce polyclonal antibodies. The CHV1 replication complex was solubilized from a membrane fraction of CHV1-infected C. parasitica hyphae. Antibodies raised against the putative viral polymerase reacted on a Western immunoblot with an 87-kDa polypeptide of the replication complex but not with comparable preparations from an isogenic uninfected strain. Analysis of the polypeptide composition of the complex by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining revealed a number of other polypeptides along with the double-stranded RNA of the virus. We conclude that this 87-kDa polypeptide is the putative RNA polymerase encoded on open reading frame B of CHV1.

Blotting, Western↗

PubMed1994

Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins.

Endothelin-1 causes vasodilation of the intact porcine pulmonary vascular bed. To determine the cause of this vasodilation, we investigated the interactions of endothelin-1 (ET-1), endothelium-derived nitric oxide (EDNO), and prostacyclin in isolated small porcine pulmonary arteries and veins under in vitro conditions. ET-1 caused concentration-dependent contractions in arteries and veins, augmented by the nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine, in pulmonary veins. BQ-123 (ETA-receptor antagonist) depressed the ET-1-induced contractions. Sarafotoxin S6C, an ETB-receptor agonist, caused contractions of pulmonary veins only. Endothelium-dependent relaxations to bradykinin and ET-1 were greater in pulmonary veins compared with arteries, inhibited by N omega-nitro-L-arginine, and reversed by L-arginine. BQ-123 augmented ET-1-induced arterial relaxation. ET-3 and sarafotoxin S6C, ETB-receptor agonists, caused comparable endothelium-dependent relaxations in arteries and veins. ET-1 caused a fourfold greater increase in prostacyclin release in pulmonary veins compared with arteries. We conclude that ET-1 is a potent vasoconstrictor of porcine pulmonary vessels and stimulates the release of EDNO and prostacyclin, which oppose the contractions to the peptide. The release of these endothelium-derived vasodilators appears greater in pulmonary veins.

Animals↗

PubMed1994

Opioid growth factor inhibits DNA synthesis in mouse tongue epithelium in a circadian rhythm-dependent manner.

In addition to neuromodulation, endogenous opioids also serve as growth factors. To investigate the involvement of the naturally occurring opioid peptide [Met5]enkephalin [termed opioid growth factor (OGF)] in the renewal of epithelium, adult mice were given systemic injections of OGF (1 mg/kg) and examined 2 h later at 0700 or 1700 h. DNA synthesis in the tongue was investigated using [3H]thymidine and autoradiography. OGF depressed DNA synthesis of the basal epithelial cells in the tip, and dorsal and ventral surfaces of the tongue (42-44% of control levels) only at 0700 h. This decrease in DNA synthesis was blocked by concomitant administration of the opioid antagonist naloxone (10 mg/kg); naloxone alone had no influence on cell replicative processes. Both OGF and its receptor, zeta (zeta), were detected in the stratified squamous epithelium of the ventral and dorsal surfaces of the tongue by immunocytochemistry. Photodensitometric measurements of immunocytochemical preparations revealed almost twofold more OGF and zeta-receptor immunoreactivity at 1700 h than at 0700 h. These results indicate that an endogenous opioid peptide and its receptor are present and govern cellular renewal processes in the tongue and regulate DNA synthesis in a circadian rhythm-dependent fashion.

Animals↗

PubMed1994

Altered adenylyl cyclase activities and G-protein abnormalities in portal hypertensive rabbits.

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. We hypothesized that alterations in the activity of a guanine-nucleotide regulatory protein (G-protein) might be partially responsible for the marked circulatory disturbances observed in PHT. We, therefore, determined alterations in adenylyl cyclase/cAMP system in prehepatic portal hypertensive rabbits and correlated these changes to the activity of a G-protein. Basal and G-protein-stimulated adenylyl cyclase activities were lower in the PHT superior mesenteric artery (22-26%) and thoracic aorta (31-46%) membranes, but higher (178-321%) in portal vein. The functional activity of Gi alpha proteins (pertussis toxin-catalyzed ADP-dependent ribosylation) increased in the PHT superior mesenteric artery and thoracic aorta, but decreased in portal vein. Immunodetection revealed an increase in the Gi alpha protein subunits (Gi alpha 1/Gi alpha 2 and Gi alpha 3/Go alpha) in PHT thoracic aorta, without any change in Gs alpha proteins; and a decrease in the amount of Gi alpha proteins in PHT portal vein. There was no change in the amount of Gs alpha/Gi alpha in the PHT superior mesenteric artery. We conclude the hemodynamic alterations of PHT are associated with intrinsic alterations in G-protein-enzyme effector systems. These alterations are vessels specific and suggest a possible unique global derangement underlying the vasculopathy of PHT.

Adenosine Diphosphate Ribose↗

PubMed1994

TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix.

We have recently reported the cloning of a novel protein, TRiC-P5, with significant homology with protein 1 of the t-complex (TCP1). In the present study, the cellular localization of TRiC-P5 in Raji cells has been determined using an antiserum raised against a 18.5 kDa fusion protein. Results from cell fractionation and immunoblot studies indicate that TRiC-P5 is mainly localized in the cytoplasm. In addition, a significant part of TRiC-P5 is also found in the nucleus where it is attached to the nuclear matrix, a complex filament network involved in essential cellular functions such as DNA replication, and RNA transcription and maturation. Immunofluorescence experiments using the anti-TRiC-P5 antibodies confirm these results. We also provide evidence that, in the cytoplasm, TRiC-P5 is part of a large protein complex, most probably the TCP1-ring complex (TRiC), a hetero-oligomeric ring complex that plays a role of molecular chaperone in the folding of actin and tubulin.

Chaperonin Containing TCP-1↗

PubMed1994

Effects of total coumarins of Fructus cnidii on skeleton of ovariectomized rats.

Total coumarins of Fructus Cnidii (TCFC), 5 g.kg-1 by intragastric gavage, 6 d/wk, x 7 wk, was effective for prevention of bone loss in ovariectomized (OVX) rats. In comparison to aging control rats, the proximal tibia of placebo-treated OVX rats were characterized by an increase in eroded perimeter (+298%), label perimeter (+77%), osteoid perimeter (+47%), mineral apposition rate (+32%) and bone formation rate (+130%). These changes indicated a high bone turnover in OVX rats leading to a rapid bone loss (-44%) in proximal tibial metaphysis. In contrast, the TCFC-treated OVX rats showed an increase of cancellous bone area (+41%) compared with placebo-treated OVX rats and decrease in all the above indices of bone turnover to near aging control levels except that of the osteoid area (+88%) which was higher than that in aging control, but mineralization lag time did not show significant changes. The results suggested that the TCFC inhibited the high bone turnover and reversed the bone loss at early menopausal stage.

Animals↗

PubMed1994

[Mechanism of changes in coagulation after electric burns in rabbits].

The changes in local lesion after high-voltage electric burns ares dependent on many factors. One of the important factors is the change in coagulation. In this paper, a high-voltage electrical burn model was reproduced in rabbits for the purpose of investigating the coagulation mechanism. It was found that AT-III and PC showed elevation and declination, respectively, at 6h and 12h postburn. PAI:A and t-PA:A also showed obvious changes, while FDP showed continuous elevation at 6h up to 5d postburn. The findings probable provided the explanation of the occurrence of thrombosis at 6h to 12h postburn, and the second episode of thrombosis on the 5th day.

Animals↗

PubMed1994

Condition judgement of dry eye in sicca syndrome.

In this paper, we presented 32 dry eyes of 16 random patients with primary Sicca Syndrome graded with rose bengal (rb), Break up time of tear film (BUT) and Schirmer 1 test (S1T). Of them, the lip biopsy and tear beta 2-M level were examined and overall studied. The results showed that the grade of dry eye was closely related with both the degree of lymphocyte infiltration of lip glands and level of tear beta 2-M, and indicated that our grading method for dry eye based on rb, BUT and S1T is depandable, and the lymphocyte infiltration of both lip and lacrymal gland may be the same qualitatively and quantitatively. so, how many lymphocytes appeared in the lip gland, how much concentration would be the tear beta 2-M Therefore judging the condition of dry eye by these 5 tests is dependable and simple too, as they need no complicated equipment.

Adult↗

PubMed1994

[Comparative study of organ storage solutions for rat liver preservation: effects of HX and Collins I solution on sinusoidal lining cells and hepatic functions].

The liver sinusoidal lining cell injury and biochemical function changes were studied with isolated perfusion after rat livers had been preserved in HX solution or in Collins II solution. Seventy inbred Wistar rats were randomly divided into control group (n = 10), group H (preserved with HX solution, n = 30), and group C (preserved with Collins II solution, n = 30). The effects of the storage solutions were assessed by measuring the sinusoidal lining cell mortality (SLCM), Krebs-Henseleit perfusate ketone body ratio (PKBR), the hepatic sugar release (SL), and the number of livers secreting bile during isolated perfusion. The results suggest that the HX solution be much superior to Collins II solution in preventing sinusoidal lining cell injury and maintaining normal hepatic functions.

Animals↗

PubMed1994

[An experimental model of electric injury by high voltage].

A standardized 10,000-volt, 2 + 0.15-A, 5-s electric burn rabbit model was established. Microscopic examination revealed that there was patchy cellular necrosis intermingled with viable cells in the muscle in the burn area. Grossly, there was a distinct interface between viable and nonviable tissues. The resulted injury correlated well with clinical features of electric burn.

Animals↗

PubMed1994

Expression of the O6-methylguanine-DNA methyltransferase gene in eight human tumor cell lines.

O6-methylguanine-DNA methyltransferase (MGMT) gene expression in 6 Mer+ (HeLa S3, SMMC-7721, SGC-7901, B-239, AGZY83-a, and Cc801) and 2 Mer- (SHG-44, and HeLa MR) human tumor cell lines was examined. Southern blot analysis revealed no deletion, amplification, or rearrangement of the MGMT gene in these cell lines. However, approximately 1.0 kb transcripts were detected in the 6 Mer+ cell lines but not in the 2 Mer- cell lines by Northern blot analysis. Furthermore, a rough correlation between MGMT activity and mRNA level in these cell lines was observed. These results suggest that transcriptional regulation of the MGMT gene is the molecular basis of the absence of MGMT activity in Mer- cell lines.

Gene Expression Regulation, Neoplastic↗

PubMed1994

[A new diarrhea pathogen: entero-SLTs-producing and invasive Escherichia coli was over-looked as normal flora E. coli].

In clinical laboratories of Beijing, China, no known entero-pathogen but almost pure E. coli strains could be isolated from more than 60% fecal samples of diarrheal patients, which had been recognized as normal flora E. coli and dismissed. We suspected that some of the so-called normal flora E. coli strains might be virulent. To prove our idea. We collected 172 strains of E. coli isolated from diarrheal patients from whom no other enteric bacterial pathogens had been identified, including EPEC, EIEC, ETEC. With plasmid DNA analysis, Hep-2 cell adherence assay and 10 DNA probe hybridization, we found that the so-called normal flora E. coli was abnormal, 44% of them were virulent, of which 16 (9.3) were EHEC, 8 EPEC (4.7%), 11 EAggEC (6.8%). Fifty-four of 172 strains were hybridized with INV and SLT1 or SLT2 probes, which had never been reported. These strains could invade Hep-2 cells, but were lack of ipaB gene, a key gene of invasiveness gene cluster of Shigella species and EIEC. The aggregative adherence to Hep-2 cells was observed, but the strains were not hybridized with EAggEC specific DNA probe. The purified toxin protein and cell filtrate were toxic to vero cells. Based on the data obtained, we believed that this is a new category of diarrhea-genic E. coli, named as entero-SLTs-producing and invasive E.coli (ESIEC). ESIEC occupied 31.4% of the strains tested, the isolation of it was probably higher than those of ETEC, EPEC in P R China.

Adult↗

PubMed1994

[Synthesis of N-(4-carbomethoxy-4-phthalimidobutanoyl)-N-substituted glycines, proline and pyroglutamic acid].

This paper reports the synthesis of eleven N-(4-carbomethoxy-4-phthalimidobutanoyl)-N-substituted glycines (VII1-9), proline (VII10) and pyroglutamic acid (VII11) expected to have inhibitory activity on angiotensin converting enzyme. All of the compounds mentioned above and the corresponding t-butyl esters of VII1-9 were not reported in the literature previously. The structures were confirmed through their IR, 1HNMR, MS spectra and elemental analysis. In preliminary test in rats, compounds VII8, VII9 and VII10 showed marked hypotensive activity.

Angiotensin-Converting Enzyme Inhibitors↗