Identification of Toll-like receptor 4 (Tlr4) as the sole conduit for LPS signal transduction: genetic and evolutionary studies.
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Animals↗
Biomedical subjects
X Du
Publications and source records attributed to X Du.
Stable clonal expansion of the T-cell receptor V beta 6, V beta 17 and V beta 19 T cells in a cGVHD case using genescan analysis.
OBJECTIVE: To investigate the distribution and clonality of the T-cell receptor (TCR) V beta repertoire in chronic graft versus host disease (cGVHD). METHODS: The complementarity determining region 3 (CDR3) of the TCR beta gene with 24 variable regions was amplified in peripheral blood mononuclear cells drawn from one cGVHD patient after allogenic bone marrow transplantation (allo-BMT) 35, 39, 43 or 45 months respectively, using RT-PCR, to observe the expression of TCR V beta repertoire T cells. The PCR products were further analyzed by genescan to evaluate clonality of T cells. RESULTS: Fourteen or 16 TCR V beta subfamily T cells were detected in each sample of cGVHD case. Oligoclonal T cells were identified in TCR V beta 6, 16, 17, 19 and 21 subfamilies. The stable clonal T cells in all samples were identified in V beta 6, V beta 17 and V beta 21 subfamilies. CONCLUSION: Skewing distribution and stable clonal expansion of T cells can be found in cGVHD cases and it may be related to the initiation of cGVHD.
Adult↗
[The development of a respiration and temperature monitor].
This paper introduces the design of a monitoring system to measure the respiration and temperature of a body with an 8Xc196 single-chip microcomputer. This system can measure and display the respiration wave, respiration frequency and the body temperature in real-time with a liquid crystal display (LCD) and give an alarm when the parameters are beyond the normal scope. In addition, this device can provide a 24 hours trend graph of the respiration frequency and the body temperature parameters measured. Data can also be exchanged through serial communication interfaces (RS232) between the PC and the monitor.
Body Temperature↗
[Quantitative measurement on degradation degree of ecosystem in hilly region of western Liaoning Province].
Exactly measuring the degradation degree of ecosystems is the basis and precondition of restoring ecosystems. At present, degradation degree is usually analyzed qualitatively. In this paper, quantitative classification method was used to study the degradation degree of ecosystem in hilly region of western Liaoning, which was measured by the degradation degree of habitat. The result shows that the habitat in the northern slope of mountains has been degraded to certain stage between shrubbery and pioneer tree forest, which provides theoretical basis for vegetation restoration practice. Moreover, the result is beneficial for studying the degradation degree of ecosystems in other regions or of other types.
China↗
[Observation on biological characteristics of Hedyotis diffusa].
The present work enunciats the phenophase and plant organ development of Hedyotis diffusa Willd, at Nanjing region. These results can give a reference for the plant growing practice.
Hedyotis↗
[Phacofragmentation of dislocated lens in vitreous cavity].
OBJECTIVE: To discuss the surgical techniques and therapeutic effects of phacofragmentation of the dislocated lens in the vitreous cavity. METHODS: Phacofragmentation was performed on 23 eyes of 23 patients with dislocated lens or subluxated lens in the vitreous cavity. With high suction and moderate ultrasound, the nucleus could be emulsified. Energy and time of emulsification: 50%-60% of energy was set up and emulsification spent 43 s to 3 min 23 s (mean 1 min 57 s). The pressure of maximum vacuum aspiration was 110-120 mm Hg (1 mm Hg = 0.133 kPa). In 11 eyes, anterior chamber intraocular lens (ACIOL) was implanted. Cryoapplications and encircling procedure were also performed on one eye. RESULTS: Phacofragmentation was successful in all patients. After follow-up for 5-19 months (mean 7.2 months), the corrected visual acuity was obviously improved in the cases of ACIOL and Marfan's syndrome, with 12 patients achieving visual acuity of 0.12-0.6. The major complications were corneal edema and damage of iris. CONCLUSIONS: It is demonstrated that phacofragmentation in the central vitreous cavity is safe and fairly easy procedure without adverse effects on retina and sclera. It helps to reduce intraoperative risks of alternative methods, avoiding a large opening of the anterior chamber and hypotony of the globe.
Adult↗
Crystal structure of an intracellular protease from Pyrococcus horikoshii at 2-A resolution.
The intracellular protease from Pyrococcus horikoshii (PH1704) and PfpI from Pyrococcus furiosus are members of a class of intracellular proteases that have no sequence homology to any other known protease family. We report the crystal structure of PH1704 at 2.0-A resolution. The protease is tentatively identified as a cysteine protease based on the presence of cysteine (residue 100) in a nucleophile elbow motif. In the crystal, PH1704 forms a hexameric ring structure, and the active sites are formed at the interfaces between three pairs of monomers.
Amino Acid Sequence↗
Evidence that beta3 integrin-induced Rac activation involves the calpain-dependent formation of integrin clusters that are distinct from the focal complexes and focal adhesions that form as Rac and RhoA become active.
Interaction of integrins with the extracellular matrix leads to transmission of signals, cytoskeletal reorganizations, and changes in cell behavior. While many signaling molecules are known to be activated within Rac-induced focal complexes or Rho-induced focal adhesions, the way in which integrin-mediated adhesion leads to activation of Rac and Rho is not known. In the present study, we identified clusters of integrin that formed upstream of Rac activation. These clusters contained a Rac-binding protein(s) and appeared to be involved in Rac activation. The integrin clusters contained calpain and calpain-cleaved beta3 integrin, while the focal complexes and focal adhesions that formed once Rac and Rho were activated did not. Moreover, the integrin clusters were dependent on calpain for their formation. In contrast, while Rac- and Rho-GTPases were dependent on calpain for their activation, formation of focal complexes and focal adhesions by constitutively active Rac or Rho, respectively, occurred even when calpain inhibitors were present. Taken together, these data are consistent with a model in which integrin-induced Rac activation requires the formation of integrin clusters. The clusters form in a calpain-dependent manner, contain calpain, calpain-cleaved integrin, and a Rac binding protein(s). Once Rac is activated, other integrin signaling complexes are formed by a calpain-independent mechanism(s).
Amino Acid Substitution↗
The mechanism of GTP hydrolysis by Ras probed by Fourier transform infrared spectroscopy.
Time-resolved Fourier transform infrared spectroscopy (FTIR) in combination with photo-induced release of (18)O-labeled caged nucleotide has been employed to address mechanistic issues of GTP hydrolysis by Ras protein. Infrared spectroscopy of Ras complexes with nitrophenylethyl (NPE)-[alpha-(18)O(2)]GTP, NPE-[beta-(18)O(4)]GTP, or NPE-[gamma-(18)O(3)]GTP upon photolysis or during hydrolysis afforded a substantially improved mode assignment of phosphoryl group absorptions. Photolysis spectra of hydroxyphenylacyl-GTP and hydroxyphenylacyl-GDP bound to Ras and several mutants, Ras(Gly(12))-Mn(2+), Ras(Pro(12)), Ras(Ala(12)), and Ras(Val(12)), were obtained and yielded valuable information about structures of GTP or GDP bound to Ras mutants. IR spectra revealed stronger binding of GDP beta-PO(3)(2-) moiety by Ras mutants with higher activity, suggesting that the transition state is largely GDP-like. Analysis of the photolysis and hydrolysis FTIR spectra of the [beta-nonbridge-(18)O(2), alphabeta-bridge-(18)O]GTP isotopomer allowed us to probe for positional isotope exchange. Such a reaction might signal the existence of metaphosphate as a discrete intermediate, a key species for a dissociative mechanism. No positional isotope exchange was observed. Overall, our results support a concerted mechanism, but the transition state seems to have a considerable amount of dissociative character. This work demonstrates that time-resolved FTIR is highly suitable for monitoring positional isotope exchange and advantageous in many aspects over previously used methods, such as (31)P NMR and mass spectrometry.
Guanosine Triphosphate↗
14-3-3zeta interacts with the alpha-chain of human interleukin 9 receptor.
Interleukin 9 (IL-9) exerts its pleiotropic effects through the IL-9 receptor (IL-9R) complex, which consists of the IL-9R alpha-chain, which determines the cytokine specificity, and the IL-2 receptor gamma-chain. In the present study we used a modified yeast two-hybrid system to isolate cDNA species encoding proteins that interacted with the intracellular domain of the human IL-9R alpha-chain (hIL-9Ralpha). We have identified 14-3-3zeta as an hIL-9Ralpha-interacting protein. We also mapped residues 518-522 (Arg-Ser(519)-Trp-Thr(521)-Phe) in hIL-9Ralpha and helix I of 14-3-3zeta as being important for interaction. Moreover, peptide competition experi-ments suggested that interaction between hIL-9Ralpha and 14-3-3zeta requires the phosphorylation of Ser(519) or Thr(521). This is the first demonstration that 14-3-3 can interact with a non-tyrosine kinase receptor. The interaction between 14-3-3 and IL-9Ralpha but not IL-4Ralpha also suggests a potential role for 14-3-3 in determining cytokine specificity.
14-3-3 Proteins↗
Prevalence, treatment, control, and awareness of high blood pressure and the risk of stroke in Northwest England.
OBJECTIVES: The aim of this study was to examine the prevalence, treatment, control, and awareness of hypertension in patients with first-ever stroke and in controls sampled from the same primary care physician's population register. METHODS: A population-based case-control study was conducted in East Lancashire, England, using cases identified from the stroke register in 1994-1995. Information on blood pressure (BP) and other predefined factors was extracted from the practice medical records. Postal questionnaires were used for information on patients' awareness of hypertension. RESULTS: A total of 267 stroke cases and 534 controls were included. Sixty-one percent of cases and 43% of controls had BP >= 160/95 mm Hg on >= 2 occasions within 3 months or received antihypertensives. High proportions of cases (82%) and controls (85%) were on treatment. There was a continuous relationship between the risk of stroke and levels of BP control. Of 73 cases and 135 controls who were hypertensive and responded to the postal questionnaire, 56 and 83%, respectively, were aware of hypertension (P<0.01). CONCLUSIONS: The prevalence of hypertension was high among stroke patients. In those treated, <30% of patients had their BP adequately controlled to <140/90 mm Hg. Patient awareness of previous hypertension or high BP was very poor and attention needs to be paid to patient education.
Age Distribution↗
Brain tissue PO(2), PCO(2), and pH during cerebral vasospasm.
BACKGROUND: The purpose of the present study was to assess brain tissue monitoring for detection of ischemia due to vasospasm in aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS: After obtaining informed consent, a burr hole was made in 10 patients and a Neurotrend 7 probe was inserted ipsilateral to the region of SAH. In eight patients the probe was inserted during surgery for clipping the aneurysm and in two patients the probe was inserted in the neurosurgery ICU. Brain tissue gases and pH were collected over 6-hour periods for 7 to 10 days until the termination of monitoring. The onset of vasospasm was confirmed by angiography and xenon computed tomography (Xe/CT) cerebral blood flow studies. RESULTS: Seven patients did not develop vasospasm during monitoring and were considered as controls. In this group, brain tissue oxygen pressure (PO(2)) remained above 20 mmHg, carbon dioxide pressure (PCO(2)) stabilized at 40 mmHg and pH remained between 7.1 and 7.2. In three patients who developed vasospasm during monitoring, PO(2) was not different from the control group. However, PCO(2) increased to 60 mmHg and pH decreased to 6.7 (p < 0.001). CONCLUSION: In this study, patients with SAH who developed vasospasm had significantly lower brain tissue pH and higher PCO(2) compared to controls. However, there was no significant change in PO(2) levels associated with vasospasm. Brain tissue monitoring can provide an indication of ischemia during vasospasm.
Aged↗
Stroke risk from multiple risk factors combined with hypertension: a primary care based case-control study in a defined population of northwest England.
PURPOSE: To examine how hypertension interacts with other known risk factors in affecting the risk of stroke in a primary care based setting. METHODS: Cases were patients with first-ever stroke identified from the community-based stroke register in 1994-95 in northwest England. Two controls per case were randomly selected from the same primary care site and matched by age and sex. Information on predefined risk factors was extracted from medical records. RESULTS: 267 cases and 534 controls were included. Adjusted odds ratio (OR) for stroke from hypertension was 2.6 (95% confidence interval: 1.7-3.9). In hypertensives who were current smokers, risk of stroke was increased 6 fold as compared to non-smokers without hypertension. Hypertensives who had a preexisting history of myocardial infarction or obesity or diabetes had 3 fold higher risks of stroke. Subjects with hypertension and with a history of transient ischemic attack or atrial fibrillation had > or = 8 fold excess risk of stroke. Among them, the risk was greater in those with poorly controlled or untreated hypertension and in those with well or moderately controlled as compared to subjects without both risk factors. There appeared to be a steady increase in risk of stroke according to the number of risk factors present, particularly in hypertensive subjects. CONCLUSIONS: Stroke risks in hypertensives associated with combinations of other risk factors appeared to follow an additive model. Subjects with multiple risk factors should be targeted in order to reduce the overall risk for stroke.
Aged↗
Aryl ureas represent a new class of anti-trypanosomal agents.
BACKGROUND: The trypanosomal diseases including Chagas' disease, African sleeping sickness and Nagana have a substantial impact on human and animal health worldwide. Classes of effective therapeutics are needed owing to the emergence of drug resistance as well as the toxicity of existing agents. The cysteine proteases of two trypanosomes, Trypanosoma cruzi (cruzain) and Trypanosoma brucei (rhodesain), have been targeted for a structure-based drug design program as mechanistic inhibitors that target these enzymes are effective in cell-based and animal models of trypanosomal infection. RESULTS: We have used computational methods to identify new lead scaffolds for non-covalent inhibitors of cruzain and rhodesain, have demonstrated the efficacy of these compounds in cell-based and animal assays, and have synthesized analogs to explore structure activity relationships. Nine compounds with varied scaffolds identified by DOCK4.0.1 were found to be active at concentrations below 10 microM against cruzain and rhodesain in enzymatic studies. All hits were calculated to have substantial hydrophobic interactions with cruzain. Two of the scaffolds, the urea scaffold and the aroyl thiourea scaffold, exhibited activity against T. cruzi in vivo and both enzymes in vitro. They also have predicted pharmacokinetic properties that meet Lipinski's 'rule of 5'. These scaffolds are synthetically tractable and lend themselves to combinatorial chemistry efforts. One of the compounds, 5'(1-methyl-3-trifluoromethylpyrazol-5-yl)-thiophene 3'-trifluoromethylphenyl urea (D16) showed a 3.1 microM IC(50) against cruzain and a 3 microM IC(50) against rhodesain. Infected cells treated with D16 survived 22 days in culture compared with 6 days for their untreated counterparts. The mechanism of the inhibitors of these two scaffolds is confirmed to be competitive and reversible. CONCLUSIONS: The urea scaffold and the thiourea scaffold are promising leads for the development of new effective chemotherapy for trypanosomal diseases. Libraries of compounds of both scaffolds need to be synthesized and screened against a series of homologous parasitic cysteine proteases to optimize the potency of the initial leads.
Animals↗
What drove changes in the use of breast conserving surgery since the early 1980s? The role of the clinical trial, celebrity action and an NIH consensus statement.
BACKGROUND: Three important events in the history of breast cancer treatment occurred between 1983 and 1995: a large clinical trial, first lady Nancy Reagan's choice of mastectomy and the publishing of an NIH consensus statement. OBJECTIVE: To assess the effects of these events on use of breast conserving surgery (BCS). RESEARCH DESIGN: Data from the cohort study of the surveillance, epidemiology and end results (SEER) Program from 1983 to 1995 were divided into four periods: Baseline, Trial, Celebrity, and Consensus. SUBJECTS: Of the women, 169,466 diagnosed with early stage breast cancer in nine SEER areas. MEASURES: Monthly percentages of BCS. RESULTS: A linear regression model generated a separate intercept and slope term for four time periods, adjusting for demographic characteristics of breast cancer patients. For the Baseline, Celebrity and Consensus Periods, slopes indicated an increasing use of BCS which varied between 0.24% and 0.28% per month. Slopes for these three periods were not statistically different (p = 0.120). In contrast, there was no change in use of BCS during the trial period (p = 0.247). We tested the magnitude of discontinuity between periods. At the beginning of the trial, celebrity and consensus periods, there were increases in BCS of 5.54% (p < 0.001), -3.55% (p < 0.001), and 2.37% (p < 0.001), respectively. CONCLUSIONS: The use of BCS was substantially affected by the reports of a clinical trial of BCS and by celebrity action. These effects were abrupt but transient. The NIH consensus statement stimulated a small change in use of BCS and may be an important intervention for maintaining the increasing trend in use of BCS since the 1990s.
Adult↗
Penetration of N-nitrosonornicotine (NNN) across oral mucosa in the presence of ethanol and nicotine.
The effects of ethanol concentrations of 5, 15, 20, 25, 27, 30 and 50% on the penetration of the tobacco-specific carcinogen, nitrosonornicotine (NNN), across porcine oral mucosa were examined using an in vitro perfusion system. Concentrations of ethanol of 25% and above significantly increased the permeability of oral mucosa to NNN, although this increase ceased with 50% ethanol, possibly due to a fixative effect. Nicotine is a consistent component of smoked and smokeless tobacco; the presence of 0.2% nicotine significantly increased the permeability of oral mucosa to NNN and 2% nicotine caused a further increase. Combined use of nicotine and ethanol significantly increased the penetration of NNN across oral mucosa over that of ethanol alone until the concentration of ethanol reached 50%. The results of this study suggest that the synergy between tobacco and alcohol in the etiology of oral cancer may be explained, at least in part, by the local permeabilizing effects of alcohol on the penetration of tobacco-specific (and other) carcinogens across oral mucosa.
Analysis of Variance↗
Accuracy and completeness of Medicare claims data for surgical treatment of breast cancer.
BACKGROUND: Although a number of studies have used Medicare claims data to study trends and variations in breast cancer treatment, the accuracy and completeness of information on surgical treatment for breast cancer in the Medicare data have not been validated. OBJECTIVES: This study assessed the accuracy and completeness of Medicare claims data for breast cancer surgery to determine whether Medicare claims can serve as a source of data to augment information collected by cancer registries. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) Cancer Registry-Medicare data and compared Medicare claims on surgery with the surgery recorded by the SEER registries for 23,709 women diagnosed with breast cancer at > or =65 years of age from 1991 through 1993. RESULTS: More than 95% of women having mastectomies according to the Medicare data were confirmed by SEER. For breast-conserving surgery, 91% of cases were confirmed by SEER. The Medicare physician services claims and inpatient claims were approximately equal in accuracy on type of surgery. The Medicare outpatient claims were less accurate for breast-conserving surgery. In terms of completeness, when the 3 claims sources were combined, 94% of patients receiving breast cancer surgery according to SEER were identified by Medicare. CONCLUSIONS: The combined Medicare claims database, which includes the inpatient, outpatient, and physician service claims, provides valid information on surgical treatment among women known to have breast cancer. The claims are a rich source of data to augment the information collected by tumor registries and provide information that can be used to follow long-term outcomes of Medicare beneficiaries.
Breast Neoplasms↗
Effects of drugs on glucose measurements with handheld glucose meters and a portable glucose analyzer.
Thirty drugs used primarily in critical care and hospital settings were tested in vitro to observe interference on glucose measurements with 6 hand-held glucose meters and a portable glucose analyzer. Paired differences of glucose measurements between drug-spiked samples and unspiked control samples were calculated to determine bias. A criterion of +/- 6 mg/dL was used as the cutoff for interference. Ascorbic acid interfered with the measurements on all glucose devices evaluated. Acetaminophen, dopamine, and mannitol interfered with glucose measurements on some devices. Dose-response relationships help assessment of drug interference in clinical use. High dosages of these drugs may be given to critically ill patients or self-administered by patients without medical supervision. Package inserts for the glucose devices may not provide adequate warning information. Hence, we recommend that clinicians choose glucose devices carefully and interpret results cautiously when glucose measurements are performed during or after drug interventions.
Blood Glucose↗