Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 91 records · Page 5Linked to original sources

PubMed2005

Vasopressin induces depolarization and state-dependent firing patterns in rat thalamic paraventricular nucleus neurons in vitro.

The thalamic midline paraventricular nucleus (PVT) is prominently innervated by vasopressin-immunoreactive neurons from the suprachiasmatic nucleus (SCN), site of the brain's biological clock. Using patch-clamp recordings in slice preparations taken from Wistar rats during the subjective day, we examined 90 PVT neurons for responses to bath-applied AVP (0.5-2 microM; 1-3 min). In current clamp at resting membrane potentials (-65 +/- 1 mV), PVT neurons displayed low-threshold spikes (LTSs) and burst firing patterns. In 50% of cells tested, AVP induced a slowly rising, prolonged membrane depolarization and tonic firing, returning to burst firing upon recovery. AVP modulated hyperpolarization-activated LTSs by decreasing the time to the initial sodium spike at the onset of LTS, also increasing the duration of the afterdepolarization. Responses were blockable with a V(1a) receptor antagonist (Manning compound). Under voltage clamp, AVP induced a TTX-resistant, slowly rising, and prolonged (approximately 15 min) inward current (<40 pA). Current-voltage relationship (I-V) analyses of the AVP responses revealed a decrease in membrane conductance to 73.1 +/- 6.2% of control, with net AVP current reversing at -106 +/- 4 mV, and decreased inward rectification at negative potentials. These observations are consistent with an AVP-induced closure of an inwardly rectifying potassium conductance. On the basis of these in vitro observations, we suggest that the SCN vasopressinergic innervation of PVT is excitatory in nature, possibly releasing AVP with circadian rhythmicity and contributing to state-dependent firing patterns in PVT neurons over the sleep-wake cycle.

Animals↗

PubMed2005

Male erectile dysfunction following spinal cord injury: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVE: To review sexuality in persons with spinal cord injuries (SCIs), and to report the effectiveness of erectile interventions. METHODS: Reports from six databases (1966-2003), selected annual proceedings (1997-2002) and manufacturer's information were screened against eligibility criteria. Included reports were abstracted and data pooled from case-series reports regarding intracavernous injections and sildenafil. RESULTS: From 2127 unique reports evaluated, 49 were included. Male sexual dysfunction was addressed in these reports of several interventions (behavioural therapy, topical agents, intraurethral alprosatadil, intracavernous injections, vacuum tumescence devices, penile implants, sacral stimulators and oral medication). Penile injections resulted in successful erectile function in 90% (95% CI: 83%, 97%) of men. Sildenafil resulted in 79% (95% CI: 68%, 90%) success; the difference in efficacy was not statistically significant. Five case-series reports involving 363 participants with penile implants demonstrated a high satisfaction rate, but a 10% complication rate. CONCLUSIONS: A large body of evidence addressing sexuality in males focuses on erection. Penile injection, sildenafil and vacuum devices generally obviate the need for penile implants to address erectile dysfunction. Interventions may positively affect sexual activity in the short term. Long-term sexual adjustment and holistic approaches beyond erections remain to be studied. Rigorous study design and reporting, using common outcome measures, will facilitate higher quality research. This will positively impact patient care. SPONSORSHIP: Agency for Healthcare Research and Quality, US Department of Health and Human Services, 2101 East Jefferson Street, Rockville, MD 20852, USA.

Clinical Trials as Topic↗

PubMed2005

Cadmium, lead, and thallium in mainstream tobacco smoke particulate.

The deliveries of cadmium, thallium, and lead in mainstream smoke particulate from cigarettes with different smoke delivery designs were determined by inductively coupled plasma-mass spectrometry in order to investigate their impact on the delivery of these known toxic compounds. Analyses showed that the levels of all three metals in smoke particulate were associated with their tar delivery category. After normalizing the metal concentrations to tar, there were no longer any statistically significant delivery differences between full-flavor, light or ultra-light cigarettes. When the concentrations were normalized to nicotine, the mean levels from the three delivery groups were much smaller than before normalization. But unlike the case using tar to normalize, in some of the cases, there were still some statistically significant differences in the nicotine-normalized results. These findings suggest that if smokers compensate for differences in nicotine intake, they receive exposures to toxic heavy metals from ultra-light, light and full-flavor cigarettes that are more similar than results would suggest from using the Federal Trade Commission method alone.

Cadmium↗

PubMed2005

Chinese herbal medicine for schizophrenia.

BACKGROUND: Traditional Chinese medicine (TCM) was the main form of treatment in China for psychiatric illnesses until the development of antipsychotic drugs in the 1950's. Antipsychotic drugs have become the primary intervention for schizophrenia, although herbal medicines can still form part of the treatment. OBJECTIVES: To review Chinese herbal medicine, used alone or as part of a TCM approach, for people with schizophrenia and related psychoses. SEARCH STRATEGY: We undertook electronic searches of the Cochrane Schizophrenia Group's register (December 2003), the Traditional Chinese Medical Literature Analysis and Retrieval Database (TCMLARS) (October 2003), Chinese Biomedical Database (CBM) (December 2003), China National Knowledge Infrastructure Database (May 2004), Complementary Medicine Database (AMED) (December 2003). We contacted the Chinese Cochrane Centre, the Cochrane Complementary Medicine Field and first authors of included studies and inspected reference lists for additional studies. SELECTION CRITERIA: We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, allocated to Chinese herbal medicine, including any Chinese herbs (single or mixture), compared with placebo/no treatment or antipsychotic drugs. DATA COLLECTION AND ANALYSIS: We independently extracted data and calculated fixed effects relative risk (RR), the 95% confidence intervals (CI) for homogeneous dichotomous data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: Only one small trial of the seven included studies truly evaluated TCM for schizophrenia. The other trials evaluated Chinese herbs for schizophrenia. We found one study comparing Chinese herbal medicine with antipsychotic drugs. Data for the global state outcome 'no change/worse' favoured people allocated to antipsychotic medication (n=90, RR 1.88 CI 1.2 to 2.9, NNH 4 CI 2 to 12). Six trials compared Chinese herbal medicine in combination with antipsychotic with antipsychotic drugs alone. One trial found global state 'not improved/worse' favoured the herbal medicine/antipsychotic combination (n=123, RR 0.19 CI 0.1 to 0.6, NNT 6 CI 5 to 11). Two studies (n=103) also found short-term data from the Clinical Global Impression scale favoured the herbal medicine plus antipsychotic group (WMD -0.46 CI -0.9 to -0.1) compared with those given only antipsychotics. Significantly fewer people in the experimental group left the study early compared with those given antipsychotics alone (n=1004, 6 RCTs, RR 0.30 CI 0.16 to 0.58, NNT 21 CI 18 to 35). Reports of constipation were significantly lower in the treatment group compared to those receiving antipsychotics (n=67, 1 RCT, RR 0.03 CI 0.0 to 0.5, NNH 2 CI 2 to 4). AUTHORS' CONCLUSIONS: Chinese herbal medicines, given in a Western biomedical context, may be beneficial for people with schizophrenia when combined with antipsychotics. Traditional Chinese medicine is also under-evaluated, but results from one pioneering study that attempted to evaluate TCM should encourage further trials.

Antipsychotic Agents↗

PubMed2005

Decomposing rhythmic hippocampal data to obtain neuronal correlates.

Characterizing hippocampal electrical rhythmic activities requires a broadly applicable methodology that lends itself to physiological interpretation. In the intact hippocampal preparation, spontaneous rhythmic field potentials are exhibited in the 3--4 Hz range which evidence suggests is due to discharges in the inhibitory interneuron population. Because field rhythms arise as a network effect and models must be built from the neuron up, we focus on developing a methodology to de-construct the non-stationary rhythms into its important constituents. This study uses 50 CA1/CA3 local field potentials to determine the important constituents, and an additional field recording and two intracellular recordings are examined subsequently. We determine the suitability of several time-frequency techniques. Distinct regions in the time-frequency domain which account for the signal behaviour are then characterized in terms of duration and frequency. These characteristics are interpreted as arising from a statistical mixture distribution. The decomposition of the 50 recordings yields three components whose patterns of activity match those of the intracellular recordings. We suggest that the statistical variability of the local field data can be linked to the variability of neuronal activities seen in intracellular data.

Action Potentials↗

PubMed2005

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment.

AIMS/HYPOTHESIS: Glucose toxicity and glucosamine-induced insulin resistance have been attributed to products of glucosamine metabolism. In addition, endothelial cell nitric oxide synthase is inhibited by glucosamine. Since insulin has endothelial nitric-oxide-dependent vasodilatory effects in muscle, we hypothesise that glucosamine-induced insulin resistance in muscle in vivo is associated with impaired vascular responses including capillary recruitment. MATERIALS AND METHODS: Glucosamine (6.48 mg kg(-1) min(-1) for 3 h) was infused with or without insulin (10 mU kg(-1) min(-1)) into anaesthetised rats under euglycaemic conditions. RESULTS: Glucosamine infusion alone increased blood glucosamine (1.9+/-0.1 mmol/l) and glucose (5.4+/-0.2 to 7.7+/-0.3 mmol/l) (p<0.05) but not insulin. Glucosamine induced both hepatic and muscle insulin resistance as evident from measures of glucose appearance and disposal as well as hind-leg glucose uptake, which was inhibited by approx. 50% (p<0.05). Insulin-mediated increases in femoral arterial blood flow and capillary recruitment were completely blocked by glucosamine. CONCLUSION/INTERPRETATION: Glucosamine mediates a major impairment of insulin action in muscle vasculature associated with the insulin resistance of muscle. Further studies will be required to assess whether the impaired capillary recruitment contributes to insulin resistance.

Algorithms↗

PubMed2005

Initial diagnoses given to persons with the fragile X associated tremor/ataxia syndrome (FXTAS).

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly described disorder that occurs in premutation carriers of the fragile X mental retardation 1 (FMR1) gene. Fifty-six patients with FXTAS were given 98 prior diagnoses: most were in the categories of parkinsonism, tremor, ataxia, dementia, or stroke. Data from this study and others were used to develop guidelines for FMR1 diagnostic testing for FXTAS.

Age Factors↗

PubMed2005

The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy of gefitinib and the epidermal growth factor receptor (EGFR) mutation to gefitinib response in a series of Chinese patients with pretreated advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 98 patients who had failed at least one platinum-based regimen received gefitinib 250 mg once daily. The mutation analysis of the EGFR kinase domain was performed for 30 patients using paraffin-embedded tumor tissue. RESULTS: The response rate was 31.6% and the disease control rate was 67.3%. Objective response was correlated with adenocarcinoma, female gender and non-smokers. Median progress free survival (PFS) was 7.0 months, median overall survival (OS) was 12.0 months and 1-year survival was 53.1%. The median PFS and OS were improved among patients with adenocarcinoma, gefitinib responders and non-smokers. Active gene mutation was detected in 12 patients. Mutation rates were higher among gefitinib responders, non-smokers, patients with adenocarcinoma and female patients. OS was longer for patients with gene mutation than for patients without mutation. CONCLUSION: Gefitinib demonstrated significant antitumor activity with a favorable toxicity profile for pretreated Chinese patients with advanced NSCLC. The active mutation of the EGFR kinase domain was strongly associated with response to gefitinib and prolonged overall survival.

Adenocarcinoma↗

PubMed2005

Microsatellite analysis of Rosa damascena Mill. accessions reveals genetic similarity between genotypes used for rose oil production and old Damask rose varieties.

Damask roses are grown in several European and Asiatic countries for rose oil production. Twenty-six oil-bearing Rosa damascena Mill. accessions and 13 garden Damask roses were assayed by molecular markers. Microsatellite genotyping demonstrated that R. damascena Mill. accessions from Bulgaria, Iran, and India and old European Damask rose varieties possess identical microsatellite profiles, suggesting a common origin. At the same time, the data indicated that modern industrial oil rose cultivation is based on a very narrow genepool and that oil rose collections contain many genetically identical accessions. The study of long-term vegetative propagation of the Damask roses also reveals high somatic stability for the microsatellite loci analyzed.

Cluster Analysis↗

PubMed2005

HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumour cells through activation of TRAIL-R1 and TRAIL-R2 death signalling receptors. Here, we describe the characterisation and activity of HGS-ETR1, the first fully human, agonistic TRAIL-R1 mAb that is being developed as an antitumour therapeutic agent. HGS-ETR1 showed specific binding to TRAIL-R1 receptor. HGS-ETR1 reduced the viability of multiple types of tumour cells in vitro, and induced activation of caspase 8, Bid, caspase 9, caspase 3, and cleavage of PARP, indicating activation of TRAIL-R1 alone was sufficient to induce both extrinsic and intrinsic apoptotic pathways. Treatment of cell lines in vitro with HGS-ETR1 enhanced the cytotoxicity of chemotherapeutic agents (camptothecin, cisplatin, carboplatin, or 5-fluorouracil) even in tumour cell lines that were not sensitive to HGS-ETR1 alone. In vivo administration of HGS-ETR1 resulted in rapid tumour regression or repression of tumour growth in pre-established colon, non-small-cell lung, and renal tumours in xenograft models. Combination of HGS-ETR1 with chemotherapeutic agents (topotecan, 5-fluorouracil, and irinotecan) in three independent colon cancer xenograft models resulted in an enhanced antitumour efficacy compared to either agent alone. Pharmacokinetic studies in the mouse following intravenous injection showed that HGS-ETR1 serum concentrations were biphasic with a terminal half-life of 6.9-8.7 days and a steady-state volume of distribution of approximately 60 ml kg(-1). Clearance was 3.6-5.7 ml(-1) day(-1) kg(-1). These data suggest that HGS-ETR1 is a specific and potent antitumour agent with favourable pharmacokinetic characteristics and the potential to provide therapeutic benefit for a broad range of human malignancies.

Animals↗

PubMed2005

Respiratory system responsiveness in rabbits in vivo is reduced by prolonged continuous positive airway pressure.

Active, nonanesthetized, tracheotomized rabbits were subjected to continuous positive airway pressure (CPAP) for 4 days to determine the effects of chronic mechanical strain on lung and airway function. Rabbits were maintained for 4 days at a CPAP of 6 cmH(2)O (high CPAP), at a CPAP of 0 cmH(2)O (low CPAP), or without tracheostomy (no CPAP). After treatment with CPAP, changes in respiratory resistance in response to increasing concentrations of inhaled ACh were measured during mechanical ventilation to evaluate respiratory system responsiveness in vivo. Intraparenchymal bronchial segments were isolated from the lungs of all animals to evaluate airway smooth muscle responsiveness and bronchial compliance in vitro. Rabbits maintained for 4 days at high CPAP demonstrated significantly lower responsiveness to ACh compared with rabbits that were maintained at low CPAP or with no CPAP. Airways isolated from the lungs of animals subjected to the chronic application of high CPAP were also less responsive to ACh in vitro than the airways isolated from animals subjected to low CPAP or no CPAP. The persistence of the decreased responsiveness in the excised airway tissues suggests that the decreased respiratory system responsiveness observed in vivo results primarily from direct effects on the airways. The results demonstrate that the application of prolonged mechanical strain in vivo can reduce airway reactivity.

Acetylcholine↗

PubMed2005

Chronic strain alters the passive and contractile properties of rabbit airways.

Pathophysiological conditions of the lung may shift the balance of forces so as to chronically alter the amount of strain imposed on the airways. This chronic strain could result in changes in the structure and/or function of the airways that affect its physiological properties. We evaluated the effects of imposing physiological levels of chronic mechanical strain on the passive and active physiological properties of intraparenchymal rabbit airways. Isolated bronchial segments were cultured for 48 h at transmural pressures of 0 cmH(2)O (No Strain) or 7 cmH(2)O (Strain). Effects of strain on small parenchymal airways were evaluated in lung tissue slices cultured under conditions of No Strain or approximately 50% increased in diameter (Strain). Chronic strain resulted in a higher passive compliance of the bronchial segments and larger airway lumen size. In addition, bronchi not subjected to chronic Strain were more responsive to ACh than bronchi subjected to chronic Strain, and airways in lung slices subjected to No Strain narrowed more in response to ACh than airways in lung slices subjected to Strain. The greatest effects of chronic strain occurred in the smallest sized airways. Our results suggest that chronic distension of the airways has physiologically important effects on their passive and active properties, which are most prominent in the smaller, more peripheral airways.

Animals↗

PubMed2005

Expression and immunolocalisation of odorant-binding and chemosensory proteins in locusts.

We have identified, cloned and expressed a new chemosensory protein (CSP) in the desert locust Schistocerca gregaria belonging to a third sub-class of these polypeptides. Polyclonal antibodies stained a band of 14 kDa, as expected, in the extracts of antennae and palps of the adults, but not in the 4th and 5th instars. In the related species Locusta migratoria, instead, the same antibodies cross-reacted only with a band of apparent molecular mass of 35 kDa in the extract of 1st-5th instars, but not in the adults. The recombinant protein binds the fluorescent probe N-phenyl-1-naphthylamine, but none of the compounds so far reported as pheromones for S. gregaria. The expression of the odorant-binding protein (OBP) and of CSPs of sub-classes I and II was also monitored in antennae, tarsi, palpi, wings and other organs of solitary and gregarious locusts in their nymphal and adult stages. OBP was found to be antenna specific, where it is expressed at least from the 3rd instar in both solitary and gregarious locusts. CSPs, instead, appear to be more ubiquitous, with different expression patterns, according to the sub-class. Immunocytochemistry experiments revealed that OBP is present in the sensillum lymph of sensilla trichodea and basiconica, while CSP-I and CSP-III were found in the outer sensillum lymph of sensilla chaetica and in the sub-cuticular space between epidermis and cuticle of the antenna. Sensilla chaetica on other parts of the body showed the same expression of CSP-I as those on the antenna.

1-Naphthylamine↗

PubMed2005

JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells.

We recently identified two thiazolidin compounds, 5-[(4-methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin (DBPT), that inhibit the growth of human non-small-cell lung and colon cancer cells independent of P-glycoprotein and p53 status. Here we further investigated the mechanism by which these thiazolidin compounds mediate their anticancer effects. Treatment of cancer cells with MMPT and DBPT led to a time-dependent accumulation of cells arrested in the G2/M phase with modulation of the expression of proteins such as cyclin B1, cdc25C, and phosphorylated histone H3. Moreover, treatment with MMPT and DBPT increased M-phase arrest with abnormal spindle formation. DBPT-mediated G2/M phase arrest and phosphorylation of cdc25C and histone H3 were abrogated when JNK activation was blocked either with SP600125, a specific JNK inhibitor, or a dominant-negative JNK1 gene. Moreover, DBPT-mediated microtubule disruption was also blocked by SP600125 treatment. Our results demonstrate that thiazolidin compounds can effectively induce G2/M arrest in cancer cells and that this G2/M arrest requires JNK activation.

Aniline Compounds↗

PubMed2005

[KIS-RIS-PACS integration: the Marburg approach].

When describing the development of data processing at the Department of Radiology at the Philipps University of Marburg, three phases can be identified covering the areas of patient care, education, and research as well as administrative and organizational aspects. The first phase (1987-1995) was centered on radiology and characterized by the early implementation of the radiology information system (RIS) and installation of a picture archiving and communication system (PACS). The experiences gained during this phase led to intensive discussion on application-oriented information processing. The second phase (1996-2000) describes the changes in the general framework brought by Internet technology and international standards. The course was set for the future of data processing in the hospital setting. The phase ended with implementation of a clinical workplace system (KAS) as the basis for a comprehensive electronic patient record and the switch in radiology to an integrated RIS solution. The third phase (2001-2006) addressed further implementation and development of clinical data management in which both regular documentation of patient data and information processing not related to patients are optimized by making use of Intranet/Internet technology. It includes the hospital wide implementation of PACS and the forthcoming phase of information processing increasingly shaped by workflow and decision support.

Database Management Systems↗

PubMed2005

Persistent shedding of viable SARS-CoV in urine and stool of SARS patients during the convalescent phase.

In order to further the present knowledge of the emerging severe acute respiratory syndrome-associated coronavirus (SARS-CoV), 486 different specimens from 54 patients with a clinical diagnosis of SARS were investigated for the presence of viral RNA, and 314 plasma specimens of 73 patients were examined for IgM and IgG antibodies specific against SARS-CoV using an indirect ELISA. Viral RNA was detectable in 28 of the 54 patients tested. Cumulative data showed that 67 of the 73 SARS patients demonstrated seroconversion by week 5 of illness. In contrast, only 1 of 278 healthy subjects enrolled in the study was found to be positive for the IgG antibody. Coexistence of viral RNA in plasma and specific antibodies was simultaneously observed over three consecutive weeks in two critical cases. In three convalescent patients in particular, cultivable SARS-CoV was detected in stool or urine specimens for longer than 4 weeks (29-36 days). These findings suggest that SARS-CoV may remain viable in the excretions of convalescent patients.

Adult↗

PubMed2005

Nitrate tolerance aggravates postischemic myocardial apoptosis and impairs cardiac functional recovery after ischemia.

OBJECTIVES: This study examined the effects of nitrate tolerance (NT) on myocardial ischemia reperfusion (MI/R) injury and elucidated the potential mechanisms involved. Furthermore, the effects of GSH on postischemic myocardial apoptosis in NT rats were investigated. METHODS AND RESULTS: Male Sprague-Dawley rats were randomized to receive nitroglycerin (60 microg/kg/h) or saline for 12 h followed by 40 min of MI and 4 h of reperfusion. Myocardial apoptosis, infarct size, nitrotyrosine formation, plasma CK and LDH activity, and cardiac function were determined. MI/R resulted in significant apoptotic cell death, which was further increased in animals with NT. In addition, NT further increased plasma CK and LDH activity, enlarged infarct size, and impaired cardiac functional recovery after ischemia. Myocardial nitrotyrosine, a footprint for cytotoxic reactive nitrogen species formation, was further enhanced in the NT heart after MI/R. Treatment of NT animals with exogenous GSH inhibited nitrotyrosine formation, reduced apoptosis, decreased infarct size, and improved cardiac functional recovery. CONCLUSION: Our results demonstrate that nitrate tolerance markedly enhances MI/R injury and that increased peroxynitrite formation likely plays a role in this pathologic process. In addition, our results suggest that GSH could decrease peroxynitrite formation and reduce MI/R injury in nitrate tolerant hearts.

Adaptation, Physiological↗

PubMed2005

Identification of one intron loss and phylogenetic evolution of Dfak gene in the Drosophila melanogaster species group.

Intron loss and its evolutionary significance have been noted in Drosophila. The current study provides another example of intron loss within a single-copy Dfak gene in Drosophila. By using polymerase chain reaction (PCR), we amplified about 1.3 kb fragment spanning intron 5-10, located in the position of Tyr kinase (TyK) domain of Dfak gene from Drosophila melanogaster species group, and observed size difference among the amplified DNA fragments from different species. Further sequencing analysis revealed that D. melanogaster and D. simulans deleted an about 60 bp of DNA fragment relative to other 7 Drosophila species, such as D. elegans, D. ficusphila, D. biarmipes, D. takahashii, D. jambulina, D. prostipennis and D. pseudoobscura, and the deleted fragment located precisely in the position of one intron. The data suggested that intron loss might have occurred in the Dfak gene evolutionary process of D. melanogaster and D. simulans of Drosophila melanogaster species group. In addition, the constructed phylogenetic tree based on the Dfak TyK domains clearly revealed the evolutionary relationships between subgroups of Drosophila melanogaster species group, and the intron loss identified from D. melanogaster and D. simulans provides a unique diagnostic tool for taxonomic classification of the melanogaster subgroup from other group of genus Drosophila.

Amino Acid Sequence↗