bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of end4+, a gene required for endocytosis in Schizosaccharomyces pombe
Authors: Iwaki Tomoko , Tanaka Naotaka , Takagi Hiroshi , Giga‐Hama Yuko , Takegawa Kaoru 
Published: August 2004

AbstractTo understand endocytic trafficking in Schizosaccharomyces pombe, we constructed an end4 disruption mutant. The end4+ gene encodes a protein homologous to Sla2p/End4p, which is essential for the assembly and function of the cytoskeleton and endocytosis in Saccharomyces cerevisiae. We characterized the fission yeast mutant end4Δ as well as ypt7Δ, which is deficient in vacuolar fusion and, hence, endocytosis. The delivery of FM4‐64 to the vacuolar membrane, accumulation of Lucifer yellow CH and internalization of plasma membrane protein Map3–GFP were inhibited in the end4 mutant. Deletion of end4 resulted in pleiotropic phenotypes consistent with F‐actin depolarization, including high temperature sensitivity, abnormal morphology and mating defects. Extensive missorting of carboxypeptidase Y was detected in the ypt7 mutant; however, little missorting was detected in the end4 mutant. These results indicate that End4p is essential for the internalization process and Ypt7p affects endocytosis at a post‐internalization step after the intersection of the endocytic and the vacuolar protein‐sorting pathways in fission yeast. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of Candida albicans orthologue of the Saccharomyces cerevisiae signal‐peptidase‐subunit encoding gene SPC3
Authors: De la Rosa José M. , González José M. , Gutiérrez Fernando , Ruíz Teresa , Rodríguez Luis 
Published: August 2004

AbstractThe Candida albicans orthologue of the SPC3 gene, which encodes one of the subunits essential for the activity of the signal peptidase complex in Saccharomyces cerevisiae, was isolated by complementation of a thermosensitive mutation in the S. cerevisiae SEC61 gene. The cloned gene (CaSPC3) encodes a putative protein of 192 amino acids that contains one potential membrane‐spanning region and shares significant homology with the corresponding products from mammalian (Spc22/23p) and yeast (Spc3p) cells. CaSPC3 is essential for cell viability, since a hemizygous strain containing a single copy of CaSPC3 under control of the methionine‐repressible MET3 promoter did not grow in the presence of methionine and cysteine. The cloned gene could rescue the phenotype associated with a spc3 mutation in S. cerevisiae, indicating that it is the true C. albicans orthologue of SPC3. However, in contrast with results previously described for its S. cerevisiae orthologue, CaSPC3 was not able to complement the thermosensitive growth associated with a mutation in the SEC11 gene. The heterologous complementation of the sec61 mutant suggests that Spc3p could play a role in the interaction that it is known to occur between the translocon (Sec61 complex) and the signal peptidase complex, at the endoplasmic reticulum membrane. Copyright © 2004 John Wiley & Sons, Ltd.
Novel Operative Technique for Vagal Nerve‐ and Pyloric Sphincter‐preserving Distal Gastrectomy Reconstructed by Interposition of a 5 cm Jejunal J Pouch with a 3 cm Jejunal Conduit for Early Gastric Cancer and Postoperative Quality of Life 5 Years after Operation
Authors: Tomita Ryouichi , Tanjoh Katsuhisa , Fujisaki Shigeru 
Published: August 2004

AbstractThe importance of the vagal nerve and pyloric sphincter, the need for pouch reconstruction, and the ideal pouch volume are all matters of controversy. A novel operative technique for vagal nerve‐ and pyloric sphincter‐preserving distal gastrectomy reconstructed by interposition of a 5 cm jejunal J pouch with a 3 cm jejunal conduit was developed as a function‐preserving surgical technique to prevent postgastrectomy disorders. The application criteria and technique are outlined in this article. Postoperative quality of life was also investigated clinically. Twenty subjects who underwent this surgical operation (group A: 16 men and 4 women aged 41 to 70 years, mean age 59.5 years) were interviewed to inquire about postoperative gastrointestinal symptoms. These patients were compared with 44 others who underwent conventional distal gastrectomy with D2 lymphadenectomy (group B: 30 men and 14 women aged 43 to 73 years, mean age 62.6 years). Included were patients with early cancer [mucosal or submucosal 1 (SM1) cancer and no lymph node metastasis (N0)] in the middle or lower third of stomach (or both) who were either not eligible for endoscopic excision of gastric mucosa or for partial gastric excision in the mucosa = 3.5 cm or SM1 5.5 cm, or further in distance from the anal margin of the cancer to the pyloric sphincter. Cases in which the remnant stomach would become one‐third or less of the original size were also applied. During excision with lymph nodes, the hepatic and celiac branches bifurcating from the anterior and posterior trunks of the vagal nerve were preserved. The antrum was severed 1.5 cm from the pyloric sphincter, preserving the arteria supraduodenalis. The substitute stomach was created as a 5 cm jejunal pouch with a 3 cm jejunal conduit for orthodromic peristaltic movement using an automatic suture instrument to complete a side‐to‐side anastomosis of the folded jejunum. The anal side of the gastric remnant was manually anastomosed with the jejunal J pouch, and anastomosis of the pyloric antrum with the jejunal conduit was manually completed by stratum anastomosis. Postoperatively, the procedure in group A alleviated gastrointestinal symptoms such as appetite loss, epigastric fullness, reflux esophagitis, early dumping syndrome, body weight loss, endoscopic reflux esophagitis, and endoscopic gastritis in the remnant stomach, postprandial stasis of the substitute stomach, and postgastrectomy cholecystolithiasis better than in group B. The results suggest that the proposed technique is a function‐preserving gastric operation appropriate for preventing postgastrectomy disorder.
Desmoplastic Reaction Influences Pancreatic Cancer Growth Behavior
Authors: Hartel Mark , di Mola Fabio F. , Gardini Andrea , Zimmermann Arthur , Di Sebastiano Pierluigi , Guweidhi Ahmed , Innocenti Paolo , Giese Thomas , Giese Nathalia , Büchler Markus W. , Friess Helmut 
Published: August 2004

AbstractConnective tissue growth factor (CTGF), which is regulated by transforming growth factor‐ß (TGFß), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46‐fold increase in CTGF mRNA expression (p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFß‐induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation (p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) (p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFß, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.
Dependence of Positive Effects of Granulocyte Colony‐stimulating Factor on the Antibiotic Regimen: Evaluation in Rats with Polymicrobial Peritonitis
Authors: Bauhofer Artur , Torossian Alexander , Lorenz Wilfried , Middeke Martin , Plaul Ulrike , Schütz Philipp , Stinner Benno , Hattel Markus , Celik Ilhan ,   Lucerne Sepsis Study Group
Published: August 2004

AbstractWe tested the hypothesis that the ability of granulocyte colony‐stimulating factor (G‐CSF) to prevent death from fecal peritonitis is influenced by the composition of the antibiotic regimen with which it is administered. We used a rodent model of polymicrobial peritoneal contamination and infection and the concept of clinical modeling randomized trials (CMRTs), which includes the conditions of randomized, clinical trials and complex clinical interventions (e.g., anesthesia, volume substitution, antibiotics, surgery, postoperative analgesia). With the peritonitis model we obtained a mortality dose‐response curve that was sensitive to antibiotic prophylaxis. G‐CSF was most efficacious when it was administered both prophylactically and after the onset of peritonitis. Cefuroxime/metronidazole, ofloxacin/metronidazole, and amoxicillin/clavulanate improved survival in combination with G‐CSF best, whereas cefotaxime or ceftriaxone with and without metronidazole did not. G‐CSF administration was associated with improved polymorphonuclear neutrophil phagocytosis and enhanced bacterial clearance. Pro‐inflammatory cytokine release (tumor necrosis factor‐a, interleukin‐6, macrophage inflammatory protein‐2) was decreased in plasma and in the peritoneal fluid. Their expression was lowered in various organs on the protein and mRNA level. The results were used to design a clinical trial to test the ability of G‐CSF to prevent serious infections in patients with colorectal cancer surgery. In this trial G‐CSF application and antibiotic prophylaxis were performed with the most effective scheduling and combinations (cefuroxime/metronidazole and ofloxacin/metronidazole) as defined here.
Prognostic Impact of Fas Ligand on Hepatocellular Carcinoma after Hepatectomy
Authors: Lee Wei‐Chen , Yu Ming‐Chin , Chen Miin‐Fu 
Published: August 2004

AbstractThe expression of Fas ligand on tumor cells may counterattack the host’s immunity and worsen the prognosis. Knowledge of the prognostic impact of Fas ligand on patients with hepatocellular carcinoma (HCC) after hepatectomy is still limited. Fas ligand expression in HCCs was examined in 59 patients who underwent hepatectomy for HCC. The prognosis was analyzed and correlated to the expression of Fas ligand. Expression of Fas ligand was detected by immunohistochemical staining in 27 of the 59 HCCs (45.8%). The Fas ligand was expressed in only a small number of cancer cells. However, even though only a few cancer cells expressed it, the prognosis for patients whose HCCs showed Fas ligand expression was worse than that for patients with an HCC without Fas ligand expression. The mean disease‐free survival was only 10.83 ± 1.90 months when HCCs expressed Fas ligand compared with 43.51 ± 7.02 months for those without Fas ligand expression (p = 0.0007). The overall patient survival was 28.34 ± 4.08 months when the HCC expressed Fas ligand compared with 55.31 ± 5.37 months for HCC without Fas ligand expression (p = 0.0003). The expression of Fas ligand did not correlate with the presentation of other prognostic factors. Fas ligand expression is thus an independent prognostic factor for HCC. Thus the HCC expressing Fas ligand has a worse prognosis than the HCC without Fas ligand expression.
Pleurodesis in Patients with Malignant Pleural Effusions: Talc Slurry or Bleomycin? Results of a Prospective Randomized Trial
Authors: Haddad Fabio José , Younes Riad Naim , Gross Jefferson Luiz , Deheinzelin Daniel 
Published: August 2004

AbstractThe purpose of this study was to evaluate the efficacy, safety, and cost of bedside pleurodesis for malignant pleural effusions using talc slurry (TS) or bleomycin (BL) in a prospective randomized trial, and to determine prognosticators for procedure failure. From June 1997 to June 1999 a series of 71 patients entered this trial. They underwent 37 procedures with TS (4 g) and 34 with BL (60 units) via tube thoracostomy. Success was defined as no recurrence of pleural effusion or asymptomatic recurrence of a small amount of effusion. Pleural effusion‐free survival curves were used to analyze the success rates and the prognosticators of failure. Follow‐up ranged from 3 days to 26 months (median 2.5 months). No difference in success rates was detected between TS or BL (log‐rank test: p = 0.724). There were no major complications related to the procedure. The independent prognosticators of failed pleurodesis were the use of steroids (p = 0.004) and the volume of pleural fluid drained during the first thoracentesis when it was more than 900 ml (p = 0.029). The average cost of intervention per patient was significantly lower for TS (p < 0.001). There was no significant difference between the success rates for TS and BL as agents of bedside pleurodesis for malignant pleural effusions. Because of its significantly lower cost, TS should be considered the agent of choice. The use of steroids and the volume drained during the first thoracentesis (if more than 900 ml) were independent prognosticators of pleurodesis failure. The role of this latter finding as a marker of pleurodesis failure awaits more data.
Cell‐specific Cytotoxicity of Human Pancreatic Adenocarcinoma Cells Using Rat Insulin Promoter Thymidine Kinase‐directed Gene Therapy
Authors: Tirone Thomas A. , Wang Xaio‐Ping , Templeton Nancy S. , Lee Tim , Nguyen Liz , Fisher William , Brunicardi F. Charles 
Published: August 2004

AbstractThe formation of a normal pancreas and the activation of insulin production are, in part, dependent on the expression and activation of the pancreatic duodenal homeobox gene 1 (PDX‐1). The expression of PDX‐1 also has been detected in various human pancreatic ductal adenocarcinoma (PDA) cell lines. This has made it possible to generate a cancer cell‐specific gene expression system to treat human pancreatic cancer. In this study, we have developed a cell‐specific cytotoxic model of PDA cells using the expression of herpes simplex virus thymidine kinase (TK) under the control of the rat insulin promoter (RIP‐TK). We have shown that the cell‐specific cytotoxicity in human PDA cells depends on the presence of PDX‐1. Our results also demonstrate that in vivo PDA‐specific cytotoxicity can be achieved with RIP‐TK using an intraperitoneal liposomal gene delivery method followed by a short period of ganciclovir treatment in severe combined immunodeficient (SCID) mice. Furthermore, PDX‐1 protein was found in all six freshly isolated human pancreas cancer specimens and two liver metastasis samples that were group‐tested, suggesting the feasibility of using RIP‐TK gene therapy in humans. This study may provide an alternative strategy for the future treatment of pancreatic cancer.
Venous Thromboembolism Prophylaxis after Head and Spinal Trauma: Intermittent Pneumatic Compression Devices Versus Low Molecular Weight Heparin
Authors: Kurtoglu Mehmet , Yanar Hakan , Bilsel Yilmaz , Guloglu Recep , Kizilirmak Sevda , Buyukkurt Dincay , Granit Volkan 
Published: August 2004

AbstractAlthough there are alternative methods and drugs for preventing venous thromboembolism (VTE), it is not clear which modality is most suitable and efficacious for patients with severe (stable or unstable) head/spinal injures. The aim of this study was to compare intermittent pneumatic compression devices (IPC) with low‐molecular‐weight heparin (LMWH) for preventing VTE. We prospectively randomized 120 head/spinal traumatized patients for comparison of IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color‐flow Doppler sonography of the lower extremities was performed each week of hospitalization and 1 week after discharge. When there was a suspicion of pulmonary embolism (PE), patients were evaluated with spiral computed tomography. Patients were analyzed for demographic features, injury severity scores, associated injuries, type of head/spinal trauma, complications, transfusion, and incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4 patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There was no statistically significant difference regarding a reduction in DVT, PE, or mortality between groups (p = 0.04, p > 0.05, p > 0.05, respectively). IPC can be used safely for prophylaxis of VTE in head/spinal trauma patients.
Long‐term Results of Through‐knee Amputation with Dorsal Musculocutaneous Flap in Patients with End‐stage Arterial Occlusive Disease
Authors: Kock Hans‐Juergen , Friederichs Jan , Ouchmaev Alexander , Hillmeier Joachim , von Gumppenberg Stephan 
Published: August 2004

AbstractA modified technique of knee joint disarticulation using a dorsal musculocutaneous flap of the gastrocnemius muscle was first described in 1985. The operative results in 66 patients (33 women, 33 men; mean age 66.7 ± 11.3 years, range 42–93 years) with gangrene due to peripheral vascular disease with 69 knee disarticulations are reported. After a mean survival period of 35.2 months (0–116 months), 88% (n = 58) of the patients had died owing to cardiopulmonary reasons. The in‐hospital 48‐day mortality was 9%. Nine patients (14%) underwent reamputation at the above‐knee level, and five patients underwent operative revision of the soft tissue. After discharge from the hospital, 35 of 60 patients (58%) were able to walk with the aid of a prosthesis. We conclude that knee disarticulation with the use of a myocutaneous gastrocnemius flap is a safe, functionally acceptable operative method in high risk vascular patients.
Factors Predicting Malignancy of Hürthle Cell Tumors of the Thyroid: Influence on Surgical Treatment
Authors: Pisanu Adolfo , Sias Luigi , Uccheddu Alessandro 
Published: August 2004

AbstractControversy still exists about the ability to differentiate between malignant and benign Hürthle cell tumors (HCTs) before and during surgery. Diagnostic difficulties make surgical decisions debatable. The aim of this study was to evaluate factors predicting the malignancy of HCT and to plan its appropriate management. From January 1998 to May 2003 a series of 41 patients underwent thyroidectomy in our surgical department because of HCT. A cross‐sectional study of 23 patients with carcinoma and 18 patients with adenoma was carried out: demographic data, tumor characteristics, diagnostic results of fine‐needle aspiration cytology (FNAC), frozen section (FS), MIBI scan scintigraphy, surgical indications, and treatment were evaluated. The mean tumor size was significantly greater for carcinomas than adenomas (3.1 vs. 1.9 cm; p = 0.006). Threshold sizes of more than 3.0 cm and 4.0 cm, respectively, were significant for predicting malignancy (p = 0.025 and p = 0.012). Conversely, 47.8% of carcinomas had a diameter smaller than 3.0 cm. FNAC and FS sensitivities for carcinoma detection were 23.8% and 33.3%, respectively. The positive uptake on MIBI scan imaging was likely to be similarly malignant or benign. Because of the lack of accuracy of all diagnostic studies for predicting malignancy, all oxyphilic cell nodules should be referred to surgery. Different tumor sizes cannot be the only factor on which to base a surgical decision. Therefore, because of diagnostic uncertainties, we believe that an experienced surgeon can safely perform total thyroidectomy in all patients with an HCT.
Hepatitis C Virus Infection is a Risk Factor for Tumor Recurrence after Resection of Small Hepatocellular Carcinomas
Authors: Huo Teh‐Ia , Wu Jaw‐Ching , Hsia Cheng‐Yuan , Chau Gar‐Yang , Lui Wing‐Yiu , Huang Yi‐Hsiang , Lee Pui‐Ching , Chang Full‐Young , Lee Shou‐Dong 
Published: August 2004

AbstractHepatocellular carcinoma (HCC) is closely associated with chronic hepatitis B or C virus (HBV, HCV) infection. Tumor recurrence frequently occurs after surgical resection and may adversely affect the outcome. This study aimed to investigate the effect of viral hepatitis in association with HCC recurrence after resection. A total of 248 patients [HBV in 165, HCV in 44, dual HBV+HCV in 15, and non‐B non‐C (NBNC) in 24] who underwent curative resection for HCC were included. The cumulative recurrence rate was compared according to the etiology of the underlying hepatitis and was stratified by tumor size and other clinicopathologic parameters. Altogether, 116 patients (47%) had a tumor recurrence within 17 ± 11 months after resection. No significant difference in recurrence was noted among the four groups of patients (HBV, HCV, HBV+HCV, NBNC) (p = 0.248). Persistent hepatitis was more common in the HCV group (p < 0.001) after resection. Among the 157 patients with a small (= 5 cm) tumor, the recurrence rate was significantly higher in the HCV group than in the HBV, HBV+HCV, and NBNC groups (p = 0.036). Cox multivariate analysis showed that HCV infection [relative risk (RR) 4.4, 95% confidence interval (CI) 1.3–14.8, p = 0.018] and vascular invasion (RR 3.2, 95% CI 1.2–8.9, p = 0.044) were independent predictors of tumor recurrence. Stratified analysis in other parameters did not show significant differences in terms of tumor recurrence among the four virologic groups (p > 0.1 for all parameters). In conclusion, patients with small HCCs and concurrent HCV infection are at a high risk of tumor recurrence after resection.
Palliation of Malignant Gastroduodenal Obstruction with Open Surgical Bypass or Endoscopic Stenting: Clinical Outcome and Health Economic Evaluation
Authors: Johnsson Erik , Thune Anders , Liedman Bengt 
Published: August 2004

AbstractGastroduodenal outlet obstruction is a complication of advanced gastrointestinal malignant disease. In the past it was usually treated by an open surgical bypass procedure. During the last decade, endoscopic self‐expandable stents (SEMS) have been used. The aim of this study was to compare these two palliative strategies concerning clinical outcome and health economy. A series of 36 patients with incurable malignant disease and gastroduodenal outlet obstruction syndrome were treated in a prospective study. According to the attending hospital and endoscopist on duty, 21 of the 36 patients were endoscopically treated with SEMS and 15 underwent an open surgical gastroenteroanastomosis. Health economic evaluation was based on the monetary charges for each patient associated with the procedure, postoperative care, and hospital stay. The hospital stay was 7.3 days for the stented group compared with 14.7 days for the open surgery group (p > 0.05). The survivals were 76 and 99 days, respectively (NS). In the stented group all 15 patients (100%) alive after 1 month were able to eat or drink, and 11 (73%) of them tolerated solid food. In the surgical bypass group,9 out of 11 (81%) patients alive after 1 month could eat or drink, and 5 of them (45%) could eat solid food. The mean charges (U.S. dollars) during the hospital stay were $7215 for the stented group and $10,190 for the open surgery group (p < 0.05). Palliation of the gastroduodenal obstruction in patients with malignant disease were at least as good, and the charges were lower for the endoscopic stenting procedure than for an open surgical bypass.