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Biomedical subjects

L Sun

Publications and source records attributed to L Sun.

At least 289 records · Page 16Linked to original sources
PubMed1998

Beaver response to recurrent alien scents: scent fence or scent match?

By repeatedly presenting an alien scent to territory-owning beavers, Castor canadensis, we tested two competing hypotheses about the function of scent marking: scent fence and scent matching. The scent-fence hypothesis predicts that territory owners should respond increasingly strongly over time towards a recurrent alien scent because of the ineffectiveness of previous responses. The scent-matching hypothesis predicts that the intensity of response should be the same or decrease because, without the presence of the intruding signaller coupled with the chemical signal, the presence of the scent itself does not advertise the ownership of a territory. The response level of resident beaver families was stable to strangers' anal gland secretions (AGSs) and decreased to strangers' castoreum during a period of 6 days. These results support the scent-matching hypothesis but not the scent-fence hypothesis. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1998

Identification and characterization of the Spodoptera littoralis nucleopolyhedrovirus type B lef-3 gene.

We have identified a gene from the Spodoptera littoralis nucleopolyhedrovirus type B (SpliNPV-B) with several characteristics that suggest that it is homologous to the lef-3 genes of the Autographa californica and Orgyia pseudotsugata NPVs (AcMNPV and OpMNPV, respectively). The SpliNPV-B lef-3 gene was mapped between 43.6 and 45.5 map units of the SpliNPV-B genome. Northern blot analysis showed that SpliNPV-B lef-3 was expressed as a 1.6 Kb transcript at 5 h post infection (p.i.), reached high levels at 24 h p.i., and remained highly expressed at 56 h p.i. Transcription of SpliNPV-B lef-3 initiated at two distinct sites downstream from a TATA-box motif and terminated 25 nucleotides downstream from the translation stop site of the putative LEF-3 polypeptide. The 5'-boundaries of lef-3 promoter elements were investigated by transient expression assays, which revealed that the major components of the lef-3 promoter are within a 183 base pair region upstream of the distal transcription initiation site. Transfection of SpliNPV-B infected Sf9 cells with anti-sense oligonucleotides designed to inhibit LEF-3 expression resulted in substantial reduction of viral DNA replication, suggesting that the role of SpliNPV-B lef-3 may be similar to that of AcMNPV and OpMNPV lef-3 genes, which are essential for viral DNA replication.

Amino Acid Sequence↗
PubMed1998

Integrilin prevents prolonged bleeding times after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass reduces platelet number and function, increases postoperative bleeding time, and is the major, unsolved cause of nonsurgical bleeding after open heart operations. Temporary inhibition of platelet function during cardiopulmonary bypass (platelet anesthesia) protects platelets and reduces postoperative bleeding time and bleeding. METHODS: Integrilin, a short-acting, reversible platelet glycoprotein IIb/IIIa inhibitor was studied in 28 baboons that had 60 minutes of normothermic cardiopulmonary bypass using peripheral cannulas. A control group, two groups that received different doses of Integrilin, and a group that received a combination of Integrilin and low-dose Iloprost were studied. Blood samples for platelet count, aggregation to adenosine diphosphate, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, and fibrinopeptide A were obtained at seven time points. Template bleeding times were measured before and at five intervals after cardiopulmonary bypass. RESULTS: Both doses of Integrilin and the combination of Integrilin and Iloprost significantly protected platelet number, inhibited the response to adenosine diphosphate, and reduced postoperative bleeding times, but they did not reduce beta-thromboglobulin release except in the high-dose Integrilin group. Thrombin formation and activity were qualitatively, but not significantly, reduced in all treatment groups. Bleeding times were not significantly different from baseline at the time protamine was given in the combination group and 60 minutes after protamine administration in all treatment groups. CONCLUSIONS: Integrilin alone or in combination with Iloprost significantly reduces platelet activation during cardiopulmonary bypass and produces normal or near-normal bleeding times at the time protamine is given.

Animals↗
PubMed1998

The synthesis of neoglycophospholipid conjugates via reductive amination of omega-oxoalkylglycosides and phosphatidylethanolamines.

Phospholipid conjugates of mono- and disaccharides tethered with an n-decanyl spacer were efficiently synthesized via an improved reductive amination of deprotected omega-oxodecanyl beta-glycosides and phosphatidylethanolamines with or without alkenyl groups. The omega-oxodecanyl beta-glycosides were prepared by stereoselective glycosidation of glycosyl halides with 1, 10-decanediol followed by pyridinium dichromate oxidation. The acetyl groups of the omega-oxodecanyl beta-glycosides were removed with sodium methoxide prior to their conjugation with phosphatidylethanolamines.

Carbohydrate Sequence↗
PubMed1998

Enoxaparin suppresses thrombin formation and activity during cardiopulmonary bypass in baboons.

OBJECTIVE: This study tests the hypotheses that enoxaparin, a low molecular weight heparin and potent inhibitor of factor Xa, alone or in combination with standard heparin, inhibits thrombin formation and activity and modulates complement activation and neutrophil elastase release during cardiopulmonary bypass in baboons. METHODS: After preliminary studies to determine doses and possible species differences to anticoagulants and protamine, 27 anesthesized baboons had normothermic cardiopulmonary bypass with standard, unfractionated, porcine intestinal heparin, enoxaparin, or a combination of heparin and enoxaparin. Protamine in appropriate doses was used to reverse anticoagulation. Blood samples were obtained at 6 time points. Activated clotting times were monitored; template bleeding times were measured before and up to 24 hours after cardiopulmonary bypass. RESULTS: Hemodynamic measurements were not affected by the anticoagulant. Activated clotting times remained above 400 seconds throughout bypass, and no clots were observed. The anticoagulant did not alter platelet count, aggregation to adenosine diphosphate, release of beta-thromboglobulin, release of neutrophil elastase, or complement C3b/c and C4b/c. Enoxaparin alone, but not in combination, significantly reduced plasma levels of prothrombin fragment F1.2, fibrinopeptide A, and thrombin-antithrombin complexes but prolonged template bleeding times for more than 24 hours. CONCLUSION: Enoxaparin significantly reduces thrombin formation and activity during cardiopulmonary bypass but does not suppress complement activation and neutrophil elastase release and is not adequately reversed by protamine after bypass.

Animals↗
PubMed1998

Arginine vasopressin transport and metabolism in the pigmented rabbit conjunctiva.

The purpose of this study was to evaluate the transepithelial transport and metabolism of arginine vasopressin (AVP) in the pigmented rabbit conjunctiva, both in the absence and presence of protease inhibitors. The apparent permeability coefficient, P(app), for 3H-AVP was determined in the modified Ussing chamber, and AVP metabolites were monitored by reversed phase HPLC using a C18 column. At 50 nM donor 3H-AVP, the P(app) in the mucosal-to-serosal (ms) direction was about five times higher than that in the opposite direction. Excess (0.1 mM) AVP decreased the P(app) for labelled AVP in the mucosal-to-serosal (ms) direction by about 50%. However, intact AVP transport showed neither concentration nor direction dependence. HPLC analysis revealed two subspecies of 3H-AVP in the receiver fluid and virtually no degradation products in the donor fluid following 3 h flux experiments. 3H-AVP transported in the ms direction underwent extensive hydrolysis (73%), which was decreased by 33% with mucosal application of 2 mM camostat mesylate (an aminopeptidase inhibitor) or by 27% with 0.5 mM leupeptin (a serine protease inhibitor). By contrast, 3H-AVP transported in the serosal-to-mucosal (sm) direction resulted in only 37% hydrolysis, and mucosal application of either inhibitor did not significantly affect the P(app) for intact AVP. These data suggest that intact AVP transport in the conjunctiva may be mediated mostly by passive diffusion and enzymatic degradation of AVP may be mediated by proteolytic enzymes present on the mucosal side of the conjunctiva.

Animals↗
PubMed1998

Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes.

Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the immunosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin 1 that inhibits calcineurin-mediated signal transduction. The interaction between Cabin 1 and calcineurin is dependent on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants inhibits the transcriptional activation of calcineurin-responsive elements in the interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell activation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross-talk between protein kinases and calcineurin.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Regulated chromosomal DNA replication in the absence of a nucleus.

Using Xenopus egg extracts, we have developed a completely soluble system for eukaryotic chromosomal DNA replication. In the absence of a nuclear envelope, a single, complete round of ORC-dependent DNA replication is catalyzed by cytosolic and nuclear extracts added sequentially to demembranated sperm chromatin or prokaryotic plasmid DNA. The absence of rereplication is explained by an activity present in the nucleus that prevents the binding of MCM to chromatin. Our results indicate that the role of the nuclear envelope in DNA replication is to concentrate activators and inhibitors of replication inside the nucleus. In addition, they provide direct evidence that metazoans use the same strategy as yeast to activate DNA replication and to restrict it to a single round per cell cycle.

Animals↗
PubMed1998

Identification of a calcium channel modulator using a high throughput yeast two-hybrid screen.

The interaction of the N-type calcium channel beta3 subunit with the alpha1B subunit alters the activation/inactivation kinetics and the maximal conductance of the channel. The defined protein-protein interaction of the human alpha1B and beta3 subunits provides a target for small-molecule modulation of N-type channel activity. We describe a high throughput screen based on a counterselection yeast two-hybrid assay, which was used to identify small molecules that disrupt alpha1B-beta3 subunit interactions and inhibit N-type calcium channel activity. These small molecules may be a new class of calcium channel antagonists with therapeutic potential.

Calcium Channel Blockers↗
PubMed1998

Inhibition of cell differentiation by G alpha q in the renal epithelial cell line LLC-PK1.

LLC-PK1, an epithelial cell line derived from the kidney proximal tubule, was used to study the ability of the G protein alpha-subunit, G alpha q, to regulate cell differentiation. A constitutively active mutant protein, alpha qQ209L, was expressed using the LacSwitch-inducible mammalian expression system. Induction of alpha qQ209L expression with isopropyl-beta-D-thiogalactopyranoside (IPTG) enhanced phospholipase C activity maximally by 6- to 7.5-fold. Increasing concentrations of IPTG progressively inhibited the activity of two differentiation markers, Na(+)-dependent hexose transport and alkaline phosphatase activity. Induction of alpha qQ209L expression also caused a change from an epithelial to a spindle-shaped morphology. The effects of alpha qQ209L expression on cell differentiation were similar to those observed with 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment. However, protein kinase C (PKC) levels were downregulated in TPA-treated cells but not in alpha qQ209L-expressing cells, suggesting that the regulation of PKC by G alpha q may be different from regulation by TPA. Interestingly, the PKC inhibitor GF-109203X did not inhibit the effect of IPTG on the development of Na(+)-dependent hexose transport in alpha qQ209L-expressing cells. These data implicate PKC delta and PKC epsilon in the pathway used by G alpha q to block the development of Na(+)-dependent hexose transport in IPTG-treated cells.

Alkaline Phosphatase↗
PubMed1998

Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal cells.

The accumulation of hyaluronan (HA) in the renal cortex is a characteristic feature of inflammatory renal diseases. Fragments of HA derived from high molecular weight precursors are known to display inflammatory effects in vitro and could, therefore, participate in immune renal injury. To understand the mechanisms of HA fragmentation in vivo we examined the expression of recently characterized mammalian hyaluronidases in normal and autoimmune kidneys and in cell lines. We found that transcripts for the lysosomal-type hyaluronidases Hyal1 and Hyal2 were constitutively expressed in normal and autoimmune kidneys as well as in tubular epithelial cells and in a macrophage cell line. The expression of hyaluronidase genes in the cell lines did not increase in response to treatment with tumor necrosis factor alpha or gamma interferon. Interestingly, transcripts for the testicular-type hyaluronidase PH-20 (Spam1, Hyal3) were also detected in normal and autoimmune kidneys as well as in tubular cells and macrophages. Transcript levels were higher in kidneys from male mice as compared with age-matched females. Again, transcript levels did not change in vitro in response to cytokines. We conclude that mRNA for three different hyaluronidases is found in murine kidneys. The functional role played by these hyaluronidases in the degradation and metabolism of HA remains to be investigated further.

Animals↗
PubMed1998

Characteristic matrix and tubular basement membrane abnormalities in the CBA/Ca-kdkd mouse model of hereditary tubulointerstitial disease.

CBA/CaH-kdkd mice develop hereditary tubulointerstitial disease with mononuclear cell infiltration and cyst formation, possibly representing a model of human nephronophthisis. The purpose of the present investigation was to examine the components of the fibrotic changes which typically develop in the kidneys of these mice. By conventional histology, kdkd mice displayed progressive interstitial fibroblast and matrix accumulation. Immunohistological analysis of kdkd kidneys showed marked deposition of fibronectin in the tubulointerstitial space and revealed prominent irregularities for laminin and collagen type IV in the tubular basement membrane (TBM), including thickening, widening and folding. Electron microscopy confirmed the TBM abnormalities and showed marked undulation and thickening in areas of proximal tubular (PT) degeneration. Immunofluorescence staining analysis for the fibronectin receptors VLA-4 and VLA-5 showed no expression on injured proximal tubules, whereas the expression of the laminin receptor VLA-6 was increased and irregular on altered PT. Analysis of RNA derived from kdkd kidneys revealed marked upregulation of steady-state mRNA levels for the fibrogenic growth factor TGF-beta. We conclude that TBM alterations, matrix accumulation and changes in integrin expression together with enhanced TGF-beta production are typical features of kdkd tubulointerstitial disease and suggest that characteristic TBM or matrix alterations could contribute to the pathogenesis of the disease in these mice.

Animals↗
PubMed1998

Cyclical expression of GnRH and GnRH receptor mRNA in lymphoid organs.

Gonadotropin-releasing hormone (GnRH) is known to possess direct immunomodulatory effects. We have previously demonstrated that the administration of GnRH analogues modulates the expression of murine lupus independently of effects on gonadal steroids. We speculate that GnRH exerts direct actions at the level of the immune cells. GnRH receptors have been identified on lymphocytes. Because GnRH and GnRH receptor (GnRH-R) expression varies with the estrous cycle at the levels of the hypothalamus and pituitary, we speculated that similar cyclicity might be demonstrable in lymphoid tissue. In this report, we used competitive reverse transcription PCR to quantitate the expression of GnRH and GnRH-R mRNA in lymphoid organs throughout the estrous cycle in mice. We demonstrate that the pattern of expression of GnRH-R mRNA in spleen agrees closely with the pattern in the pituitaries of the same mice and the pattern previously reported in the rat pituitary, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. A similar pattern is seen with GnRH-R mRNA expression in the thymus. Furthermore, we show that the expression of GnRH mRNA in both thymus and spleen agrees closely with the pattern of expression of its receptor, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. Additional in vitro studies demonstrate that both GnRH and estradiol significantly increase the expression of GnRH-R mRNA in immune cells. These findings support an active role for GnRH in the immune system.

Animals↗
PubMed1998

Clinical features associated with the homozygous Trp64Arg mutation of the beta3-adrenergic receptor: no evidence for its association with obesity in Japanese.

To characterize the clinical features associated with the Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR), the effects of this mutation, in particular the homozygous state (Arg/Arg), on obesity, blood pressure, and plasma lipoproteins were investigated in 2 populations: subjects residing on a small isolated island (group 1; n=746) and patients residing in Tokyo who attend a clinic for metabolic diseases (group 2; n=371). The allelic frequency of the Trp64Arg mutation was 23.4% in group 1 and 18.3% in group 2. No significant difference in the body mass index was observed between subjects with 3 different genotypes in each group. There was a trend that the Arg/Arg had higher systolic blood pressure than the Trp/Trp in both groups, but the differences were not statistically significant. The plasma LDL cholesterol levels were significantly lower in Arg/Arg than in Trp/Trp in men from the group 1 cohort (2.82+/-0.84 versus 3.19+/-0.7 mmol/L, P<0.05). These results suggest that the homozygous Trp64Arg mutation is not a major contributing factor for obesity, but potentially contributed to higher systolic blood pressure and low plasma levels of LDL cholesterol in Japanese men.

Arginine↗
PubMed1998

Agonist-induced phosphorylation of the endogenous AT1 angiotensin receptor in bovine adrenal glomerulosa cells.

A polyclonal antibody was raised in rabbits against a fusion protein immunogen consisting of bacterial maltose-binding protein coupled to a 92-amino acid C-terminal fragment of the rat AT1b angiotensin II (Ang II) receptor. The antibody immunoprecipitated the photoaffinity-labeled bovine AT1 receptor (AT1-R), but not the rat AT2 receptor, and specifically stained bovine adrenal glomerulosa cells and AT1a receptor-expressing Cos-7 cells, as well as the rat adrenal zona glomerulosa and renal glomeruli. The antibody was employed to analyze Ang II-induced phosphorylation of the endogenous AT1-R immunoprecipitated from cultured bovine adrenal glomerulosa cells. Receptor phosphorylation was rapid, sustained for up to 60 min, and enhanced by pretreatment of the cells with okadaic acid. Its magnitude was correlated with the degree of ligand occupancy of the receptor. Activation of protein kinase A and protein kinase C (PKC) also caused phosphorylation of the receptor, but to a lesser extent than Ang II. Inhibition of PKC by staurosporine augmented Ang II-stimulated AT1-R phosphorylation, suggesting a negative regulatory role of PKC on the putative G protein-coupled receptor kinase(s) that mediates the majority of AT1-R phosphorylation. The antibody should permit further analysis of endogenous AT1-R phosphorylation in Ang II target cells.

Angiotensin II↗
PubMed1998

Telomerase Activation in Malignant Bone Tumors.

Background: Telomerase is a ribonucleoprotein that can reconstitute the ends (telomeres) of chromosomes after cell division and thus circumvent the cumulative damage that occurs during mitotic cycles of cells. A unique association has been established between telomerase activity and neoplastic transformation and cellular immortalization. The measurement of telomerase activity has also been considered to be a diagnostic marker for human malignant tumors; however, little is known about the status of telomerase activity in malignant bone tumors. Methods and Results: Thirty-five human bone sarcomas and adjacent noncancerous tissues were subjected for the first time by the modified telomeric repeat amplification protocol (TRAP)-silver staining assay for telomerase activity. The results showed that telomerase activity was present in 82.9% (29/35) of malignant bone tumors. Twenty-two of 26 (84.6%) osteosarcomas, 3 of 5 (60%) chondrosarcomas, 2 of 2 (100%) malignant fibrous histiocytomas, and 2 of 2 (100%) rhabdomyosarcomas contained telomerase activity. In contrast, there was no telomerase activity in 19 adjacent noncancerous tissues. Conclusions: The findings suggest that telomerase might play an important role in the development of malignant bone tumors. The detection of telomerase in malignant bone tumors may have value in increasing the accuracy of diagnosis of malignant bone tumors.

Journal Article↗
PubMed1998

Vinorelbine induces apoptosis and caspase-3 (CPP32) expression in leukemia and lymphoma cells: a comparison with vincristine.

Vinorelbine (NVB) is a novel vinca alkaloid FDA approved for use in some advanced carcinomas. However, its role in non-Hodgkin's lymphoma (NHL) is still not well defined. NVB is an antimicrotubule agent, but as yet, it is not known whether it induces apoptosis. By flow cytometry using nuclear staining (propidium iodide) and annexin V, we demonstrated that NVB and vincristine (VCR) induced both mitotic arrest and apoptosis in leukemia and lymphoma cells, in a drug exposure time dependent manner. Cell cycle kinetics in 3 different cell lines varied during vinca alkaloid treatment. The annexin V method showed that apoptosis, as opposed to necrosis, was the dominant mode of cell kill of chemosensitive leukemia and lymphoma cells. Phosphatidylserine expression on the cell surface was detectable as a hallmark of apoptosis at earlier drug exposure when compared to conventional flow cytometry with PI staining. By Western blot analysis, we demonstrated that CPP32 or caspase-3, a critical apoptosis inducer, and its active subunits p20 and p11 were upregulated in chemo- and apoptosis-sensitive lymphoma and leukemia cells treated with NVB. Our data contributes to the emerging hypothesis suggesting that widely divergent exogenous stimuli and chemotherapeutic agents can effect apoptosis in cancer cells via different pathways involving the caspases. We believe that vinorelbine may be a potentially important drug in the treatment of NHL in the future.

Annexin A5↗