bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular transport of human lysosomal α-mannosidase and α-mannosidosis-related mutants
Authors: HANSEN Gaute , BERG Thomas , RIISE STENSLAND Hilde M. F. , HEIKINHEIMO Pirkko , KLENOW Helle , EVJEN Gry , NILSSEN Øivind , TOLLERSRUD Ole K. 
Published: July 2004

Human LAMAN (lysosomal α-mannosidase) was synthesized as a 120 kDa precursor in transfected COS cells [African-green-monkey kidney cells], which was partly secreted as a single-chain form and partly sorted to the lysosomes being subsequently cleaved into three peptides of 70, 40 and 15 kDa respectively. Both the secreted and the lysosomal forms contained endo H (endoglucosidase H)-resistant glycans, suggesting a common pathway through the trans-Golgi network. A fraction of LAMAN was retained intracellularly as a single-chain endo H-sensitive form, probably in the ER (endoplasmic reticulum). The inherited lack of LAMAN causes the autosomal recessive storage disease α-mannosidosis. To understand the biochemical consequences of the disease-causing mutations, 11 missense mutations and two in-frame deletions were introduced into human LAMAN cDNA by in vitro mutagenesis and the resulting proteins were expressed in COS cells. Some selected mutants were also expressed in Chinese-hamster ovary cells. T355P (Thr355→Pro), P356R, W714R, R750W and L809P LAMANs as well as both deletion mutants were misfolded and arrested in the ER as inactive single-chain forms. Six of the mutants were transported to the lysosomes, either with less than 5% of normal specific activity (H72L, D196E/N and R220H LAMANs) or with more than 30% of normal specific activity (E402K LAMAN). F320L LAMAN resulted in much lower activity in Chinese-hamster ovary cells when compared with COS cells. Modelling into the three-dimensional structure revealed that the mutants with highly reduced specific activities contained substitutions of amino acids involved in the catalysis, either co-ordinating Zn2+ (His72 and Asp196), stabilizing the active-site nucleophile (Arg220) or positioning the active-site residue Asp319 (Phe320).
Control of expression of the lectin-like protein Reg-1 by gastrin: role of the Rho family GTPase RhoA and a C-rich promoter element
Authors: ASHCROFT Felicity J. , VARRO Andrea , DIMALINE Rod , DOCKRAY Graham J. 
Published: July 2004

The expression of members of the Reg family of secreted lectin-like proteins is increased in response to stress, inflammation and damage in many tissues. In the stomach, Reg is located in enterochromaffin-like cells, where its expression is stimulated by the gastric hormone gastrin. We have examined the mechanisms by which gastrin stimulates expression of Reg-1. Deletional mutations of 2.1 to 0.1 kb of the rat Reg-1 promoter in a luciferase reporter vector were transiently transfected into gastric cancer AGS-GR cells. All promoter fragments tested showed similar relative increases in luciferase expression in response to gastrin (1 nM). The response to gastrin of the smallest (104 bp) construct was 4.2±0.4-fold over basal. These responses were reduced by Ro-32-0432, a protein kinase C inhibitor, by C3-transferase, a Clostridium botulinum toxin and a selective inhibitor of the Rho family GTPase RhoA, and by co-transfection with a dominant negative form of RhoA. Co-transfection with a constitutively active form of RhoA stimulated expression 11.6±1.7-fold over basal. Mutations through the 104 bp construct identified a C-rich element (C−79CCCTCCC−72) required for responses to gastrin, PKC (protein kinase C) and L63RhoA (the constitutively active form of human RhoA protein containing a glutamine-to-leucine substitution at position 63). EMSAs (electrophoretic-mobility-shift assays) using nuclear extracts of control and gastrin-stimulated AGS-GR cells and a probe spanning −86 to −64 bp revealed multiple binding proteins. There was no effect of gastrin on the pattern of binding. Supershift assays indicated that transcription factors Sp1 and Sp3 bound the C-rich sequence. We conclude that gastrin stimulates Reg expression via activation of PKC and RhoA, that a C-rich region (−79 to −72) is critical for the response and that Sp-family transcription factors bind to this region of the promoter.
The water- and salt-stress-regulated Asr1 (abscisic acid stress ripening) gene encodes a zinc-dependent DNA-binding protein
Authors: KALIFA Yossi , GILAD Ayelet , KONRAD Zvia , ZACCAI Michele , SCOLNIK Pablo A. , BAR-ZVI Dudy 
Published: July 2004

Tomato (Lycopersicon esculantum) ASR1 (abscisic acid stress ripening protein), a small plant-specific protein whose cellular mode of action defies deduction based on its sequence or homology analyses, is one of numerous plant gene products with unknown biological roles that become over-expressed under water- and salt-stress conditions. Steady-state cellular levels of tomato ASR1 mRNA and protein are transiently increased following exposure of plants to poly(ethylene glycol), NaCl or abscisic acid. Western blot and indirect immunofluorescence analysis with anti-ASR1 antibodies demonstrated that ASR1 is present both in the cytoplasmic and nuclear subcellular compartments; approx. one-third of the total ASR1 protein could be detected in the nucleus. Nuclear ASR1 is a chromatin-bound protein, and can be extracted with 1 M NaCl, but not with 0.5% Triton X-100. ASR1, overexpressed in Escherichia coli and purified to homogeneity, possesses zinc-dependent DNA-binding activity. Competitive-binding experiments and SELEX (systematic evolution of ligands by exponential enrichment) analysis suggest that ASR1 binds at a preferred DNA sequence.
Suppression of matrix metalloproteinase-9 transcription by transforming growth factor-β is mediated by a nuclear factor-κB site
Authors: OGAWA Kenji , CHEN Feifei , KUANG Chenzhong , CHEN Yan 
Published: July 2004

TGF-β (transforming growth factor-β) plays a critical role in modulating the inflammatory response and other biological processes through its regulation of the production of MMPs (matrix metalloproteinases). In both Mono-Mac-6 and RAW264.7 monocyte/macrophage cells, TGF-β abrogated lipopolysaccharide-induced increases in the enzymic activity and mRNA level of MMP-9. A fragment of the human MMP-9 promoter was used to characterize its regulation by TGF-β signalling. In RAW264.7 cells, TGF-β or its downstream signalling protein, Smad3 (Sma- and Mad-related protein 3), inhibited lipopolysaccharide-stimulated promoter activity. The suppressive activity of TGF-β on the MMP-9 promoter was abrogated by an inhibitory Smad, Smad7. The MMP-9 promoter contains a putative TIE (TGF-β inhibitory element). However, neither mutation nor deletion of the TIE had any effect on the inhibitory activity of TGF-β on MMP-9 transcription, indicating that the consensus TIE is not required for this effect of TGF-β. Analysis using a series of deletion mutants of the MMP-9 promoter revealed that a region containing a consensus NF-κB (nuclear factor-κB) site is required for the basal activity and TGF-β-mediated suppression of the promoter. Mutation of the putative NF-κB site not only markedly reduced the basal transcriptional activity of the promoter, but also abrogated the responsiveness of the promoter to TGF-β. In addition, a minimal promoter containing one copy of the NF-κB sequence was responsive to TGF-β treatment. Furthermore, an electrophoretic mobility shift assay was performed with the nuclear extracts from RAW264.7 cells, and it was found that TGF-β treatment did not disrupt the binding of NF-κB p50 and p65 proteins to the NF-κB sequence. Taken together, these studies indicate that the NF-κB site is indispensable for the suppressive activity of TGF-β in the regulation of MMP-9 transcription.
The second RNA-binding domain of the human splicing factor ASF/SF2 is the critical domain controlling adenovirus E1A alternative 5′-splice site selection
Authors: DAUKSAITE Vita , AKUSJÄRVI Göran 
Published: July 2004

The human splicing factor ASF/SF2 (alternative splicing factor/splicing factor 2) is modular in structure with two RNA-binding domains (RBD1 and RBD2) and a C-terminal domain rich in arginine–serine dipeptide repeats. ASF/SF2 is an essential splicing factor that also functions as an important regulator of alternative splicing. In adenovirus E1A (early region 1A) alternative pre-mRNA splicing, ASF/SF2 functions as a strong inducer of proximal 5′-splice-site selection, both in vitro and in vivo. In the present study, we tested the functional role of individual domains of ASF/SF2 in alternative splicing in vitro. We show that ASF/SF2-RBD2 is the critical domain controlling E1A alternative splicing. In fact, RBD2 alone is sufficient to mimic the activity of the full-length ASF/SF2 protein as an inducer of proximal 5′-splice-site selection in vitro. The RBD2 domain induces a switch to E1A-proximal 5′-splice-site usage by repressing distal 12 S splicing and simultaneously stimulates proximal 13 S splicing. In contrast, the ASF/SF2-RBD1 domain has a more general splicing enhancer phenotype and appears to stimulate preferentially cap-proximal 5′-splice-site selection. Furthermore, the SWQDLKD motif, which is conserved in all SR proteins (serine/arginine-rich proteins) containing two RBDs, and the ribonucleoprotein-1-type RNA recognition motif were both found to be necessary for the alternative splice-site-switching activity of ASF/SF2. The RNP-1 motif was necessary for efficient RNA binding, whereas the SWQDLKD motif most probably contributes by functioning as a surface-mediating critical protein–protein contact during spliceosome assembly.
The use and safety of transoesophageal echocardiography in the general ICU – a minireview
Authors: Hüttemann E. , Schelenz C. , Kara F. , Chatzinikolaou K. , Reinhart K. 
Published: July 2004

Background:  The efficacy of transoesophageal echocardiography (TEE) has been evaluated predominantly in medical and cardiac surgical ICUs. This article reviews the pertinent literature and evaluates the impact of TEE in a general surgical ICU.Methods:  Twenty studies on TEE in the ICU were evaluated for complications, indications, diagnostic, therapeutic, and surgical impact on patient management. Diagnostic impact was defined as identification of the underlying cardiovascular pathology, therapeutic impact as changes in patient management and surgical impact as indication for operative procedures. In addition, we reviewed the TEE reports and patient charts of 216 critically ill patients in a 16‐bed multidisciplinary surgical ICU at our university hospital, who underwent a TEE for differential diagnosis of hemodynamic instability from July 1995 to December 1998 to assess the impact of TEE on patient management in a general surgical ICU.Results:  The diagnostic, therapeutic and surgical impact in a total of 2,508 patients ranged from 44 to 99% (weighted mean 67.2%), 10–69% (36.0%), and 2–29% (14.1%), respectively. The complication rate was 2.6%, with no examination related mortality. In our series in a general surgical ICU, a diagnostic, therapeutic and surgical impact was inferred in 191 (88.4%), 148 (68.5%) and 12 (5.6%) patients, respectively. Adverse effects were observed in 5.6%.Conclusion:  TEE is safe, well‐tolerated and useful in the management of critically ill patients. This applies as well for hemodynamically unstable patients in a general surgical ICU.
Aminotransferases after experimental pneumoperitoneum in dogs
Authors: Nesek‐Adam V. , Rašic Z. , Kos J. , Vnuk D. 
Published: July 2004

Background:  Laparoscopic surgery has rapidly become a popular and widely used technique. Elevated intra abdominal pressure due to gas insufflation for laparoscopic surgery may result in a number of local and systemic effects on the organism. The effects of pneumoperitoneum on the cardiovascular and respiratory system are well known today, but very few studies have been carried out on the consequences of pneumoperitoneum on hepatic integrity. The aim of the present study was to assess changes in aminotransferases, bilirubin and prothrombin time after pneumoperitoneum in dogs.Methods:  The effects of different levels and duration of intra abdominal pressure and different gases on liver function test were investigated in dogs. The levels of aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, and prothrombin time, according to the duration and the level of pneumoperitoneum and gas, were measured at 6, 12, 24 and 48 h of desufflation.Results:  The levels of total bilirubin, direct bilirubin and prothrombin time showed no significant alteration. A statistically significant (P < 0.01) elevation of aspartate aminotrasferase and alanine aminotransferase was recorded in the group of animals with higher intra abdominal pressure and longer duration of pneumoperitoneum. They returned to normal values within 48 h.Conclusion:  Transient elevation of hepatic transaminases occurred after laparoscopic surgery, but they returned to normal values within 48 h. These increases were more prominent with higher and longer intra abdominal pressures irrespective of the type of insufflated gas. Alteration in aminotransferases was not associated with any clinical signs of hepatic dysfunction in experimental animals.
Can chronic poststernotomy pain after cardiac valve replacement be reduced using thoracic epidural analgesia?
Authors: Jensen M. K. , Andersen C. 
Published: July 2004

Background:  The aim of our study was to evaluate the use of thoracic epidural analgesia (TEA) in acute pain management after cardiac valve replacement and determine if the incidence of chronic pain related to the sternotomy was reduced by the use of TEA. This patient group was chosen to exclude pain related to the use of the internal mammary artery and angina pectoris.Methods:  Patients scheduled for elective cardiac valve replacement were offered TEA. A match‐control group was selected. Epidural catheter placement, complications and postoperative neurological state were noted for both groups. Eighteen months postoperatively, a questionnaire was sent out concerning pain management, wound discomfort and pain.Results:  Forty‐nine patients were included. The TEA group consisted of 35 patients. At 18 months' follow up, 37% from the TEA group and 21% from the control group had pain or discomfort related to the sternum (NS). Two in the TEA group had severe pain.Conclusion:  We found in our small material that TEA provided excellent analgesia in the peri‐ and postoperative period, but we did not find a protective effect of TEA on chronic poststernotomy pain, neither weak pain nor severe pain.
Effects of neuromuscular‐blocking drugs in rats in vivo: Direct measurements in the diaphragm and tibialis anterior muscle
Authors: Itoh H. , Shibata K. , Matsumoto T. , Nitta S. , Nishi M. , Kobayashi T. , Yamamoto K. 
Published: July 2004

Background:  Effects of neuromuscular‐blocking drugs are often investigated in rodents using both the diaphragm in vitro and the tibialis anterior muscle in vivo. Differences in the properties of these muscles cannot be neglected. We evaluated the neuromuscular effects of drugs on the rat diaphragm in vivo in comparison with the tibialis anterior muscle, directly measuring twitch tension with a force transducer.Methods:  Respectively using sternotomy and an approach via the gluteal space, transducers were attached to the diaphragm and the tibialis anterior muscle. Phrenic and sciatic nerves were stimulated supramaximally by single square pulses to record isometric contraction of muscles. Pancuronium, vecuronium, or rocuronium was infused continuously at a rate adjusted repeatedly until stable tension was obtained. Effective doses for 50% (ED 50) and 90% (ED 90) depression of tension were calculated, using a cumulative infusion dosing method.Results:  Isometric contraction of the diaphragm could be recorded despite movements of the heart and lungs. For all three drugs, both mean ED 50 and ED 90 were more than twice as large for the diaphragm as for the tibialis anterior (P<0.05). In addition, slopes of dose–response curves for the diaphragm were significantly less steep than those of the tibialis anterior for the three drugs.Conclusion:  Neuromuscular‐blocking effects on the diaphragm can be recorded in vivo. According to direct contractile force measurement, the diaphragm is more resistant to non‐depolarizing neuromuscular‐blocking drugs than the tibialis anterior muscle.
Anaesthesia in day case laparoscopic female sterilization: a comparison of two anaesthetic methods
Authors: Rognås L. K. , ElkjÆr P. 
Published: July 2004

Background:  Laparoscopic sterilization (LS) in women is a procedure frequently carried out in a day case setting. The purpose of the study was to measure postoperative pain, nausea and vomiting (PONV), the incidence of unplanned overnight admissions and patient satisfaction with two different anaesthetic methods.Methods:  From August 1997 to January 1999 the LS patients were anaesthetized with propofol + fentanyl/alfentanil, N2O and atracurium, and from January 1999 to end of 2001 they were given TIVA with propofol + remifentanil. Postoperative pain was managed with standardized high doses of paracetamol and NSAID in both groups. Data were collected from hospital records and from questionnaires given to all the patients.Results:  Six hundred and eighty‐one women were sterilized. There were no significant differences in postoperative pain between the two groups, with 8.2 and 12.1 per cent, respectively, experiencing severe pain. Significantly fewer patients experienced moderate or severe postoperative nausea after the introduction of remifentanil anaesthesia (3.3 vs. 11.7%, P = 0.001). Eleven patients (1.8%) were admitted overnight, with no difference between the two groups. 94.5% and 96.3% of the patients were either satisfied or very satisfied with their treatment (P = 0.50).Conclusion:  Both anaesthetic methods provide equally good postoperative pain relief, few unplanned admissions and a high degree of patient satisfaction when combined with postoperative paracetamol and NSAID. Patients anaesthetized with remifentanil and propofol have less postoperative nausea.
Adaptive versus Proactive Behavior in Service Recovery: The Role of Self‐Managing Teams
Authors: Jong Ad de , De Ruyter Ko 
Published: July 2004

ABSTRACTIn this article, we develop a conceptual model of adaptive versus proactive recovery behavior by self‐managing teams (SMTs) in service recovery operations. To empirically test the conceptual model a combination of bank employee, customer, and archival data is collected. The results demonstrate support for independent group‐level effects of intrateam support on adaptive and proactive recovery behavior, indicating that perceptual consensus within service teams has incremental value in explaining service recovery performance. In addition, we provide evidence that adaptive and proactive recovery behavior have differential effects on external performance measures. More specifically, higher levels of adaptive performance positively influence customer‐based parameters (i.e., service recovery satisfaction and loyalty intentions), while employee proactive recovery behavior contributes to higher share of customer rates.
Restaurant Revenue Management at Chevys: Determining the Best Table Mix
Authors: Kimes Sheryl E. , Thompson Gary M. 
Published: July 2004

ABSTRACTRevenue management has been used in a variety of industries and generally takes the form of managing demand by manipulating length of customer usage and price. Supply mix is rarely considered, although it can have considerable impact on revenue. In this research, we focused on developing an optimal supply mix, specifically on determining the supply mix that would maximize revenue. We used data from a Chevys restaurant, part of a large chain of Mexican restaurants, in conjunction with a simulation model to evaluate and enumerate all possible supply (table) mixes. Compared to the restaurant's existing table mix, the optimal mix is capable of handling a 30% increase in customer volume without increasing waiting times beyond their original levels. While our study was in a restaurant context, the results of this research are applicable to other service businesses.
Evaluating the Deming Management Model of Total Quality in Services*
Authors: Douglas Thomas J. , Fredendall Lawrence D. 
Published: July 2004

ABSTRACTThis article uses the Deming management model developed by Anderson et al. (1994b) as an initial template to analyze total quality in services. While the literatures addressing quality management have developed separately for products and services, the founders of total quality portrayed this management philosophy as universally oriented. Our study first replicates two earlier studies that tested the Deming management model in manufacturing industries. Using hospitals as our unit of analysis, we realized findings similar to the earlier manufacturing studies. Next, we used contributions from the MBNQA literature to test an enhanced model. Our subsequent findings support the MBNQA concept that “leadership drives the system that creates results” and provides evidence of the ubiquitous importance of leadership for ensuring the success of a quality improvement program. Finally, an anomaly of this study and those published earlier is the inability to find support for the relationship between continuous improvement and customer satisfaction. Integrating the substantial work in the service quality literature focused on customer satisfaction measurement is recommended to future researchers to help resolve this issue and further enhance the model.
The Role of Clinical and Process Quality in Achieving Patient Satisfaction in Hospitals
Authors: Marley Kathryn A. , Collier David A. , Meyer Goldstein Susan 
Published: July 2004

ABSTRACTManagers constantly struggle with where to allocate their resources and efforts in managing the complex service delivery system called a hospital. In the broadest sense, their decisions and actions focus on two important aspects of health care—clinical or technical medical care that emphasizes “what” the patient receives and process performance that emphasizes “how” health care services are delivered to patients. Here, we investigate the role of leadership, clinical quality, and process quality on patient satisfaction. A causal model is hypothesized and evaluated using structural equation modeling for a sample of 202 U.S. hospitals. Statistical results support the idea that leadership is a good exogenous construct and that clinical and process quality are good intermediate outcomes in determining patient satisfaction. Statistical results also suggest that hospital leadership has more influence on process quality than on clinical quality, which is predominantly the doctors' domain. Other results are discussed, such as that hospital managers must be mindful of the fact that process quality is at least as important as clinical quality in predicting patient satisfaction. The article concludes by proposing areas for future research.
A Mathematical Model of Service Failure and Recovery Strategies*
Authors: Zhu Zhen , Sivakumar K. , Parasuraman A. 
Published: July 2004

ABSTRACTUnderstanding the nature of service failures and their impact on customer responses and designing cost‐effective recovery strategies have been recognized as important issues by both service researchers and practitioners. We first propose a conceptual framework of service failure and recovery strategies. We then transform it into a mathematical model to assist managers in deciding on appropriate resource allocations for outcome and process recovery strategies based on customer risk profiles and the firm's cost structures. Based on this mathematical model we derive optimal recovery strategies, conduct sensitivity analyses of the optimal solutions for different model parameters, and illustrate them through numerical examples. We conclude with a discussion of managerial implications and directions for future research.