bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐HT stimulates eEF2 dephosphorylation in a rapamycin‐sensitive manner in Aplysia neurites
Authors: Carroll Matthew , Warren Otis , Fan Xiaotang , Sossin Wayne S. 
Published: September 2004

AbstractIn Aplysia, serotonin mediates behavioral sensitization by increasing the strength of the synapse between sensory and motor neurons, a process known as facilitation. The retention of long‐term facilitation is blocked by rapamycin, an inhibitor of a specific translational pathway. One possible rapamycin‐sensitive target is the increased translation of 5′‐terminal oligopyrimidine mRNAs. These transcripts encode components of the translational machinery and have been proposed to be important for retention of long‐term facilitation. We have cloned the 5′‐terminal oligopyrimidine mRNA encoding eukaryotic elongation factor 2 and shown that serotonin increased its translation in synaptosomes. Another possible rapamycin‐sensitive target is the inactivation of eukaryotic elongation factor 2 kinase. Eukaryotic elongation factor 2 kinase phosphorylates and inactivates eukaryotic elongation factor 2, blocking translational elongation. Serotonin application decreased eukaryotic elongation factor 2 phosphorylation in synaptosomes and in isolated neurites, and this was blocked by rapamycin. We propose a role for the rapamycin‐sensitive pathway in neurons. Stimulation blocks translation by inducing calcium entry and phosphorylation of eukaryotic elongation factor 2. This block is reversed through activation of the rapamycin‐sensitive system and dephosphorylation of eukaryotic elongation factor 2.
Acetylcholinesterase inhibitors increase ADAM10 activity by promoting its trafficking in neuroblastoma cell lines
Authors: Zimmermann Martina , Gardoni Fabrizio , Marcello Elena , Colciaghi Francesca , Borroni Barbara , Padovani Alessandro , Cattabeni Flaminio , Di Luca Monica 
Published: September 2004

AbstractAcetylcholinesterase inhibitors (AChEIs) are the only currently available drugs for treating Alzheimer's Disease (AD). Some authors have suggested a function of AChEIs not only in the induction of AChE overproduction and alternative splicing shifts but also a possible role of these drugs in amyloid metabolism beyond their well‐known symptomatic effect. Here, we investigate the mechanisms of action of the AChEI donepezil on APP (amyloid precursor protein) metabolism and on the activity/trafficking of the alpha‐secretase candidate ADAM 10, in differentiated human neuroblastoma cells (SH‐SY5Y). In these cells, the activity of AChE is significantly decreased after 2 h of donepezil treatment. Further, SH‐SY5Y cells released significantly more sAPPα into the medium, whereas total APP levels in cell lysates were unchanged. Interestingly, treated cells showed increased ADAM 10 levels in membrane compartments. This effect was prevented by pretreatment with tunicamycin or brefeldin, suggesting that donepezil affects trafficking and/or maturation of ADAM 10; additionally, this pretreatment significantly decreased sAPPα levels. Pre‐incubation with atropine decreased release of sAPPα significantly but did not revert ADAM 10 activity to control levels further suggesting that donepezil acts not solely through a purely receptor mediated pathway. These findings indicate that donepezil exerts multiple mechanisms involving processing and trafficking of key proteins involved in AD pathogenesis.
Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor‐kappa B in interleukin‐1β‐induced matrix metalloproteinase‐9 expression in rat brain astrocytes
Authors: Wu Cheng‐Ying , Hsieh Hsi‐Lung , Jou Mei‐Jie , Yang Chuen‐Mao 
Published: September 2004

AbstractMatrix metalloproteinase (MMP)‐9 expression induced by interleukin‐1β (IL‐1β) was investigated in rat brain astrocyte‐1 (RBA‐1). Here we report that the mitogen‐activated protein kinases (MAPKs) and nuclear factor‐kappa B (NF‐κB) pathways participate in the induction of MMP‐9 expression by IL‐1β. Zymographic, western blotting, and RT‐PCR analyses showed that IL‐1β increased expression of MMP‐9 mRNA and protein, which were inhibited by inhibitors of MEK1/2 (U0126), p38 (SB202190), and JNK (SP600125). In accordance with these findings, IL‐1β stimulated phosphorylation of p42/p44 MAPK, p38, and c‐Jun N‐terminal kinase (JNK), which was attenuated by U0126, SB202190, or SP600125, respectively. Furthermore, this up‐regulation of MMP‐9 mRNA and protein was blocked by a specific NF‐κB inhibitor helenalin. Consistently, IL‐1β‐stimulated translocation of NF‐κB into the nucleus and degradation of inhibitory kappa B‐α (IκB‐α) was revealed by western blotting and immunofluorescence staining, which was blocked by helenalin, but not by U0126, SB202190, or SP600125. Taken together, these results suggest that in RBA‐1 cells, activation of p42/p44 MAPK, p38, JNK and NF‐κB pathways is essential for IL‐1β‐induced MMP‐9 gene expression via transcription and translation processes. An increased understanding of the signal transduction pathways involved in IL‐1β‐induced MMP‐9 expression on RBA‐1 may be of potential therapeutic value in the treatment of inflammatory disease.
Application of proteasomal inhibitors to mouse sympathetic neurons activates the intrinsic apoptotic pathway
Authors: Lang‐Rollin Isabelle , Vekrellis Konstantinos , Wang Qiaohong , Rideout Hardy J. , Stefanis Leonidas 
Published: September 2004

AbstractProteasomal dysfunction may play a role in a number of neurodegenerative conditions, and in particular Parkinson's disease (PD) and related Lewy body (LB) diseases. Application of proteasomal inhibitors to neuronal cell culture systems is associated with survival‐promoting effects or with cell death depending on the model system. We have applied pharmacological proteasomal inhibitors to cultured neonatal mouse sympathetic neurons in order to investigate whether these catecholaminergic neurons, which are affected in PD, are sensitive to proteasomal inhibition and, if so, which cell death pathway is activated. We report here that proteasomal inhibition leads to apoptotic death of mouse sympathetic neurons. This death is accompanied by caspase 3 activation and cytochrome c release from the mitochondria and is abrogated by caspase inhibition. Bax deletion prevented both cytochrome c release and caspase 3 activation, and also provided complete protection against proteasomal inhibition‐induced death. Bcl‐2 overexpression achieved a similar survival‐promoting effect. There was no change in Bax levels following proteasomal inhibition, suggesting that Bax itself is not regulated by the proteasome in this cell culture system, and that a primary increase in Bax is unlikely to account for death. In contrast, levels of the BH3‐only protein, Bim, increased with proteasomal inhibition. We conclude that proteasomal inhibition of mouse sympathetic neurons activates the intrinsic apoptotic pathway involving bcl‐2 family members and the mitochondria.
Neuregulin induces GABAA receptor β2 subunit expression in cultured rat cerebellar granule neurons by activating multiple signaling pathways
Authors: Xie Fang , Raetzman Lori T. , Siegel Ruth E. 
Published: September 2004

AbstractThe GABAA receptor β subunit is required to confer sensitivity to γ‐aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS. In previous studies we demonstrated that the growth and differentiation factor neuregulin 1 (NRG1) selectively induced expression of the β2 subunit mRNA and encoded protein in rat cerebellar granule neurons in culture. In the present report we examine the signaling pathways that mediate this effect. These studies demonstrate that the effects of NRG1 on β2 subunit polypeptide expression require activation of the ErbB4 receptor tyrosine kinase; its effects are inhibited by pharmacological blockade of ErbB4 phosphorylation or reduction of receptor level with an antisense oligodeoxynucleotide. The NRG1‐induced activation of ErbB4 stimulates the mitogen‐activated protein kinase (MAPK), phosphatidylinositol 3‐kinase (PI3K) and cyclin‐dependent kinase‐5 (cdk5) pathways. Pharmacological blockade of any of these pathways inhibits increased β2 subunit expression, demonstrating that all three pathways are required to mediate the effects of NRG1 on GABAA receptor subunit expression in cerebellar granule neurons. These studies provide novel information concerning the actions of NRG1 on GABAA receptor expression in the CNS.
System dynamics modelling for supply‐chain management: A case study on a supermarket chain in the UK
Authors: Ge Y. , Yang J.‐B. , Proudlove N. , Spring M. 
Published: September 2004

AbstractThis paper presents a system dynamics (SD) approach for the analysis of the demand amplification problem, also known as the bullwhip effect, which has been studied fairly extensively in the literature. The construction of an SD model is reported using a part of a supermarket chain system in the UK as an example. Based on the model, the causes of the dynamic behaviour of the system and the sources of amplification from the downstream to the upstream of the chain are investigated. The impact of information delays, demand forecasting and information sharing on the performance of the multi‐echelon supply chain is analysed. Some implementation issues are also addressed based on the simulation analysis.
A parallel hybrid local search algorithm for the container loading problem
Authors: Mack D. , Bortfeldt A. , Gehring H. 
Published: September 2004

AbstractIn this contribution, a parallel hybrid local search algorithm for the three‐dimensional container loading problem (CLP) is proposed. First a simulated annealing method for the CLP is developed, which is then combined with an existing tabu search algorithm to form a hybrid metaheuristic. Finally, parallel versions are introduced for these algorithms. The emphasis is on CLP instances with a weakly heterogeneous load. Numerical tests based on the well‐known 700 test instances from Bischoff and Ratcliff are performed, and the outcome is compared with methods from other authors. The results show a high solution quality obtained with reasonable computing time.
Applying the shortest‐path‐counting problem to evaluate the importance of city road segments and the connectedness of the network‐structured system
Authors: Oyama Tatsuo , Morohosi Hozumi 
Published: September 2004

AbstractWe consider the shortest‐path‐counting problem (SPCP), which asks how many shortest paths is each edge of a network contained in? There are n(n−1) shortest paths in a network with n nodes, so among all these shortest paths the SPCP requires us to count the number of shortest paths passing through each edge. We obtain theoretical results in the form of explicit expressions for special types of networks such as trees, grid type, circular type, etc. We apply the SPCP to measure the importance of city road segments, which will certainly contribute to estimate the traffic congestion of the city road segments. Then we propose a quantitative method for evaluating the stable connectedness of the network‐structured system using shortest‐path‐counting methods. We define the stable‐connection function and the expected stable‐connection function for the network‐structured system. Then we derive some theoretical results for some special types of network such as single path, cycle graph, and complete graph. Several properties and characteristics of the stable‐connection function are also shown with some theoretical results. We show the application of the Monte Carlo method to estimate the expected stable‐connection function. This method can be applied to measure the strength of connectedness of the Japanese road network system.
Resident forum abstracts EVALUATION OF THROMBOELASTOGRAPHY (TEG) IN NORMAL CATS
Authors: Alwood AJ , Downend AB , Slensky KA , Fox JA , Simpson SA , Donahue SM , Waddell LS , Otto CM 
Published: September 2004

Objective: To establish normal parameters of thromboelastography (TEG) in healthy adult cats.Background: Thromboelastography (TEG) is an in vitro test of coagulation that has been shown to be useful in humans, dogs and select species to identify and quantify alterations of hemostasis (e.g., hypercoagulable and hypocoagulable states). It has also been demonstrated to be useful in monitoring effects of anticoagulant therapies. This test has not been evaluated in cats.Methods: Blood was collected from 25 clinically normal cats by venipuncture using a 21 gauge×3 1/2 inch butterfly catheter and syringe for medial saphenous or jugular venipuncture. A single 1.8 mL sample in 3.8% Sodium Citrate (9:1) was collected from each cat. Recalcified whole blood was analyzed 30 minutes following collection with the TEG® 5000 analyzer (Haemoscope, Niles, IL). Analysis temperature was 37.6°C. TEG parameters recorded included: R‐value (represents initial fibrin formation), K (time from R to standard fixed measure of clot firmness which represents contributions of platelets and fibrinogen), maximum amplitude (MA; represents absolute clot strength), and alpha angle (α; the slope of TEG tracing which represents rate of clot formation). The coagulation index (CI) was derived from the formula generated for humans to provide an overall assessment of whether the sample was hyper‐ or hypocoagulable.Results: Values for the 25 normal cat samples are reported as mean ±2 standard deviations. R=2.97; 1.23–4.72; K=1.54, 0.38–2.71; α=70.70, 57.76–83.65; MA=58.50, 45.26–71.74 and CI=2.27, 0.07–4.46. Compared to historical information obtained on normal dogs, cats have significantly shorter R and K and larger α, MA and CI.Conclusions: TEG does have reproducible performance when used to evaluate coagulation status in normal cats. Compared to dogs, normal cats favor a hypercoagulable state. Species‐specific normal values are necessary for interpretation of TEG results. This test bears potential value for use in future experimental and clinical work to investigate hemostasis in cats receiving anticoagulant therapies or in cats suffering from diseases such as cardiomyopathy which are thought to be associated with altered coagulation status.
ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME IN CATS: 65 CASES (1993–2003)
Authors: Sauvé V , Parent C , Seiler G , French A , VanWinkle TJ , King LG 
Published: September 2004

Objectives: 1) Describe the clinical course and diagnostic findings of cats with histopathologic evidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). 2) Identify risk factors for ALI/ARDS in cats.Animals: Sixty‐five client‐owned cats with moderate to severe interstitial pneumonia, pneumonitis or alveolitis consistent with ALI/ARDS on post‐mortem examination and clinical evidence of respiratory compromise.Procedure: Retrospective evaluation of medical records, postmortem examination and radiographs.Results: Cats in this study tended to be middle aged (mean 6.5±4.9 years). They had a short duration of illness (median 4 days; range 0–120 days) and of dyspnea (median 1 day; range 1–7 days). On presentation, the cats were tachypneic (mean respiratory rate 53±23 bpm) and relatively bradycardic (mean heart rate 166±43 bpm). The majority of cats were dyspneic (n=39) at presentation; all others developed respiratory difficulties during hospitalization. The mean white blood cell count was within normal limits (14.6±14.0 k/μL); 8 cats had a leukocytosis and 7 were leucopenic. Clinical findings consistent with SIRS (n=39) and sepsis (n=10) were common. Thoracic radiographs were reviewed in 31 cats and alveolar disease was the most frequent pattern (105 lung lobes) followed by interstitial disease (86 lung lobes). No cat had normal thoracic radiographs throughout hospitalization. Underlying disease was not identified on post‐mortem examination in 15 cats (23%), but in the remaining cats underlying diseases included infectious systemic disease (n=11), neoplasia (n=8), respiratory (n=8) and urinary (n=7) system disorders, acute pancreatitis (n=7), hepatic diseases (n=5), major trauma (n=4), sepsis (n=3), CNS (n=2) and other systems (n=5). Nine cats had more then one underlying process.Conclusions: This study describes a naturally‐occurring syndrome of ALI/ARDS in cats analogous to that which occurs in dogs and humans. In cats, ALI/ARDS occurs as a sequela of a variety of underlying systemic diseases, but in approximately one‐quarter of patients an underlying cause is not identified at necropsy. It is important to consider ALI/ARDS in systemically ill cats who become dyspneic; in cats with pulmonary disease with acute worsening of respiratory status and in cats with pulmonary infiltrates for which no other cause can be identified.
ANALYZER‐CALCULATED OXYHEMOGLOBIN SATURATION AND OXYGEN CONTENT VALUES ARE COMPARABLE TO HAND‐CALCULATED VALUES USING A NORMAL CANINE OXYHEMOGLOBIN DISSOCIATION RELATIONSHIP IN UNSEDATED HEALTHY DOGS
Authors: Scott NE , Haskins SC , Aldrich J 
Published: September 2004

Introduction: The amount of oxygen in blood is an important measure of lung function. There are three ways to quantify the amount of oxygen in blood: 1) the oxygen tension (PO2); 2) the percent of hemoglobin saturated with oxygen (HbO2); and 3) the absolute content of oxygen in the blood (ContO2). PO2 is commonly measured. HbO2 and ContO2 are usually calculated from the normal human oxyhemoglobin relationship, but can be measured directly. The canine curve is similar to, but not the same as, that of humans. The purpose of this study was to compare, in dogs, direct measurements of HbO2 and ContO2 with analyzer‐calculated values derived using the human oxyhemoglobin curve, and with hand‐calculated values derived using a canine oxyhemoglobin curve.Materials And Methods: Arterial and jugular venous samples from 17 healthy dogs were analyzed by an ABL 705 blood gas and electrolyte analyzer, an OSM3 co‐oximeter, and a LexO2con oxygen content analyzer. HbO2 was calculated from the measured PO2 using a published formula based on normal canine data (Reeves, 1982), and compared to measured and analyzer‐calculated values. ContO2 values were calculated, and compared to measured and analyzer‐calculated values. Means and standard deviations were compared by analysis of variance for repeated measures. Differences were considered significant at p<0.05.Results: Arterial HbO2 determined by the ABL 705 factory‐programmed algorithm, reported by the OSM3 co‐oximeter, and calculated from Reeves' canine formula were significantly different (97.1±0.57, 98.2±0.58, and 96.6±0.74, respectively). The calculated canine HbO2 was significantly lower than that measured by the OSM3 or calculated by the ABL for both arterial and jugular venous samples. Calculated and measured arterial and venous ContO2 were similar, as were arterial‐venous ContO2 differences. However, values derived from the calculated canine HbO2 (canine‐calculated) resulted in the greatest arterial‐venous ContO2 difference.Conclusion: ABL‐calculated and canine‐calculated HbO2 were similar to measured values. Likewise, ABL‐calculated, canine‐calculated, and OSM3‐calculated ContO2 were very similar to measured values. Although some of the values generated by the different methods are statistically significantly different, these differences are unlikely to be clinically important in the healthy dog.
CRANIAL TIBIAL ARTERY CATHETER FOR MONITORING PRESSURES AND SAMPLING
Authors: Crowe DT 
Published: September 2004

A technique for placement of a long‐term arterial catheter that the author developed was used in 20 canine patients. The catheter was used for pressure monitoring and arterial blood sampling. The technique involved the following steps post‐sedation and placement of a local anesthetic:

Clipping and prepping of the medial aspect of the distal tibia and proximal metatarsal region;
Incision over the medial tibial malleolus just caudal to the cranial tibial muscle‐tendon;
Blunt dissection of the space just caudal to the cranial tibialis tendon;
Isolation of the cranial tibial artery and loop placement proximally and distally;
Placement of a 3 Fr. polyurethane 4–8 cm catheter using a Seldinger wire technique;
Placement of a suture in the periosteium of the distal tibia and anchoring of the catheter with this suture;
Closure of the skin incision with sutures or staples;
Bandage application to hold the catheter in place.

The entire surgical procedure was done using sterile technique. The catheter was able to be kept in place and working for up to 9 days (averaged 4 days). This compared favorably retrospectively over dorsalis pedis catheters that lasted only a maximum of 4 days. (average 1.5 days). Because of the size of the catheter (3 Fr.) it provided improved waveforms over that observed with the dorsalis pedis catheter (22 g) and its occlusion rate was very low (2 in 20). The cranial tibial artery catheter was found to be particularly effective because the catheter was able to be inserted several cm up the artery and the catheter was able to be anchored well. No major complications were observed with this technique. Because of its effectiveness it is recommended to be used routinely over femoral artery and dorsal pedis artery catheters.
SIMPLE AUTOTRANSUSION IN SEVERE HEMORRHAGE: SUCCESS IN 8 OF 12 DOGS
Authors: Crowe DT 
Published: September 2004

A simple technique for autotransfusion has been developed and used in the successful resuscitation of dogs suffering severe trauma and /or hemorrhage. The purpose of this abstract is three‐fold: 1) Describe the criteria used in case selection; 2) Describe the method used; and 3) Describe the results of its use in a limited number of cases.Case Selection: The criteria used were the following: 1. Ongoing significant hemorrhage or severe hemorrhage noted in a body cavity where the blood could be collected; 2. Acute hemorrhage amounts deemed to be life‐threatening (>40% calculated blood volume [88 ml/kg]); 3. Where other choices (fresh or stored homologus blood, Oxyglobin) in amounts needed were not possible.Method: Blood was aspirated into a suction canister using a Pool or Yankauer suction tip, with the tip placed under the pool (s) of blood to eliminate as many bubbles in the collection process as possible. If the canister was not sterilized it was scrubbed with a surgical prep solution and then rinsed with tap water prior to blood collection. The blood in the canister was poured into a wide opening in a hanging empty plastic intravenous fluid bag with a blood administration set inserted. The blood was intravenously administered by gravity drip as needed. No attempt was made to use any anticoagulant. Amounts of blood given, clinical responses, and complications were recorded.Results: The procedure was used in 12 dogs: 5 abdominal hemorrhage, 3 thoracic hemorrhage, 2 hemorrhage from both abdomen and chest, 2 vertebral vein hemorrhage. All blood administered was given during the operation or within 2 hours. Amounts transfused ranged from 30 to 120 ml/kg (body weight [mean 48 ml/kg]). No animals died acutely from signs thought to be associated with the transfusion of this blood. Those cases surviving to discharge were 4 abdominal, 2 thoracic, 1 combined, and 1 vertebral vein. There were no infections attributed to the autotransfusion. It is concluded that this technique can be recommended and may be considered life‐saving in selected cases.