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Biomedical subjects

C Z Lu

Publications and source records attributed to C Z Lu.

At least 19 recordsLinked to original sources
PubMed2005

Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke.

OBJECTIVE: To investigate whether the extent of white matter lesions (WML) on fluid attenuated inversion recovery (FLAIR) MRI sequences is an independent risk factor for recurrent stroke, and to document the pattern of acute cerebral infarcts using diffusion weighted imaging (DWI) in patients with different severities of WML. METHODS: In a prospective cohort study, 228 consecutive stroke patients were studied between 1999 and 2001 in a community hospital. The severity of WML was graded as 0 (no WML), 1 (mild), 2 (moderate), or 3 (severe) according to the FLAIR appearances. DWI was used to document the location and size of the infarct. RESULTS: 31 patients had grade 0 WML, 69 had grade 1, 59 had grade 2, and 69 had grade 3. Age was independently associated with WML on logistic regression analysis (p = 0.0001). Acute cerebral infarcts in deep white matter were correlated with increasing severity of WML. On a median follow up of 23.0 months, life table analysis showed that recurrent stroke was related to the severity of WML (recurrence rate 7.8% in grade 0, 9.3% in grade 1, 17.7% in grade 2, 43.7% in grade 3; p = 0.0001). Survival was reduced in patients with severe WML (p = 0.0068). A Cox proportional hazards model showed WML to be predictive of recurrent stroke (p = 0.000, hazard ratio = 4.177 (95% confidence interval, 2.038 to 8.564)) and also for survival (p = 0.040, hazard ratio = 2.021 (1.032 to 3.960)). CONCLUSIONS: Patients with severe leukoaraiosis have increased risk of deep subcortical stroke and a higher risk of recurrent stroke.

Acute Disease↗
PubMed2004

Correlation between serum level of neuron-specific enolase and long-term functional outcome after acute cerebral infarction: prospective study.

OBJECTIVE: To determine the value of measuring serum levels of neuron-specific enolase in predicting extent of disease and short- and long-term functional outcome after acute cerebral infarction. DESIGN: Prospective study. SETTING: Neurology departments at two university teaching hospitals, Shanghai. PATIENTS: Thirty-eight patients who presented for acute cerebral infarction between October 1998 and October 2000 were divided into two groups: those whose infarction extended to the cerebral cortex in the carotid artery region (cortical group) and those with an infarction in the subcortical carotid artery region (subcortical group). MAIN OUTCOME MEASURES: Using a solid-phase enzyme immunoassay, we measured serum levels of neuron-specific enolase on admission and on days 2, 3, and 15. Infarct volume was measured by computed tomography on day 5. The Activities of Daily Living scale was used to assess the clinical outcome at 1-, 3-, and 6-month follow-up after onset. RESULTS: Mean (standard deviation) serum neuron-specific enolase levels were significantly higher among patients with acute cerebral infarction than among controls (18.48 [16.61] ng/mL versus 9.00 [2.70] ng/mL; P<0.001). The neuron-specific enolase level was also higher in the cortical group than in the subcortical group (33.54 [29.71] ng/mL versus 15.97 [5.91] ng/mL; P<0.01). Levels peaked after 2.11 (0.86) days and correlated positively with the infarct volume (r=0.81; P<0.01) and negatively with clinical outcome at 1 month (r= -0.37; P<0.05), 3 months (r= -0.45; P<0.01), and 6 months (r= -0.65; P<0.001), as assessed on the Activities of Daily Living scale. CONCLUSION: Serum neuron-specific enolase levels after cerebral infarction may be a useful marker to predict infarct volume and short- or long-term functional outcome.

Activities of Daily Living↗
PubMed2003

Prevalence and predictors of renal artery stenosis in Chinese patients with coronary artery disease.

BACKGROUND: Ischaemic nephropathy is currently a major public health issue in atherosclerotic populations. Although atherosclerotic cardiovascular disease in Asia has reached epidemic proportions over the last two decades, there is little published data on the prevalence of atherosclerotic renal artery stenosis (ARAS) in Oriental subjects. Because ARAS may be clinically silent until end-stage renal failure sets in, it is important to identify patients with significant but clinically unsuspected ARAS. ARAS and coronary artery disease (CAD) often coexist. AIMS: The purpose of the present study was to evaluate the prevalence and predictors of ARAS among Chinese patients with CAD. METHODS: A total of 230 consecutive Chinese patients with CAD confirmed by coronary angiography underwent an abdominal aortogram in the same sitting to screen for ARAS. Patient demographics and comorbidities were analysed for any association with ARAS. RESULTS: A total of 34 (14.8%) patients was found to have significant ARAS. Age and multivessel CAD were independent predictors of ARAS. Hypertension, renal insufficiency, extracranial cerebrovascular disease and female gender were also associated with a higher risk of ARAS but did not independently predict ARAS. CONCLUSION: Clinically silent yet angiographically significant ARAS is common among CAD patients. The prevalence and predictors of ARAS among Chinese patients with CAD are similar to those reported for Caucasian subjects. Underlying ARAS should be suspected in CAD patients with such comorbidities as hypertension, renal insufficiency, extracranial cerebrovascular disease, and more so in the elderly and those with multivessel disease.

Age Distribution↗
PubMed2001

A coiled-coil from the RNA polymerase beta' subunit allosterically induces selective nontemplate strand binding by sigma(70).

For transcription to initiate, RNA polymerase must recognize and melt promoters. Selective binding to the nontemplate strand of the -10 region of the promoter is central to this process. We show that a 48 amino acid (aa) coiled-coil from the beta' subunit (aa 262--309) induces sigma(70) to perform this function almost as efficiently as core RNA polymerase itself. We provide evidence that interaction between the beta' coiled-coil and region 2.2 of sigma(70) promotes an allosteric transition that allows sigma(70) to selectively recognize the nontemplate strand. As the beta' 262--309 peptide can function with the previously crystallized portion of sigma(70), nontemplate recognition can be reconstituted with only 47 kDa, or 1/10 of holoenzyme.

Allosteric Regulation↗
PubMed2001

Binding of the initiation factor sigma(70) to core RNA polymerase is a multistep process.

The interaction of RNA polymerase and its initiation factors is central to the process of transcription initiation. To dissect the role of this interface, we undertook the identification of the contact sites between RNA polymerase and sigma(70), the Escherichia coli initiation factor. We identified nine mutationally verified interaction sites between sigma(70) and specific domains of RNA polymerase and provide evidence that sigma(70) and RNA polymerase interact in at least a two-step process. We propose that a cycle of changes in the interface of sigma(70) with core RNA polymerase is associated with progression through the process of transcription initiation.

Bacterial Proteins↗
PubMed2001

[The development of cerebral circulation analyzer].

In this paper a new cerebral circulation analyzer is introduced, inducing the main structure, the operating principle, the software program and its clinical applications. We can get the cerebrovascular hemodynamics indexes such as resistance, compensatorg blood flow etc., from the blood velocity, pressure waveform, and arterial diameter detected in carotid and vertebral arteries.

Algorithms↗
PubMed2000

Cardioplegia and ischemia in the canine heart evaluated by 31P magnetic resonance spectroscopy.

BACKGROUND: Warm continuous blood cardioplegia provides excellent protection, but must be interrupted by ischemic intervals to aid visualization. We hypothesized that (1) as ischemia is prolonged, the reduced metabolic rate offered by cooling gives the advantage to hypothermic cardioplegia; and (2) prior cardioplegia mitigates the deleterious effects of normothermic ischemia. METHODS: Isolated cross-perfused canine hearts underwent cardioplegic arrest followed by 45 minutes of global ischemia at 10 degrees C or 37 degrees C, or 45 minutes of normothermic ischemia without prior cardioplegia. Left ventricular function was measured at baseline and during 2 hours of recovery. Metabolism was continuously evaluated by phosphorus-31 magnetic resonance spectroscopy. RESULTS: Adenosine triphosphate was 71% +/- 4%, 71% +/- 7%, and 38% +/- 5% of baseline at 30 minutes, and 71% +/- 4%, 48% +/- 5%, and 39% +/- 6% at 42 minutes of ischemia in the cold ischemia, warm ischemia, and normothermic ischemia without prior cardioplegia groups, respectively. Left ventricular systolic function, left ventricular relaxation, and high-energy phosphate levels recovered fully after cold cardioplegia and ischemia. Prior cardioplegia delayed the decline in intracellular pH during normothermic ischemia initially by 9 minutes, and better preserved left ventricular relaxation during recovery, but did not ameliorate the severe postischemic impairment of left ventricular systolic function, marked adenosine triphosphate depletion, and creatine phosphate increase. Left ventricular distensibility decreased in all groups. CONCLUSIONS: When cardioplegia is followed by prolonged ischemia, better protection is provided by hypothermia than by normothermia. Prior cardioplegia confers little advantage on recovery after prolonged normothermic ischemia but delays initial ischemic metabolic deterioration, which would contribute to the safety of brief interruptions of warm cardioplegia.

Adenosine Triphosphate↗
PubMed1999

The interface of sigma with core RNA polymerase is extensive, conserved, and functionally specialized.

The sigma subunit of eubacterial RNA polymerase is required throughout initiation, but how it communicates with core polymerase (alpha(2)betabeta') is poorly understood. The present work addresses the location and function of the interface of sigma with core. Our studies suggest that this interface is extensive as mutations in six conserved regions of sigma(70) hinder the ability of sigma to bind core. Direct binding of one of these regions to core can be demonstrated using a peptide-based approach. The same regions, and even equivalent residues, in sigma(32) and sigma(70) alter core interaction, suggesting that sigma(70) family members use homologous residues, at least in part, to interact with core. Finally, the regions of sigma that we identify perform specialized functions, suggesting that different portions of the interface perform discrete roles during transcription initiation.

Amino Acid Sequence↗
PubMed1999

Structural features required for the interaction of the Hsp70 molecular chaperone DnaK with its cochaperone DnaJ.

Hsp70 family members together with their Hsp40 cochaperones function as molecular chaperones, using an ATP-controlled cycle of polypeptide binding and release to mediate protein folding. Hsp40 plays a key role in the chaperone reaction by stimulating the ATPase activity and activating the substrate binding of Hsp70. We have explored the interaction between the Escherichia coli Hsp70 family member, DnaK, and its cochaperone partner DnaJ. Our data show that the binding of ATP, subsequent conformational changes in DnaK, and DnaJ-stimulated ATP hydrolysis are all required for the formation of a DnaK-DnaJ complex as monitored by Biacore analysis. In addition, our data imply that the interaction of the J-domain with DnaK depends on the substrate binding state of DnaK.

Adenosine Triphosphatases↗
PubMed1998

Interaction of the Hsp70 molecular chaperone, DnaK, with its cochaperone DnaJ.

Chaperones of the Hsp70 family bind to unfolded or partially folded polypeptides to facilitate many cellular processes. ATP hydrolysis and substrate binding, the two key molecular activities of this chaperone, are modulated by the cochaperone DnaJ. By using both genetic and biochemical approaches, we provide evidence that DnaJ binds to at least two sites on the Escherichia coli Hsp70 family member DnaK: under the ATPase domain in a cleft between its two subdomains and at or near the pocket of substrate binding. The lower cleft of the ATPase domain is defined as a binding pocket for the J-domain because (i) a DnaK mutation located in this cleft (R167H) is an allele-specific suppressor of the binding defect of the DnaJ mutation, D35N and (ii) alanine substitution of two residues close to R167 in the crystal structure, N170A and T173A, significantly decrease DnaJ binding. A second binding determinant is likely to be in the substrate-binding domain because some DnaK mutations in the vicinity of the substrate-binding pocket are defective in either the affinity (G400D, G539D) or rate (D526N) of both peptide and DnaJ binding to DnaK. Binding of DnaJ may propagate conformational changes to the nearby ATPase catalytic center and substrate-binding sites as well as facilitate communication between these two domains to alter the molecular properties of Hsp70.

Adenosine Triphosphatases↗
PubMed1998

Presynaptic changes of neuromuscular transmission in mice induced by passive transfer of plasma with anti-presynaptic membrane receptor antibodies from a patient with myasthenia gravis.

Electrophysiological studies were conducted in three groups of mice to determine the possible involvement of the antibodies to presynaptic membrane receptor (PsmR), a beta-bungarotoxin (beta-BuTX) binding protein, in the pathogenesis of myasthenia gravis (MG). Mice were untreated (untreated group, n = 8) or were injected (i.p.) with blood plasma from a MG patient, which contained antibodies to PsmR, at a dose of 1 ml per day for more than 2 months (MG plasma group, n = 12) or with plasma from healthy subjects (normal plasma group, n = 10). Prior to plasma injection, cyclophosphamide was given at 300 mg/kg (i.p.) to all three groups. About three weeks after plasma injection, most mice of the MG plasma group became less mobile in comparison with those of the two control groups. Electrophysiological recording showed three main changes in the MG plasma group: (1) the increase in the frequency of miniature endplate potentials (mEPPs) induced by Krebs solution with high K+ concentration (17.5 mM) was significantly lowered, which was confirmed in mice injected with IgG (50 mg per day) from this patient for two days; (2) the quantal content of EPP was decreased; and (3) the decrement in the amplitude of a train EPP (50 Hz) was quickened. Our results suggest that this experimental model is different from that of Lambert-Eaton myasthenic syndrome and that antibodies to PsmR may also be involved in the pathogenesis of MG.

Animals↗
PubMed1997

Ischemic intervals during warm blood cardioplegia in the canine heart evaluated by phosphorus 31-magnetic resonance spectroscopy.

OBJECTIVE: Warm blood cardioplegia requires interruption by ischemic intervals to aid visualization. We evaluated the safety of repeated interruption of warm blood cardioplegia by normothermic ischemic periods of varying durations. METHODS: In three groups of isolated cross-perfused canine hearts, left ventricular function was measured before and for 2 hours of recovery after arrest, which comprised four 15-minute periods of cardioplegia alternating with three ischemic intervals of 15, 20, or 30 minutes (I15, I20, and I30). Metabolism was continuously measured by phosphorus 31-magnetic resonance spectroscopy. RESULTS: Adenosine triphosphate level fell progressively as ischemia was prolonged; after recovery, adenosine triphosphate was 99% +/- 6%, 90% +/- 1% (p = 0.0004 vs control), and 68% +/- 3% (p = 0.0002) of control levels in I15, I20, and I30, respectively. Intracellular acidosis with ischemia was most marked in I30. After recovery, left ventricular maximal systolic elastance at constant heart rate and coronary perfusion pressure was maintained in I15 but fell to 85% +/- 3% in I20, (p = 0.003) and to 65% +/- 6% (p = 0.003) of control values in I30, while relaxation (tau) was prolonged only in I30 (p = 0.007). CONCLUSIONS: Hearts recover fully after three 15-minutes periods of ischemia during warm blood cardioplegia, but deterioration, significant with 20-minute periods, is profound when the ischemic periods are lengthened to 30 minutes. This suggests that in the clinical setting warm cardioplegia can be safely interrupted for short intervals, but longer interruptions require caution.

Adenosine Triphosphate↗
PubMed1997

Retardation of pain development: a case of recovery from congenital insensitivity to pain.

Congenital analgesia is a rare genetic disorder. We report here that a 12-year-old boy was able to recover from congenital insensitivity to pain. Neurological examinations revealed that there was a 'stocking' distribution of pain decrement on the lower extremities under the patient's knee joints. Magnetic Resonance Imaging (MRI) of his brain showed gyrus thinning with sulcus widening at both sides of the parietal lobe. Southern blot hybridization probed with cDNAs of various opioid receptors did not detect any significant abnormality. Our results suggest that this rare case may not be genetically determined.

Arthropathy, Neurogenic↗
PubMed1995

Analysis of three DnaK mutant proteins suggests that progression through the ATPase cycle requires conformational changes.

DnaK, the bacterial homolog of the eukaryotic hsp70 proteins, is an ATP-dependent chaperone whose basal ATPase is stimulated by synthetic peptides and its cohort heat shock proteins, DnaJ and GrpE. We have used three mutant DnaK proteins, E171K, D201N, and A174T (corresponding to Glu175, Asp206, and Ala179, respectively, in bovine heat stable cognate 70) to probe the ATPase cycle. All of the mutant proteins exhibit some alteration in basal ATP hydrolysis. However, they all exhibit more severe defects in the regulated activities. D201N and E171K are completely defective in all regulated activities of the protein and also in making the conformational change exhibited by the wt protein upon binding ATP. We suggest that the inability of D201N and E171K to achieve the ATP activated conformation prevents both stimulation by all effectors and the ATP-mediated release of GrpE. In contrast, the defect of A174T is much more specific. It exhibits normal binding and release of GrpE and normal stimulation of ATPase activity by DnaJ. However, it is defective in the synergistic activation of its ATPase by DnaJ and GrpE. We suggest that this mutant protein is specifically defective in a DnaJ/GrpE mediated conformational change in DnaK necessary for the synergistic action of DnaJ+GrpE.

Adenosine Triphosphatases↗
PubMed1995

rpoE, the gene encoding the second heat-shock sigma factor, sigma E, in Escherichia coli.

In Escherichia coli, the heat shock response is under the control of two alternative sigma factors: sigma 32 and sigma E. The sigma 32-regulated response is well understood, whereas little is known about that of sigma E, except that it responds to extracytoplasmic immature outer membrane proteins. To further understand this response, we located the rpoE gene at 55.5' and analyzed the role of sigma E. sigma E is required at high temperature, and controls the transcription of at least 10 genes. Some of these might contribute to the integrity of the cell since delta rpoE cells are more sensitive to SDS plus EDTA and crystal violet. sigma E controls its own transcription from a sigma E-dependent promoter, indicating that rpoE transcription plays a role in the regulation of E sigma E activity. Indeed, under steady-state conditions, the transcription from this promoter mirrors the levels of E sigma E activity in the cell. However, it is unlikely that the rapid increase in E sigma E activity following induction can be accounted for solely by increased transcription of rpoE. Based upon homology arguments, we suggest that a gene encoding a negative regulator of sigma E activity is located immediately downstream of rpoE and may function as the target of the E sigma E inducing signal.

Amino Acid Sequence↗
PubMed1993

Interleukin-2 secreting cells in multiple sclerosis and controls.

To evaluate systemic T cell activation and reactivity against putative autoantigens in multiple sclerosis (MS), numbers of interleukin-2 (IL-2) secreting cells were determined in peripheral blood of 32 patients with MS, 7 patients with acute aseptic meningitis (AM) and 12 patients with tension headache (TH). Numbers of IL-2 secreting cells were higher in MS patients compared to patients with AM + TH after stimulation with myelin proteolipid protein (PLP), myelin associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG), but not after stimulation with myelin basic protein (MBP). In response to MAG, MOG and acetylcholine receptor (AChR) the frequencies of IL-2 secreting cells were higher in patients with MS than TH, while there were no differences between AM and TH to any of the tested antigens. Between patients with MS and AM there was no difference regarding frequency of IL-2 secreting cells in response to any of the tested antigens except MAG to which the response was higher in MS patients. Six of 10 MS patients had IL-2 secreting cells in response to all four myelin antigens (MBP + PLP + MAG + MOG) or to three antigens, while this broad reactivity was not found in any control patient. There was no correlation between numbers of IL-2 secreting cells in MS patients and clinical variables, including exacerbation versus remission, disability and duration of disease. The results suggest that the systemic T cell response in patients with MS is directed to several antigens.

Adult↗
PubMed1993

Antibody-secreting cells to acetylcholine receptor and to presynaptic membrane receptor in seronegative myasthenia gravis.

Peripheral blood and bone marrow from seronegative and seropositive myasthenics were evaluated for antibody-secreting cells (ASC). Cells secreting antibody to acetylcholine receptor (AchR) and to presynaptic membrane receptor (prsmR) were counted using an immunospot assay. Immunoglobulin G (IgG) anti-AchR ASC were present in peripheral blood lymphocytes (PBL) from nine of 13 seronegative and nine of 12 seropositive myasthenics and in bone marrow lymphocytes (BML) from nine of 13 seronegative and eight of 12 seropositive myasthenics. The mean number of IgG anti-AchR ASC was lower for seronegative than for seropositive patients (P < 0.01 for PBL and P < 0.0001 for BML). In seropositive patients the mean number of IgG anti-AchR ASC was higher for BML than for PBL (P < 0.01); in seronegative patients it was not. IgG anti-prsmR ASC were detected in PBL from four of eight seronegative and six of eight seropositive myasthenics and in BML from three of eight seronegative and five of eight seropositive patients. The mean number of IgG-anti-prsmR ASC did not differ between seronegative and seropositive patients for PBL but for BML the value was higher for seropositive than for seronegative patients (P < 0.01). We conclude that seronegative myasthenia gravis is an autoimmune disease and that ASC to AchR and to prsmR are present both in the blood and the bone marrow in seronegative patients as in seropositive ones. A major difference between the groups lies in the significantly greater number of ASC found in the bone marrow in the seropositive cohort.

Adolescent↗