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Biomedical subjects

W Luo

Publications and source records attributed to W Luo.

At least 127 records · Page 7Linked to original sources
PubMed1997

Phospholamban ablation enhances relaxation in the murine soleus.

Phospholamban (PLB) is expressed in slow-twitch skeletal, cardiac, and smooth muscles. Several studies have indicated that it is an important regulator of basal contractility and the stimulatory responses to isoproterenol in the mammalian heart. To determine whether PLB is also a key modulator of slow-twitch skeletal muscle contractility, we examined isometric twitch contractions of isolated, intact soleus muscles from wild-type (WT) and PLB-deficient mice in parallel. Soleus muscles from PLB-deficient mice exhibited a significant (25%) decrease in the time to half relaxation, with no change in contraction time compared with WT soleus muscles. The observed enhancement of relaxation in the PLB-deficient soleus was not associated with alterations in the protein levels of either the sarcoplasmic reticular Ca(2+)-adenosinetriphosphatase or the ryanodine receptor. Examination of the effects of isoproterenol on the twitch kinetics of these muscles revealed 1) no effect on the contraction times of either WT or PLB-deficient muscles and 2) a significant decrease in the half relaxation time of the WT soleus, whereas this parameter remained unchanged in the PLB-deficient muscle. Furthermore, with maximal isoproterenol stimulation, the half relaxation time of the WT soleus was similar to that of the nonstimulated PLB-deficient soleus. These results suggest that PLB is a key determinant of relaxation in slow-twitch skeletal muscle under basal conditions and during isoproterenol stimulation.

Adenosine Triphosphatases↗
PubMed1997

Phospholamban deficiency alters inactivation kinetics of L-type Ca2+ channels in mouse ventricular myocytes.

Entry of Ca2+ through voltage-dependent L-type Ca2+ channels is critical for contraction in cardiac cells. In recent studies, cells from phospholamban (PLB) knockout (PLB-KO) mouse hearts showed significantly increased basal contractility with enhanced sarcoplasmic reticulum (SR) Ca2+ uptake. To test whether these effects of PLB ablation were associated with alterations of L-type Ca2+ channel function, we compared the properties of Ca2+ channel currents (I(Ca)) in ventricular myocytes isolated from wild-type (WT) and PLB-KO mouse hearts. L-type Ca2+ channels from mouse myocytes exhibited voltage-dependent gating and sensitivity to dihydropyridine drugs, similar to other mammalian species, and these properties were not altered by PLB ablation. I(Ca) from both WT and PLB-KO cells revealed two (fast and slow) components of inactivation kinetics. However, the proportion of the faster component was significantly larger in PLB-KO cells. Ryanodine (10 microM) reduced the rate of inactivation of I(Ca) for both WT and PLB-KO cells, but the reduction was more prominent in PLB-KO cells compared with WT cells. In contrast, the inactivation in a Ba2+ solution could be fitted by a single exponential similar to the slower component in Ca2+, and this was not altered in PLB-KO cells. The increase in the fast Ca2+-dependent inactivation component in PLB-KO cells supports the hypothesis that Ca2+ released from the SR regulates Ca2+ channel inactivation by affecting the levels of Ca2+ near the channel and suggests that this may be an important compensatory mechanism in the hyperdynamic PLB-KO heart.

Animals↗
PubMed1997

beta-Adrenergic regulation of cAMP and protein phosphorylation in phospholamban-knockout mouse hearts.

The stimulatory effects of beta-adrenergic agonists reflect increases in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels and phosphorylation of key regulatory proteins in the heart. One of these phosphoproteins is phospholamban (PLB) in sarcoplasmic reticulum, and ablation of PLB is associated with attenuation of the contractile responses to beta-adrenergic stimulation in the mouse heart. To determine whether this attenuation of beta-stimulation is due to altered phosphorylation characteristics of the other key cardiac phosphoproteins and/or to compensatory responses occurring in the absence of PLB, PLB-knockout and wild-type hearts were perfused and their protein phosphorylation patterns examined. The beta-adrenergic receptor density, adenylyl cyclase activity, tissue cAMP levels, and the basal phosphoprotein pattern were similar between PLB-knockout and wild-type hearts. Isoproterenol perfusion resulted in similar increases in the tissue cAMP levels and the degree of phosphorylation of troponin I, C protein, and the 21-kDa microsomal protein in wild-type and PLB-knockout hearts. These findings indicate that the attenuation of isoproterenol-mediated increases in contractility of the PLB-knockout hearts is not due to alterations in the beta-adrenergic signal transduction pathway or the degree of phosphorylation of the key cardiac regulatory phosphoproteins in myofibrils and sarcolemma.

Animals↗
PubMed1997

Targeted ablation of the phospholamban gene is associated with a marked decrease in sensitivity in aortic smooth muscle.

Phospholamban (PLB) is a protein associated with the Ca(2+)-ATPase of the sarcoplasmic reticulum (SR) in cardiac, slow-twitch skeletal, and smooth muscle. PLB inhibits the SR Ca(2+)-ATPase in cardiac muscle; this inhibition is relieved on phosphorylation. The role of PLB in smooth muscle contractility is less clear. To elucidate the role of PLB in vascular smooth muscle contractility in vivo, we used a model in which the PLB gene was targeted in murine embryonic stem cells, generating mice deficient in PLB (PLB-). The PLB- mice exhibited no gross developmental abnormalities, but marked changes in aortic contractility were observed. The time course of force development with phenylephrine stimulation was faster in the PLB- aorta, suggesting changes in SR Ca2+ release. No differences were observed for KCl contractures between tissue types for either maximum forces observed or time course of force production; relaxation was faster in 7 of 11 arteries, but this trend did not attain statistical significance. The cumulative concentration-isometric force relations for the PLB- aorta were to the right of the wild-type for both KCl and phenylephrine stimulation, indicating a less sensitive tissue. To investigate whether the observed changes were related to SR function, we inhibited the SR Ca(2+)-ATPase with cyclopiazonic acid (CPA). CPA treatment resulted in a leftward shift of the concentration-isometric force relations for both aorta types, as expected after removal of a major Ca2+ uptake system. Most interestingly, the differences between PLB and wild-type aorta were abolished by SR inhibition. Our results suggest that PLB is a regulator of the SR Ca2+ pump in mouse aorta and plays a regulatory role in both KCl-induced and receptor-mediated contractility in vascular smooth muscle.

Animals↗
PubMed1997

Monomeric phospholamban overexpression in transgenic mouse hearts.

Phospholamban, a prominent modulator of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity and basal contractility in the mammalian heart, has been proposed to form pentamers in native SR membranes. However, the monomeric form of phospholamban, which is associated with mutating Cys41 to Phe41, was shown to be as effective as pentameric phospholamban in inhibiting Ca2+ transport in expression systems. To determine whether this monomeric form of phospholamban is also functional in vivo, we generated transgenic mice with cardiac-specific overexpression of the mutant (Cys41-->Phe41) phospholamban. Quantitative immunoblotting indicated a 2-fold increase in the cardiac phospholamban protein levels compared with wild-type controls, with approximately equal to 50% of phospholamban migrating as monomers and approximately 50% as pentamers upon SDS-PAGE. The mutant-phospholamban transgenic hearts were analyzed in parallel with transgenic hearts overexpressing (2-fold) wild-type phospholamban, which migrated as pentamers upon SDS-PAGE. SR Ca(2+)-uptake assays revealed that the EC50 values for Ca2+ were as follows: 0.32 +/- 0.01 mumol/L in hearts overexpressing monomeric phospholamban, 0.49 +/- 0.05 mumol/L in hearts overexpressing wild-type phospholamban, and 0.26 +/- 0.01 mumol/L in wild-type control mouse hearts. Analysis of cardiomyocyte mechanics and Ca2+ kinetics indicated that the inhibitory effects of mutant-phospholamban overexpression (mt) were less pronounced than those of wild-type phospholamban overexpression (ov) as assessed by depression of the following: (1) shortening fraction (25% mt versus 45% ov), (2) rates of shortening (27% mt versus 48% ov), (3) rates of relengthening (25% mt versus 50% ov) (4) amplitude of the Ca2+ signal (21% mt versus 40% ov), and (5) time for decay of the Ca2+ signal (25% mt versus 106% ov) compared with control (100%) myocytes. The differences in basal cardiac, myocyte mechanics and Ca2+ transients among the animal groups overexpressing monomeric or wild-type phospholamban and wild-type control mice were abolished upon isoproterenol stimulation. These findings suggest that pentameric assembly of phospholamban is important for mediating its optimal regulatory effects on myocardial contractility in vivo.

Adrenergic beta-Agonists↗
PubMed1997

[Immunological features of steroid-resistant asthma].

OBJECTIVE: To investigate the pathogenesis and treatment of steroid-resistant (SR) asthma. METHODS: Changes of serum levels of soluble interleukin-2 receptor (sIL-2R) after oral prednisone (20 mg/d) therapy were observed, and the peripheral blood T cell inhibitory effects of dexamethasone, oxymatrine and thymus-derived immunoinhibiting agents were studied in vitro by lymphocyte proliferation assay. RESULTS: After prednisone therapy, serum levels of sIL-2R were significantly decreased in steroid-sensitive (SS) asthmatics (P < 0.001) but not in SR asthmatics (P > 0.5). The inhibitory effects of dexamethasone (10(-7) mol/L) on the proliferation of T cells from SR asthmatics were significantly less than those from SS asthmatics (P < 0.002). Oxymatrine and thymus-derived immuno-inhibiting agents inhibited T cell proliferation to a similar degree between SR and SS asthmatics. CONCLUSIONS: Persistent T cell activation due to relative unresponsiveness of T cells to glucocorticoids was a feature of SR asthma. The therapeutic benefit of immuno-inhibiting agents other than glucocorticoids in the management of SR asthma deserves further investigation.

Adult↗
PubMed1997

[Pleural amyloidosis].

OBJECTIVE: To evaluate the clinical significance of systemic amyloidosis in the differential diagnosis of pleural effusion. METHOD: Retrospective analysis of the incidence and the characteristics of pleural effusion in systemic amyloidosis. RESULTS: Seven (47%) of 15 cases of systemic amyloidosis were complicated with pleural effusion, of them 4 cases were confirmed by positive Congo red stain of percutaneous pleural biopsies specimens. CONCLUSIONS: Systemic amyloidosis involving pleura was not rare. Pleural amyloidosis should be suspected in pleural effusion complicated by multiorgan disease. Percutaneous pleural biopsy with Congo red stain can confirm the diagnosis.

Adult↗
PubMed1997

[Analysis of 37 cases of pneumonia of Legionnaires' disease].

OBJECTIVE: To heighten our awareness of pneumonia of Legionnaires' disease (LP). METHODS: 37 cases of LP were reviewed. RESULTS: Besides the characteristics of pneumonia, extrapulmonary manifestations, including gastrointestinal, hepatic, renal and neurologic abnormalities, occurred in 35% of the patients, pleural effusion was more common (40%), 38% and 17% of the patients showed hyponatremia and pulmonary abscess respectively. Roentgenographic changes appeared to last longer and resoluted later than the clinical improvement occurred. CONCLUSION: Erythromycin shows good effects in treating LP.

Adolescent↗
PubMed1997

[The effect of epithelium on inhibition of histamine-induced contraction of guinea-pig isolated trachea by potassium channel opener Rp 52891].

To evaluate whether the relaxant effect of Rp 52891 on isolated normal or sensitized guinea-pigs trachea is influenced by the removal of airway epithelium, twenty-four normal and sensitized guinea-pigs were randomly divided into two groups: epithelium-intact trachea and epithelium-denuded trachea. The effect of Rp 52891 on contraction elicited by histamine in epithelium-intact and epithelium-denuded trachea was investigated, and it was compared with that of aminophylline or isoprenaline. The results revealed that there was no significant difference in histamine-induced contractile response between normal and sensitized isolated trachea. The inhibitory effect of Rp 52891 on the contractile response of histamine was significantly reduced by removing the epithelium but that of aminophylline or isoprenaline was not changed. These results suggested that Rp 52891 may directly relax the airway smooth muscle of guinea-pigs in vitro, the epithelium of guinea-pigs trachea may modulate the relaxant effect of Rp 52891.

Aminophylline↗
PubMed1997

[Effects of calcium channel blockers and calmodulin inhibitors on the secretion of endothelin-1 in cultured endothelial cells].

OBJECTIVE: The study is to investigate the effects of calcium channel blockers and calmodulin inhibitors on the secretion of endothelin-1 (ET-1) in cultured endothelial cells from human umbilical veins. RESULTS: Results showed that calcium channel blockers verapamil (5.5 x 10(-6) mol/L, 5.5 x 10(-5) mol/L), diltiazen (2.4 x 10(-4) mol/L) and calmodulin inhibitors chlorpromazine (3.1 x 10(-5) mol/L, 3.1 x 10(-4) mol/L), berbamine (1.6 x 10(-5) mol/L, 1.6 x 10(-4) mol/L) significantly decreased medium ET-1 levels in cultured endothelial cells. CONCLUSION: It was also indicated that extracellular calcium influx and calmodulin activity were necessary to the secretion of ET-1. In addition, nitroglycerine (2.2 x 10(-3) mol/L) remarkably reduced medium ET-1 levels in cultured endothelial cells, which suggested that nitric oxide might inhibit the secretion of ET-1.

Alkaloids↗
PubMed1997

Auditory P300, CT scans and cognitive state in Binswanger's disease.

The P300 component of evoked potential can reflect cognitive state in dementia patients. The purpose of this study was to investigate the value of P300 as an indicator of cognition in Binswanger's disease (BD) and to explore the possible causes of dementia in BD patients. P300 was measured at Cz site in 21 patients with BD and 21 controls matched with age, sex, handedness, and education. This measurement included P300 latency and amplitude. All patients were also given WAIS-RC test and scanned with computerized tomography (CT), and were treated with hyperbaric oxygenation (HBO). The relationships among P300, CT and WAIS-RC score were studied. BD patients had significantly prolonged P300 latency and a tendency of low amplitude P300, but the amplitude difference was not significant compared with controls. P300 latency was found to be negatively correlated with WARS-RC scale, and positively correlated with the change of white matter low attenuation (WMLA). WMLA was also correlated with WAIS-RC score. Treatment with HBO reduced P300 latency and had effect on the cognitive part of P300 but had no effect on CT changes. The significant association between neurophysiological and neuropsychological measurement suggests that P300 measurement reflects a disrupted aspect of cognitive function in BD patients, and it may be a useful means to assess the degree of subcortical cognitive deterioration and the effect of therapy. White matter lesion in BD is concerned to the occurrence of dementia by disturbing axonal conduction.

Aged↗
PubMed1997

Problem-based learning at the University of Southern California School of Dentistry.

Responding to the recent Institute of Medicine report on dental education, the Center for Craniofacial Molecular Biology (CCMB) of the University of Southern California School of Dentistry has developed a parallel track program in dental education leading to the D.D.S. degree. This program was proposed in May of 1995, and the first class of twelve students was admitted in September of that year. Currently two classes are enrolled and plans to admit a further twelve students (Class of 2001) are in place. The educational strategy for this program is totally problem-based. Students work in groups of six with a faculty facilitator, not necessarily a content expert. Facilitators are largely drawn from the multidisciplinary pool of research faculty at the center. All learning is mediated through biomedical and biodental problem cases. No formal lectures or classes are scheduled. The learning of clinical dental skills is promoted through focussed dental patient simulations in which students review clinical charts, radiographs, medical reports and then explore identified, hands-on learning needs using patient simulators in a clinical context. Early patient exposure is obtained through dental office visits and other special patient clinics. Initial experience with this program suggests that the problem-based learning (PBL) students learn as well (if not better) than their traditional program peers and develop excellent group and cognitive analytical skills. The absence of a pool of dentally related biomedical cases suitable for a PBL program has necessitated the use of innovative approaches to their development and presentation. It is believed that this educational approach will produce dental clinicians equipped with the self-motivated, life-long learning skills required in the ever-changing world of bio-dental sciences in the twenty-first century.

California↗
PubMed1997

CGP 41251 and tamoxifen selectively inhibit mitogen-activated protein kinase activation and c-Fos phosphoprotein induction by substance P in human astrocytoma cells.

The substance P (SP) receptor (NK-1 subtype) is widely expressed in primary human astrocytomas and glioblastomas and many brain tumor-derived cell lines. SP receptor activation stimulates the mitogen-activated protein (MAP) kinase pathway and the expression of immediate-early genes (e.g., c-Fos and c-Myc), resulting in an increase in DNA synthesis in human astrocytoma U-373 MG cells. In this study, we investigated the role of protein kinase C (PKC) in SP receptor activation of the MAP kinase pathway. SP peptide, epidermal growth factor, and the PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the tyrosine phosphorylation of the Erk1 and Erk2 MAP kinases in a concentration-dependent manner in U-373 MG cells. Pretreatment of the cells with PKC inhibitors, CGP 41251 or tamoxifen, inhibited tyrosine phosphorylation of Erk1 and Erk2 MAP kinases induced by low concentrations of SP or TPA and significantly attenuated phosphorylation at high concentrations of SP or TPA. The inhibitory effect exhibited by tamoxifen on SP-induced MAP kinase activation is similar to that exhibited by the selective PKC inhibitor CGP 41251, suggesting that the PKC enzyme is the in situ target for both inhibitors. Furthermore, SP-induced c-Fos phosphoprotein expression is inhibited by CGP 41251 or tamoxifen with similar efficacy. Importantly, neither CGP 41251 nor tamoxifen has any detectable effect on the MAP kinase activation by epidermal growth factor, consistent with the ability of this growth factor to activate the MAP kinase pathway by a PKC-independent mechanism. Prolonged treatment with TPA resulted in down-regulation of PKC and selective inhibition of TPA- and SP-induced Erk1 and Erk2 tyrosine phosphorylation in U-373 MG cells. Consistent with the in situ results, CGP 41251 and tamoxifen significantly inhibited endogenous PKC enzymatic activity from U-373 MG cells in vitro. In contrast to CGP 41251 and tamoxifen, Gö 6976, a highly selective inhibitor for PKC alpha and PKC beta 1 isozymes, did not inhibit SP- or TPA-induced tyrosine phosphorylation of Erk1 and Erk2 MAP kinases; rather, it inhibited a signaling pathway leading to the phosphorylation of cAMP-responsive element binding protein in U-373 MG cells. To investigate whether selective PKC isozyme(s) are involved in the activation of the MAP kinase pathway by SP, we determined the expression of PKC isozymes in U-373 MG cells. We found that U-373 MG cells express nine different PKC isozymes (alpha, beta I, beta II, epsilon, delta, eta, zeta, iota, and mu) and that stimulation with SP results in significant and selective translocation of PKC epsilon isozyme from cytosolic to membrane fraction. This establishes a correlation between the ability of SP to activate the MAP kinase pathway and its ability to translocate PKC epsilon. In conclusion, the results presented in this study demonstrate that SP receptor activation of PKC, possibly PKC epsilon, leads to the activation of the MAP kinase pathway, and that this pathway can be inhibited by known PKC inhibitors.

Astrocytoma↗
PubMed1997

Kinetics in parasite abundance in susceptible and resistant mice infected with an avirulent strain of Toxoplasma gondii by using quantitative competitive PCR.

The kinetics of changes in Toxoplasma gondii abundance were evaluated with a quantitative competitive (QC)-polymerase chain reaction (PCR) assay at various sites in both C57BL/6 and BALB/c mice. Higher mortality was apparent in C57BL/6 mice than in BALB/c mice when infected with a high dose of cysts. There were significant differences in cyst number when infected with a low dose of cysts, although there was no significant difference in mortality between the 2 mouse strains. One day after infection with a low dose of an avirulent Fukaya strain, T. gondii was detected in peripheral blood, mesenteric lymph nodes, spleen, lungs, and brain. Two weeks after infection, the number of T. gondii in the brain greatly increased in C57BL/6 mice but not in BALB/c mice. Thus, it would appear that the first to second week after infection is a critical period in determining T. gondii abundance. QC PCR allows the detection of low numbers of T. gondii at an early stage of infection in the murine model. This is useful for the early diagnosis of toxoplasmosis and to understand reactivation of toxoplasmosis.

Animals↗
PubMed1997

[Effect of ischemic preconditioning on adenine nucleotide levels of graft lung from canine donor].

Twelve canine left lung allotransplantation were performed. In the ischemic preconditioning group (Group IP, n = 6), left donor lung was preconditioned with 10 min ischemia followed by 15 min reperfusion using the occuluding left hilum before resection and cold perfusion. The control group (Group C, n = 6) underwent the same treatment but without ischemic preconditioning. Adenine nucleotides (ATP, ADP, AMP) of the donor lung tissue were measured using rHPLC after 2 hr of resection and cold perfusion with Euro-Collins solution (ECS). The results showed that contents of ATP and total adenine nucleotides (TAN) were much higher in Group IP than in Group C (322.9 +/- 61.2, 942.9 +/- 134.5 and 200.0 +/- 50.0, 668.4 +/- 59.6 mumol.g-1 respectively, P < 0.05). Histologic examination of the donor lung in Group IP showed less damage than in Group C after 2 hr of transplantation. The results suggest that IP combined with cold ECS perfusion can reduce the energy metabolism in canine donor lung.

Adenosine Diphosphate↗
PubMed1997

[Effects of ischemic preconditioning on protection of canine donor lung].

The authors examined the effects of ischemic preconditioning on lung preservation using a canine single left lung transplantation. Twelve adult mongrel dogs underwent left lung allotransplantation. Donor lungs were perfused and flushed with cold Euro-Collins solution (ECS) and stored at 4 degrees C ECS for 2 hours. Six donors were preconditioned by occuluding left lung hilum for 10 minutes and releasing for 15 minutes before flushing (Group PC); other six donors without ischemic preconditioning served as the controls (Group C). Left inferior pulmonary vein blood gas analysis, mean pulmonary artery pressure measurement and donor lung histology examination were made to evaluate the function of transplanted lung after transplantation. Oxygen tension at 2 hrs after reperfusion were significantly better in Group PC than in Group C (431 +/- 130 mmHg vs 246 +/- 66 mmHg, P < 0.05); mean pulmonary artery pressure was much lower in Group PC than in Group C after reperfusion (20.6 +/- 1.3 mmHg vs 36.9 +/- 3.1 mmHg, P < 0.01). Histological findings showed less injury in Group PC. These indicate that ischemic preconditioning combined with cold ECS perfusion is superior to cold ECS perfusion alone in canine lung preservation of 3 hours ischemia with 2 hours reperfusion.

Animals↗
PubMed1996

Determination of lincomycin residues in salmon tissues by gas chromatography with nitrogen-phosphorus detection.

A sensitive method for the determination of lincomycin residues in fish tissues is described. Lincomycin was extracted from fish tissues with phosphate buffer (pH 4.5). The extract was concentrated with a C18 solid-phase extraction cartridge and further cleaned up by solvent extraction. Lincomycin was derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide to form a trimethylsilyl derivative before being analyzed by gas chromatography with nitrogen-phosphorus detection. Coumaphos was used as the internal standard. Assays showed good linearity in the range 25-250 ppb (ng/g) (r = 0.9994). Recoveries of fortified lincomycin at 50, 100 and 200 ppb were > 80% with relative standard deviations < 6%. The limit of detection of the method was 1.7 ppb and the limit of quantitation was 3.8 ppb.

Acetamides↗