bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of adenylate cyclase activation by cholera toxin: Inhibition of GTP hydrolysis at the regulatory site
Authors: Cassel Dan , Selinger Zvi 
Published: May 2006

Treatment of turkey erthrocyte membranes with cholera toxin caused an enhancement of the basal and catecholamine-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activities. Both of these activities required the presence of GTP. The toxin effect on the adenylate cyclase activity concided with an inhibition of the catecholamine-stimulated guanosinetriphosphatase activity. Inhibition of the guanosinetriphosphatase, as well as enhancement of the adenylate cyclase activity, showed the same dependence on cholera toxin concentrations, and the effect of the toxin on both activities was dependent on the presence of NAD.
It is proposed that continuous GTP hydrolysis at the regulatory guanyl nucleotide site is an essential turn-off mechanism, terminating activation of the adenylate cyclase. Cholera toxin inhibits the turn-off guanosinetriphosphatase reaction and thereby causes activation of the adenylate cyclase. According to this mechanism GTP should activate the toxin-treated preparation of adenylate cyclase, as does the hydrolysis-resistant analog guanosine 5′-(β,γ-immino)triphosphate [Gpp(NH)p]. Indeed, the toxin-treated adenylate cyclase was maximally activated, in the presence of isoproternol, by either GTP or Gpp(NH)p, while adenylate cyclase not treated with toxin was stimulated by hormone plus GTP to only one-fifth of the activity achieved with hormone plus Gpp(NH)p. Furthermore, the toxin-treated adenylate cyclase activated by isoproterenol plus GTP remained active for and extended period (half-time of 3 min) upon subsequent addition of the β-adrenergic blocker, propranolol. The native enzyme, however, was refractory to propranolol only if activated by Gpp(NH)p but not by GTP.
PROPER SELECTION OF COLONOSCOPE ACCORDING TO GENDER, AGE AND BMI OF THE PATIENT
Authors: Matsushima Masashi , Suzuki Takayoshi , Tokiwa Kayoko , Teraoka Hiromichi , Ushiyama Atsushi , Saitoh Tetsuro , Watanabe Ken‐ichi , Sakamoto Ichiko , Kobayashi Kenji , Watabe Reiko , Shirai Takayuki , Mine Tetsuya 
Published: May 2006

Background and Aim:  Various types of colonoscope are available for total colonoscopy, including those with variable stiffness (VS) and/or magnetic endoscope imaging (MEI). Factors related to the patient, such as gender, age and body mass index (BMI), also affect the degree of technical difficulty associated with the procedure. The present study investigated, using retrospective analyses, which type of colonoscope was appropriate, in relation to gender, age and BMI, in order to overcome procedural difficulties.Methods:  Three types of colonoscope (CF‐240I, fixed stiffness type; CF‐240AI, VS type; CF‐240DI, VS type with MEI) were used for a total of 433 consecutive patients who underwent total colonoscopy by five experienced endoscopists at Tokai University Hospital from August 2001 to August 2003. Cases with a history of abdominal surgery, requests by physicians for a particular type of colonoscope, or sedation during the procedure were excluded. Age, gender, body height and weight, and cecal intubation time (primary endpoint) were recorded.Results:  Use of the VS scope resulted in a shorter intubation time in the subgroups of female, younger (age < 40 years) or older (age ≥  60 years), and thin (BMI < 20 kg/m2) patients when compared with a conventional scope. There was no significant difference between results obtained with VS and VS + MEI in any subgroup.Conclusion:  The VS type of colonoscope seems to be the best choice for an easier procedure in particular patient subgroups. In the present study, no advantage was demonstrated for VS + MEI over VS alone.
LESIONS WITH A HIGH RISK OF CARCINOGENESIS IN THE GALLBLADDER OF PATIENTS WITH A LONG COMMON CHANNEL
Authors: Kamisawa Terumi , Kuwata Go , Yui Chen Pong , Tu Yuyang , Fujiwara Takashi , Endoh Junko , Arakawa Takeo , Koizumi Kouichi , Nakajima Hitoshi , Egawa Naoto 
Published: May 2006

Background:  Pancreaticobiliary maljunction (PBM) is characterized by a markedly long common channel. In this condition, the sphincter of Oddi does not functionally affect the junction of the pancreatic and bile ducts. Reflux of pancreatic juice into the biliary duct of patients with PBM occurs, resulting in a high incidence of carcinogenesis in the gallbladder. Hence, the gallbladder mucosa of PBM appears to be in a precancerous state. However, the relationship between a relatively long common channel and precancerous lesions of the gallbladder is unknown. The present study aimed to investigate histopathological changes in the gallbladder of patients with a relatively long common channel.Methods:  High confluence of pancreaticobiliary ducts (HCPBD) was defined as presence of a common channel ≥ 6 mm in which communication between the pancreatic and bile ducts was disrupted with sphincter contraction. We histopathologically examined the resected or autopsied gallbladder specimens from patients with HCPBD (n = 20), PBM without biliary dilatation (n = 15) and controls (n = 10); focusing on mucosal height and hyperplastic change. Proliferation activity was also examined with Ki‐67 immunostaining.Results:  The gallbladder mucosa was significantly higher in PBM and HCPBD than in controls. Hyperplastic mucosal changes were detected more frequently in PBM (73.3%, P < 0.01 vs controls) and in HCPBD (45.0%, P < 0.05 vs controls). Ki‐67 labeling index of the gallbladder epithelium was significantly higher in both PBM and HCPBD than in controls (P < 0.01).Conclusions:  In HCPBD, the gallbladder mucosa displayed hyperplastic changes with increased cellular kinetics and appeared precancerous, with a similar appearance to that in PBM.
SAFETY MEASURES AND CURRENT PREFERENCES FOR SEDATION DURING COLONOSCOPY: HOW TO ENSURE REPEAT CUSTOMERS IN THE AGING SOCIETY
Authors: Imatake Kazuhiro , Matsui Teruaki , Arakawa Yasuyuki 
Published: May 2006

Background:  It is important to establish an endoscopy protocol that maximizes safety and comfort (ensuring repeat customers) by analyzing the current procedure for sedation during colonoscopy at our institution.Methods:  The effectiveness of sedation for colonoscopy was compared in patients younger than 65 years relative to patients 65 years or older. Oxyhemoglobin saturation levels (O2 sat), the type and amount of sedative drugs and the frequency of complications were also compared between groups exhibiting cardiovascular disease versus healthy controls. Among patients recommended for a 1‐year follow up due to positive findings such as a colon polyp, we compared the revisit rate between patients who were sedated during the first procedure versus those who received no sedation.Results:  There were no complications associated with the use of sedative drugs, with flunitrazepam given to 95.9% of patients. Among patients who received sedation, the 1‐year revisit rate was 68.1%, whereas the revisit rate was only 31.9% for patients who were not sedated. Although there was no difference in O2 sat between young and old groups, O2 sat was significantly lower in old patients with cardiovascular disease relative to healthy old patients.Conclusion:  To ensure repeat customers for colonoscopy, we therefore suggest that sedation is used to manage patient discomfort, but that elderly patients with cardiovascular disease are monitored carefully throughout the procedure.
High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?
Authors: Silvestri M. , Bontempelli M. , Giacomelli M. , Malerba M. , Rossi G. A. , Di Stefano A. , Rossi A. , Ricciardolo F. L. M. 
Published: May 2006

SummaryBackground
Severe asthma is characterized by elevated levels of pro‐inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of ‘systemic’ inflammation, may be a feature of amplified inflammation in severe asthma.Objective
To detect differences in IL‐8, TNF‐α, IL‐16 and IL‐13 levels in the serum(s) of stable severe and mild–moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels.Methods
We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild–moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89±3] and 14 severe asthmatics [FEV1(%pred): 49±2].Results
IL‐8 and TNF‐α levels were higher in severe asthmatics than in mild–moderate asthmatics or in controls (P<0.05). No differences in IL‐16 and IL‐13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild–moderate asthmatics (P<0.05). We found positive correlation between TNF‐α levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics.Conclusion
sTNF‐α and sIL‐8 are markers of ‘systemic’ inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil‐derived cytokine pattern in severe asthma.
The effect of a synergistic concentration of a Piper nigrum extract used in conjunction with pyrethrum upon gene expression in Drosophila melanogaster
Authors: Jensen H. R. , Scott I. M. , Sims S. R. , Trudeau V. L. , Arnason J. T. 
Published: May 2006

AbstractAn ethyl acetate extract of Piper nigrum L. (Piperaceae) peppercorns was tested as a synergist for the botanical insecticide pyrethrum. A high synergist ratio of 11.6 against Drosophila melanogaster was obtained for the combination of pyrethrum supplemented with P. nigrum. The effect of this combination was investigated using cDNA microarray analysis of gene expression profiles in D. melanogaster. Treatment of D. melanogaster with pyrethrum alone resulted in a large number of differentially expressed genes, principally associated with stress responses. Seven genes were identified as being commonly expressed in D. melanogaster treated with at least two of the following treatments: P. nigrum, pyrethrum or P. nigrum plus pyrethrum. These are likely implicated in Drosophila defence responses to toxins.
A systematic review of multivitamin and multimineral supplementation for infection
Authors: Stephen A. I. , Avenell A. 
Published: May 2006

AbstractBackground  Infections are major causes of morbidity and mortality worldwide. Micronutrients have important functions in the body's immune system. This systematic review examined the evidence from randomized controlled trials (RCTs) on whether multivitamin and multimineral supplementation is effective in reducing infection.Methods  Electronic databases searched: Cochrane Controlled Trials Register, EMBASE, MEDLINE, BIOSIS, CAB abstracts. Hand searching of nutrition journals and reference lists was carried out. RCTs and quasi‐randomized trials of supplementation of adults with at least two vitamins or minerals or a combination were selected. Study results were combined in meta‐analysis plots where appropriate.Results  Twenty studies were included in the review. Small numbers were available for each meta‐analysis. Results are presented here without the Chandra group studies. No significant difference was found in the number of episodes of infection in older people (≥65 years) between those supplemented and those not supplemented; (WMD) 0.06 [95% confidence interval (CI) −0.04, 0.16], P = 0.25. In other adults groups, there were significantly less episodes of infection in those supplemented; (WMD) −1.20 (95% CI −2.08, −0.32), P = 0.008. There was no significant difference between those older people supplemented and those not supplemented in the number with at least one infection; relative risk (RR) 0.98 (95% CI 0.86, 1.11), P = 0.77. Similarly, there was no significant difference in the numbers in other adult groups who had at least one episode of infection between those supplemented and those taking placebo; (RR) 0.81 (95% CI 0.65, 1.00), P = 0.06. Subgroup analyses suggested that supplemented people aged 65 years or over may benefit more if they are undernourished and supplemented for over 6 months, WMD −0.67 infections (95% CI −1.24, −0.10), P = 0.02.Conclusion  Further large trials are needed, particularly in undernourished older people. Trials of supplementation periods of over 6 months are recommended.
Effect of Pentoxifylline on Levels of Pro‐inflammatory Cytokines During Chronic Hepatitis C
Authors: Gutierrez‐Reyes G. , Lopez‐Ortal P. , Sixtos S. , Cruz S. , Ramirez‐Iglesias M. T. , Gutierrez‐Ruiz M. C. , Sanchez‐Avila F. , Roldan E. , Vargas‐Vorackova F. , Kershenobich D. 
Published: May 2006

AbstractThe cellular and humoral natural immune response induced by hepatitis C virus (HCV) is commonly unable to eradicate the virus. HCV is a highly mutable, hepatotropic RNA virus that causes acute and chronic hepatitis, an infection that involves the production of various cytokines. The aim of the study is to analyse the expression of pro‐inflammatory cytokines IL‐1β, TNF‐α, IFN‐γ and the chemokine CXCL8 (IL‐8) in liver tissue and their expression and secretion in PBMC of patients with chronic hepatitis C (CHC), in response to pentoxyfilline (PTX). We studied six CHC patients, naive to treatment. Patients received PTX 400 mg twice a day/8 weeks. Pentoxyfilline resulted in decreased expression of mRNA of liver IL‐1β, TNF‐α and IFN‐γ: 144.2 versus 83.5 molecules of IL‐1β (P < 0.05), TNF‐α 194.3 versus 17.6 molecules (P = 0.03) and IFN‐γ 26.1 versus 0.5 molecules (P = 0.04). Following PTX, PBMC exhibited a decrease in IFN‐γ mRNA 12.2 versus 1.5 molecules (P = 0.028) and CXCL8 4.2 versus 2.5 molecules (P = 0.027). In PBMC, only the secretion of TNF‐α was decreased 1109 versus 933.5 pg/ml, P = 0.046. Production of cytokines both locally (within the liver) and systemically (PBMC) may serve as biomarkers of the infection with hepatitis C. PTX inhibits the expression of several pro‐inflammatory cytokines in the liver. These results indicate that it is worth exploring PTX in hepatitis in future clinical trials in nonresponders to antiviral treatment.
Sequential Analysis of Anti‐αGal Natural Antibody‐Producing B Cells in GalT Knockout Mice in Cyclophosphamide‐Induced Tolerance
Authors: Shimizu Ichiro , Tomita Yukihiro , Iwai Toshiro , Kajiwara Takashi , Okano Shinji , Nomoto Kikuo , Tominaga Ryuji 
Published: May 2006

AbstractPreviously, we have shown that cyclophosphamide (CP)‐induced tolerance, marked by permanent acceptance of donor skin graft and establishment of donor mixed chimerism, was readily induced with treatment with donor spleen cells (SC), CP, busulfan (BU) and donor bone marrow cells (BMC). Here, we investigated the mechanism of anti‐donor natural antibody (nAb) producing B‐cell tolerance in our CP‐induced tolerance systems in α1,3‐galactosyltransferase‐deficient knockout mice (GalT KO; GalT–/–, H‐2b/d). After induction of tolerance using donor AKR SC and BMC, survival of donor heart and skin grafts and production of anti‐Galα1‐3Galβ1‐4GlcNAc (anti‐αGal) Ab in recipient GalT KO mice were analyzed. In addition, the production of anti‐αGal Ab and the presence of Gal‐BSA binding B cells in GalT KO mice were analyzed by flow cytometry (FCM) after treatments with rabbit red blood cells (RRBC) and CP. Permanent acceptance of donor skin and heart grafts and abrogation of anti‐αGal Ab were achieved in GalT KO mice treated with donor SC + CP/BU + BMC. However, in the GalT KO mice treated with donor SC and CP, donor skin grafts were acutely rejected, even though anti‐αGal Ab was undetectable. Similarly, anti‐αGal Ab was undetectable in GalT KO mice treated with RRBC and CP. Our data strongly indicated the following mechanisms: the clonal destruction in the early stage and the clonal anergy or ignorance in the late stage after conventional conditioning with RRBC and CP. In conclusion, our drug‐induced tolerance protocols are effective to induce tolerance in recipients that produce anti‐donor nAb.
Effects of oral alpha‐tocopherol on lung response in rat model of allergic asthma
Authors: SUCHANKOVA Jana , VOPRSALOVA Marie , KOTTOVA Martina , SEMECKY Vladimir , VISNOVSKY Peter 
Published: May 2006

Objective and background:  Asthma is a chronic inflammatory disease in which an oxidant/antioxidant imbalance plays an important role. d‐alpha‐tocopherol (biologically the most active form of vitamin E) has redox properties and by scavenging the free radicals can act as an antioxidant. The aim of this study was to examine the effects of orally administered alpha‐tocopherol in a rat model of allergic asthma.Methodology:  Actively sensitized rats (OA) were treated with alpha‐tocopherol (400 mg/kg/day for 10 days) or vehicle; 1 h after the last dose, they were challenged with antigen aerosol. The antigen‐induced airway hyperresponsiveness to direct bronchoconstrictor (serotonin), the inflammatory cell infiltrate and histological changes were determined 1 or 24 h after the antigen challenge.Results:  Alpha‐tocopherol pretreatment was not significantly effective at reducing the studied parameters when compared with controls, even though there was a tendency to a reduction in bronchial responsiveness and in eosinophil and neutrophil infiltration.Conclusion:  Alpha‐tocopherol when administered in the chosen study design in an animal model of asthma had no major effect on airway inflammation. The effect of antioxidants deserves further evaluation.
Glutamatergic autoinhibition of quantal release augments the early phase of releases after a depolarization pulse
Authors: Dudel Josef 
Published: May 2006

AbstractAt the crayfish neuromuscular junction, glutamatergic autoinhibition of quantal excitatory postsynaptic current (qEPSC) release is mediated by a presynaptic dl‐glutamate transporter and its associated Cl– conductance. I investigated whether it also affects the time course of release. qEPSCs were recorded with a perfused macroelectrode through which depolarization pulses and d‐ or l‐glutamate could be applied to a terminal. In order to represent the time course of release, cumulative delays of qEPSCs were determined and scaled to a common final value. At 10 °C, on the application of d‐ or l‐glutamate, release increased relative to the controls especially during its first millisecond, taking the mean of 20 experiments (P < 0.01). Also, in many single experiments the respective shifts in the time courses of release were highly significant. The relative surplus of early releases decreased with time constants τ1 of 86 µs and τ2 of 0.75 ms. At 0 °C, in the presence of glutamate, the surplus of early delays was increased relative to the controls to a significantly greater extent and for a longer time than at 10 °C. The τ1 of 240 µs was almost three times larger than at 10 °C. Autoinhibition was inactivated in Cl–‐free solution. In such solutions the surplus of early releases also disappeared and the shortening of early delays reverted to a lengthening. Interaction of the inhibitory autoreceptor and its associated Cl– flow with the release machinery is discussed.
Differential modulation of sodium channel Nav1.6 by two members of the fibroblast growth factor homologous factor 2 subfamily
Authors: Rush Anthony M. , Wittmack Ellen K. , Tyrrell Lynda , Black Joel A. , Dib‐Hajj Sulayman D. , Waxman Stephen G. 
Published: May 2006

AbstractFHF2A and FHF2B are two members of the fibroblast growth factor homologous factor 2 (FHF2) subfamily with distinct N termini. Using a generic antibody and electrophysiological methods, we previously showed that FHF2 is expressed in hippocampus and dorsal root ganglion (DRG) neurons and is colocalized with sodium channel Nav1.6 at sensory but not motor nodes of Ranvier, and that FHF2B associates with Nav1.6, causing an increase in current density and a small depolarizing shift in availability of channels. Using immunolabeling of adult rat tissue, we demonstrate that FHF2A is present within DRG but not in hippocampal or cerebellar neurons or at nodes of Ranvier in sciatic nerve, and that Nav1.6 and FHF2A are colocalized in nonmyelinated fibers. We also show that FHF2A binds directly to Nav1.6, and that the two proteins coimmunoprecipitate from transfected HEK293 cells. Because Nav1.6 has been associated with rapid firing rates, we examined the possible effects of FHF2B and the sister isoform, FHF2A, on electrophysiological properties of this channel in the DRG‐derived ND7/23 cell line. We show that FHF2B inhibits accumulation of inactivation in response to trains of stimulation at high frequencies. In marked contrast, FHF2A causes an accumulation of inactivated channels at all frequencies tested due to a slowing of recovery from inactivation. Thus different FHF2 subfamily members have different functional effects on Nav1.6 and are differentially distributed in DRG neurons and their axons. This suggests that FHF2A and FHF2B may selectively alter firing behaviour of specific neuronal compartments via differential modulation of Nav1.6.
The role of the basolateral amygdala in stimulus–reward memory and extinction memory consolidation and in subsequent conditioned cued reinstatement of cocaine seeking
Authors: Fuchs Rita A. , Feltenstein Matthew W. , See Ronald E. 
Published: May 2006

AbstractThe consolidation of cue–cocaine associations and extinction learning (i.e. cue–no cocaine associations) into long‐term memory probably regulates the long‐lasting control of conditioned stimuli (CS) over cocaine‐seeking behaviour, and the basolateral amygdala (BLA) may play a role in this phenomenon. To test this hypothesis, rats previously trained to self‐administer cocaine underwent a single classical conditioning (CC) session, during which they received passive pairings of cocaine infusions and a novel light + tone stimulus complex. After additional self‐administration sessions in the absence of CS presentation and subsequent extinction training sessions, the ability of the CS to reinstate cocaine‐seeking on five test days was assessed. Rats received intra‐BLA microinfusions of vehicle or the Na+‐channel blocker tetrodotoxin (TTX) immediately after CC (consolidation of CS–cocaine associations) or immediately after reinstatement testing (consolidation of extinction learning). TTX administered immediately after CC attenuated subsequent CS‐induced reinstatement. In contrast, TTX administered after the first reinstatement test impaired the extinction of cocaine‐seeking behaviour during a second reinstatement test by disrupting extinction memory. Overall, these findings suggest that Na+ channel‐mediated mechanisms within the BLA mediate the consolidation of both cocaine–stimulus association and extinction learning, two processes that have opposite effects on subsequent cue‐induced cocaine‐seeking behaviour.