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Y Ni

Publications and source records attributed to Y Ni.

At least 73 records · Page 4Linked to original sources
PubMed1997

Proteolysis of platelet cortactin by calpain.

Cortactin, a substrate of pp60(c-)src and a potent filamentous actin binding and cross-linking protein, is abundant in circulating platelets. After stimulation of platelet aggregation with collagen, cortactin undergoes a dramatic increase in tyrosine phosphorylation followed by a rapid degradation. The cleavage of platelet cortactin was detected in lysates prepared using either Triton-containing buffer or SDS-sample buffer. However, the degradation of cortactin was not observed in platelets derived from a Glanzmann's patient, who lacked functional integrin alphaIIbbeta3 (GPIIb-IIIa). In addition, the proteolysis of cortactin was abolished by treating platelets before but not after collagen stimulation with EGTA or calpeptin. Furthermore, recombinant cortactin was digested by mu-calpain in vitro in a dose-dependent manner, indicating that cortactin is a substrate for calpain. We also observed that the calpain-mediated digestion in vitro is dependent on the presence of a sequence containing a proline-rich region and multiple tyrosine residues that are phosphorylated by pp60(c-)src. Tyrosine phosphorylation by pp60(c-)src up-regulates the activity of calpain toward cortactin. Our data suggest that the calpain-mediated proteolysis of tyrosine-phosphorylated cortactin may provide a mechanism to remodel irreversibly the cytoskeleton in response to platelet agonists.

Blood Platelets↗
PubMed1997

Ex vivo experiment on radiofrequency liver ablation with saline infusion through a screw-tip cannulated electrode.

PURPOSE: To investigate whether radiofrequency (RF) therapy with hypertonic saline infusion through a hollow screw-tip electrode can cause a lesion size suitable for liver tumor ablation. MATERIALS AND METHODS: RF tissue ablation of 180 sites was performed by using a hollow screw-tip electrode in 40 freshly excised swine livers. Under both power and temperature control modes, the ablation effects with and without various regimes of 5% hypertonic saline (1 ml/min) prior to and/or during the procedure were compared by measuring the size of lesions at dissection and confirmed by T1 and T2 weighted magnetic resonance (MR) imaging. RESULTS: The maximal lesion diameter of 5.5 cm was reached at 30 W with saline infusion 1 min prior to and during 12 min of ablation. The smaller sizes (P < 0.01) between 0.3 and 2.5 cm in diameter were met with noninfusion or preinfusion-only groups. The RF ablation lesions appeared as hyper- and hypointense areas on T1 and T2 MR images, respectively. CONCLUSIONS: RF ablation in combination with present hollow screw-tip electrode and saline infusion allows for necrotic development of suitable size for liver tumor ablation. Such ablated lesions can be visualized with MR imaging.

Animals↗
PubMed1997

Down-regulation of the filamentous actin cross-linking activity of cortactin by Src-mediated tyrosine phosphorylation.

Cortactin, a prominent substrate for pp60(c-src), is a filamentous actin (F-actin) binding protein. We show here that cortactin can promote sedimentation of F-actin at centrifugation forces under which F-actin is otherwise not able to be precipitated. Electron microscopic analysis after negative staining further revealed that actin filaments in the presence of cortactin are cross-linked into bundles of various degrees of thickness. Hence, cortactin is also an F-actin cross-linking protein. We also demonstrate that the optimal F-actin cross-linking activity of cortactin requires a physiological pH in a range of 7.3-7.5. Furthermore, pp60(c-src) phosphorylates cortactin in vitro, resulting in a dramatic reduction of its F-actin cross-linking activity in a manner depending on levels of tyrosine phosphorylation. In addition, pp60(c-src) moderately inhibits the F-actin binding activity of cortactin. This study presents the first evidence that pp60(c-src) can directly regulate the activity of its substrate toward the cytoskeleton and implies a role of cortactin as an F-actin modulator in tyrosine kinase-regulated cytoskeleton reorganization.

Actins↗
PubMed1997

Upregulation of cortactin expression during the maturation of megakaryocytes.

Cortactin is a potent filamentous actin-binding protein acting as a prominent substrate of Src tyrosine kinases. We have evaluated cortactin expression in a series of murine tissues and shown an abundant expression of cortactin in megakaryocytes and platelets. Cortactin, but not its related protein HS1, is upregulated during the phorbol 12-myristate 13-acetate (PMA)-mediated maturation of a human megakaryoblastic cell line CMK. Although the expression of Src-related kinases is also upregulated more rapidly than cortactin in PMA-treated CMK cells, tyrosine phosphorylation of cortactin appears to be only transiently elevated 4 days after PMA stimulation. In addition, cortactin expression is induced by thrombopoietin and interleukin-3 in megakaryocytes derived from murine bone marrow cells. Thus, cortactin represents a megakaryocyte-specific gene in bone marrow and the interaction of Src kinases with cortactin may be involved in the maturation of megakaryocytes.

Animals↗
PubMed1997

Gestation increases nitric oxide-mediated vasodilation in rat uterine arteries.

OBJECTIVE: The purpose of this study was to determine the influence of endothelium-released nitric oxide on uterine arterial tone and reactivity during pregnancy. STUDY DESIGN: The effects of pregnancy on endothelial function were evaluated in isolated pressurized rat uterine arteries from late-pregnant rats (day 19 to 20) versus age-matched nonpregnant controls. The effects of nitric oxide synthase inhibition (N(omega)-nitro-L-arginine) on arterial tone and reactivity under basal and activated (phenylephrine) conditions were determined, as was arterial reactivity to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators, by evaluating changes in lumen diameter. RESULTS: (1) Maximal constriction to N(omega)-nitro-L-arginine was significantly enhanced under basal (nonstimulated) conditions in arteries from late-pregnant versus nonpregnant rats (changes in lumen diameter 37% +/- 8% vs 9.3 +/- 6.2%, respectively, p < 0.05). (2) Nitric oxide synthase blockade with 1 nmol/L N(omega)-nitro-L-arginine significantly increased phenylephrine sensitivity in arteries from late-pregnant animals (median effective concentration 115 +/- 23 nmol/L vs 33 +/- 8 nmol/L, control vs treated vessels, p < 0.05) but was without statistically significant effect on arteries from nonpregnant animals (control 255 +/- 164 nmol/L, treated 250 +/- 102 nmol/L, p > 0.05). (3) The threshold concentration of acetylcholine required to elicit endothelium-dependent dilation was significantly lower in late-pregnant versus nonpregnant arteries (1.4 +/- 0.2 nmol/L vs 12.2 +/- 3.8 nmol/L, p < 0.05). (4) Vascular smooth muscle sensitivity to an exogenous nitrodilator (sodium nitroprusside) was identical in late-pregnant versus nonpregnant vessels. CONCLUSION: Endothelial vasodilator influences are augmented during pregnancy under basal, activated (phenylephrine), and chemically provoked (acetylcholine) conditions in uterine arteries by enhanced release of nitric oxide.

Acetylcholine↗
PubMed1997

Localization and determination of infarct size by Gd-Mesoporphyrin enhanced MRI in dogs.

BACKGROUND: Accurate localization and sizing of a myocardial infarction are necessary for clinical decision making and even more in research. Gd-Mesoporphyrin enhanced magnetic resonance imaging (MRI) was recently shown to specifically delineate necrosis in liver tumors, renal and muscle necrosis and myocardial infarction in rats. In this study, we investigated this technique's potential to accurately delineate myocardial infarction in a larger animal species, the dog. METHODS: Myocardial infarction was induced in 8 dogs by ligation of the left anterior descending coronary artery, 4 of which were reperfused after 3 hr Gd-Mesoporphyrin (0.05 mmol/kg) was injected intravenously 210 min after the onset of ischemia (n = 6) or after 24 hr in 2 dogs with non-reperfused infarctions. MRI was performed 10 hr after administration of Gd-Mesoporphyrin. In vivo MRI consisted of EKG-triggered, respiratory gated T1-weighted spin echo and segmented turboFLASH long and short axis measurements. Post-mortem, a spin echo short axis measurement was repeated. Infarct size was determined planimetrically by TTC staining of left ventricular slices. RESULTS: In all instances, there was a very close qualitative agreement between the MRI and TTC defined myocardial infarction. Quantitatively, the linear regression from post-mortem MRI to TTC determined infarct size yielded a result very close to the line of identity (regression coefficient: 0.980 +/- 0.026, p < 0.000001, adjusted R2 = 0.964). CONCLUSION: We conclude that Gd-Mesoporphyrin enhanced MRI is a promising tool for the accurate delineation of myocardial infarction.

Animals↗
PubMed1997

Comparison of manganese biodistribution and MR contrast enhancement in rats after intravenous injection of MnDPDP and MnCl2.

PURPOSE: To compare the time course of the MR enhancing properties and biodistribution of manganese (Mn) in rats given i.v. Mn dipyridoxyl diphosphate (MnDPDP) or Mn chloride (MnCl2). MATERIAL AND METHODS: Twenty-four adult rats were injected i.v. with 5 mumol/kg MnDPDP or MnCl2, or with 0.5 ml/kg saline. High resolution T1-weighted MR imaging was performed during early (10 min), mid (2 h) and late (24 h) phases after injection. Mn concentrations in major organs were measured by using an ICP-AES technique, and correlated with MR findings. RESULTS: Variable degrees of signal enhancement of major organs observed in MR images corresponded with the amount of Mn uptake after injection of MnDPDP or MnCl2. A prominently lower cardiac, pancreatic and hepatic uptake of Mn was seen at 10 min in rats injected with MnDPDP compared with those given MnCl2 and this was reflected in a difference in signal intensity (SI) in the MR images. At 2 h, the Mn content and SI in the major organs were similar with both MnDPDP and MnCl2. An overall Mn clearance was achieved at 24 h without any important organ retention, with kidney excretion of Mn seen only with MnDPDP. CONCLUSION: With both MnDPDP and MnCl2, the Mn uptake correlates with the SI enhancement in tissues. The reduced initial cardiac uptake of Mn after MnDPDP treatment compared to MnCl2 may account for the favourable cardiovascular safety of the contrast agent. These data contribute to an understanding of SI enhancement by MnDPDP, and are consistent with other studies showing that at a dose of 5 mumol/kg, MnDPDP can be safely used as a potent MR organ-specific contrast agent.

Animals↗
PubMed1997

Clinical implications of studies with MnDPDP in animal models of hepatic abnormalities.

Mangafodipir trisodium (manganese dipyridoxal diphosphate or MnDPDP) has been introduced as a hepatobiliary MR contrast agent (Teslascan). Its potential to assist in the characterisation of focal liver lesions, the diagnosis of local and global obstructive cholestasis and the evaluation of hepatic function in diffuse liver diseases has been explored in multiple pre-clinical experiments with appropriate animal models. The prompt negative contrast enhancement and delayed peritumoural rim-enhancement seen after i.v. injection of MnDPDP are 2 typical features of primary and secondary liver tumours with high malignancy, while the persistent positive enhancement is a sign of liver tumours of well preserved hepatocytic nature. Liver with local and total biliary obstruction can be visualized in MnDPDP-enhanced MR images as a region with prolonged signal enhancement. This agent could also be used to non-invasively evaluate diffuse liver diseases of different causes. In the present paper, we review the experimental data in the literature, provide some unpublished results and discuss the potential impact on the clinical use of MnDPDP in the liver. We conclude that MnDPDP is a promising MR liver contrast agent for the detection and characterisation of focal and diffuse liver diseases.

Animals↗
PubMed1997

Magnetic resonance imaging-histomorphologic correlation studies on paramagnetic metalloporphyrins in rat models of necrosis.

RATIONALE AND OBJECTIVES: The authors intended to confirm previous findings that paramagnetic porphyrins are avid only for intratumoral nonviable tissues, but not for viable tumor cells, and to test the hypothesis that necrosis, regardless of location and origin, can be visualized by metalloporphyrin enhanced magnetic resonance imaging (MRI). METHODS: Intravenous administrations of gadolinium mesoporphyrin (Gd-MP), manganese tetraphenylporphyrin (Mn-TPP), manganese methylpyrroporphyrin-gadopentetate dimeglumine complex (Mn-MPP-Gd) and manganese tetra(4-sulfonatophenyl)porphyrin (MnTPPS4) at 0.05 mmol/kg were compared with those of gadopentetate dimeglumine (Gd-DTPA) at 0.1 mmol/kg in 38 rats with cholestatic liver necrosis, alcohol- and laser-induced coagulation necrosis in liver, and skeletal muscle, reperfused hepatic infarction, and segmental renal infarction. T1-weighted spin echo MRI (TR/TE = 300/15 mseconds) was acquired before and as long as 48 hours after injection, matched with histologic findings, and correlated with Gd/ Mn tissue content measurements. RESULTS: Both Gd-DTPA and the four metalloporphyrins initially caused a similar nonspecific negative contrast enhancement in the necrosis. However, a strong and persisting positive enhancement (necrosis-to-normal contrast ratio ranging from 1.5 to 2.0) developed only with metalloporphyrins in all types of necrosis. In liver and kidney, Gd and Mn concentrations at 24 hours were comparable in necrotic and normal tissues. In muscle, the concentrations were more than eight times higher in necrotic than in normal tissue. CONCLUSIONS: The implied affinity of metalloporphyrins for necrosis with presumably increased relaxivity suggests a possible mode of targetability for MRI contrast media that may elicit novel applications.

Animals↗
PubMed1997

Pregnancy augments uteroplacental vascular endothelial growth factor gene expression and vasodilator effects.

This study examined a potential role for vascular endothelial growth factor (VEGF) in uterine artery remodeling and vasodilation during pregnancy. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect VEGF mRNA in uterine tissues from nonpregnant (NP), midpregnant (MP, 15-16 days), and late-pregnant (LP, 19-21 days) rats and in placentas from MP and LP rats. VEGF mRNA levels in uteri and placentas were determined by Northern blotting, and the vasorelaxant activity of recombinant human VEGF (rh-VEGF) was tested and compared in isolated uterine arteries from LP and NP animals. VEGF120 and VEGF164 were the major isoforms detected in uterine tissues; all members of the VEGF family (VEGF120, VEGF164, VEGF188, and VEGF205) were expressed in LP placentas. VEGF mRNA levels increased 60% in MP and 80% in LP above those in NP (P < 0.05) in uterine tissues; VEGF mRNA levels were also detectable in placentas and elevated approximately fivefold in LP vs. MP tissues (P < 0.01). Phenylephrine-preconstricted uterine arcuate arteries (NP and LP) dilated in response to rhVEGF, an effect that was completely abolished by endothelial denudation or pretreatment with genistein, a tyrosine kinase inhibitor. The magnitude of dilation to an intermediate concentration of rhVEGF (1 nM) was greater in LP than in NP vessels (55 +/- 8 vs. 24 +/- 11%; P < 0.05), and this effect was diminished comparably in both groups (approximately 60% by N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis. These results suggest that VEGF may play a role in the vascular remodeling and vasodilation that lead to decreased uterine vascular resistance and increased uterine blood flow during pregnancy.

Animals↗
PubMed1996

Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals.

The ability of oxidative stress to induce apoptosis, and the effect of Ginkgo biloba extract (EGb761) on this induction were studied in primary cultured rat cerebellar neuronal cells. Cells were exposed to hydroxyl radicals by treating them with 20-50 microM hydrogen peroxide (H2O2) and 100 microM ferrous sulfate. Hydroxyl radical treatment fragmented the DNA in a manner typical of apoptosis cells, producing a ladder pattern of 200 base pair increments on 1% agarose gel electrophoresis. Pretreatment of cells with 100 micrograms/ml EGb reduced hydroxyl radical induced cells apoptosis (determined by flow cytometry) and DNA fragmentation. The results indicate that hydroxyl radicals induce apoptosis in rat cerebellar neuronal cells and this induction can be prevented by EGb.

Animals↗
PubMed1996

Purification, characterization, and pathogenicity of urease produced by Vibrio parahaemolyticus.

Vibrio parahaemolyticus is a halophilic bacterium associated with gastroenteritis and traveller's diarrhea. The urease-positive, Kanagawa-negative V. parahaemolyticus had been isolated from patients and the environment in the Pacific Northwest, first reported by Kelly et al. (5). Recently, we purified the urease produced by a clinical isolated of V. parahaemolyticus, and its characterization and pathogenicity has been studied. The urease isolation procedure included a water extraction and anion exchange chromatography. The molecular weight for the native enzyme was 275 KDa, and the three subunits of 85 KDa, 59 KDa, and 33 KDa were determined. The isoelectric focusing of urease was 5.2. The purified urease also can cause intestinal fluid accumulation and demonstrate a positive result in the suckling mouse test. These results suggested that the urease produced by V. parahaemolyticus may be another important indicator for the pathogenesis of the bacteria.

Animals↗
PubMed1996

Detection and characterization of primary liver cancer in rats by MS-264-enhanced MRI.

A new MR contrast agent, MS-264 (Gd(1RS)-1-(p-butylbenzyl)-DTPA), was developed to achieve hepatobiliary specificity and its potential evaluated for detecting and characterizing liver tumors in rats with chemically induced hepatocellular carcinoma (HCC). In seven rats with 66 HCC lesions, enhancements of different abdominal organs and tumors were compared on T1-weighted images after intravenous administration of Gd-DTPA (0.3 mmol/kg) and MS-264 (0.05 mmol/kg). MR images were correlated with postmortem microangiographic and histological findings. An overall enhancement of different organs, which normalized within 24 h, was observed after Gd-DTPA and MS-264 injection. MS-264 caused a higher relative enhancement (RE) in liver (60%), compared with that of Gd-DTPA (40%), which resulted in a prompt negative contrast enhancement in 59 of 66 HCCs. All were moderately to poorly differentiated (Grades II-IV) tumors. Six of these 59 negative contrast-enhancing lesions showed a positively enhanced peritumoral rim, which corresponded histologically to malignant infiltration (n = 2) or compression (n = 4). On the other hand, six well differentiated HCCs showed prolonged positive enhancement. However, one well differentiated HCC was not positively enhanced by MS-264, probably due to poor access of the agent to the lesion. In comparison to that of the precontrast images, enhancement with Gd-DTPA and MS-264 increased the number of detected lesions by 22 and 42%, respectively. In this animal study, MS-264 proved to be useful in detection and characterization of primary liver cancers.

Animals↗
PubMed1996

Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by MRI.

In previous experiments in tumors we demonstrated that metalloporphyrins are particularly avid for nonviable tumor components. This study was performed to find out whether these agents can be used as MRI contrast agents for the visualization of acute myocardial infarction (MI). A total of 44 rats, 6 normal controls and 38 with occlusive MI (2-24 h old), were used. Gadolinium mesoporphyrin (Gd-MP) or manganese tetraphenylporphyrin (Mn-TPP) was intravenously injected at doses of 0.1, 0.05, and 0.01 mmol/kg. Three to 24 h after injection, axial and coronal T1-weighted (TR/TE 300/15 ms) spin-echo MR images were obtained before and after killing the animals and correlated with triphenyl tetrazolium chloride (TTC) histochemical preparations. The Gd-MP content in infarcted and noninfarcted myocardium was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). MRI without contrast media could not discern the MI. However, 3-24 h after injection of either Gd-MP or Mn-TPP, the infarcted area was positively stained on MR images. This area matched well with the negatively TTC-stained area on the heart slices (r = 0.97). The contrast ratios between the infarcted necrotic myocardium and the noninfarcted regions varied from 150 to 300% depending on the type of agents and doses used. Neither false-positive nor false-negative findings were encountered. The metalloporphyrin concentration was more than 10 times higher in the infarcted than in the noninfarcted heart. Metalloporphyrins appear to be promising MRI contrast agents for detection and quantification of necrosis in MI. These preclinical results may open new perspectives in cardiac imaging.

Animals↗
PubMed1996

Lectin-carbohydrate interaction in the immune system.

The immune system consists of various types of cells and molecules that specifically interact with each other to initiate the host defense mechanism. Recent studies have shown that carbohydrates and lectins (carbohydrate-binding proteins) play an essential role in mediating such interactions. Both lectins and carbohydrates are widely distributed in the mammalian tissues as well as in microorganisms. Carbohydrates, due to their chemical nature, can potentially form structures that are more variable than proteins and nucleic acids. Lectins can exist in either soluble or cell-associated form, and although overall structures vary, invariably possess carbohydrate-recognition domains (CRD) with various specificities. The interaction between lectins and carbohydrates have been shown to be involved in such activities as opsonization of microorganisms, phagocytosis, cell adhesion and migration, cell activation and differentiation, and apoptosis. The number of lectins identified in the immune system is increasing at a rapid pace. The development in this area has opened a new aspect in studying the immune system, and at the same time, provided new therapeutic routes for the treatment and prevention of disease.

Animals↗
PubMed1996

Magnetic resonance imaging of experimental tracheal transplantation.

RATIONALE AND OBJECTIVES: We evaluated the feasibility of using contrast-enhanced magnetic resonance (MR) imaging for in vivo monitoring of tracheal transplants in rabbits. METHODS: Plain and gadolinium-enhanced, high-resolution MR images were obtained from six rabbits 4 weeks to 6 months after an orthotopic tracheal transplantation (after heterotopic revascularization). The animals were sacrificed after the MR examination, and comparisons were made among the MR images, macroscopic observations, and histologic sections. RESULTS: All transplants were clearly identifiable on the MR images; they produced slight-to-moderate narrowing of the airway diameter. Enhancement of the transplant tissues was clearly present. There was close correspondence between the MR morphology and the macroscopic and histologic sections. CONCLUSION: MR imaging can be used to monitor in vivo tracheal transplantation after heterotopic revascularization.

Anastomosis, Surgical↗
PubMed1996

Cardiac papillary fibroelastoma.

Papillary fibroelastomas are rare and benign heart tumors. We present two cases with these lesions. A young female patient with cerebral infarction was operated to resect the tumor on the mitral valve and the valve was successfully repaired. Another male patient had a history of bradycardia. On examination, coronary stenosis and a tumor in the left ventricle was found. Tumor excision combined with aorto-coronary artery bypass grafting was performed. Echocardiography proved to be highly effective to diagnose these tumors. Because of the potential cerebral and coronary embolization, these tumors should be excised. Surgical results are good.

Adult↗