bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of postsynaptic 5‐HT1A receptors by fluoxetine despite the loss of firing‐dependent serotonergic input: Electrophysiological and neurochemical studies
Authors: Sprouse J. , Braselton J. , Reynolds L. , Clarke T. , Rollema H.
Published: August 2002

Systemic doses of fluoxetine slow dorsal raphe cell firing by blocking the reuptake carrier located in the cell body region with the surplus 5‐HT thus generated activating inhibitory autoreceptors. The concurrent actions of fluoxetine on postsynaptic receptors in raphe projection areas has not been as thoroughly investigated, although it is presumed that a reduction in cell firing should curtail these targeted effects. The goal of the present studies was to assess the degree of postsynaptic receptor activation obtained with fluoxetine and relate it to cell body autoreceptor activation and the level of extracellular 5‐HT obtained at the nerve endings. Changes in firing rates of CA3 hippocampal neurons following systemic administration of fluoxetine were used as a marker of SSRI‐dependent changes in postsynaptic 5‐HT receptor activation; monitoring of unit activity of neurons in the dorsal raphe nucleus served to gauge the degree of serotonergic input in a parallel series of animals. Estimates of the corresponding changes in terminal 5‐HT release in the CA3 region were analyzed by microdialysis. The results indicate that fluoxetine inhibits hippocampal cell firing in a dose‐dependent manner (ED50 = 4.4 mg/kg i.v.) and one sensitive to pretreatment with the 5‐HT1A antagonist WAY‐100,635. Within the same dose range, increases in hippocampal extracellular 5‐HT approaching 300% above basal levels were achieved. Both the changes in hippocampal neuronal activity and extracellular 5‐HT are evident at doses of fluoxetine in excess of that required to inhibit dorsal raphe cell firing (ED50 = 1.1 mg/kg i.v.). Taken together, these data suggest that increases in extracellular levels of 5‐HT on the order of that observed are sufficient to alter postsynaptic excitability and that this accumulation of synaptic 5‐HT and the subsequent activation of postsynaptic 5‐HT1A receptors are achievable despite loss of firing‐dependent 5‐HT release. Synapse 41:49–57, 2001. © 2001 Wiley‐Liss, Inc.
A model for deploying life‐cycle process standards in the change management of complex systems
Authors: Bendz Johan , Lawson Harold W.
Published: August 2002

A model for deploying international systems and software life‐cycle process standards within large organizations/enterprises is presented. The model defines a limited number of actor (stakeholder) categories and identifies their roles and responsibilities in respect to the change management of complex systems. While the main thrust of this paper is related to process deployment, the need for achieving balance between the system related key aspects of architecture, processes, methods and tools, organization, and competence is emphasized. Principles for the integration of systems as aggregates of entities (components, tasks, and other aggregates) are presented. An “agreement pipe” abstraction is introduced to conceptualize the flow of products and services between model actors. The importance of centralized intelligence and support functions is considered. Finally, the means of instrumentation of the model via international system and software life cycle process standards is presented and illustrated via an adaptation (tailoring) of the development process from ISO/IEC 12207. © 2001 John Wiley & Sons, Inc. Syst Eng 4: 107–117, 2001
Full dynamic analysis of Tehran telecommunication tower; linear and nonlinear responses
Authors: Khaloo A. R. , Asadpour N. , Horr A. M.
Published: August 2002

Dynamic response of large concrete tower structures with passive or active damping is important in terms of performance under dynamic loads. Structural instability mostly arises as a result of losing the energy capacity in the system, which forces the system to act as a mechanism. The purpose of this paper is to present three different finite element models to investigate the linear and nonlinear response of the Tehran telecommunication tower. The tower is ranked the fourth tallest structure in the world and has been under construction since 1997. Using a mathematical model, an efficient method is used to take into account the cracking and crushing of the reinforced concrete material as well as large deformation effects. The linear and nonlinear dynamic characteristics of the large tower may be defined by using an advanced formulation for the concrete element. Then, the proposed advanced element is used to model a full‐scale finite element mesh to derive the dynamic response of the Tehran telecommunication tower structure with use of a computer program. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of zinc and benzalkonium chloride on Nitrosomonas communis and potential nitrification in soil
Authors: Frühling W. , Rönnpagel K. , Ahlf W.
Published: August 2002

A bacterial contact assay is described which uses a chemoautotrophic microorganism, Nitrosomonas communis (strain Nm2) to evaluate the biological effect of contaminated soils. The effects of two toxicants on the ammonium oxidation activity of the autochthonous microbial population in the soil are compared with inhibition of the same biological response in the new monospecies bioassay. Experiments were performed using soil samples dosed with organic and inorganic contaminants (benzalkonium chloride and zinc) to demonstrate the mode of operation and the sensitivity of the bioassay. The EC50 values of zinc and benzalkonium chloride were calculated to be 171 and 221 mg kg−1 soil, respectively. The toxic response provided by the bioassay can thus predict the effect of soil pollutants on the autochthonous nitrifying bacteria. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 439–443, 2001
Construction of FLAG and histidine tagging vectors for Schizosaccharomyces pombe
Authors: Huang Ying , Hamada Mitsuhiro , Patel Jimit , Maraia Richard J.
Published: August 2002

Schizosaccharomyces pombe is becoming an increasingly popular model system for investigating important cellular processes. To facilitate detection, purification and functional studies of Sz. pombe gene products, we constructed two tagging expression vectors for use in Sz. pombe. These vectors allow proteins to be expressed ectopically as fusion proteins with a FLAG epitope and six histidine residue tags attached to their N‐terminus or C‐terminus. The function and applicability of these vectors were examined and the results are shown using the N‐terminal tagging vector encoding Sfc6p, a subunit of the Sz. pombe RNA polymerase III general transcription factor, TFIIIC. Copyright © 2001 John Wiley & Sons, Ltd.
14‐3‐3 Proteins are essential for regulation of RTG3‐dependent transcription in Saccharomyces cerevisiae
Authors: van Heusden G. Paul H. , Steensma H. Yde
Published: August 2002

14‐3‐3 proteins comprise a family of highly conserved proteins that bind more than 60 different, mostly phosphorylated, proteins. The yeast Saccharomyces cerevisiae has two genes, BMH1 and BMH2, encoding 14‐3‐3 proteins. Disruption of both genes together is lethal. In this study we constructed a mutant with a single, temperature‐sensitive bmh allele. Recessive mutations in SIN4 and RTG3 can suppress the temperature‐sensitive phenotype of this mutant. These genes encode a global transcriptional regulator and a basic helix–loop–helix transcription factor, respectively. The yeast 14‐3‐3 proteins were shown to bind to the Rtg3 protein. Overexpression of RTG3 is lethal even in wild‐type cells. These genetic and biochemical data are consistent with a model in which the 14‐3‐3 proteins are required to keep the Rtg3 protein in an inactive state, which is (one of) the essential function(s) of the 14‐3‐3 proteins. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of early rearing experience on adult behavior and nesting in captive Hawaiian crows (Corvus hawaiiensis)
Authors: Harvey Nancy C. , Farabaugh Susan M. , Druker Bill B.
Published: August 2002

Behavioral data were collected during the breeding season on eight pairs of Hawaiian crows (Corvus hawaiiensis) housed at two facilities on different islands. All data were collected from videocamera time‐lapse recordings of the nesting platforms. Behaviors included frequency of nest cup manipulation, percent of time spent on nest, allopreening, play, and stereotypy. The number of breeding pairs increased from four in 1996 to six in 1997, to seven in 1998, and to eight in 1999. Five of the older birds (three males and two females) were solitary‐reared for most if not all of their first year, while the remaining 12 birds were all socially reared. Significant differences were found between isolate‐ and socially‐reared birds, with isolate‐reared birds having higher rates of solo play (P = 0.0041) and stereotypies (P = 0.0090). Pairs that were comprised of at least one isolate‐reared bird engaged in significantly less allopreening (P = <0.0001) than pairs in which both birds were socially reared. From 1996 to 1999, 87 eggs were laid, with a mean of 1.88 ± 0.24 SEM eggs per clutch. Only three females produced clutches every year, and they were responsible for 85.1% of the eggs laid. Although not significant, the mean number of clutches produced per pair decreased from 2.50 ± 0.65 in 1996 to 0.87 ± 0.99 in 1999. Age of females does not appear to be a critical factor in the decrease in clutch production. New pairing combinations are under way in an effort to improve propagation in this highly endangered species. Zoo Biol 21:59–75, 2002. © 2002 Wiley‐Liss, Inc.
Remaining Small Bowel Length: Association with Catheter Sepsis in Patients Receiving Home Total Parenteral Nutrition: Evidence of Bacterial Translocation
Authors: Terra Ricardo M. , Plopper Caio , Waitzberg Dan L. , Cukier Celso , Santoro Sérgio , Martins Juliana R. , Song Rubens J. , Gama‐Rodrigues Joaquim
Published: August 2002

Patients with short bowel syndrome (SBS) receiving total parenteral nutrition (TPN) have a high incidence of catheter‐related sepsis, one of its major complications. The aim of this study was to correlate the length of remaining small bowel (RSB) with septic episodes related to the central venous catheter in a group of patients with severe SBS with home TPN. The length of the RSB (<50 cm or ≥50 cm) was related to the frequency of catheter sepsis, time until the first episode, and the agents responsible in eight SBS patients receiving home TPN. There were 13 episodes of catheter infection (0.88 per patient‐year). The group with a shorter RSB length (five patients) presented 1.3 to 2.76 infections/year and 2 to 9 months until the first episode, compared to 0 to 0.75 infections/year (p= 0.0357) and 11 to 65 months until the first episode (p= 0.0332) in the group with the longer RSB. In the first group, the agents isolated were Enterobacteriae (Enterobacter sp., Klebsiella sp., Pseudomonas sp., and Proteus sp.) in eight episodes and Candida sp. in one. In the latter sepsis was caused by Staphylococcus sp. in three episodes and Pseudomonas sp. in one. Therefore patients with remaining small bowel shorter than 50 cm have a higher frequency of catheter‐related sepsis, particularly by enteric microorganisms. This might be an evidence of the occurrence of bacterial translocation and its role in the pathogenesis of catheter‐related sepsis in patients with an extremely short RSB receiving home TPN.
Changes in Venous Hemodynamics after Superficial Vein Surgery for Mixed Superficial and Deep Venous Insufficiency
Authors: Ting Albert C.W. , Cheng Stephen W.K. , Wu Lisa L.H. , Cheung Grace C.Y.
Published: August 2002

The purpose of this study was to determine the hemodynamic changes after superficial vein surgery in patients with mixed superficial and deep venous insufficiency (MVI). Between July 1996 and June 1998, all patients with MVI together with saphenofemoral reflux were evaluated prospectively with air plethysmography (APG) and duplex scanning before and 1 month after superficial vein surgery. Saphenofemoral flush ligation without stripping was performed with multiple small incisions for avulsion of varicosities. Seventy‐eight patients with 102 operated limbs were included for analysis. The venous filling index (VFI), ejection fraction (EF), and residual volume fraction (RVF) improved significantly after superficial vein surgery (mean VFI 5.99 ± 3.39 vs. 1.82 ± 1.21 ml/s, p < 0.001; mean EF 48.39% ± 11.74% vs. 52.78% ± 14.33%, p < 0.05; mean RVF 49.80% ± 11.18% vs. 36.19% ± 12.98%, p < 0.001, respectively, before and after operation). The proportion of limbs with deep venous incompetence on duplex scanning at more than one site decreased from 70% to 44% after operation. The mean number of sites with deep venous incompetence decreased from 2.14 ± 0.96 to 1.52 ± 1.21 after operation (p < 0.001). In conclusion, superficial vein surgery resulted in significant improvement in hemodynamic parameters in limbs with MVI. There was also abolition of deep venous reflux after superficial vein surgery alone. Superficial vein surgery should be the first line of treatment in limbs with MVI, with deep vein reconstructive surgery reserved for those not responding to superficial vein surgery.
Correlation between Graft‐Versus‐Host Induced Immunosuppression and Host Natural Killer Cell Activity in Small Bowel Transplantation
Authors: Fändrich Fred , Schröder Jörg , Exner Beate , Papachrysanthou Athanasios , Peters Jochen , Chambers William , Zavazava Nicholas
Published: August 2002

The occurrence of graft‐versus‐host disease (GvHD) following small bowel transplantation (SBTx) can be tuned by the recipient’s initial natural killer (NK) cell activity, which modifies the immunogeneic balance between donor and host immunocompetent cells. This study was aimed to investigate the role of host NK cells on the incidence and severity of GvHD following SBTx. Intraperitoneal administration of 50 μl ascites fluid of the highly specific anti‐NKR‐P1 monoclonal antibody (mAb) 3.2.3 into F1 recipient animals on three consecutive days prior to SBTx was performed to suppress NK activity in F1 hybrids. In vivo treatment with 3.2.3 mAb effectively depleted recipient NK activitiy for at least 10 days in spleens and mesenteric lymph nodes of F1 hosts. In contrast to nontreated F1 recipients, all 3.2.3 mAb‐pretreated F1 animals suffered from severe signs of GvHD, and the mean survival time was decreased significantly from 16.0 ± 0.9 days to 11.0 ± 0.8 days (p< 0.01) in nontreated and NKR‐P1‐depleted F1 animals, respectively. Other sequelae included earlier onset of GvH manifestations, pronounced damage of primary and secondary lymphatic organs, substantial increase in spleen index, and lower CD4+/CD8+ratios over the course of progressing GvHD. Our results underline the important immunoregulatory role of NK cells as a first defensive line acting on the alloreactivity of donor‐derived immunocompetent cells in this model of solid organ transplantation.
Transthoracic Transdiaphragmatic Approach for Hepatectomy of Couinaud’s Segments VII and VIII
Authors: Ko Saiho , Nakajima Yoshiyuki , Kanehiro Hiromichi , Aomatsu Yukio , Yoshimura Atsushi , Taki Junichiro , Kin Tatsuya , Yagura Kazuaki , Ohashi Kazuo , Nakano Hiroshige
Published: August 2002

For hepatectomy of Couinaud’s segment VII or VIII, severe compression and mobilization of the liver is required to establish the operative field via the usual transabdominal approach. Compression of the cirrhotic liver impairs hepatic and systemic blood circulation, which may cause liver dysfunction. We adopted a transthoracic transdiaphragmatic approach for hepatectomy of segment VII or VIII in cirrhotic patients to establish a good operative field without compressing the liver. The aim of this study was to evaluate the benefits of this approach. Forty‐four patients with hepatocellular carcinoma (HCC) complicating liver cirrhosis who underwent limited hepatectomy of Couinaud’s segment VII or VIII were studied. The patients were randomized to two groups preoperatively: group I (n= 22), transabdominal approach; group II (n= 22), transthoracic transdiaphragmatic approach. There were no differences in preoperative liver function tests, hepatic functional reserve, or extent of tumor between the two groups. The operative time in group II was significantly shorter than that in group I (243 ± 50 versus 313 ± 80 minutes;p< 0.01). Operative blood loss in group II was also significantly smaller than that in group I (1190 ± 1098 versus 2679 ± 2267 g;p< 0.01). Serum lactate dehydrogenase levels on postoperative day 1 in group II were significantly lower than those in group I (587 ± 154 versus 791 ± 383 IU/L;p< 0.05). Major postoperative complications were significantly fewer in group II. It was concluded that the transthoracic transdiaphragmatic approach is a useful method for hepatectomy of segments VII and VIII in cirrhotic patients.
Intrahepatic Cholangiocarcinoma
Authors: Chu Kent‐Man , Lai Edward C.S. , Al‐Hadeedi Sabah , Arcilla Crisostomo E. , Lo Chung‐Mau , Liu Chi‐Leung , Fan Sheung‐Tat , Wong John
Published: August 2002

Intrahepatic cholangiocarcinoma is an uncommon neoplasm of liver compared with hepatocellular carcinoma. Hepatic resection seems to provide the only chance for therapeutic success. The records of 77 patients with intrahepatic cholangiocarcinoma treated over a 28‐year period were studied to determine demographics, clinical features, laboratory findings, diagnostic tests, operative management, and results of therapy. Survival was analyzed according to three treatment groups: conservative management, palliative operation, and hepatic resection. Conservative management was used for 15 patients, and hepatic resections were performed in 39 patients. The remaining 23 patients had laparotomy alone (10 patients), bile duct intubation (4 patients), hepatic artery ligation (3 patients), bilienteric bypass (3 patients), gastrojejunostomy (1 patient), insertion of a hepatic artery port for regional chemotherapy (1 patient), or open drainage of an abscess (1 patient). The median survival after conservative management, palliative operation, and hepatic resection were 1.8, 2.9, and, 12.2 months, respectively. After hepatic resection, patients without lymphatic permeation (p< 0.02) or hilar nodal metastases (p< 0.0003) survived significantly longer. We concluded that hepatic resection is indicated for intrahepatic cholangiocarcinoma when it is deemed resectable.
Recent Advances in Molecular Genetics of Colorectal Cancer
Authors: Baba Shozo
Published: August 2002

Advances in molecular biology have identified two important genes responsible for the hereditary colorectal cancers familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer. They are the APC gene and mismatch repair genes. The role of these genes in colorectal carcinogenesis has been studied intensively. The adenoma–carcinoma sequence was initially proposed by Vogelstein, and the multistep carcinogenesis theory is now well accepted. The various functions of the APC gene have been elucidated. APC genes are considered to play a role in shedding of the epithelial cells into the lumen. The mechanism behind formation of a unicryptal adenoma is now better understood. Adenoma formation is a monoclonal event with two hits of the APCgene. There is no zonal extension of the proliferative zone in the background colonic mucosa of FAP patients. In addition to the adenoma–carcinoma sequence, there seem to be various carcinogenetic pathways in the development of colorectal cancer. A depressed type of early cancer was recently found by the use of magnifying endoscopy. The incidence of K‐ras mutation was extremely low in this group of early cancers. Some of the minute cancers show the p53mutation before the occurrence of APC mutation. Cancers of microsatellite mutator phenotype show exaggerated genomic instability at simple repeat sequences, such as TGFβRII. These genes may play a suppressor role in a p53 independent pathway of colorectal carcinogenesis. We are now in an exciting era of this progressing field of science. This genetic information may be more widely applicable clinically in the near future (e.g., for presymptomatic diagnosis, selection of patients for the most appropriate treatments, and assessment of malignant potential).
Expression of CD44 Variant 6 and Lymphatic Invasion: Importance to Lymph Node Metastasis in Gastric Cancer
Authors: Kurozumi Kazushi , Nishida Toshirou , Nakao Kazuyasu , Nakahara Masaaki , Tsujimoto Masahiko
Published: August 2002

Lymph node metastasis is a critical prognostic factor for gastric cancer. In the present investigation we examined clinicopathologic factors influencing the metastatic processes to the lymph node and their prognostic importance. A randomly selected group of 98 patients with adenocarcinomas of the stomach who underwent gastrectomy plus systematic lymph node dissection at Osaka Police Hospital from 1991 to 1996 were analyzed. Altogether 37 (38%) cancers were positive for CD44 variant 6 (v6) staining, 31 (32%) were intermediately stained, and 30 (30%) were negative. CD44‐v6 expression correlated well with lymph node metastasis. Expression of CD44‐v6 and lymphatic invasion were independent risk factors for metastatic lymph nodes. Among the patients with CD44‐v6‐positive and lymphatic invasion‐positive cancers, 88% had lymph node metastasis, whereas only 13% of patients negative for both factors had lymph node metastasis. Although CD44‐v6 expression and lymphatic invasion have been reported to be risk factors for recurrence and a poor prognosis, in this investigation these factors were found not to be significant for hematogenous and lymphatic recurrences or overall survival rates. Thus expression of CD44‐v6 and lymphatic invasion may regulate lymph node metastases from gastric cancer.
Development and Progress in Resective Surgery for Pancreatic Cancer
Authors: Howard John M.
Published: August 2002

Pancreatoduodenectomy was developed from experience gained with transduodenal ampullectomy, preceded by a relatively bloodless cholecystoenterostomy. Although Codivilla (1898) and Kausch (1909) each achieved a single survivor following pancreatoduodenectomy, further development of the operation had to await discovery of vitamin K and a description of human blood types, the latter leading to the development of blood banks. After vitamin K and blood banks became available, Allen O. Whipple and his resident C.R. Mullins developed the two‐stage pancreatoduodenectomy (1934–1935) and Whipple the one‐stage procedure (1940). Although the mortality rate from pancreatoduodenectomy remained approximately 33% for more than 25 after Whipple's reports, concentration of resection in “centers of specialization” has now reduced mortality rates below 5%. Thus operative survival has been achieved, but long‐term survival has not kept pace. Long‐term data remain inadequate because they are usually expressed as Kaplan‐Meier estimates and because of the nonuniformity of reporting (e.g., exclusion of postoperative deaths and palliative resections, intraoperative adjuvant therapies, and variations of operative techniques). Widely based Kaplan‐Meier estimates of 5‐year survival range from 12% to 15% after resection and more than 20% in selected categories. Total pancreatectomy has not improved short‐ or long‐term survival rates. Extended lymphadenectomy and resection of peripancreatic soft tissues, as currently developed in several surgical clinics in Japan, suggest a higher incidence of complications but perhaps more long‐term survivors. Interpretation of their data is currently subject to the same limitations noted above. As our surgical forebears needed vitamin K and blood banks to achieve postresection survival, we and our students need effective adjuvant therapy of micrometastases and better modalities for early diagnosis to improve long‐term survival.
Computer Simulation of Hypothermia during “Damage Control” Laparotomy
Authors: Hirshberg Asher , Sheffer Nadav , Barnea Ofer
Published: August 2002

“Damage control” is a surgical strategy for the staged repair of severe trauma that aims to avoid an irreversible physiologic insult marked by a self‐propagating combination of hypothermia, coagulopathy, and acidosis. The point beyond which the physiologic insult becomes irreversible, however, remains ill‐defined. The aim of this study was to address this problem by means of a dynamic computer model of heat loss during laparotomy for exsanguinating hemorrhage. A single compartment model was developed using a graphic modeling tool and was implemented to calculate the time interval from the beginning of laparotomy to a core temperature of 32°C, which is a marker of irreversible physiologic derangement in injured patients. A series of simulation runs showed that the exposed peritoneum is the dominant factor contributing to heat loss; the bleeding rate has a less marked effect. Elevation of the ambient temperature and rapid abdominal closure are effective interventions available to the surgeon to modify the heat loss curve. This study shows that during a “damage control” laparotomy for exanguinating hemorrhage the window of opportunity for salvage before the onset of an irreversible physiologic insult is no longer than 60 to 90 minutes.
Activation of Monocytes and Endothelial Cells Depends on the Severity of Surgical Stress
Authors: Aosasa Suefumi , Ono Satoshi , Mochizuki Hidetaka , Tsujimoto Hironori , Osada Shun‐ichi , Takayama Eiji , Seki Shuhji , Hiraide Hoshio
Published: August 2002

Surgical injury not only induces a systemic endocrine‐metabolic response but also influences the function of the leukocytes and endothelial cells leading to various systemic responses. These responses appear to depend on the severity of surgical stress, which differs according to the surgical procedures. In this study, we investigated the response of monocytes and endothelial cells, and the development of systemic inflammatory response syndrome (SIRS) in relation to the severity of surgical stress. The postoperative clinical course was evaluated between patients undergoing an esophagectomy (ER group) and a distal gastrectomy (DG group). The tumor necrosis factor α (TNFα) production of monocytes, the serum interleukin 6 (IL‐6) levels, the CD11b expression on either monocytes or granulocytes, and the intercellular adhesion molecule‐1 (ICAM‐1) expression on human umbilical vein endothelial cells (HUVECs) stimulated with culture supernatants of monocytes were compared between the 2 groups. The development of SIRS was observed in all patients in the ER group, whereas no patients demonstrated SIRS in the DG group. The serum IL‐6 levels, TNFα production of monocytes, and CD11b intensity on monocytes or granulocytes in the ER group were higher than those in the DG group. In the ER group, the ICAM‐1 intensity on HUVECs with monocytes immediately after operation significantly increased compared with before the operation. In conclusion, both the CD11b expression on monocytes and the TNFα production of monocytes are considered to reflect the degree of surgical stress, and the activation of endothelial cells stimulated with these activated leukocytes may therefore lead to both tissue and organ injury.
Angiographic Embolization for Intraperitoneal and Retroperitoneal Injuries
Authors: Velmahos George C. , Chahwan Santiago , Falabella Andres , Hanks Sue Ellen , Demetriades Demetrios
Published: August 2002

Angiographic embolization (AE) has been used extensively for bleeding control after injuries to the face and neck. Its role in abdominal trauma requires further exploration. We reviewed the medical records of 137 consecutive patients who underwent angiography with the intent to embolize bleeding sites within the abdomen. Of them, 97 (71%) had blunt and 40 (29%) had penetrating trauma. AE was performed for hemorrhage associated with pelvic fractures (97 patients), liver lacerations (n= 26), renal lacerations (n= 12), splenic lacerations (n= 5), other injuries (n= 9), and multiple injuries (n= 12). On angiography, 102 patients were found to have bleeding sites and underwent AE, with angiographic and clinical bleeding control in 93 (91%). The rate of successful hemostasis by AE was identical in blunt and penetrating trauma patients. There was no major morbidity after AE. No factors predicted patients with a high likelihood to have a positive angiogram. Patients who had AE before or after a period of attempted hemodynamic stabilization in the intensive care unit were no different with respect to hemodynamic parameters immediately before AE or effectiveness of AE for bleeding control. AE is a safe and effective method for controlling bleeding after blunt and penetrating intra‐ and retroperitoneal injuries. Early AE may be used in selected patients as a front‐line therapeutic intervention that offers expeditious hemostasis and prevents delays in definitive bleeding control.
Woodchuck hepatocytes remain permissive for hepadnavirus infection and mouse liver repopulation after cryopreservation
Authors: Dandri Maura , Burda Martin R. , Gocht Andreas , Török Eva , Pollok Jörg M. , Rogler Charles E. , Will Hans , Petersen Jörg
Published: August 2002

Isolated hepatocytes represent a relevant model of the liver and are highly required both for research and therapeutic applications. However, sources of primary liver cells from human beings and from some animal species are limited. Therefore, cryopreservation of hepatocytes could greatly facilitate advances in various research areas. The aim of this study was to evaluate whether cryopreserved primary woodchuck hepatocytes could be used for woodchuck hepatitis B virus (WHV) infection studies, and whether they could maintain their regenerative potential in vivo after thawing. Critical steps for good quality of cryopreserved hepatocytes included the use of University of Wisconsin (UW) solution as a main component of the freezing medium, stepwise reduction of dimethylsulfoxide (DMSO) to avoid osmotic shock, and maintenance of low concentrations of DMSO in the culture medium. After cryopreservation, cell viability was still high (70% to 80%), and 50% to 60% of thawed cells attached to the plates. The appearance of covalently closed circular (ccc)DNA and of WHV-replicative forms a few days after in vitro infection demonstrated that thawed woodchuck hepatocytes were still susceptible to viral infection, thus proving maintenance of a very high hepatocyte-specific differentiation status. Furthermore, transplantation of woodchuck hepatocytes into the liver of urokinase-type plasminogen activator (uPA)/recombination activation gene-2 (RAG-2) mice, a model of liver regeneration, demonstrated that cryopreserved cells retained the ability to divide and to extensively repopulate a xenogenic liver. Notably, in vivo susceptibility to infection with WHV and proliferative capacity of frozen/thawed woodchuck hepatocytes in recipient mice were identical to those observed by transplanting fresh hepatocytes.
Intermittent ischemia reduces warm hypoxia-reoxygenation-induced JNK1/SAPK1 activation and apoptosis in rat hepatocytes
Authors: Crenesse Dominique , Laurens Marina , Gugenheim Jean , Heurteaux Catherine , Cursio Raffaele , Rossi Bernard , Schmid-Alliana Annie
Published: August 2002

Prolonged liver ischemia followed by reperfusion (I/R) causes functional and structural damage to liver cells, resulting in necrosis and apoptosis. c-jun N-terminal kinase 1/stress-activated protein kinase 1 (JNK1/SAPK1) is activated during I/R and participates in the onset of the apoptosis program. Excessive blood loss during surgery can hinder postoperative recovery. Intermittent portal triad clamping (PTC) is better tolerated than prolonged continuous ischemia. This study was designed to demonstrate that intermittent ischemia could improve postischemic survival rates by a decrease of JNK1/SAPK1 and caspase 3 activation, which were involved in the apoptosis process. Rats were subjected to intermittent 1-hour ischemia (15-minute ischemia/5-minute reperfusion, 4 times), followed by 220-minute reperfusion, or to continuous ischemia (1 hour), followed by 240-minute reperfusion. Mortality rates were assessed on day 7. Serum aspartate transaminase (AST), alanine transaminase (ALT), and lactate deshydrogenase levels (LDH) were measured 6 hours after ischemia. This study was completed in primary cultured isolated rat hepatocytes, subjected to the same continuous or intermittent hypoxic conditions. The activation status of JNK1/SAPK1 was evaluated by immunoprecipitation or Western blotting experiments. Apoptosis was assessed by measuring caspase activation and by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) reaction. Eighty percent of the intermittent-ischemia group was alive 7 days after surgery and serum enzyme levels were significantly decreased. Intermittent hypoxia or ischemia did not lead to JNK1/SAPK1 activation, but at least 3 hypoxia-reoxygenation (H/R) sets were necessary to inhibit kinase activation. Consequently, caspase 3 activation and apoptosis were dramatically reduced. Intermittent ischemia is a powerful, protective way to reduce I/R damage of the liver, by reduction of JNK1/SAPK1 activation associated with a down-regulation of caspase 3 activity, which leads to inhibition of hepatocyte apoptosis.
Outcome of liver transplantation in patients with diabetes mellitus: A case-control study
Authors: John Preeti R. , Thuluvath Paul J.
Published: August 2002

The influence of preexisting diabetes mellitus (DM) on outcome after orthotopic liver transplantation (OLT) has not been well defined. The objective of our study was to compare the morbidity and mortality after OLT in 57 patients with preexisting DM (3 type I, 54 type II) with 114 age-, sex-, and race-matched patients without DM (case controls). The demographics were similar in both groups. Pretransplantation serum creatinine was significantly higher in the diabetic group compared with case controls. The incidence of the following complications was significantly higher in the diabetic group after OLT: cardiovascular (61.4% vs. 21.9%, P < .001), major (54.4% vs. 29.8%, P = .002) and minor infections (29.8% vs. 7.9%, P < .0001), renal (59.7% vs. 20.2%, P < .001), ophthalmologic (10.5% vs. 0.9%, P = .01), respiratory (24.6% vs. 7.0%, P = .001), neurologic (31.6% vs. 7.0%, P < .001), hematologic (19.3% vss 2.6%, P = .001), musculoskeletal (24.6% vs. 5.3%, P = .001), and malignancy (22.8% vs. 10.5%, P = .03). The duration of hospital stay, cost of hospitalization, retransplantation, and overall graft survival were similar. Acute rejection was seen in 50.9% of diabetics compared with 25.4% in controls (P = .0009). One-year (87% vs. 77%) and 2-year (81.6% vs. 70.1%) patient survival was similar, but 5-year survival was lower in the DM group (34.4% vs. 67.7%, P = .002). In conclusion, preexisting diabetes is associated with a significant post-OLT morbidity and mortality, and our observations suggest that patients with DM warrant more rigorous pre- and post-OLT evaluation.
High frequency of epithelial chimerism in liver transplants demonstrated by microdissection and STR-analysis
Authors: Kleeberger Wolfram , Rothämel Thomas , Glöckner Sabine , Flemming Peer , Lehmann Ulrich , Kreipe Hans
Published: August 2002

It has recently been shown that epithelial cells derived from stem cells originating outside the liver are integrated into liver allografts. Whether epithelial intragraft chimerism protects transplants from rejection or chronic transplant dysfunction, and whether it interferes with recurrence of primary liver disease, is not known. Twenty-seven sequential biopsies derived from 9 liver-transplant recipients were studied for chimerism of hepatocytes and cholangiocytes. The target cells were isolated by laser microdissection after cytokeratin immunolabeling and genotyped using DNA analysis of a highly polymorphic short tandem repeat. Irrespective of whether early (up to 4 weeks) or late (more than 12 months) posttransplantation biopsies were studied, cholangiocyte chimerism was almost constantly found in 91% of the samples. No significant differences occurred between samples derived from patients with chronic organ dysfunction (n = 3), recurrent hepatitis (n = 3), or mild, unspecific changes (n = 3). By contrast, hepatocyte chimerism tended to occur later (55% vs. 22%) and appeared to be associated with recurrent hepatitis (67% vs. 27%). In this respect, chronic organ dysfunction did not differ from mild, unspecific changes. While cholangiocyte chimerism represents a constant and early phenomenon in liver transplantations, an enhanced chimeric integration of recipient-derived hepatocytes can be observed in recurrent hepatitis, supporting the concept of an increased recruitment of extrahepatic progenitor cells to the liver in chronic hepatitis.
Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: Further evidence for an etiologic association
Authors: Pagano Gianfranco , Pacini Giovanni , Musso Giovanni , Gambino Roberto , Mecca Fabio , Depetris Nadia , Cassader Maurizio , David Ezio , Cavallo-Perin Paolo , Rizzetto Mario
Published: August 2002

This study aims to determine the presence of the components of the metabolic syndrome in primary nonalcoholic steatohepatitis (NASH) and to assess the role of liver disease in the genesis of peripheral hyperinsulinemia. Nineteen patients (18 men and 1 woman; mean age, ± SD, 38 ± 10 years; body mass index [BMI], 26 ± 2 kg/m2) with histologic evidence of NASH were enrolled; 19 age- and sex-matched normal subjects were investigated as controls. Plasma glucose, insulin, and C-peptide levels were measured during an oral glucose tolerance test, and a frequently sampled intravenous glucose tolerance test (FSIGT), analyzed by minimal modeling technique, was performed. Compared with controls, the NASH group had lower insulin sensitivity (3.84 ± 2.44 vs. 7.48 ± 3.01 10−4 × min−1/μU/mL; P = .0003) and higher total insulin secretion (21 ± 13 vs. 10 ± 3 nmol/L in 240 minutes; P = .001). Hepatic insulin extraction was similar in both groups (69.8% ± 16.1% vs. 70.2% ± 18.3%; P = .854). According to the results of the oral glucose tolerance test, no patient was classified as diabetic, 5 were classified as glucose intolerant, and 1 was classified as having impaired fasting glycemia. Nine patients (47%) had at least the 2 minimum criteria required to define the metabolic syndrome according to the European Group for the Study of Insulin Resistance (EGIR). In conclusion, hyperinsulinemia and insulin resistance occur frequently in patients with NASH; these conditions do not stem from a reduced hepatic insulin extraction but from an enhanced pancreatic insulin secretion compensatory to reduced insulin sensitivity. The derangement of insulin regulation, often associated with the metabolic syndrome, may play a causal role in the pathogenesis of NASH.
Primary biliary cirrhosis with additional features of autoimmune hepatitis: Response to therapy with ursodeoxycholic acid
Authors: Joshi Supriya , Cauch-Dudek Karen , Wanless Ian R. , Lindor Keith D. , Jorgensen Roberta , Batts Kenneth , Heathcote Jenny E.
Published: August 2002

Patients with primary biliary cirrhosis (PBC) may have additional features of autoimmune hepatitis (AIH). Corticosteroids usually contraindicated in PBC have been advocated for these patients. Patients with antimitochondrial antibody (AMA)-positive PBC from two previous randomized, controlled trials were assessed for features of AIH. Their biochemical, immunologic, and histologic responses to ursodeoxycholic acid (UDCA) versus placebo were compared with those without AIH features. The survival of patients testing positive or negative for antinuclear antibodies (ANA) was also examined. Features of AIH were defined by the presence of 2 or more of the following: 1) alanine transaminase (ALT) > 5× the upper limit of normal (ULN); 2) immunoglobulin G (IgG) > 2× ULN or positive anti-smooth muscle antibody (ASMA); and 3) moderate to severe lobular inflammation on pretreatment liver biopsy. Testing for AMA, ASMA, and ANA was done by immunofluorescence. The change in serum bilirubin, alkaline phosphatase (ALP), transaminases, IgM, and IgG from baseline to 2 years was compared. Of the 331 patients randomized, 16 (4.8%) had features of AIH (12 UDCA, 4 placebo). The median percent change in serum biochemistry and immunoglobulin values were similar in patients with PBC ± features of AIH after 2 years of therapy with UDCA. Over 2 years, little change in histologic features of AIH was observed. Survival was similar for patients with PBC with and without ANA. In conclusion, features of AIH in PBC may be transient and response to UDCA therapy similar to patients with PBC without features of AIH.
Derivation, characterization, and phenotypic variation of hepatic progenitor cell lines isolated from adult rats
Authors: Yin Li , Sun Mingzeng , Ilic Zoran , Leffert Hyam L. , Sell Stewart
Published: August 2002

Liver progenitor cells (LPCs) cloned from adult rat livers following allyl alcohol injury express hematopoietic stem cell and early hepatic lineage markers when cultured on feeder layers; under these conditions, neither mature hepatocyte nor bile duct, Ito, stellate, Kupffer cell, or macrophage markers are detected. These phenotypes have remained stable without aneuploidy or morphological transformation after more than 100 population doublings. When cultured without feeder layers, the early lineage markers disappear, and mature hepatocyte markers are expressed; mature hepatocytic differentiation and cell size are also augmented by polypeptide and steroidal growth factors. In contrast to hepatocytic potential, duct-like structures and biliary epithelial markers are expressed on Matrigel. Because they were derived without carcinogens or mutagens, these bipotential LPC lines provide novel tools for models of cellular plasticity and hepatocarcinogenesis, as well as lines for use in cellular transplantation, gene therapy, and bioreactor construction.
α-Fetoprotein mRNA in the circulation as a predictor of postsurgical recurrence of hepatocellular carcinoma: A prospective study
Authors: Ijichi Masayoshi , Takayama Tadatoshi , Matsumura Masayuki , Shiratori Yasushi , Omata Masao , Makuuchi Masatoshi
Published: August 2002

α-fetoprotein (AFP) messenger RNA (mRNA) has been proposed as a marker of hepatocellular carcinoma (HCC) cells disseminated into the circulation, but its clinical significance remains controversial. We prospectively assessed the prognostic value of AFP mRNA in patients undergoing curative hepatic resection for HCC. Peripheral blood samples were taken from 87 patients before and after surgery to determine the presence of AFP mRNA by use of a reverse-transcription polymerase chain reaction. A primary endpoint was recurrence-free interval. AFP mRNA was detectable preoperatively in 31 patients (36%) and postoperatively in 30 patients (34%). With a median follow-up period of 28 months (range, 3-41 months), HCC recurred in 46 patients (53%). Among 4 groups separated according to preoperative and postoperative AFP mRNA status, patients with consistent positivity of AFP mRNA showed the highest recurrence rate (85%) and trend to distant or multiple recurrence. The recurrence-free interval was significantly shorter in patients with postoperative positivity of AFP mRNA than in those without (53% [95% CI, 36-71] vs. 88% [95% CI, 79-96] at 1 year, 37% [95% CI, 17-57] vs. 60% [95% CI, 46-75] at 2 years; P = .014), whereas the preoperative positivity of AFP mRNA provided no significance (P = .100). Cox's proportional-hazards model identified the postoperative positivity of AFP mRNA as an independent prognostic factor for HCC recurrence (relative risk, 2.33; 95% CI, 1.26-4.34; P = .007). In conclusion, postsurgical recurrence of HCC can be predicted by detecting AFP mRNA-expressing cells in peripheral blood.
Interparticle sliding in the presence of adhesion
Authors: C Thornton
Published: August 2002

Contact mechanics theories for the normal and tangential interactions between two non-adhering elastic spheres are well established and the tangential sliding criterion is given by Amontons' law. For micron-sized particles, however, surface adhesion effects due to van der Waals forces become significant. Theories to describe the particle interactions in the presence of adhesion have been developed but a rigorous analytical solution is intractable since the stress distribution in the spheres depends on the surface interaction which depends on the exact shape of the deformed surfaces and that is only known if the stress distribution is known. Accepting the approximate nature of existing analytical solutions, the authors have re-examined the tangential behaviour and conclude that, in the presence of adhesion, the contact must 'peel' before sliding can occur. This leads to a new sliding criterion which shows encouraging agreement with experimental results, even for negative normal loads.
Moving loads on an infinite plate strip of constant thickness
Authors: M A Elattary
Published: August 2002

The dynamic response of an infinite plate under an arbitrarily distributed transverse-moving load is treated within the framework of three-dimensional elasticity theory. A closed-form solution in terms of elementary functions is obtained for each harmonic component of the load by the Fourier transform method in conjunction with contour integration. Dispersion relations are presented and frequencies for modes of free vibration which are symmetric and antisymmetric are discussed in detail.
The effect of specimen dimensions on high strain rate compression measurements of copper
Authors: D A Gorham
Published: August 2002

The flow stress of many metals is known to vary more strongly with strain rate epsilon above a critical value epsiloncthan below it. An analysis of previous authors' measurements on copper indicates that the value of epsiloncvaries systematically with specimen size. An estimate of inertial stress shows that inertia may be an important mechanism behind this observation. Qualitative arguments suggest that deformation velocity, friction and wave propagation could also contribute.
The classification of rough surfce contacts in relation to tribology
Authors: C Y Poon  , R S Sayles
Published: August 2002

Height and wavelength parameters of surface roughness are varied to show that three types of surface contact can exist in relation to tribology. These are (i) predominantly plastic asperity contact with gaps in the contact interface, (ii) the same contact geometry but with predominantly elastic asperity contact and (iii) almost total surface contact under an elastic state of stress (this state approaches the theoretical smooth surface conditions). These contact states are confirmed by rough surface contact techniques of a ball-on-flat geometry. Results from simple boundary-lubricated sliding tests are also presented to show that the frictional and tribological behaviour differs significantly for each of these contact states. The fundamental implications for tribology are discussed in relation to this work.
On the relationship between the modulus of particulate media and the surface energy of the constituent particles
Authors: C Thornton
Published: August 2002

Considers the mathematical formulation for the macroscopic elastic properties of particulate media in terms of the distribution of the stiffnesses at the contacts between the constituent particles. Both random and regular arrays are considered. If the particles are sufficiently small the analysis leads to a relationship between the ensemble modulus and the surface energy of the solid particles. It has been previously suggested that, for random isotropic assemblies of spheres, this relationship could be predicted by a simple density scaling rule based on the solution for a simple cubic packing. The paper re-examines this analysis and identifies an inconsistency in the definition of the contact stiffness. An alternative analysis is also presented which is based on the solution for a body centred cubic packing. The new analysis suggests that the original theory overestimates the ensemble modulus and underpredicts the surface energy of the solid particles.