PubMed Health⌕ Search

Biomedical subjects

M Deng

Publications and source records attributed to M Deng.

At least 37 records · Page 2Linked to original sources
PubMed2000

Inhibition of TATA-binding protein function by SAGA subunits Spt3 and Spt8 at Gcn4-activated promoters.

SAGA is a 1.8-MDa yeast protein complex that is composed of several distinct classes of transcription-related factors, including the adaptor/acetyltransferase Gcn5, Spt proteins, and a subset of TBP-associated factors. Our results indicate that mutations that completely disrupt SAGA (deletions of SPT7 or SPT20) strongly reduce transcriptional activation at the HIS3 and TRP3 genes and that Gcn5 is required for normal HIS3 transcriptional start site selection. Surprisingly, mutations in Spt proteins involved in the SAGA-TBP interaction (Spt3 and Spt8) cause derepression of HIS3 and TRP3 transcription in the uninduced state. Consistent with this finding, wild-type SAGA inhibits TBP binding to the HIS3 promoter in vitro, while SAGA lacking Spt3 or Spt8 is not inhibitory. We detected two distinct forms of SAGA in cell extracts and, strikingly, one lacks Spt8. Conditions that induce HIS3 and TRP3 transcription result in an altered balance between these complexes strongly in favor of the form without Spt8. These results suggest that the composition of SAGA may be dynamic in vivo and may be regulated through dissociable inhibitory subunits.

Acetyltransferases↗
PubMed2000

Analysis of the "Learning in Regular Classrooms" movement in China.

The Learning in Regular Classrooms experiment has evolved in response to China's efforts to educate its large population of students with disabilities who, until the mid-1980s, were denied a free education. In the Learning in Regular Classrooms, students with disabilities (primarily sensory impairments or mild mental retardation) are educated in neighborhood schools in mainstream classrooms. Despite difficulties associated with developing effective inclusive programming, this approach has contributed to a major increase in the enrollment of students with disabilities and increased involvement of schools, teachers, and parents in China's newly developing special education system. Here we describe the development of the Learning in Regular Classroom approach and the challenges associated with educating students with disabilities in China.

Child↗
PubMed2000

The selective muscarinic M1 agonist AF102B decreases levels of total Abeta in cerebrospinal fluid of patients with Alzheimer's disease.

beta-Amyloid (Abeta) deposits in diffuse and compact senile plaques in the brain are one of the defining histopathological features of Alzheimer's disease (AD). Preventing Abeta deposition is a goal of drug therapy for AD, because excessive amounts of Abeta may be toxic to neurons. In preclinical studies, activation of the muscarinic M1 receptor subtype inhibited Abeta secretion from cultured cells. To determine whether a similar sequence occurs in human beings, we administered the selective M1 agonist AF102B to 19 AD patients and measured total Abeta (Abeta(total)) levels in cerebrospinal fluid (CSF) before and during treatment. Abeta(total) levels in CSF decreased in 14 patients by 22%, increased in 3 patients, and were unchanged in 2 patients; the overall decrease in the group as a whole was statistically significant. To test the specificity of the M1 effect, we also measured the relative changes in Abeta(total) levels in CSF during treatments in separate sets of AD patients with the acetylcholinesterase inhibitor physostigmine or the anti-inflammatory drug hydroxychloroquine. CSF Abeta(total) levels did not change significantly in the 9 AD patients in the physostigmine protocol or in the 10 AD patients in the hydroxychloroquine study. These data provide evidence that the activation of M1 receptors reduces Abeta levels in the CSF of AD patients. If this effect also occurs in brain, M1 agonists may have long-term therapeutic benefits by lowering amyloid in AD.

Aged↗
PubMed2000

[Quantitative determination of EAIgG by ABC-ELISA and its clinical significance].

OBJECTIVE: To explore a method for diagnosis of autoimmune hemolytic anemia (AIHA) and evaluate its clinical significance. METHODS: Erythrocyte associated IgG (EAIgG) was quantified in 60 healthy people, 44 patients with warm antibody AIHA (WAIHA), 108 non-immune anemia and 44 other immune diseases (total 256 cases) by using ABC-ELISA were estimated. RESULTS: EAIgG in WAIHA patients were significantly higher than those in other groups (P < 0.01). In the 44 WAIHA patients, 38 were Coombs positive and 6 Coombs negative. EAIgG in Coombs negative was significantly high. The dynamic changes of EAIgG in 12 WAIHA patients were observed during treatment. When patient's condition got better, Hb and RBC increased and EAIgG decreased. CONCLUSION: Quantitative detection of EAIgG is an index in the diagnosis of WAIHA, especially in AIHA with negative Coombs' test. It is also a useful factor for evaluating therapeutic effect and prognosis in WAIHA.

Adolescent↗
PubMed1999

The European experience of Novacor left ventricular assist (LVAS) therapy as a bridge to transplant: a retrospective multi-centre study.

OBJECTIVE: Artificial heart devices have suffered from a negative press based on the early Jarvik experience of the 1980s. This is in stark contrast to realities of current left ventricular assist (LVAS) therapy. The Novacor N100 PC wearable left ventricular assist system (LVAS) was introduced in Europe in late 1993. This system allows implanted recipients to be completely autonomous with the system controlled by a small computer and powered by rechargeable batteries. This report represents the initial European experience with the Novacor LVAS. METHODS: Since the system was introduced with regulatory approval as a commercial product, clinicians were not bound by the constraints of a study protocol and only minimal data were collected. This report presents the results of a retrospective study of 118 consecutive patients who had the LVAS implanted as a bridge to transplant, in 19 centres over the three year period ending in November 1996. RESULTS: Mortality and morbidity varied widely between centres. The median implant time was 115 days (0-585 days) and 33% of patients returned home, supported by the LVAS. The overall survival on LVAS was 64%. The major causes of death were infection (14%) and MOF (6%). There were no significant device or system failures despite a cumulative patient experience of 24.8 years outside of a hospital environment. Patient selection and management varied greatly between centres and this was reflected in disparate outcomes. CONCLUSIONS: Optimal selection and management of LVAS patients has still to be established. While the data available for this report lacked the detail necessary to demonstrate direct causal relationships between selection and management, it was clear from the inter-centre differences that these two factors have a major impact on outcomes. This early experience has directed attention towards improved management regimes. Given the results obtained from the best centres and the ability to discharge patients to lead near-normal lives in the community, the authors believe that the Novacor LVAS now offers a real therapeutic alternative for selected end-stage heart failure patients for whom a donor heart is unavailable or who are unsuitable for transplantation.

Adolescent↗
PubMed1999

Effective gene transfer in the rat myocardium via adenovirus vectors using a coronary recirculation model.

BACKGROUND: Gene therapy promises to play an important role in the treatment of heart disease and in transplantation. The limited effectiveness of gene transfer, however, remains an unresolved problem. The aim of the study was to create a model for more effective gene transfer using adenovirus vectors carrying the lacZ-reporter gene (AdV-lacZ). METHODS: Beating Lewis rat hearts perfused with oxygenated Krebs-Henseleit solution were harvested, after which an atrial septal defect (ASD) was created. All vessels were tied and AdV-lacZ was injected into the aortic root. The solution was recirculated through the ASD to the left side of the heart and pumped back to the coronary arteries by the left ventricle. Incubation was allowed for 20 min at 15 degrees C and the hearts were subsequently transplanted heterotopically in syngeneic rats. This method was compared to AdV-lacZ injection into cardioplegic hearts. The hearts were harvested after 2, 7, or 14 days and evaluated histologically for expression of the lacZ gene. RESULTS: Maximal gene expression was achieved after 7 days by the recirculation model. There was less efficient gene expression at day 2 and at day 14. No evidence of ischemic injury of the myocardium was noticed histologically. Almost no successful gene expression was seen in the arrested hearts. CONCLUSION: This novel recirculation method lets the vector be repeatedly exposed to the endothelium, resulting in an effective gene expression after 7 days incubation time rather than after 14, when a decline has set in presumably due to immunologic response.

Adenoviridae↗
PubMed1999

[Enantiomeric resolution of trans-1,2-disubstituted cyclopropane by high performance liquid chromatography].

The enantiomeric resolution of racemic mixtures of thirteen trans-1,2-disubstituted cyclopropane was achieved with HPLC by using Chiralcel OD and Chiralcel OJ as chiral stationary phase and hexane/2-propanol mixtures with different concentrations as eluent. The chromatographic parameters of these racemates on Chiralcel OD and Chiralcel OJ columns were examined. The results showed that enantiomeric resolution ability of the racemic mixtures of trans-1,2-disubstituted cyclopropane on Chiralcel OD and Chiralcel OJ was strongly dependent on the site and the property of substituents on the benzene cycle. On the other hand, some racemated of trans-1,2-disubstituted cyclopropane with aliphatic group were also separated on the columns. The results showed that the chiral recognition process was the sum of all the possible chiral interaction (the dipole-dipole, hydrogen bond-hydrogen bond and pi-pi interactions) between the chiral stationary phase and trans-1,2-disubstituted cyclopropane. This method has been applied to identify the optical purity of trans-1,2-disubstituted cyclopropane.

Chromatography, High Pressure Liquid↗
PubMed1998

Study of creep behavior of ultra-high-molecular-weight polyethylene systems.

The short- and long-term creep behaviors of ultra-high-molecular-weight polyethylene (UHMWPE) systems (compression-molded UHMWPE sheets and self-reinforced UHMWPE composites) have been investigated. The short-term (30-120 min) creep experiment was conducted at a load of 1 MPa and a temperature range of 37-62 degrees C. Based on short-term creep data, the long-term creep behavior of UHMWPE systems at 1 MPa and 37 degrees C was predicted using time-temperature superposition and analytical formulas. Compared to actual long-term creep experiments of up to 110 days, the predicted creep values were found to well describe the creep properties of the materials. The creep behaviors of the UHMWPE systems were then evaluated for a creep time of longer than 10 years, and it was found that most creep deformation occurs in the early periods. The shift factors associated with time-temperature superposition were found to increase with increasing temperature, as per the Arrhenius equation. The effects of temperature, materials, and load on the shift factors could be explained by the classical free volume theory.

Hot Temperature↗
PubMed1998

Modulations in lipid A and phospholipid biosynthesis pathways influence outer membrane protein assembly in Escherichia coli K-12.

The assembly defect of a mutant outer membrane protein, OmpF315, can be corrected by suppressor mutations that lower lipopolysaccharide (LPS) levels and indirectly elevate phospholipid levels. One such assembly suppressor mutation, asmB1, is an allele of lpxC (envA) whose product catalyses the first rate-limiting step in the lipid A (LPS) biosynthesis pathway. Besides reducing LPS levels, asmB1 confers sensitivity to MacConkey medium. A mutation, sabA1, that reverses the MacConkey sensitivity phenotype of asmB1 maps within fabZ (whose product is needed for phospholipid synthesis from a precursor) is also required for lipid A synthesis. In addition to reversing MacConkey sensitivity, the sabA1 mutation reverses the OmpF315 assembly suppression phenotype of asmB1. These results show that OmpF315 assembly suppression by asmB1, which is achieved by lowering LPS levels, can be averted by a subsequent aberration in phospholipid synthesis at a point where the biosynthetic pathways for these two lipid molecules split. OmpF315 assembly suppression can also be achieved in an asmB+ background where FabZ expression is increased. The data obtained in this study provide genetic evidence that elevated phospholipid levels and/or phospholipid to LPS ratios are necessary for assembly suppression.

Bacterial Outer Membrane Proteins↗
PubMed1998

Emergency versus elective/urgent left ventricular assist device implantation.

BACKGROUND: The risk and outcome in patients undergoing left ventricular assist device (LVAD) implantation on an emergency basis is still unclear. METHODS: Since April 1993, 40 patients received a Novacor and 8 patients a Heartmate LVAD in our institution. Patients with emergency LVAD placement were compared with the remainder in a retrospective manner. Parameters studied included underlying heart disease, preimplantation dysfunction of kidney, liver, lung, and cerebrum, interval of mechanical support, outcome, and complications. RESULTS: Patients with emergency LVAD placement predominantly were seen with postcardiotomy heart failure (47%) or acute myocarditis (20%) (group A) whereas elective and urgent candidates for LVAD implantation mainly had dilative cardiomyopathy (67%) or ischemic heart disease (30%) (group B). The incidence of secondary organ failure was significantly higher for all organs in group A patients (p < .01). Mean support interval in patients who underwent emergency LVAD implantation was lower (74+/-79 days vs 115+/-80 days), and fewer patients could be forwarded to heart transplantation in this group (22% vs 78%, p < .01). Moreover, bleeding complications were increased in group A (66% vs 30%, p < .01), but not thromboembolism and infection. CONCLUSION: In conclusion, the overall success rate after emergency LVAD implantation was lower, with bleeding being the most frequent complication. To achieve acceptable outcomes in disastrous situations, LVADs should be placed as early as possible.

Adult↗
PubMed1997

Properties of self-reinforced ultra-high-molecular-weight polyethylene composites.

The physical properties of ultra-high-molecular-weight polyethylene (UHMWPE) fibre/UHMWPE matrix composites have been characterized. It was found that the tensile strength and modulus, and creep resistance, were significantly increased after incorporating UHMWPE fibres into a UHMWPE matrix. The longitudinal tensile strength of the resulting self-reinforced composite increased with fibre content, according to the law of mixtures. The transverse strength did not change for fibre content of up to 7%. The double-notch impact strength of the composites was higher than plain UHMWPE. There was no difference in wear properties between the composites and plain UHMWPE. The cross-section and tensile fracture surfaces of the composites were examined by scanning electron microscopy (SEM). Overall results indicate that the self-reinforced UHMWPE composites may be good candidates for load-bearing biomedical applications.

Chemical Phenomena↗
PubMed1996

Serotonin 5-HT2a and 5-HT2c receptors stimulate amyloid precursor protein ectodomain secretion.

Alzheimer's disease amyloid consists of amyloid beta-peptides (Abeta) derived from the larger precursor amyloid precursor protein (APP). Non-amyloidogenic APP processing involves regulated cleavage within the Abeta domain followed by secretion of the ectodomain (APPs). APPs secretion can be stimulated by muscarinic acetylcholine receptors coupled to phospholipases and kinases. To determine whether other receptor classes can regulate APP processing, we examined the relation between serotonin receptors and APPs secretion. Serotonin increased APPs release 3-4-fold in 3T3 cells stably overexpressing 5-HT2aR or 5-HT2cR. The increase was dose-dependent and was blocked by serotoninergic antagonists. Phorbol esters also increased APPs secretion, but neither kinase inhibitors nor down-regulation of PKC blocked the serotonin-induced increase in APPs secretion. Thus PKC is not necessary to stimulate APPs secretion. Phospholipase A2 (PLA2) inhibitors blocked the 5-HT2aR-mediated increase in APPs secretion, suggesting a role of PLA2 in coupling 5-HT2aR to APP processing. In contrast, coupling of 5-HT2cR to APPs secretion involved both PKC and PLA2. Serotonin also stimulated the release of the APLP2 ectodomain, suggesting that additional members of the APP multigene family are processed via similar regulated pathways. Inasmuch as generation of APPs precludes the formation of amyloidogenic derivatives, serotonin receptors provide a novel pharmacological target to reduce these derivatives in Alzheimer's disease.

3T3 Cells↗
PubMed1996

A differential scanning calorimetry study of retrieved orthopedic implants made of ultrahigh molecular weight polyethylene.

Differential scanning calorimetry (DSC) was used to examine thermal and thermooxidative properties of ultrahigh molecular weight polyethylene (UHMW-PE) of five acetabular components of failed orthopedic implants retrieved at revision of total hip arthoplasty. The results were compared with controls (unimplanted acetabular cups, a 20-year-old slab of UHMW-PE, and raw material). Profiles of exothermic peaks indicated increased levels of oxidation in all retrieved cups. In three retrieved cups, DSC revealed an additional peak of endotherm that was not seen in control samples. The additional endotherm peaks were not artifacts due to oxidation during scanning, heat buildup during cutting of the samples, or the sterilization method after retrieval. The additional peak was associated with the bulk of the polymer that was extracted with hexane. It varied in relative area, depending on its original location of the sample in a cup, implicating local variability in the extent of changes in material property. The distribution of the changes suggests that, during implantation, tissue exposure and friction affected the level of oxidation and degree of crystallinity in the UHMW-PE to a greater degree than did loading alone. Overall results showed that DSC may be a useful tool in evaluating changes in the properties of UHMW-PE orthopedic components in vivo.

Acetabulum↗
PubMed1996

Beating heart implantation of a wearable NOVACOR left-ventricular assist device.

Implantable left-ventricular assist devices (LVAD) are successfully used as a bridge to transplant if the patient's condition is worsening and no donor organ is available. They allow recovery of compromised organ function. However, postoperative bleeding, thrombemboelism, and right-heart failure may jeopardize the important improvement of organ function and may even lead to death. We introduce our strategy for implantation of the Novacor LVAD system, which aims at minimal bleeding and maintained right-heart function. The Novacor LVAD was implanted with the heart beating during extracorporeal circulation in 8 patients, 3 of whom had previous cardiac surgery. Postoperatively, no patient developed right heart failure or had to undergo redo thoracotomy.

Adult↗
PubMed1996

Coronary compliance in patients following orthotopic heart transplantation. An intravascular ultrasound study.

BACKGROUND: The aim of this study was to investigate coronary compliance in patients early and 71.8 weeks after orthotopic heart transplantation. METHODS: Thirty patients (mean age 51.4 years, women n = 6) underwent coronary angiography early after orthotopic heart transplantation (mean interval 11.6 +/- 5.5 weeks), by which time 12 recipients had already been treated for episodes of rejection. A total of 153 different coronary segments were investigated using a mechanical 30 MHz intravascular ultrasound system. In all segments, the intimal index and the circumferential extension of the vessel wall, which had a three-layered appearance, were assessed. Systolic-diastolic changes in area, and pressure with respect to vessel wall area, were used to study normalized compliance. All measurements were repeated in a subgroup of 13 patients 71.8 +/- 10.7 weeks after transplantation. RESULTS: At the first investigation, the mean intimal index of all estimated cross-sectional areas was 0.07 +/- 0.10. The mean circumferential extension of the 'three-layered' coronary vessel wall was 74 degrees +/- 101 degrees. No correlation could be found between normalized compliance and the intimal index (r = -0.322, P < 0.001) or between normalized compliance and the circumferential extension of the three-layered vessel wall (r = -0.362, P < 0.001). Donor age did not correlate with normalized compliance either (r = -0.515, P = 0.004). In 12 patients with proven rejection periods before the first investigation, normalized compliance was significantly lower (1.76 +/- 0.81 mmHg-1) than in those without rejection (2.95 +/- 1.22 mmHg-1, P = 0.005). Both the intimal index and the circumferential extension of the three-layered architecture of the vessel wall were significantly higher in recipients with rejection periods. A comparison of the subgroup of 13 recipients between first and second investigation showed that the intimal index increased slightly from 0.03 +/- 0.03 to 0.09 +/- 0.13 (ns) 71.8 weeks after transplantation, but that normalized compliance did not differ significantly between the first and the follow-up investigation. CONCLUSIONS: Early after orthotopic heart transplantation, normalized compliance does not correlate with donor age or the extent of atherosclerotic vessel alterations identifiable by intravascular ultrasound. Early rejection periods are associated with reduced coronary arterial compliance. Using intravascular ultrasound, this adverse functional effect on arterial compliance can be observed together with an increase in the intimal index.

Adult↗
PubMed1996

Examination of AsmA and its effect on the assembly of Escherichia coli outer membrane proteins.

asmA mutations were isolated as extragenic suppressors of an OmpF assembly mutant, OmpF315. This suppressor locus produced a protein that was present in extremely low levels and could only be visualized by Western blotting in cells where AsmA expression was induced from a plasmid. Detailed fractionation analyses showed that AsmA localized with the inner membrane. Curiously, however, the mutant OmpF assembly step influenced by AsmA occurred in the outer membrane, perhaps indicating an indirect involvement of AsmA in the assembly of outer membrane proteins. Biochemical examination of the outer membrane showed that asmA null mutations reduce lipopolysaccharide (LPS) levels, thereby lowering the ratios of glycerolphospholipids to LPS and envelope proteins to LPS in the outer membrane. Despite these quantitative alterations, no apparent structural changes in LPS or major phospholipids were noted. Reduced LPS levels in asmA mutants indicate a possible role of AsmA in LPS biogenesis. Data presented in this study suggest that asmA-mediated OmpF assembly suppression may have been achieved by altering the outer membrane fluidity, thus making it more amenable for the assembly of mutant proteins.

Bacterial Outer Membrane Proteins↗