Biomedical subjects

W Lu

Publications and source records attributed to W Lu.

At least 217 records · Page 12Linked to original sources

PubMed1998

Identification of the active site serine of penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus by electrospray mass spectrometry.

Penicillin-binding protein 2a (PBP2a), a high molecular mass PBP, is the primary enzyme responsible for the beta-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA). Inhibition of a PBP such as PBP2a by beta-lactams is due to covalent modification of an active site serine residue. Based on the sequence alignment with well studied beta-lactamases, DD-carboxypeptidases and other high molecular mass PBPs, the serine of a tetrad S403XXK in PBP2a was tentatively identified as the penicillin-binding site. However, direct evidence for the involvement of serine403 has not been reported. In this study, a method which combines liquid chromatography/electrospray mass spectrometry (LC/MS) and nano-electrospray MS for the identification of the active site serine in PBP2a is described. The covalent binding of the beta-lactams was carried out in vitro with the recombinant PBP2a. Peptide mapping of the cyanogen bromide fragments from penicilloyl-PBP2a, using microbore LC/MS, provided a rapid identification of the modified peptide with a 334 Da mass increase. The acylated peptide was isolated and further digested with trypsin. Nano-electrospray MS/MS sequencing of the acylated peptide in the tryptic digest showed that the penicillin was indeed attached to serine403.

Acylation↗

PubMed1998

On-line capillary electrophoresis-electrospray ionization mass spectrometry using a polymerized anionic surfactant.

On-line capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) has been used to determine the tricyclic antidepressant drugs (imipramine, doxepin, and amitriptyline) as well as the beta-adrenergic blocker drugs (propranolol and alprenolol). A CE-ESI-MS interface linking a manually operated CE system and a Finnigan MAT-900 sector mass spectrometer (with an Analytica electrospray ionization source) has been constructed in-house and employed for this study. Although a water/methanol based capillary zone electrophoresis (CZE) buffer was initially used to determine these analytes, enhanced resolution was obtained by addition of a polymerized surfactant, i.e., poly-sodium undecylenic sulfate (poly-SUS), into the electrokinetic chromatography (EKC) buffer. When a low concentration of this poly-SUS surfactant was added to a volatile EKC buffer, these structurally similar cationic drugs were EKC separated and on-line detected by ESI-MS.

Adrenergic beta-Antagonists↗

PubMed1998

Single- and multiple-dose pharmacokinetic comparison of a sustained-release tablet and conventional tablets of naproxen in healthy volunteers.

The pharmacokinetics of a new sustained-release tablet of naproxen (500 mg once daily) were compared with a conventional tablet (250 mg twice daily) after single- or multiple-dose oral administration in healthy volunteers using an open, randomized two-way crossover experimental design. Naproxen was well absorbed from the sustained-release tablet (approximately 97%) compared with the conventional tablet. Pharmacokinetic data showed that the sustained-release formulation reached significantly delayed mean peak plasma levels (Cmax) in both single- and multiple-dose studies and lower Cmax in a single-dose study than the conventional formulation. However, there were no statistically significant differences in other pharmacokinetic parameters, including area under the concentration-time curve (AUC), elimination half-life (t1/2), and elimination rate constant (Ke), in either single- or multiple-dose studies between the two treatments. In addition, there were no significant differences between formulations in Cmax, minimum plasma concentration (Cmin), and fluctuation index in the multiple-dose study.

Adult↗

PubMed1998

Activation of cytokine production, tumoricidal properties, and tyrosine phosphorylation of MAPKs in human monocytes by a new synthetic lipopeptide, JBT3002.

We investigated the expression of cytokine genes and tumoricidal properties in human blood monocytes in response to a new synthetic immunomodulating lipopeptide, JBT3002. Incubation of peripheral blood monocytes with free-form JBT3002 or JBT3002 encapsulated in multilamellar phospholipid vesicles (liposomes, MLV-JBT3002) induced tumoricidal properties in a dose-dependent manner. Both MLV-JBT3002 and free-form JBT3002 induced production of tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 in a dose-dependent manner with similar kinetics. Treatment of monocytes with interferon-gamma did not significantly alter the expression of cytokine genes but increased the expression of cytokines induced by MLV-JBT3002 and free-form JBT3002. In contrast to monocyte activation by lipopolysaccharide (LPS), activation by JBT3002 was independent of serum and was not inhibited by CD14-neutralizing antibody. Incubation of monocytes with JBT3002 induced a rapid increase in tyrosine phosphorylation of proteins with apparent molecular masses of 42 and 38 kDa, a migration band shift of c-Jun NH2-terminal kinase 1 (JNK1), and activation of extracellular signaling regulated kinases. Consistent with its effect on cytokine expression, stimulation of these intracellular signaling pathways by JBT3002 was not inhibited in serum-free conditions. Collectively, the data indicate that the synthetic lipopeptide JBT3002 is a potent monocyte activator that modulates monocyte function by mechanisms similar to LPS but by a distinct receptor.

Adjuvants, Immunologic↗

PubMed1998

HSP60, HSP70 in the pathogenesis of Kawasaki disease: implication and action.

HSP60, HSP70 in plasma of 11 cases of Kawasaki diseases (KD) and 23 healthy children were determined. The two groups were controlled for age. Determination of HSP60, HSP70 was conducted in lymphocytes of 14 cases of KD and 26 healthy children. The results were compared with those of 12 patients with febrile diseases and 10 patients with tuberculosis. Our results showed that except a significant difference in plasma HSP70 found between acute phase and convalescent phase of KD (P < 0.01), no significant difference was found in HSP60, HSP70 among all groups (P > 0.05). The differences in HSP60, HSP70 in lymphocytes were relatively obvious among all groups. The levels of HSP60, HSP70 in acute phase of KD were significantly higher than those in convalescent phase or in healthy controls (P < 0.01). The levels of HSP60 in KD were significantly higher than those of patients with febrile diseases. HSP60 of KD children was significantly lower than those of children with tuberculosis (P < 0.01). The findings showed that HSP60, HSP70 might contribute to the pathogenesis of KD. Determination of HSP60, HSP70 in lymphocytes is of help in the diagnosis of KD.

Chaperonin 60↗

PubMed1998

Suppression of tumorigenicity and metastasis in murine UV-2237 fibrosarcoma cells by infection with a retroviral vector harboring the interferon-beta gene.

In this study, we endeavored to determine the effectiveness of interferon beta (IFNbeta) gene therapy against highly metastatic murine UV-2237m fibrosarcoma cells. UV-2237m cells were engineered to produce murine IFNbeta constitutively following infection by a retroviral vector harboring the murine IFNbeta gene. Parental (UV-2237m-P), control-vector-transduced (UV-2237m-Neo), and IFNbeta-transduced (UV-2237m-IFNbeta) cells were injected subcutaneously (s.c.) or intravenously (i.v.) into syngeneic mice. Parental and control-transduced cells produced rapidly growing tumors, whereas IFNbeta-transduced cells did not. The tumorigenicity of IFNbeta-sensitive or -resistant parental cells was significantly suppressed when they were injected s.c. together with IFNbeta-transduced cells. The IFNbeta-transduced cells did not inhibit growth of parental cells injected s.c. at a distant site. UV-2237m-IFNbeta cells produced s.c. tumors in nude, SCID/Beige, and natural killer(NK)-cell-compromised syngeneic mice. The IFNbeta-transduced cells were more sensitive to in vitro splenic cell-mediated lysis than were the parental or control-transduced cells. Pretreatment of C3H/HeN mice with the NK-cell-selective antiserum (anti-asialoGM1) partially abrogated the cytotoxic activity of the cells. Cytotoxic activity was not observed in mixed culture of UV-2237m-IFNbeta cells and splenic cells from SCID/Beige mice. Significant cytotoxicity against UV-2237m-IFNbeta cells was mediated by macrophages activated by either IFNgamma, lipopolysaccharide, or a combination of both. Our data led us to conclude that the constitutive expression of IFNbeta can suppress tumorigenicity and metastasis of UV-2237m cells, which is due, in part, to activation of host effector cells.

Animals↗

PubMed1998

Molecular and immunologic characterization of group A bovine rotavirus field isolates with P8[11] spike protein.

Bovine rotavirus strain B223 is the North American prototype for group A P8[11] serotype/genotype rotaviruses. Rotaviruses with this serotype/genotype are a prevalent cause of neonatal calf diarrhea and have also been isolated from asymptomatic human infants. On the basis of deduced amino acid sequence of the outer capsid viral protein 4 (VP4), strain B223 lacks a cysteine at position 318 that is conserved among all other rotavirus strains. It has been speculated that this may result in the loss of disulfide bond and a change in the structure of the VP4 that may affect the infectivity and antigenicity of the virus. This paper describes partial sequences of the VP4 gene (nucleotides 613 to 1016 coding for amino acid positions 202 to 335) of 16 bovine rotavirus field isolates with P8[11] that were obtained from calves in Nebraska and Indiana. All the isolates lack a cystein at position 203 and had a conserved valine residue at position 318, thus indicating that the prototype strain B223 is representative of group A rotaviruses with P8[11] serotype/genotype.

Amino Acid Sequence↗

PubMed1998

Lysis of CD4+ T cells expressing HIV-1 gag peptides by gag-specific CD8+ cytotoxic T cells.

The vast majority of in vitro experiments testing the cytotoxic T lymphocytes (CTL) activity in HIV infection has been performed with target cells consisting of autologous EBV-transformed B lymphoblastoid cell lines (B-LCLs) expressing Human immunodeficiency virus type I (HIV-1) proteins. However data concerning the lysis of primary CD4+ T lymphocytes expressing HIV-1 antigens by CTLs is still lacking. To study the CTL activity against such primary targets, we used a system involving PBMCs of an HIV+ asymptomatic patient (PT) as effector cells and the CD4+ lymphocytes or B-LCLs of his healthy HLA-identical twin brother (HTW) as target cells. These syngeneic targets were either infected with recombinant vaccinia virus containing HIV-1 gag gene (gag-vac), or coated with HIV-1 gag peptides. We demonstrate in this study that PT CTLs (which were CD3+, CD4-, CD8+, TCRalphabeta+, TCRgammadelta-, CD56-) specifically lysed both types of syngeneic target cells expressing gag-vac; however, CD4+ T cells expressing HIV gag proteins were lysed less efficiently than B-LCLs expressing the same HIV epitopes. On the other hand, no specific lysis was detected when the target cells were uninfected or infected by wild-type vaccinia virus.

Adult↗

PubMed1998

Biomechanical properties of absorbable implants in finger fractures.

The mechanical rigidity of five different methods of pin fixation in two proximal phalangeal fracture models was studied and absorbable implants were compared with metallic implants in a biomechanical cadaver study. Thirty phalanges were tested in apex palmar bending, compression and torsion. Results showed that rigidity of absorbable implants was comparable with metallic implants, except in torsion.

Biocompatible Materials↗

PubMed1998

Chronic ethanol administration alters hepatic rates of glycerol phosphorylation and glycerol 3-phosphate oxidation: a dynamic in vivo 31P magnetic resonance spectroscopy study.

We used dynamic in vivo 31P magnetic resonance spectroscopy to noninvasively study the metabolism of glycerol by the liver in living rats, as a means of detecting subtle metabolic changes induced by chronic ethanol consumption. Rats subjected to chronic ethanol consumption and their pair-fed controls were given a metabolic load of glycerol (0.75 or 1.3 mL glycerol x kg body mass(-1), i.p. or i.v) under normoxic or hyperoxic (98% O2) conditions. Changes in the level of glycerol 3-phosphate were followed in situ by monitoring the hepatic 31P phosphomonoester resonance every 7 or 13 min for up to 330 min. When challenged with a large dose of glycerol, chronic ethanol-treated rats exhibited less accumulation of glycerol 3-phosphate than controls, independent of the route of administration of the glycerol or whether the two groups were fasted or fed. For example, 1.3 mL glycerol x kg(-1) i.v. under normoxic conditions resulted in a two-fold increase in phosphomonoester in ethanol-treated rats compared with a five-fold increase in controls. The ethanol-treated rats also showed a slower rate of phosphorylation of glycerol and slower oxidation of glycerol 3-phosphate than controls, indicating decreased activities of the glycerol kinase and glycerol 3-phosphate dehydrogenase steps, and hence slower glycerol utilization. The rate of glycerol utilization was dose and oxygen concentration dependent. Kinetic analysis indicated that the chronic ethanol-induced decrease in the glycerol 3-phosphate dehydrogenase reaction was due to a decreased rate of NADH reoxidation in the liver, likely owing to a decrease in oxygen supply or utilization in the ethanol-treated rats. These observations support the hypothesis of pre-existing hypoxia in rat liver after chronic ethanol administration. This study demonstrates the utility of dynamic in vivo 31P magnetic resonance spectroscopy in following the metabolism of a glycerol load as a sensitive, nonperturbing, and potentially clinically applicable test of liver function.

Adenosine Triphosphate↗

PubMed1998

Effect of platelet-activating factor-receptor antagonism on endotoxin-induced lung dysfunction in sheep.

To further define the role of platelet-activating factor (PAF) in endotoxin-induced lung dysfunction, we examined the effect of ABT-299, a specific and potent PAF-receptor antagonist, on the response to endotoxemia in six chronically instrumented awake sheep. We administered Escherichia coli endotoxin (0.5 microg/kg) intravenously with or without pretreatment with ABT-299 while monitoring mean pulmonary arterial pressure (Ppa), mean systemic arterial pressure (Psa), dynamic compliance of the lungs (Cdyn), and functional residual capacity (FRC). Endotoxin administration caused pulmonary hypertension, reduced Cdyn, leukopenia, and hypoxemia while having no significant effect on Psa or FRC. Administration of ABT-299 did not affect any of the measured variables at baseline. Pretreatment with ABT-299 attenuated the peak Ppa seen after endotoxin administration but had minimal effects on endotoxin-induced changes in Cdyn, white blood cell count, or alveolar-to-arterial oxygen difference. ABT-299 was shown to completely block the pulmonary hypertension and reduction in Cdyn seen after intravenous administration of exogenous PAF. We conclude that PAF does not play an essential role in the sheep's response to endotoxin.

Animals↗

PubMed1998

Effect of cardiogenic and noncardiogenic pulmonary edema on histamine responsiveness in sheep.

We compared the effects of cardiogenic pulmonary edema, brief pulmonary vascular congestion without frank edema, and noncardiogenic pulmonary edema on responsiveness to inhaled histamine in chronically instrumented awake sheep. Histamine responsiveness was measured before and after 1) cardiogenic pulmonary edema induced by raising left atrial pressure to 35 cmH2O (Pla) for 3.5 h by partial obstruction of flow across the mitral valve, 2) brief cardiogenic congestion via Pla for 0.5 h, 3) noncardiogenic pulmonary edema induced by 25 mg/kg intravenous perilla ketone (PK), and 4) 3.5 h of monitoring without Pla or PK (controls). Treatment for 3.5 h with Pla (n = 9) and PK (n = 11) each significantly lessened the histamine dose required to cause a fall to 65% of baseline dynamic lung compliance (ED65Cdyn), i.e., increased responsiveness. Sheep treated for 0.5 h with Pla (n = 7) and controls (n = 5) showed no significant change in ED65Cdyn. Intravenous atropine (0.1 mg/kg) before the second histamine challenge altered neither the reduction of ED65Cdyn in Pla (n = 8) and PK (n = 9) sheep nor the ED65Cdyn level of controls (n = 9). These data imply that the local effects of edema, rather than bronchial vascular hemodynamics, cholinergic reflexes, and permeability changes, are germane to lung hyperresponsiveness during pulmonary edema in sheep.

Aerosols↗

PubMed1998

Role of endothelin in endotoxin-induced sustained pulmonary hypertension in sheep.

BMS182874, an endothelin receptor antagonist, blocks the effects of exogenously administered endothelins in chronically instrumented awake sheep. A possible role for endothelin in endotoxin-induced pulmonary hypertension in sheep was investigated by studying animals given intravenous endotoxin with and without pretreatment with BMS182874. BMS182874 administration alone caused a reduction in pulmonary artery pressure (P[PA]) and systemic arterial pressure (P[SA]). Endotoxin alone caused an acute, nearly threefold increase in P(PA) which was followed, from 2-5 h after endotoxin, by a sustained but less severe increase in P(PA). These changes were accompanied by a threefold increase in lung lymph flow and dramatic increases in plasma and lung lymph thromboxane B2 concentrations. Pretreatment with BMS182874 significantly attenuated the early endotoxin-induced acute increase in P(PA) and completely blocked the late sustained pulmonary hypertension (p < 0.05), while having no affect on the increases in thromboxane levels. BMS182874 shifts the dose response curve for U46619, a prostaglandin H2 analogue, to the right. BMS182874, in addition to functioning as an endothelium receptor antagonist, appears to counteract the action of thromboxane at the receptor level. We theorize that BMS182874 attenuates the early endotoxin-induced pulmonary hypertension by counteracting the effects of thromboxane, since previous studies demonstrated that the early acute rise in P(PA) is caused by thromboxane. The late sustained pulmonary hypertension of endotoxemia, on the other hand, appears to be mediated by endothelin.

Animals↗

PubMed1998

Over-expression of c-fos mRNA in the hippocampal neurons in Alzheimer's disease.

OBJECTIVE: To analyze the relationship between the proto-oncogene c-fos change and neuronal degeneration in the hippocampus of the patients with Alzheimer's disease. METHODS: The post mortem human hippocampal tissues were divided into three groups, namely, the aged, the young and Alzheimer's disease (AD) groups. Each group consisted of 10 patients. The diagnosis of AD was made by clinical manifestation and argentatine (Bodían) staining. Patients of both the young and the aged groups had no neurological disorders. The proto-oncogene c-fos mRNA was investigated in the hippocampal neurons using the method of in situ hybridization. RESULTS: The optical density of stained area and the integral within proto-oncogene c-fos mRNA revealed a significant increase in the hippocampal neurons in cases of Alzheimer's disease as compared with the controls. CONCLUSIONS: The over-expression of the proto-oncogene c-fos might play a role in the pathological process of Alzheimer's disease. These changes might result from a suffering stage of the hippocampal neurons or from a compensatory mechanism in the surviving neurons which are not yet affected-by the pathological process.

Adult↗

PubMed1998

Research on nucleolar organizer regions of hippocampal neuron in Alzheimer's disease.

OBJECTIVE: To understand the cellular genetic expression of the cell's population by studying the nucleolar organizer regions (NORs) of hippocampal neuron of Alzheimer's disease (AD). METHODS: The postmortem human hippocampal tissues were divided into three groups, namely, the young, the elderly and the AD groups. Each group contained tissues from 10 patients. The study was conducted using image pattern analysis of the nucleoli-nucleoplasms ratio of the neurons of Nissl's stained pathological cerebral hippocampal tissues, the area of stain, and the integrating absorption of nucleoli of silver-stained NORs. RESULTS: The nucleoli-nucleoplasms ratio of the neurons of Nissl's stained cerebral hippocampal tissues, the area of stain, and the integrating absorption of the nucleoli of hippocampal neuron were decreased in the elderly and the AD groups as compared with the young group. However, the area of stain and the integrating absorption of the nucleoli of the hippocampal neurons were relatively increased in the AD group in comparison with the elderly group. CONCLUSION: Nissl's stain demonstrates the hypofunction of the hippocampal neurons in the elderly and the AD patients. The Silver stain of NORs shows the decline of rDNA transcription activity of the nucleoli of the hippocampal neurons in the elderly and the AD patients. However, the transcription activity of the nucleoli of the hippocampal neurons of AD patients was relatively improved, and the cellular genetic expression of the cell's population was relatively strengthened. These cellular morphological changes have probably reflected the cellular defensive system.

Adult↗

PubMed1998

[Determination of copper, zinc, iron and calcium in wheat and maize and three nitrogen compounds in high and low risk areas of esophageal cancer].

This study reports the concentrations of copper, zinc, iron and calcium in wheat and maize from high risk area Linzhou and low risk area Yuzhou of esophageal cancer and three nitrogen compounds of four types of drinking water in Linzhou. The results showed that the concentrations of zinc and calcium in wheat and maize from Linzhou were significantly lower than these from Yuzhou, the copper concentrations in grains were higher and the iron in maize was lower. The nitrate-N concentrations in four types of drinking water from Linzhou were below the national standard but the nitrite and NH3-N concentrations were higher than the national limits. The results suggest that the low concentrations of zinc, iron and calcium and high concentrations of copper in grains as well as the high concentrations of nitrite and NH3-N may be related to the etiology of esophageal cancer.

Calcium↗

PubMed1998

[Clinical investigation on treatment of integrated traditional and Western medicine in hyperthyroidism with leukocytopenia induced by sulfourea drugs].

OBJECTIVE: To seek for a safe and effective drug to treat hyperthyroidism. METHODS: Sixty cases of hyperthyroidism with leukocytopenia induced by sulfourea drugs were divided into treatment and control groups by 31 cases who were treated by traditional medicine Syndrome Differentiation and 29 cases who were treated by conventional western medicine alone respectively at random. They were estimated by total effective rate, major symptoms, WBC and immunological tests after four weeks. RESULTS: The total effective rate in the treatment group (96.8%) was more effective than that in the control group (86.2%, P < 0.05). The symptom recovery rate in the treatment group was better than that in the control group. The WBC in both were all increased, but in the treatment group, it was better than that in the control group (P < 0.05). The positive to negative rate of thyroglobulin antibody and thyromicrosome antibody in the treatment group was better than that in the control group (P < 0.01). CONCLUSIONS: It can not only improve the symptoms and immune function, but also increase WBC by using western medicine in combination with traditional medicine in treating hyperthyroidism.

Adenine↗

PubMed1998

[Effect of nitric oxide release on epileptiform discharge in CA1 area of hippocampal slices].

Using a nitric oxide (NO)-sensitive platinum microelectrode (SNM) modified with chitosan nickel (II) complex and Nafion (Nafion-CTS (Ni)-Pt), we observed the effect of nitric oxide synthase (NOS) inhibitor 7-nitro-indazole (7-NI) and N omega-nitro-L-arginine (L-NNA) on penicillin-treated hippocampal slices by simultaneously recording the stimulus-evoked field potentials and nitric oxide release from CA1 pyramidal neurons. Our results show: (1) The linear relationship range and detection limit of SNM were 4.5 x 10(-4)-1.0 x 10(-8) mol/L and 5.0 x 10(-8) mol/L respectively. (2) Penicillin (PEN) could elevate NO release, the number and amplitude of stimulus-evoked field potentials spike (SEPS) in concentration-dependent manner; (3) Both 7-NI and L-NNA depressed NO release and partly reversed the effect of penicillin. The above findings suggest that convulsant provoking effect of NO could be inhibited by NOS inhibitors. The NO-sensitive electrode may provide an useful tool for continuous detection of NO in biological tissues.

Animals↗