bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Fyn and PI3K in H2O2-induced inhibition of apical Cl−/OH− exchange activity in human intestinal epithelial cells
Authors: Saksena Seema , Gill Ravinder K. , Tyagi Sangeeta , Alrefai Waddah A. , Ramaswamy Krishnamurthy , Dudeja Pradeep K. 
Published: June 2008

H2O2 is a highly reactive oxygen metabolite that has been implicated as an important mediator of inflammation-induced intestinal injury associated with ischaemia/reperfusion, radiation and inflammatory bowel disease. Previous studies have shown that H2O2 inhibits NaCl absorption and activates Cl− secretion in the rat and rabbit colon. To date, however, almost no information is available with respect to its effect on the human intestinal apical anion exchanger Cl−/OH− (HCO3−). The present studies were, therefore, undertaken to examine the direct effects of H2O2 on OH− gradient-driven DIDS (4,4′-di-isothiocyanostilbene-2,2′-disulfonate)-sensitive 36Cl− uptake utilizing a post-confluent transformed human intestinal epithelial cell line, Caco-2. Our results demonstrate that H2O2 (1 mM for 60 min) significantly inhibited (approx. 60%; P&lt;0.05) Cl−/OH− exchange activity in Caco-2 cells. H2O2-mediated inhibition of Cl−/OH− exchange activity involved the Src kinase Fyn and PI3K (phosphoinositide 3-kinase)-dependent pathways. H2O2 also induced phosphorylation of Fyn and p85 (the regulatory subunit of PI3K) in Caco-2 cells. Moreover, an increased association of Fyn and p85 was observed in response to H2O2, resulting in the activation of the downstream target PLCγ1 (phospholipase Cγ1). Elevated intracellular Ca2+ levels and PKCα (protein kinase Cα) functioned as downstream effectors of H2O2-induced PLCγ1 activation. Our results, for the first time, provide evidence for H2O2-induced Src kinase Fyn/PI3K complex association. This complex association resulted in the subsequent activation of PLCγ1 and Ca2+-dependent PKCα, resulting in the inhibition of Cl−/OH− exchange activity. These findings suggest that H2O2-induced inhibition of the Cl−/OH− exchange process may play an important role in the pathophysiology of diarrhoea associated with inflammatory disorders, where the amount of reactive oxygen species is markedly elevated.
Local Hospital Perspective on a Nationwide Outbreak of Pseudomonas aeruginosa Infection in Norway
Authors: Walberg Mette , Frøslie Kathrine Frey , Røislien Jo 
Published: June 2008

Objective.To implement a system for monitoring of rare events based on statistical process control charts.Design.Statistical process control plotting by g chart of clinical microbiology laboratory data.Setting.Primary and secondary care Norwegian hospital with a 9-bed intensive care unit.Results.During the winter of 2001–2002 in Norway, there was a national monoclonal nosocomial outbreak of Pseudomonas aeruginosa infection mainly affecting patients in intensive care units. In the present work, we demonstrate how the use of SPC at one of the affected hospitals would have detected this outbreak several weeks before the alert from the Norwegian National Public Health Institute (NIPH). By plotting the monthly incidence rate of P. aeruginosa infection (with a c chart), we found that the hospital would have been alerted in February, by plotting the number of days between events (with a g chart), we found that the hospital would have detected a process already out of control in early January 2002. Not until 9 weeks later (ie, mid-March) did the NIPH declare the P. aeruginosa outbreak to be national, and a commercially produced mouth swab contaminated during the manufacturing process was found to be the source.Conclusion.The plotting of rare events, such as an outbreak of nosocomial infection, with a g chart may be used for early detection of a process out of control.
Structural basis for controlling the dimerization and stability of the WW domains of an atypical subfamily
Authors: Ohnishi Satoshi , Tochio Naoya , Tomizawa Tadashi , Akasaka Ryogo , Harada Takushi , Seki Eiko , Sato Manami , Watanabe Satoru , Fujikura Yukiko , Koshiba Seizo , Terada Takaho , Shirouzu Mikako , Tanaka Akiko , Kigawa Takanori , Yokoyama Shigeyuki 
Published: June 2008

AbstractThe second WW domain in mammalian Salvador protein (SAV1 WW2) is quite atypical, as it forms a β‐clam‐like homodimer. The second WW domain in human MAGI1 (membrane associated guanylate kinase, WW and PDZ domain containing 1) (MAGI1 WW2) shares high sequence similarity with SAV1 WW2, suggesting comparable dimerization. However, an analytical ultracentrifugation study revealed that MAGI1 WW2 (Leu355–Pro390) chiefly exists as a monomer at low protein concentrations, with an association constant of 1.3 × 102 M−1. We determined its solution structure, and a structural comparison with the dimeric SAV1 WW2 suggested that an Asp residue is crucial for the inhibition of the dimerization. The substitution of this acidic residue with Ser resulted in the dimerization of MAGI1 WW2. The spin‐relaxation data suggested that the MAGI1 WW2 undergoes a dynamic process of transient dimerization that is limited by the charge repulsion. Additionally, we characterized a longer construct of this WW domain with a C‐terminal extension (Leu355–Glu401), as the formation of an extra α‐helix was predicted. An NMR structural determination confirmed the formation of an α‐helix in the extended C‐terminal region, which appears to be independent from the dimerization regulation. A thermal denaturation study revealed that the dimerized MAGI1 WW2 with the Asp‐to‐Ser mutation gained apparent stability in a protein concentration‐dependent manner. A structural comparison between the two constructs with different lengths suggested that the formation of the C‐terminal α‐helix stabilized the global fold by facilitating contacts between the N‐terminal linker region and the main body of the WW domain.
Habitat shifts of endangered species under altered climate conditions: importance of biotic interactions
Authors: PRESTON KRISTINE L. , ROTENBERRY JOHN T. , REDAK RICHARD A. , ALLEN MICHAEL F. 
Published: June 2008

AbstractPredicting changes in potential habitat for endangered species as a result of global warming requires considering more than future climate conditions; it is also necessary to evaluate biotic associations. Most distribution models predicting species responses to climate change include climate variables and occasionally topographic and edaphic parameters, rarely are biotic interactions included. Here, we incorporate biotic interactions into niche models to predict suitable habitat for species under altered climates. We constructed and evaluated niche models for an endangered butterfly and a threatened bird species, both are habitat specialists restricted to semiarid shrublands of southern California. To incorporate their dependency on shrubs, we first developed climate‐based niche models for shrubland vegetation and individual shrub species. We also developed models for the butterfly's larval host plants. Outputs from these models were included in the environmental variable dataset used to create butterfly and bird niche models. For both animal species, abiotic–biotic models outperformed the climate‐only model, with climate‐only models over‐predicting suitable habitat under current climate conditions. We used the climate‐only and abiotic–biotic models to calculate amounts of suitable habitat under altered climates and to evaluate species' sensitivities to climate change. We varied temperature (+0.6, +1.7, and +2.8 °C) and precipitation (50%, 90%, 100%, 110%, and 150%) relative to current climate averages and within ranges predicted by global climate change models. Suitable habitat for each species was reduced at all levels of temperature increase. Both species were sensitive to precipitation changes, particularly increases. Under altered climates, including biotic variables reduced habitat by 68–100% relative to the climate‐only model. To design reserve systems conserving sensitive species under global warming, it is important to consider biotic interactions, particularly for habitat specialists and species with strong dependencies on other species.
Small round blue cell tumours: diagnostic and prognostic usefulness of the expression of B7‐H3 surface molecule
Authors: Gregorio A , Corrias M V , Castriconi R , Dondero A , Mosconi M , Gambini C , Moretta A , Moretta L , Bottino C 
Published: June 2008

Aims:  To assess whether the expression of B7‐H3 surface molecule could improve differential diagnosis of small cell round tumours.Methods and results:  One hundred and one well‐characterized paraffin‐embedded small round cell tumours, stored in the pathology archive of the Gaslini Institute, were immunohistochemically analysed with the 5B14 monoclonal antibody, which recognizes the surface molecule B7‐H3. All lymphoblastic lymphomas and the blastematous component of Wilms’ tumours were completely negative and a few Ewing’s sarcoma and Burkitt’s lymphoma specimens showed focal positivity, whereas 74% of neuroblastomas, 67% of rhabdomyosarcomas and 100% of medulloblastomas were positive. The pattern of immunoreactivity of 5B14 mAb observed in rhabdomyosarcoma, neuroblastoma and medulloblastoma specimens was limited to the cytoplasmic membrane, and in neuroblastomas areas of rosette formation or of ganglion differentiation were preferentially stained. Interestingly, in neuroblastoma patients high expression of the antigen recognized by the 5B14 mAb was associated with a worse event‐free survival.Conclusions:  The 5B14 mAb represents an additional tool for the differential diagnosis of small round cell tumours and might be useful in identifying neuroblastoma patients at risk of relapse who may take advantage of more careful follow‐up.
Elevated Levels of MMP‐9 and TIMP‐1 in the Cerebrospinal Fluid of Children with Echovirus Type 30 and Mumps Meningitis
Authors: Sulik A. , Wojtkowska M. , Oldak E. 
Published: June 2008

AbstractMatrix metalloproteinases are involved in leucocyte invasion into the central nervous system (CNS) during meningitis. The aim of the study was to determine whether there are differences in the expression patterns of matrix metalloproteinase‐9 (MMP‐9) and the tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in the cerebrospinal fluid (CSF) of patients with meningitis caused by one of two known distinct viral agents. Concentrations were measured by using an enzyme‐linked immunosorbent assay (ELISA) in 16 children with mumps meningitis, in 25 children with echovirus type 30 meningitis and in a control group of 23 children without any CNS infection. Increased levels of MMP‐9 were found in children with mumps (median 0.48 ng/ml; P < 0.001) and enteroviral meningitis (median 2.76 ng/ml; P < 0.001) compared with that in controls (median: 0.01 ng/ml). Concentrations of TIMP‐1 greatly exceeded concentrations of MMP‐9 and were elevated in children with mumps (median: 56 ng/ml) and echovirus type 30 meningitis (median: 55 ng/ml) compared to controls (median: 17 ng/ml). No significant differences in MMP‐9 or TIMP‐1 levels were detected between the two meningitis groups. The MMP‐9/TIMP‐1 ratio was greater in children with echovirus type 30 than in those with mumps meningitis. There was no correlation between MMP‐9 levels and total CSF cell count. MMP‐9 correlated with CSF absolute neutrophil count in children with echovirus type 30 meningitis (r = 0.431; P < 0.05). The concentration of MMP‐9 is higher in children with viral meningitis, possibly because of infiltrating polymorphonuclear cells present in the initial phase of the disease.
Seasonal rhythms of seed rain and seedling emergence in two tropical rain forests in southern Brazil
Authors: Marques M. C. M. , Oliveira P. E. A. M. 
Published: June 2008

AbstractSeasonal tropical forests show rhythms in reproductive activities due to water stress during dry seasons. If both seed dispersal and seed germination occur in the best environmental conditions, mortality will be minimised and forest regeneration will occur. To evaluate whether non‐seasonal forests also show rhythms, for 2 years we studied the seed rain and seedling emergence in two sandy coastal forests (flooded and unflooded) in southern Brazil. In each forest, one 100 × 30‐m grid was marked and inside it 30 stations comprising two seed traps (0.5 × 0.5 m each) and one plot (2 × 2 m) were established for monthly monitoring of seed rain and a seedling emergence study, respectively. Despite differences in soil moisture and incident light on the understorey, flooded and unflooded forests had similar dispersal and germination patterns. Seed rain was seasonal and bimodal (peaks at the end of the wetter season and in the less wet season) and seedling emergence was seasonal and unimodal (peaking in the wetter season). Approximately 57% of the total species number had seedling emergence 4 or more months after dispersal. Therefore, both seed dormancy and the timing of seed dispersal drive the rhythm of seedling emergence in these forests. The peak in germination occurs in the wetter season, when soil fertility is higher and other phenological events also occur. The strong seasonality in these plant communities, even in this weakly seasonal climate, suggests that factors such as daylength, plant sensitivity to small changes in the environment (e.g. water and nutrient availability) or phylogenetic constraints cause seasonal rhythms in the plants.
EXACERBATION BY NICOTINE OF THE CYCLOSPORINE A‐INDUCED IMPAIRMENT OF β‐ADRENOCEPTOR‐MEDIATED RENAL VASODILATION IN RATS
Authors: El‐Gowilly Sahar M , Ghazal Abdel‐Rheem M , Gohar Eman Y , El‐Mas Mahmoud M 
Published: June 2008

SUMMARYNicotine is implicated in smoking‐related renovascular impairment and worsening of existing nephropathies. In the present study, we investigated whether nicotine aggravates the deleterious effect of the immunosuppressant drug cyclosporine A (CsA) on renal vasodilation induced by the β‐adrenoceptor agonist isoprenaline.Bolus isoprenaline (0.03–8.0 µmol) elicited dose‐dependent vasodilation of phenylephrine‐preconstricted perfused kidneys that was attenuated by infusion at 5 mL/min of nicotine (5 × 10−4 mol/L) or CsA (2 µmol/L). Further, chronic administration of nicotine (0.4 mg/kg per day) or CsA (20 mg/kg per day) for 3 weeks reduced isoprenaline‐induced vasodilation and elevated plasma urea and creatinine concentrations, effects that were magnified when both nicotine and CsA were administered concurrently.The role of endothelial and smooth muscle signalling in the acute nicotine/CsA renovascular interaction was investigated. Vasodilation caused by 0.25 µmol isoprenaline was attenuated by 6 µmol/L propranolol and 10 mmol/L tetraethylammonium (TEA), potentiated by 100 µmol/L hexamethonium and 7 µmol/L diclophenac, and virtually abolished in 80 mmol/L KCl‐preconstricted tissues.NG‐Nitro‐l‐arginine (l‐NNA; 200 µmol/L), methylene blue (10 µmol/L), 3‐[(3‐cholamidopropyl)‐dimethyl‐ammonio]‐1‐propane‐sulphonate (CHAPS; 0.2% for 30 s), nifedipine (750 nmol/L), atropine (1 µmol/L) and SQ22536 (an adenylyl cyclase inhibitor; 3 × 10−5 mol/L) had no effect on isoprenaline responses.Nicotine (5 × 10−4 mol/L) reduced isoprenaline‐induced vasodilation and this effect was potentiated by concurrent CsA (2 µmol/L) infusion. Nicotine‐induced impairment of the vasodilator response to isoprenaline was reduced by hexamethonium and potentiated byl‐NNA, methylene blue, CHAPS and nifedipine. Alternatively, CsA exacerbation of the nicotine–isoprenaline interaction was abolished by propranolol,l‐NNA, methylene blue, CHAPS,l‐arginine, TEA and nifedipine.In summary, nicotine and CsA produce additive impairment of kidney function and β‐adrenoceptor‐mediated renovascular control, nitric oxide (NO)–cGMP signalling tonically restrains nicotine‐induced impairment of isoprenaline vasodilation and the endothelial NO–K+pathway modulates the aggravating effect of CsA on nicotine–isoprenaline interactions.
MORPHINE DEPENDENCE PROTECTS RAT KIDNEY AGAINST ISCHAEMIA–REPERFUSION INJURY
Authors: Habibey Rouhollah , Pazoki‐Toroudi Hamidreza 
Published: June 2008

SUMMARY

Ischaemic preconditioning (IPC) protects the heart and kidneys against ischaemia–reperfusion (I/R) injury. It has been shown that opioid receptor activation can mimic cardiac IPC. In a kidney model of I/R, a single dose of morphine failed to mimic IPC. The aim of the present study was to determine the role of chronic morphine (dependence) in protection against renal I/R injury.
Male Wistar rats were treated with increasing doses of morphine (20–30 mg/kg per day, s.c., for 5 days) to develop morphine dependence (MD). Three weeks before the I/R procedure, the right kidney was removed. Ischaemia–reperfusion injury was induced by clamping the left renal artery for 45 min, followed by 24 h reperfusion. Some MD rats were pretreated with naloxone (5 mg/kg, s.c.). Twenty‐four hours later, creatinine and sodium concentrations were measured in serum and urine, then creatinine clearance (CCr) and the fractional excretion of sodium (FENa) were calculated. Blood urea nitrogen (BUN) was measured only in serum samples. Kidneys were also assessed histologically for evidence of tissue injury.
In the present study, MD decreased tissue injury (histological score), serum creatinine and BUN levels, increased CCr and decreased FENa after I/R. Pretreatment with naloxone attenuated the protective effects of MD. Morphine dependence did not have any significant effect on urine volume.
In conclusion, it seems that morphine dependence protects the kidney against I/R injury via opioid receptor‐dependent pathways. Further studies are required to clearly determine the mechanisms involved.
MODULATORY EFFECT OF NARINGENIN ONN‐METHYL‐N′‐NITRO‐N‐NITROSOGUANIDINE‐ AND SATURATED SODIUM CHLORIDE‐INDUCED GASTRIC CARCINOGENESIS IN MALE WISTAR RATS
Authors: Ganapathy Ekambaram , Peramaiyan Rajendran , Rajasekaran Devaraja , Venkataraman Magesh , Dhanapal Sakthisekaran 
Published: June 2008

SUMMARYNaringenin is a flavanone that is believed to have many biological actions, including as an anti‐oxidant, free radical scavenger and an antiproliferative agent. The global incidence of gastric carcinoma is increasing rapidly, more than for any other cancer. Therefore, in the present study, we tested the effects of naringenin on gastric carcinogenesis induced byN‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) and saturated sodium chloride (S‐NaCl) in rats.Male Wistar rats were divided into five groups and treated over a period of 20 weeks as follows: (i) a control group given corn oil (1 mL/rat, p.o.) daily 20 weeks; (ii) 200 mg/kg, p.o., MNNG on Days 0 and 14 with S‐NaCl (1 mL/rat) administered twice a week for the first 3 weeks; (iii) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin (200 mg/kg, p.o., daily) treatment for the entire 20 weeks; (iv) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin treatment (200 mg/kg, p.o., daily) initiated from 6 to 20 weeks; (v) 200 mg/kg, p.o., naringenin alone daily for 20 weeks.In Group II rats in which gastric cancer was inducted with MNNG and S‐NaCl, there was a significant increase in hydrogen peroxide and lipid peroxidation levels, with decreases in reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase and glucose 6‐phosphate dehydrogenase. In addition, in Group II rats with gastric cancer, there were significant increases in the activity of cytochrome P450, cytochromeb5and NADPH cytochromecreductase, with concomitant decreases in the activity of the phase II enzymes glutathione S‐transferase and UDP‐glucuronosyl transferase. Naringenin treatment (Groups III and IV) restored enzyme activity to near control levels.These results indicate that naringenin has a chemopreventive action against MNNG‐induced gastric carcinoma in experimental rats.
EFFECT OF THIGH CUFFS ON HAEMODYNAMIC CHANGES OF THE MIDDLE CEREBRAL ARTERY AND ON ORTHOSTATIC INTOLERANCE INDUCED BY 10 DAYS HEAD‐DOWN BED REST
Authors: Yao Yong‐Jie , Jiang Shi‐Zhong , Jiang Chang‐Lin , Sun Xi‐Qing , Cao Xin‐Sheng , Yang Chang‐Bin 
Published: June 2008

SUMMARY

Thigh cuffs are used by cosmonauts to limit fluid shift during space flight, but the appropriate level of cuff pressure and the duration of application to optimize their beneficial effects require further detailed investigations.
In the present study, 10 days head‐down tilt (HDT) bed rest was performed to assess the effects of thigh cuffs (40 mmHg, 10 h/day) on haemodynamic changes of the middle cerebral artery (MCA) and on orthostatic tolerance in six healthy male volunteers. Another six healthy male volunteers without thigh cuffs served as the control group. Haemodynamic parameters of the MCA were measured using transcranial Doppler. Orthostatic tolerance was assessed before and after HDT.
After HDT, the mean upright time in the control and thigh cuff groups was 14.0 ± 4.1 and 19.2 ± 0.7 min, respectively. Compared with values before HDT, the percentage increase in heart rate from baseline in the upright position after HDT was significantly higher in the control group and the percentage change from baseline of mean diastolic arterial blood decreased more after HDT in this group. In the control group, systolic blood velocity (Vs) and mean blood velocity (Vm) of the right MCA decreased significantly during HDT. In the thigh cuffs group, the Vs of the right MCA decreased significantly on Days 3 and 7 of HDT and the Vm of the right MCA decreased significantly on Day 7 of HDT.
The results indicate that daily use of thigh cuffs during 10 days of HDT does not completely prevent the decrease in haemodynamics of the right MCA, but is effective in preventing orthostatic intolerance.
Intravascular haemolysis in a patient on ceftriaxone with demonstration of anticeftriaxone antibodies
Authors: Dinesh D. , Dugan N. , Carter J. 
Published: June 2008

AbstractDrug‐induced haemolytic anaemia can be life threatening. We report a case of ceftriaxone‐induced severe haemolytic anaemia in a previously healthy 68‐year‐old woman. The patient had a positive direct antiglobulin test (anti‐C3d positive, anti‐immunoglobulin G negative). Serological tests showed ceftriaxone‐specific antibodies. The patient recovered after cessation of the drug. This complication may cause milder anaemia and thus be poorly recognized.