bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue‐type plasminogen activator rescues neurones from serum deprivation‐induced apoptosis through a mechanism independent of its proteolytic activity
Authors: Liot Géraldine , Roussel Benoit D. , Lebeurrier Nathalie , Benchenane Karim , López‐Atalaya José P. , Vivien Denis , Ali Carine 
Published: June 2006

AbstractAlthough the mechanism of action of tissue‐type plasminogen activator (tPA) in excitotoxic necrosis is well documented, whether this serine protease can influence the apoptotic cascade remains a subject of debate. Here, we report that tPA protects cultured cortical neurones against apoptotic cell death induced by serum deprivation, an effect associated with a reduction of caspase‐3 activation. Interestingly, blocking tPA proteolytic activity by either tPA stop or neuroserpin did not prevent this neuroprotection. Similarly, prevention of the interaction between tPA and its receptor low‐density lipoprotein receptor‐related protein (LRP) could not alter tPA anti‐apoptotic activity. Interestingly, the survival‐promoting effect of tPA was blocked by the phosphatidylinositol‐3 (PI‐3) kinase inhibitor, LY294002, but not by the mitogen‐activated protein (MAP) kinase inhibitor, U0126. In conclusion, the present demonstration of an anti‐apoptotic effect of tPA, independent of its enzymatic activity, reveals an additional level of complexity in our understanding of this critical mediator of brain physiology and pathology.
Activation of D1 dopamine receptors increases surface expression of AMPA receptors and facilitates their synaptic incorporation in cultured hippocampal neurons
Authors: Gao Can , Sun Xiu , Wolf Marina E. 
Published: June 2006

AbstractConsiderable evidence indicates that neuroadaptations leading to addiction involve the same cellular processes that enable learning and memory, such as long‐term potentiation (LTP), and that psychostimulants influence LTP through dopamine (DA)‐dependent mechanisms. In hippocampal CA1 pyramidal neurons, LTP involves insertion of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptors into excitatory synapses. We used dissociated cultures to test the hypothesis that D1 family DA receptors influence synaptic plasticity in hippocampal neurons by modulating AMPA receptor trafficking. Brief exposure (5 min) to a D1 agonist increased surface expression of glutamate receptor (GluR)1‐containing AMPA receptors by increasing their rate of externalization at extrasynaptic sites. This required the secretory pathway but not protein synthesis, and was mediated mainly by protein kinase A (PKA) with a smaller contribution from Ca2+–calmodulin‐dependent protein kinase II (CaMKII). Prior D1 receptor stimulation facilitated synaptic insertion of GluR1 in response to subsequent stimulation of synaptic NMDA receptors with glycine. Our results support a model for synaptic GluR1 incorporation in which PKA is required for initial insertion into the extrasynaptic membrane whereas CaMKII mediates translocation into the synapse. By increasing the size of the extrasynaptic GluR1 pool, D1 receptors may promote LTP. Psychostimulants may usurp this mechanism, leading to inappropriate plasticity that contributes to addiction‐related behaviors.
Results of combination treatment with pegylated interferon and ribavirin in cirrhotic patients with hepatitis C infection
Authors: Höroldt Barbara , Haydon Geoffrey , O'Donnell Katrina , Dudley Tracey , Nightingale Peter , Mutimer David 
Published: June 2006

Abstract: Background: The treatment of hepatitis C patients with advanced cirrhotic liver disease remains challenging and data on the outcome of treatment for this patient group is limited.Results: Between September 2000 and August 2004, 61 cirrhotic patients started treatment with pegylated interferon and ribavirin (42 male, age range 29–69 years, 26 Asian). Forty‐three (70%) patients were serum hepatitis C virus (HCV) RNA negative at the end of treatment and 24 (39%) achieved a sustained virological response (SVR). SVR was achieved for 35% (6/17) of patients with genotype 1, and for 39% (16/41) with genotype 3. Caucasians with genotype 3 demonstrated a higher cure rate (SVR 10/18=56%) than Asians (SVR 6/24=25%). Failure to achieve SVR was associated with lower platelet count, neutrophil count and albumin at baseline. Twenty patients suffered clinical or laboratory decompensation, five patients required hospitalization, and two patients died. Patients who experienced hepatic decompensation were older and had baseline characteristics associated with more advanced liver disease.Conclusion: The treatment of patients with advanced HCV is challenging, although many treated patients achieve SVR. Significant toxicity is experienced and there is treatment‐related mortality. This balance of efficacy and toxicity needs to be considered before commencing treatment.
Radio‐frequency ablation of hepatocellular carcinoma before liver transplantation: a histologic and ‘TUNEL’ study
Authors: Netto G. J. , Altrabulsi B. , Katabi N. , Martin P. , Burt K. , Levy M. , Sanchez E. , Watkins D. L. , Jennings L. , Klintmalm G. , Goldstein R. 
Published: June 2006

Abstract: Background: Radio‐frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers.Design: We evaluated 36 tumors from 35 patients with RFA‐treated HCC who underwent OLTX at our center between 1998 and 2002. Native livers from OLTX were extensively sampled for histologic evaluation. For each HCC, an estimate ratio of necrotic tumor areas was calculated based on hematoxylin and eosin (H&E) sections. In tumors with 10% or more residual viable areas, Tdt‐mediated UTP nick‐end labeling (TUNEL) was further performed to assess apoptosis in the morphologically ‘viable’ areas. A final ‘tumor cell death’ (TCD) ratio was recalculated for each HCC to include areas of apoptosis identified by TUNEL.Results: Based on H&E evaluation, 22/36 (61.1%) HCC revealed ≥90% necrosis including 12/36 HCC (33.3%) showing no evidence of residual viable tumor. The overall median tumor necrosis was 79%. When TUNEL findings were added, 26/36 (72.2%) HCC revealed ≥90% TCD including 14/36 HCC (38.8%) showing complete TCD (median TCD of 88.4%). None of our patients died of HCC while awaiting OLTX. Longer RFA‐to‐transplant time appears to be associated with a higher TCD rate (median of 154.5 days in patients with less than 90% TCD vs 326 days for patients with ≥90% TCD; P=0.019). There was no significant correlation between tumor grade or pre‐RFA size of the tumors and TCD rate in RFA‐treated HCC (P=0.11).Conclusion: Extensive TCD (88.4% median) can be obtained using RFA for HCC in patients awaiting OLTX. Our TUNEL findings suggest that RFA‐induced cell injury could be associated with apoptosis.
Detection of new amino acid markers of liver trauma by proton nuclear magnetic resonance spectroscopy
Authors: Ranjan Priyadarshi , Gupta Ashish , Kumar Sandeep , Nagan Gowda Gowda Ajjapa , Ranjan Aseem , Sonker Abhinav Arun , Chandra Abhijit , Kant Rama 
Published: June 2006

Abstract: Objective: We examined serum in patients of liver injury to explore the possible clinical application of abnormal micrometabolites as a marker of liver injury and severity in cases of traumatic liver damage.Methods: Serum were screened by proton nuclear magnetic resonance spectroscopy in 96 patients with varying degree of liver injury and compared with concentrations in healthy control volunteers.Results: Large quantities of phenylalanine and tyrosine were detected by spectroscopic analysis in patients with liver injury but not in those without liver injury (P<0.001). Proton nuclear magnetic resonance spectroscopy revealed two unique amino acids, phenylalanine and tyrosine, in the sera of the subjects with liver injury, irrespective of the extent and type of injury gauged by radiology or laparotomy. Phenylalanine spectrum was obtained in all 84 patients with liver injury (100% sensitivity) whereas tyrosine spectrum was present in 83 out of 84 patients (98.8% sensitivity) suggesting that these amino acids were specifically released in the patients of liver injury. Significant correlations were observed between phenylalanine and tyrosine concentrations and total bilirubin levels and albumin levels. Serum phenylalanine and tyrosine concentrations correlated well with imaging and laparotomy findings of liver injury.Conclusion: Phenylanaline and tyrosine appear to be specific and new markers of liver injury.
Ring‐shaped appearance in liver‐specific image with Levovist: a characteristic enhancement pattern for hypervascular benign nodule in the liver of heavy drinkers
Authors: Maruyama Hitoshi , Matsutani Shoichi , Kondo Fukuo , Yoshizumi Hiroaki , Kobayashi Satoshi , Okugawa Hidehiro , Ebara Masaaki , Saisho Hiromitsu 
Published: June 2006

Abstract: Background/Aims: The aim was to clarify the features of contrast‐enhanced ultrasound (CEUS) with Levovist for diagnosis of hypervascular benign nodules in the liver of heavy drinkers.Patients and methods: Seven heavy drinkers with hypervascular nodules in the liver were studied. Findings of CEUS with Levovist (wide‐band Doppler, 7/7), contrast‐enhanced computed tomography (CECT, 7/7) and magnetic resonance imaging (MRI, 5/7) were compared for one nodule in each patient.Results: Diagnosis of all seven nodules on CECT was HCC, whereas pathological results were HCC for four nodules and benign lesion for three nodules. The former four showed compatible findings for HCC on CEUS (4/4) and MRI (2/4). However, the latter three showed characteristic liver‐specific sonograms with a ring‐shaped appearance – peripheral enhancement with a central non‐enhanced area. Two of the three nodules showed decreased signal‐intensity in the periphery on SPIO‐enhanced MRI.Conclusions: The ring‐shaped appearance on liver‐specific sonograms with Levovist may be a useful sign for the differential diagnosis of hypervascular benign nodule from HCC in heavy drinkers.
Nematode infection of the liver mimicking metastasis of malignant melanoma
Authors: Maier M. , Tappe D. , Töpfer C. , Rosenwald A. , Gassel H.‐J. , Timm S. 
Published: June 2006

Abstract: Background: The differential diagnoses of a circumscribed mass of the liver are varied. Especially if a malignant tumor, capable of setting metastases to the liver, is known in a patient's medical history, there might be difficulties in differentiating the tumor's entity.Casuistry: We report a case of a 40‐year‐old male with a history of malignant melanoma in whom follow‐up investigations revealed a mass in the liver.Results: The histopathological and microbiological results, however, showed an infestation of liver tissue with nematodes. Malignant tumor cells could not be detected.Conclusions: Roundworm‐infections of the liver can present as lesions suspicious of being malignant. Therefore, along with e.g. microhamartoma, microabscesses and hepatocellular carcinoma, infestation with nematodes should be taken into consideration.
A conjugate of doxorubicin with lactosaminated albumin enhances the drug concentrations in all the forms of rat hepatocellular carcinomas independently of their differentiation grade
Authors: Di Stefano Giuseppina , Fiume Luigi , Baglioni Michele , Bolondi Luigi , Busi Corrado , Chieco Pasquale , Kratz Felix , Manaresi Francesca , Pariali Milena 
Published: June 2006

Abstract: Background/Aims: Doxorubicin (DOXO) was coupled to lactosaminated human serum albumin (L‐HSA) in order to enhance the drug concentration in the well differentiated hepatocellular carcinomas (HCCs), which can accumulate L‐HSA through the asialoglycoprotein receptor. In the present experiments we compared the DOXO concentrations produced by this conjugate (L‐HSA–DOXO) and by the uncoupled drug in the well, moderately, and poorly differentiated rat HCCs.Methods: The same dose (1 μg/g) of free or L‐HSA coupled‐DOXO was injected in rats with HCCs induced by diethylnitrosamine. At different times, the animals were killed and the neoplastic nodules of liver were isolated. Their differentiation grade was determined histologically and their DOXO content was measured.Results: Unexpectedly, we found that also in the poorly differentiated forms of HCCs, which display no or only a poor capacity of accumulating L‐HSA, the conjugate raised DOXO levels that were approximately twofold higher than those produced by the free drug.Conclusions: The conjugate L‐HSA–DOXO could improve the potential of DOXO in the treatment of all HCCs, including the poorly differentiated tumors that are the common forms in the advanced disease for which an effective chemotherapy is particularly needed.
High prevalence of infection with a single hepatitis C virus genotype in a small rural community of Argentina
Authors: Picchio Gastón R. , Baré Patricia C. , Descalzi Valeria I. , Bussy María V. , Soria Sonia M. , Raffa María P. , Mazzencio Nancy E. , Etchehun Silvina , Cámera Juan A. , Mosier Donald E. , Villamil Federico G. 
Published: June 2006

Abstract: Background: During the years preceding this study, we noticed a relatively unusual high number of individuals with elevated alanine aminotransferase (ALT) levels in O'Brien, a small rural town in Argentina. Moreover, four individuals from this town underwent liver transplantation owing to hepatitis C virus (HCV)‐induced liver cirrhosis. These findings prompted us to conduct a large population‐based survey to evaluate the prevalence of HCV in this community.Methods and Results: A total of 1637 individuals were studied. The overall HCV‐seroprevalence was 5.7% (93/1637), being slightly higher in men (45/769; 5.9%) than in women (48/868; 5.5%). HCV seroprevalence increased with age, reaching a peak rate of 23.9% among individuals between 61 and 70 years of age. HCV RNA was present in 82.7% of all HCV seropositive individuals identified and 100% of them were infected with genotype 1b. ALT elevations were detected in 44% of HCV+ patients and were only observed among viremic individuals. Hepatitis B virus infection was also prevalent (52%) among HCV‐seropositive patients. The most common risk factor associated with HCV transmission identified was the apparent use of inadequately sterilized glass syringes by a health care provider serving the community; however, other risk factors may have also played a role in the dissemination of HCV.Conclusions: Our findings provide an explanation for the relative high number of individuals with elevated ALT levels observed in this community and form the basis of future prospective studies on the natural history of genotype 1b infection.
Mild hypothermia reduces the inflammatory response and hepatic ischemia/reperfusion injury in rats
Authors: Behrends Matthias , Hirose Ryutaro , Serkova Natalie J. , Coatney John L. , Bedolli Melanie , Yardi Jason , Park Yeon Ho , Niemann Claus U. 
Published: June 2006

Abstract: Background/Aims: Hypothermia is known to protect against ischemia/reperfusion (I/R) injury. The mechanisms of protection are incompletely understood and a temperature threshold for protection has not been established.Methods: In anesthetized Wistar rats, partial (70%) hepatic ischemia was applied for 45 min. Three study groups were used. Group T31 (n=6) spontaneously cooled to 31.3±0.8°C, while group T34 (n=6) spontaneously cooled to 34°C and was then maintained at 34.0±0.1°C using a heat lamp. The normothermic group (T37, n=6) was maintained at 37.1±0.3°C. Hepatic injury, inflammation, lipid peroxidation and metabolic function (using quantitative 1H‐NMR) were assessed 24 h after reperfusion.Results: At 24 h following reperfusion, alanine aminotransferase and aspartate aminotransferase increased to 5101±2378 and 6409±4202 U/l in the normothermic T37 group (P<0.05 vs. T34 and T31), whereas transaminases in hypothermic groups (T31 and T34) were significantly lower. Severe liver necrosis was only noted with T37. Myeloperoxidase activity was increased in the T37 group when compared with hypothermic groups (223±161 (T37) vs. 16±10 (T31) and 8±5 (T34) mU/min/mg of tissue, P<0.05 vs. T31 and T34). 1H‐NMR analysis of the blood of normothermic animals revealed metabolic changes consistent with increased ischemic injury, which was almost completely ameliorated in T34 and T31 groups.Conclusions: Mild hypothermia of 34°C is sufficient to reduce I/R injury by inhibiting the inflammatory response. Further spontaneous cooling to 31°C did not demonstrate any additional protective effect.
In vitro pH effects on in vivo recovery and survival of platelets: an analysis by the BEST Collaborative
Authors: Dumont Larry J. , AuBuchon James P. , Gulliksson Hans , Slichter Sherrill J. , Elfath M. Dean , Holme Stein , Murphy James R. , Rose Leslie E. , Popovsky Mark A. , Murphy Scott 
Published: June 2006

BACKGROUND: The pH environment of stored platelet (PLT) products is recognized as an important factor and is generally used as a key surrogate measure of PLT viability. It is the only in vitro measurement that has been translated into industry standards and regulatory rules or specifications for storage of PLT products. The objective of this study was to evaluate the effect of in vitro pH on the in vivo recovery and survival of autologous PLT products.STUDY DESIGN AND METHODS: Data from individual autologous radiolabeled PLT kinetic studies were solicited from independent laboratories. PLTs stored for at least 5 days in 100 percent autologous plasma with a pH22°C of at least 6.2 were analyzed. Data were fit to a mixed‐effects regression model with fixed effects of pH22°C, time of storage, and preparation method‐storage bag combination.RESULTS: Eight research laboratories reported 476 individual recovery and survival results with associated pH before labeling from a variety of autologous, radiolabeled PLT kinetic studies from September 1999 to March 2005. These results are from 254 individual subjects who donated a total of 386 PLT units, with up to nine collections per subject reported. The effect of pH on either PLT recovery (p = 0.86) or survival (p = 0.55) was not significant. Time of storage and the method‐bag combination both had significant effects on these outcomes (p < 0.0001).CONCLUSION: These data suggest that there is no relationship between in vitro pH at a pH22°C of at least 6.2 and in vivo PLT viability as measured by radiolabeled recovery and survival of autologous PLTs.
In vivo efficacy of shipped HLA‐matched platelets
Authors: Haddad Salim A. , Lichtiger Benjamin , Klein Harvey G. 
Published: June 2006

BACKGROUND: Platelet (PLT) concentrates are currently stored in an incubator at 20 to 24°C with continuous gentle agitation. PLTs are routinely shipped for transfusion to thrombocytopenic patients, however. There is a concern that PLT concentrates may be adversely affected during the shipping process.CASE REPORT: A 40‐year‐old woman with severe aplastic anemia and immune refractory to unselected PLT transfusions was transferred to a distant medical center for a hematopoietic peripheral blood progenitor cell transplant where she continued to receive HLA‐matched PLTs from her dedicated donors. Sixteen such components were collected and air‐shipped in insulated boxes to the transplant center. Thirty‐seven plateletpheresis components from the same dedicated donors had been transfused to the patient before transfer. Corrected count increments (CCIs) at the two sites were compared, with assessment of the role of HLA‐match grades. The mean interruption time of controlled agitation during shipment was approximately 10.5 hours. The mean CCI of all distant transfusions was 14,450 ± 9700 PLTs per µL·m2 per 1011 and that of local transfusions was 10730 ± 4870. The mean donor‐paired difference between CCIs at the two sites was 1140 ± 9940. At the remote location no clinically significant bleeding occurred and one posttransfusion febrile reaction was noted.CONCLUSION: Despite the study limitations, the effectiveness, in a single patient, of leukoreduced, irradiated apheresis PLTs shipped by lengthy combined surface and airline transport is reported, as measured by posttransfusion CCIs.
TheRHCEalleleceCF: the molecular basis of Crawford (RH43)
Authors: Flegel Willy A. , Wagner Franz F. , Chen Qing , Schlanser Gloria , Frame Tom , Westhoff Connie M. , Moulds Marilyn K. 
Published: June 2006

BACKGROUND:The Crawford antigen (RH43) was described in 1980. It occurred in African American people, as a low‐prevalence Rhesus antigen, who were also VS+.STUDY DESIGN AND METHODS:Twelve blood samples were analyzed because of inquiries into discrepant reactions in routine anti‐D typing. TheRHCEalleles were determined by nucleotide sequencing from genomic DNA. The D epitope profile was determined with 60 monoclonal anti‐D. The population frequency was estimated in four major US regional blood centers.RESULTS:The novelRHce(W16C, Q233E, L245V) allele, dubbedceCF, was found to be occurring in thecdehaplotype as cause of the reactivity with the immunoglobulin M anti‐D GAMA401. The ceCF phenotype expressed few D epitopes resembling but not matching the reaction patterns observed with other RhCE variants, like R0Har, ceRT, and ceSL. The frequency of the ceCF phenotype was 0.056 percent among African American persons and 0.007 percent in the general US population.CONCLUSION:The novelRHce(W16C, Q233E, L245V) allele, which is a variant of the knowncesallele,RHce(W16C, L245V), occurs in a haplotype with theRHDdeletion and represents the molecular basis of the Crawford antigen.
A comparison of three rapid bacterial detection methods under simulated real‐life conditions
Authors: Schmidt Michael , Hourfar Michael K. , Nicol Sven‐Boris , Wahl Alexandra , Heck Julia , Weis Christina , Tonn Torsten , Spengler Hans‐Peter , Montag Thomas , Seifried Erhard , Roth W. Kurt 
Published: June 2006

BACKGROUND: Bacterial screening of all produced platelet concentrates (PCs) is implemented in many countries to reduce the risk of transfusion‐transmitted sepsis. This study compares three rapid bacterial detection methods by imitating real‐life conditions.STUDY DESIGN AND METHODS: The sensitivity of a solid‐phase scanning cytometer (optimized Scansystem, Hemosystem), fluorescence‐activated cell sorting (FACS) analysis, and 16S RNA in‐house nucleic acid testing (NAT) was evaluated by spiking PCs with four transfusion relevant bacteria (Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, and Escherichia coli ). Two different inocula (10 colony‐forming units [CFUs]/mL and 10 CFUs/bag) were used to simulate real‐life conditions. Samples were taken at 12, 16, 20, and 24 hours after spiking.RESULTS: With the high inoculum, NAT had a 100 percent rate of positive testing for all four types of bacteria (10/10 replicates) at each time point. With the exception of E. coli, the sensitivity of FACS and optimized Scansystem was comparable for the high inoculum. With the low inoculum, 60 percent of E. coli, 80 percent of B. cereus, 90 percent of K. pneumoniae, and 100 percent of S. aureus were NAT‐positive 12 hours after spiking. In contrast, only 20 percent of E. coli, 10 percent of B. cereus, and 70 percent of K. pneumoniae were FACS‐positive with the low inoculum 12 hours after spiking.CONCLUSIONS: In summary, the preliminary data revealed a higher sensitivity for NAT in comparison to FACS and optimized Scansystem under the defined study conditions. To imitate real‐life conditions, further spiking studies with a low inoculum (10 CFUs/bag) and slower growing organisms should be conducted to examine the sensitivity of available detection systems.