Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 55 records · Page 3Linked to original sources

PubMed2005

Dendritic-NK cell interactions in P. gingivalis-specific responses.

Patients with localized aggressive periodontitis have type-1 cytokines in gingival crevicular fluid and high titers of IFN-gamma-dependent IgG2 reactive with P. gingivalis in gingival crevicular fluid and serum. Localized aggressive periodontitis monocytes spontaneously differentiate into dendritic cells that can stimulate IFN-gamma production by NK cells. These relationships prompted the hypothesis that P. gingivalis-dendritic cell-NK cell interactions might promote type-1 cytokine responses. Although P. gingivalis is not a potent inducer of Th1 responses, it stimulated strong IL-12 responses by monocyte-derived dendritic cells in the presence of IFN-gamma, and IFN-gamma was produced by NK cells within 24 hrs in the presence of dendritic cells. Anti-P. gingivalis IgG2 responses were enhanced by dendritic cells, and removal of NK cells reduced IFN-gamma- and P. gingivalis-specific IgG2. Thus, P. gingivalis-dendritic cell-NK cell interactions apparently resulted in reciprocal stimulation and increased type-1 cytokine production by both dendritic cells and NK cells, and increased P. gingivalis-specific IgG2.

Adult↗

PubMed2004

The nongenotropic synthetic ligand 4-estren-3alpha17beta-diol is a high-affinity genotropic androgen receptor agonist.

The nongenotropic ligand estren (Science 298:843-846, 2002) was evaluated for its transcriptional activity mediated by the human androgen receptor (AR). Our results show that estren can bind, translocate, transactivate, and regulate two known target genes of AR in androgen-responsive cell lines. Estren binds recombinant AR with 10-fold higher affinity than either estrogen receptor (ER)-alpha or ERbeta. Estren-bound AR can translocate AR to the nucleus and stimulate the androgen response element-luciferase reporter activity with an efficacy similar to that of androgen. Estren also increased the expression of prostate-specific antigen (PSA) in a dose-dependent manner in human LnCaP cells. Using chromatin immunoprecipitation analysis, we show that the estren-bound AR coimmunoprecipitates with a region of the PSA gene promoter. Therefore, cotreatment with an AR antagonist, bicalutamide, blocked the estren-induced increase in PSA expression. In contrast, phosphoinositol 3-kinase inhibitor wortmannin, or extracellular signal-regulated kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene (U0126), and ER antagonist ICI-182780 failed to block the effects of estren. In vivo analysis of estren's action on male-orchidectomized ICR mice revealed estren's AR agonist actions on the levator ani and seminal vesicle target tissues. Taken together, our results reveal the hitherto unidentified genotropic action of estren mediated by AR in androgen-responsive cells and tissues.

Androgens↗

PubMed2004

Stimulation of beta-adrenoceptors inhibits store-operated channel currents via a cAMP-dependent protein kinase mechanism in rabbit portal vein myocytes.

Previously we have described the properties of store-operated channel currents (SOCs) in freshly dispersed rabbit portal vein smooth muscle cells. In addition to Ca(2+) store depletion these SOCs could also be activated by alpha-adrenoceptor stimulation and diacylglycerol (DAG) via a protein kinase C (PKC)-dependent mechanism. In the present study we have investigated the effect of beta-adrenoceptor stimulation on SOCs in rabbit portal vein myocytes. With whole-cell recording the selective beta-adrenoceptor agonist isoprenaline reduced the current evoked by cyclopiazonic acid (CPA, sarcoplasmic/endoplasmic reticulum ATPase inhibitor) by over 85%. With cell-attached patch recording, bath application of isoprenaline produced a pronounced inhibition of SOC activity evoked by either CPA or the acetoxymethyl ester form of BAPTA (BAPTA-AM). SOC activity evoked by CPA, the DAG analogue, 1-oleoyl-acetyl-sn-glycerol (OAG) or the phorbol ester, phorbol-12,13-dibutyrate (PDBu) was also markedly inhibited by the adenylate cyclase activator, forskolin, and the cell-permeable non-hydrolysable analogue of cyclic adenosine monophosphate (cAMP), 8-Br-cAMP. With inside-out patches, bath application of PDBu evoked channel currents with similar properties to SOCs which were inhibited by over 90% by a catalytic subunit of protein kinase A (PKA) and by 8-Br-cAMP. Moreover bath application of PKA inhibitors, H-89, KT5720 and an inhibitory peptide to quiescent cell-attached or inside-out patches, activated channel currents with similar properties to SOCs. These data suggest that in rabbit portal vein myocytes, stimulation of beta-adrenoceptors inhibits SOC activity via a cAMP-dependent protein kinase signal transduction cascade. In addition it is concluded that constitutive PKA activity has a profound inhibitory effect on SOC activity in this vascular preparation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2004

Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke.

BACKGROUND: Thrombolytic therapy is effective for acute myocardial infarction, a disease with some similarities to acute ischaemic stroke. Meta-analyses suggest a net benefit in acute ischaemic stroke. OBJECTIVES: To assess different thrombolytic agents, and different regimens, in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched to June 2003), MEDLINE (1966 to July 2003) and EMBASE (1980 to July 2003). We handsearched four Japanese journals, contacted researchers and pharmaceutical companies, and attended relevant conferences. SELECTION CRITERIA: Randomised and quasi-randomised trials of different doses of a thrombolytic agent, or different agents, or the same agent given by different routes, in people with confirmed acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality, and extracted the data. MAIN RESULTS: Ten trials involving 1641 patients, 8 conducted in Japan, 1 in China and 1 in the USA, were included. Concealment of allocation was poorly described. Different doses (of tissue plasminogen activator or urokinase) were compared in seven trials (n = 1072 patients). Different agents (tissue plasminogen activator versus urokinase; tissue-cultured urokinase versus conventional urokinase) were compared in three trials (n = 688 patients). One trial compared different routes of administration (intravenous plus intraarterial tissue plasminogen activator versus intraarterial tissue plasminogen activator alone, n = 35 patients). As some trials compared different agents and different doses, some patients contributed to two analyses. A higher dose of thrombolytic therapy was associated with a three-fold increase in fatal intracranial haemorrhages (Odds ratio (OR) 3.25, 95% confidence interval (CI) 1.32 to 7.97) compared with a lower dose of the same agent (based on 16 events among 539 higher-dose patients and 4 events among 533 lower-dose patients in 7 trials). There was no statistically significant difference in early (OR 1.01, 95% CI 0.58 to 1.74) or late (OR 0.94, 95% CI 0.58 to 1.53) deaths between lower and higher doses. Data were inadequate to assess the effect of dose on functional outcome. No statistically significant difference was shown between different thrombolytic agents tested. The data from the pilot trial comparing different routes of administration were inconclusive. REVIEWERS' CONCLUSIONS: These scant data suggest that higher doses of thrombolytic agents may lead to higher rates of bleeding. However, the evidence is inadequate to conclude whether lower doses of thrombolytic agents are more effective than higher doses, or whether one agent is better than another, or which route of administration is the best, in acute ischaemic stroke.

Brain Ischemia↗

PubMed2004

Dan Shen agents for acute ischaemic stroke.

BACKGROUND: Based mainly on experimental data which indicates improvement to the cerebral microcirculation, Dan Shen, a form of herbal medicine, is widely used in the treatment of acute ischaemic stroke in China. We aimed to assess the evidence from randomised controlled trials of their effects. OBJECTIVES: To review the randomised or quasi-randomised controlled trials of Dan Shen agents for acute ischaemic stroke. The primary objective was to determine whether Dan Shen agents improve functional outcome without causing undue harm in patients with acute ischaemic stroke. Secondary objectives were to assess the effect of Dan Shen agents on impairment and on quality of life. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2003), the register of the Cochrane Complementary Field (last searched September 2003) and the Chinese Stroke Trials Register (last searched September 2003). In addition we searched the following bibliographic databases: The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (1996 to December 2002), EMBASE (1980 to December 2002), CINAHL (1982 to December 2002), AMED (1985 to December 2002) and China Biological Medicine Database (CBM-disc 1979 to December 2002). We handsearched 10 Chinese journals, searched clinical trials and research databases, scanned reference lists and contacted the pharmaceutical company manufacturing Dan Shen. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled clinical trials comparing Dan Shen agents with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Eight potentially eligible trials were identified, of which three trials (304 patients) were included. Two trials were excluded and three trials are awaiting assessment. Numbers of deaths and dependent patients at the end of follow-up of at least three months were not reported in the three included trials. Only one trial reported adverse events. Three trials measured the outcome "significant improvement in neurological deficit at the end of treatment". Compound Dan Shen agents were associated with a significant increase in the number of patients with the outcome (Peto Odds Ratio (OR) 2.72, 95% Confidence Interval (CI) 1.10 to 6.72). No deaths were reported within the first two weeks of treatment or during the whole follow-up period (21 to 28 days). The trials did not include any assessment of quality of life. REVIEWERS' CONCLUSIONS: There were too few patients and outcome events to draw reliable conclusions from the present data. The methodological qualities of all included studies were poor. Further high-quality randomised controlled trials should be performed.

Acute Disease↗

PubMed2004

Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled study.

BACKGROUND: The histopathology of AIDS-associated myelopathy (AM) closely resembles that of myelopathies due to cobalamin or folate deficiency, with white matter vacuolization in the spinal cord. The pathogenesis of AM appears unrelated to direct HIV infection of the spinal cord. There is abnormal trans-methylation metabolism in AM, with decreased availability of the methyl group donor S-adenosyl-methionine (SAM). The authors hypothesized that treatment with l-methionine, the direct metabolic precursor of SAM, might improve AM. OBJECTIVE: To determine the safety and efficacy of l-methionine treatment in AM. METHODS: Fifty-six patients with clinical diagnosis of AM were randomized to a Phase II, double-blind, placebo-controlled study comparing the effect of l-methionine 6 g/day in two divided doses with that of placebo. Study duration was 12 weeks. All patients had somatosensory evoked potentials with prolonged central conduction time (CCT) at entry. Change in CCT was the primary endpoint of the study. Frequency of adverse events (AEs) was used to assess safety. Secondary endpoints were strength, spasticity, and urinary function. Biochemical measurements included serum methionine and homocysteine and CSF SAM. RESULTS: There were no significant differences in AEs between the two groups. Serum homocysteine increased in l-methionine-treated patients from 7.2 (+/-5.2 SD) to 12.6 (+/-6.15 SD) micromol/L. The mean CCT at baseline was 25.9 milliseconds (+/-7.3 SD) for the treatment group and 24.1 milliseconds (+/-7.0 SD) for the placebo group. At completion, it was 3.0 milliseconds (+/-6.1 SD) for the treatment group and 23.6 milliseconds (+/-5.5 SD) for the placebo group (p = 0.17). In a subset of 15 patients with CSF studies, SAM levels increased in the l-methionine but not in the placebo group (p = 0.07). There was no significant effect of treatment on strength, spasticity, or urinary function. CONCLUSIONS: l-methionine was safe and well tolerated although in some patients induced an increase of serum homocysteine. There was a nonsignificant improvement in CCT in treated patients but no benefit in any of the clinical measures.

Acquired Immunodeficiency Syndrome↗

PubMed2004

DNA microarray analysis of gene expression in alveolar epithelial cells in response to TNFalpha, LPS, and cyclic stretch.

Recent evidence suggests that alveolar epithelial cells (AECs) may contribute to the development, propagation, and resolution of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proinflammatory cytokines, pathogen products, and injurious mechanical ventilation are important contributors of excessive inflammatory responses in the lung. In the present study, we used cDNA microarrays to define the gene expression patterns of A549 cells (an AEC line) in the early stages of three models of pulmonary parenchymal cell activation: cells treated with tumor necrosis factor-alpha (TNFalpha) (20 ng/ml), lipopolysaccharide (LPS, 1 microg/ml), or cyclic stretch (20% elongation) for either 1 h or 4 h. Differential gene expression profiles were determined by gene array analysis. TNFalpha induced an inflammatory response pattern, including induction of genes for chemokines, inflammatory mediators, and cell surface membrane proteins. TNFalpha also increased genes related to pro- and anti-apoptotic proteins, signal transduction proteins, and transcriptional factors. TNFalpha further induced a group of genes that may form a negative feedback loop to silence the NFkappaB pathway. Stimulation of AECs with mechanical stretch changed cell morphology and activated Src protein tyrosine kinase. The combination of TNFalpha plus stretch enhanced or attenuated expression of multiple genes. LPS decreased microfilament polymerization but had less impact on NFkappaB translocation and gene expression. Results from this study indicate that AECs can tailor their response to different stimuli or/and combination of stimuli and subsequently play an important role in acute inflammatory responses in the lung.

Apoptosis↗

PubMed2004

Surgical wound infection as a performance indicator: agreement of common definitions of wound infection in 4773 patients.

OBJECTIVE: To assess the level of agreement between common definitions of wound infection that might be used as performance indicators. DESIGN: Prospective observational study. SETTING: London teaching hospital group receiving emergency cases as well as tertiary referrals. PARTICIPANTS: 4773 surgical patients staying in hospital at least two nights. MAIN OUTCOME MEASURES: Numbers of wound infections based on purulent discharge alone, on the Centers for Disease Control (CDC) definition of wound infection, on the nosocomial infection national surveillance scheme (NINSS) version of the CDC definition, and on the ASEPSIS scoring method. RESULTS: 5804 surgical wounds were assessed during 5028 separate hospital admissions. The mean percentage of wounds classified as infected differed substantially with different definitions: 19.2% with the CDC definition (95% confidence interval 18.1% to 20.4%), 14.6% (13.6% to 15.6%) with the NINSS version, 12.3% (11.4% to 13.2%) with pus alone, and 6.8% (6.1% to 7.5%) with an ASEPSIS score > 20. The agreement between definitions with respect to individual wounds was poor. Wounds with pus were automatically defined as infected with the CDC, NINSS, and pus alone definitions, but only 39% (283/714) of these had ASEPSIS scores > 20. CONCLUSIONS: Small changes made to the CDC definition or even in its interpretation, as with the NINSS version, caused major variation in estimated percentage of wound infection. Substantial numbers of wounds were differently classified across the grades of infection. A single definition used consistently can show changes in percentage wound infection over time at a single centre, but differences in interpretation prevent comparison between different centres.

Adult↗

PubMed2004

Oestrogen replacement therapy promotes bone healing around dental implants in osteoporotic rats.

The aim of this study was to investigate the effect of oestrogen replacement therapy on bone healing around titanium implants in osteoporotic rats. Sixty 32-week-old female SD rats were used in this study. Ovariectomies were performed in 40 rats, and other 20 rats had sham operation. Eighty-four days after surgery, osteoporotic changes in proximal tibiae were seen in four ovariectomized rats when compared with two sham-operated rats. Then pure titanium implants were placed in the bilateral proximal metaphyses of the tibiae of the remaining animals. Oestrogen replacement therapy was administrated in 18 ovariectomized rats after implantation. Nine rats from each group (ovariectomized, oestrogen-treated and sham-operated) were killed at 28 and 84 days after implantation surgery respectively, and the tibiae specimens were harvested and examined. Both at 28 and 84 days after implantation surgery, most bone histomorphometric indices in the oestrogen-treated group were significantly increased compared with those in the ovariectomized group (P < 0.05 or P < 0.01). Although the oestrogen-treated group showed lower trabecular bone volume at 28 days after implant surgery and lower mineralization rate at both the two time points than the sham-operated group, there were no significant differences in other bone histomorphometric indices between the oestrogen-treated group and the sham-operated group both at 24 and 84 days after implantation. The results of this study suggest that oestrogen replacement therapy may promote bone healing around titanium implants under osteoporotic state, and therefore it seemed to be beneficial to long-term success of dental implants in clinical postmenopausal patients.

Animals↗

PubMed2004

Comparison of pupil responses to luminance and colour in severe optic neuritis.

OBJECTIVE: The pupil response to light flux increments is abnormal in severe optic neuritis, but little is known about the effects of this condition on the pupil colour response. The aim of this study was to examine how optic neuritis affects pupil responses to light flux and colour modulation and the extent to which such pupil responses mirror the loss and recovery of vision. METHODS: A new pupil examination technique that makes use of sinusoidal modulation of either luminance contrast or chromatic saturation was employed. This technique enables the automatic extraction of both pupil response amplitude and latency and achieves a high signal to noise ratio with fewer averages. RESULTS: The study reveals a greater loss of pupil response amplitude and significantly longer latencies to chromatic modulation (i.e. approximately 80 ms). Stimulation of the unaffected eye in the optic neuritis group results in smaller response amplitudes when compared to the normal group for both light flux and colour modulation. CONCLUSIONS: Pupil response components can be affected differently in optic neuritis. These findings suggest that the pupil colour response, in particular, may provide a useful, objective estimator to judge the extent of damage and recovery in diseases of the optic nerve.

Adult↗

PubMed2004

Differential pH and capsaicin responses of Griffonia simplicifolia IB4 (IB4)-positive and IB4-negative small sensory neurons.

Protons play a key role in nociception caused by inflammation and ischaemia, but little is known about the relative sensitivities of different dorsal root ganglion (DRG) neurons. We have therefore examined the responses in vitro of rat DRG cells classified according to whether or not they bind Griffonia simplicifolia IB4 (IB4), a lectin which is widely used to distinguish between two major populations of small diameter neurons. Under voltage-clamp conditions, proton-activated inward currents were found in approximately 90% of small DRG neurons and showed one of three waveforms: transient, sustained or mixed. The majority of IB4-positive (IB4+) neurons (63%) gave rise to sustained inward currents that were sensitive to capsazepine. In contrast, the most prevalent waveform in small IB4-negative (IB4-) neurons (69%) was a mixed response containing transient and sustained components. The transient component was inhibited by amiloride whilst the sustained component showed a variable sensitivity to capsazepine. We also found that more IB4+ cells responded to capsaicin and, on average, gave rise to a larger magnitude of response than small IB4- neurons, consistent with their higher prevalence and greater amplitude of vanilloid receptor 1 (TRPV1)-like acid responses. The increase in intracellular Ca(2+) induced by capsaicin was also slightly greater in IB4+ neurons and in these cells its magnitude correlated with the level of TRPV1 immunoreactivity. Our data suggest that acid-sensing ion channels (ASICs) and TRPV1 are the major acid-sensitive receptors in small IB4- neurons, whilst TRPV1 is the predominant one in IB4+ neurons. Because ASIC-like responses were approximately 10-fold more sensitive to changes in H(+) than TRPV1-like responses, we speculate that small IB4- rather than IB4+ neurons play an essential role in sensing acid. Our results also highlight differences in capsaicin responses between IB4+ and IB4- small neurons and reveal the close link between capsaicin responses and levels of TRPV1 expression.

Amiloride↗

PubMed2004

C4d-positive acute humoral renal allograft rejection: rescue therapy by immunoadsorption in combination with tacrolimus and mycophenolate mofetil.

OBJECTIVE: We investigated the efficacy of immunoadsorption (IA) in combination with tacrolimus (FK506) and mycophenolate mofetil (MMF) rescue therapy for C4d-positive acute humoral rejection (AHR) of renal transplants. METHODS: Six of 185 cadaveric renal allograft recipients developed AHR at a mean of 4.8 +/- 0.8 days after the operation. C4d deposits were observed in peritubular capillaries (PTC) with accumulation of granulocytes. IA with staphylococcal protein A and FK506-MMF combination therapy were administered. RESULTS: After treatment with IA for 6.3 +/- 1.03 sessions combined with FK506 (0.14 to 0.16 mg.kg(-1).d(-1)) and MMF (1.5 g/d) therapy, renal function recovered in all the patients. The mean duration of treatment to a serum creatinine decrease was 14 +/- 2.9 days. The pre-IA panel reactive antibody reactivity (PRA) peaked at 50.2% +/- 6.1%, and was significantly reduced to 8.3% +/- 2.9% after IA. In four of six patients repeat allograft biopsy revealed a remission of AHR. With a mean follow-up of 18.8 +/- 5.46 months, patient and allograft survival are 100% and renal function remains stable with a mean serum creatinine of 1.2 +/- 0.22 mg/dL. CONCLUSION: The optimal treatment for alloantibody-mediated AHR remains uncertain. Our findings suggest that a therapeutic approach combining IA and FK506-MMF rescue improves the outcome of AHR.

Acute Disease↗

PubMed2004

Multi-subtype gp160 DNA immunization induces broadly neutralizing anti-HIV antibodies.

A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) resulted in high antibody titers in mice. The antibody induction was further enhanced after immunization with genes encoding HIV-1 envelopes originating from subtypes A, B and C. The sera from these animals were able to neutralize A, B and C viral isolates, whereas the sera from animals immunized solely with subtype B DNA neutralized only subtype B virus. The combined DNA vaccine gave serum antibodies with broad recognition of HIV-1 envelope epitopes as determined by peptide mapping. Cell-mediated immunity was not compromised by the increased humoral immunity. This demonstrates the ability of multiple envelope genes to induce the desired antibody response against several subtypes. Moreover, it documents the ability of rGM-CSF to enhance the potency of such a vaccine when given simultaneously. The strategy may be useful for making an HIV vaccine more potent and broadly effective against strains of different clades.

AIDS Vaccines↗

PubMed2004

Transbronchial administration of adenoviral-mediated interleukin-10 gene to the donor improves function in a pig lung transplant model.

Interleukin-10 (IL-10) gene transfection of donor lungs prior to transplantation is an attractive strategy to reduce ischemia-reperfusion induced lung injury. However, experimental data with gene therapy in large animal models of lung transplantation are generally lacking. We have developed a simple clinically applicable technique for adenoviral-mediated gene delivery of human IL-10 to the lung of large animals that provides homogenous gene expression after 12-24 h of transfection. Using this technique of gene delivery, we have studied the dynamics of adenoviral gene delivery to the lung in the setting of lung transplantation. Although there is a persistent inflammatory response to the adenoviral vector, we achieved significant expression of human IL-10 in lung tissue before lung retrieval to obviate the deleterious impact of the adenoviral vector on the donor lung. The administration of adenoviral-mediated human IL-10 to the donor lung reduced ischemia-reperfusion injury and improved graft function after lung transplantation in this pig lung transplantation model. Transfection of adenoviral-mediated human IL-10 to the donor lung prevented the release of inflammatory cytokines such as IL-6 in lung tissue and plasma. We have demonstrated that IL-10 gene therapy has significant potential to prevent or treat the inflammatory response associated with ischemia-reperfusion injury in lung transplantation. In the future, IL-10 gene therapy could also be used for immunomodulation or tolerance induction.

Adenoviridae↗

PubMed2004

The effect of smoking on outcome following external radiation for localized prostate cancer.

PURPOSE: We investigated whether a smoking habit affects biochemical and survival outcome after curative external beam radiation therapy (EBRT) for localized prostate cancer. MATERIALS AND METHODS: The study population comprised 601 men treated with curative EBRT between 1994 and 1997 who had a smoking history available. Pretreatment prognostic factors were examined and high risk was defined as any of prostate specific antigen greater than 20, Gleason greater than 7 or stages T3-4. Biochemical outcome (bNED) was assessed by American Society for Therapeutic Radiology and Oncology, and Houston criteria. Biochemical, clinical, prostate cancer and nonprostate cancer death rates were examined by univariate and multivariate statistics. RESULTS: Of the men 15% were current smokers, 55% were former smokers and 31% were nonsmokers. Current smokers were younger than former smokers or nonsmokers by a mean of 2.5 years (p <0.001). Current smokers had higher risk cancers than former smokers or nonsmokers (high risk 60%, 40% and 43%, respectively, p = 0.017). Five-year bNED rates for smokers were significantly worse than for former smokers or nonsmokers (55%, 69% and 73%, p = 0.01 and 0.0019, respectively). Median followup was 59 months. Multivariate analysis confirmed smoking as an independent adverse factor for bNED (p = 0.013) even when controlling for prostate specific antigen (p <0.0001), Gleason score (p <0.0001), stage (not significant), radiation dose (not significant) and neoadjuvant hormone use (p = 0.0014). Local and metastatic failure did not differ among the groups. Prostate cancer specific mortality was nonsignificantly worse in smokers but overall mortality was much greater. CONCLUSIONS: Smokers present with higher risk prostate cancers. Outcomes following EBRT are poorer, even when accounting for differences in known pretreatment factors.

Aged↗

PubMed2004

Cytochrome P450 in neurological disease.

Advances in a multitude of disciplines support an emerging role for cytochrome P450 enzymes and their metabolic substrates and end-products in the pathogenesis and treatment of central nervous system disorders, including acute cerebrovascular injury, such as stroke, chronic neurodegenerative disease, such as Alzheimer's and Parkinson's disease, as well as epilepsy, multiple sclerosis and psychiatric disorders, including anxiety and depression. The neural tissue contains its own unique set of P450 genes that are regulated in a manner that is distinct from their molecular regulation in peripheral tissue. Furthermore, brain P450s catalyze the formation of important brain signaling molecules, such as neurosteroids and eicosanoids, and metabolize substrates as diverse as vitamins A and D, cholesterol, bile acids, as well as centrally acting drugs, anesthetics and environmental neurotoxins. These unique characteristics allow this family of proteins and their metabolites to perform such vital functions in brain as neurotrophic support, neuroprotection, control of cerebral blood flow, temperature control, neuropeptide release, maintenance of brain cholesterol homoeostasis, elimination of retinoids from CNS, regulation of neurotransmitter levels and other functions important in brain physiology, development and disease.

Anesthetics↗

PubMed2004

Volatile organic compound adsorption in a gas-solid fluidized bed.

Fluidization finds many process applications in the areas of catalytic reactions, drying, coating, combustion, gasification and microbial culturing. This work aims to compare the dynamic adsorption characteristics and adsorption rates in a bubbling fluidized bed and a fixed bed at the same gas flow-rate, gas residence time and bed height. Adsorption with 520 ppm methanol and 489 ppm isobutane by the ZSM-5 zeolite of different particle size in the two beds enabled the differentiation of the adsorption characteristics and rates due to bed type, intraparticle mass transfer and adsorbate-adsorbent interaction. Adsorption of isobutane by the more commonly used activated carbon provided the comparison of adsorption between the two adsorbent types. With the same gas residence time of 0.79 seconds in both the bubbling bed and fixed bed of the same bed size of 40 mm diameter and 48 mm height, the experimental results showed a higher rate of adsorption in the bubbling bed as compared to the fixed bed. Intraparticle mass transfer and adsorbent-adsorbate interaction played significant roles in affecting the rate of adsorption, with intraparticle mass transfer being more dominant. The bubbling bed was observed to have a steeper decline in adsorption rate with respect to increasing outlet concentration compared to the fixed bed. The adsorption capacities of zeolite for the adsorbates studied were comparatively similar in both beds; fluidizing, and using smaller particles in the bubbling bed did not increase the adsorption capacity of the ZSM-5 zeolite. The adsorption capacity of activated carbon for isobutane was much higher than the ZSM-5 zeolite for isobutane, although at a lower adsorption rate. Fourier transform infra-red (FTIR) spectroscopy was used as an analytical tool for the quantification of gas concentration. Calibration was done using a series of standards prepared by in situ dilution with nitrogen gas, based on the ideal gas law and relating partial pressure to gas concentration. Concentrations up to 220 ppm for methanol and 75 ppm for isobutane were prepared using this method.

Adsorption↗

PubMed2004

Nitrite accumulation by aeration controlled in sequencing batch reactors treating domestic wastewater.

The feasibility of obtaining and keeping stable nitrite accumulation in Sequencing Batch Reactors (SBRs) treating domestic wastewater is studied. The final product of ammonium oxidation is either reproducible nitrate or nitrite depending on the aeration strategy. With the aerobic-anoxic sequence, two SBRs fed with domestic wastewater are operated in parallel. One SBR (SBR1) is controlled by the aeration control strategy, and the other SBR (SBR2) by alternate aeration control strategy. Based on the on-line indirect measurements of DO and pH, the relationship between pH (or DO) and nitrogen concentration (NH4+-N, NO(3-)-N and NO(2-)-N) is investigated. The result indicates that pH and DO can be used as control parameters for the real-time aeration control strategy to obtain nitritation in SBR treating domestic wastewater. The result of SBR1 indicates that long-term stable nitritation is possible at 32+/-1 degrees C. The result of SBR2 indicates that the aeration control strategy is necessary for nitritation during the acclimation period, because the nitrite accumulation disappears when the aeration is extended.

Bacteria, Anaerobic↗