bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Metastasis to Non‐sentinel Nodes by Sentinel Node Status and Primary Tumor Characteristics in Primary Breast Cancer in Taiwan
Authors: Yu Jyh‐Cherng , Hsu Giu‐Cheng , Hsieh Chung‐Bo , Sheu Lai‐Fa , Chao Tsu‐Yi
Published: June 2005

We aimed to determine how to approach the axilla after finding a positive sentinel node (SN) for a woman with breast cancer in Taiwan. We used blue dye staining to identify the SN in 824 procedures on 811 patients with breast cancer small than 3 cm by a single surgeon. All patients underwent SN biopsy, followed by at least level II axillary dissection. All SNs were evaluated histologically and immunohistochemically with anti‐cytokeratin antibodies. Non‐SNs were examined by routine histology. SNs were identified in 814/824 procedures (98.8%). SN metastases were found in 286/814 (35.1%). Subsequent axillary dissections revealed tumors in non‐SNs in 188 (65.7%) of these patients. There was a relatively high incidence of non‐SN metastases in our population. Tumor exhibiting high nuclear grading, ER‐, PR‐, Erb‐2/neu overexpression, lymphovascular invasion, increasing tumor size, multiple positive SNs, and macrometastatic size in SNs (> 2 mm) were all significantly correlated with non‐SN metastases. Multivariate analysis showed that tumor size, the number of positive SNs, and the metastatic size in SNs were independent factors predicting the presence of positive non‐SNs. Small (< 2 cm) cancers, having only micrometastatic foci in the SN and having only one SN involved are closely correlated with the tumor‐free non‐SNs. Our data will assist such patients regarding the need for axillary dissection after finding a positive SN.
Non‐Oriental Primary Intrahepatic Lithiasis: Experience with 48 Cases
Authors: Herman Paulo , Bacchella Telesforo , Pugliese Vincenzo , Montagnini André L. , Machado Marcel Autran C. , Cunha José Eduardo M. da , Machado Marcel C.C.
Published: June 2005

An experience with the diagnosis and treatment of patients with non‐Oriental primary intrahepatic lithiasis (PIHL) is described. A group of 48 native Brazilian patients with symptomatic PIHL were studied, and the patients’ characteristics, diagnoses, treatment protocols based on the presentation of the disease, prognostic factors, and late results were analyzed. Liver resection was performed in patients with an irreversible lesion, such as parenchymal atrophy or biliary stenosis; and biliary drainage procedures were employed in patients with bilateral disease. Late results were considered good when no postoperative symptoms were observed and poor if there was pain recurrence or cholangitis. Overall good results were observed in 73.4% of the patients. Good late results were observed in 94.1% and 62.1% of the patients with unilateral and bilateral stones, respectively. None of the analyzed parameters (gender, age, previous biliary surgery, bilirubin level, serum leukocyte counts, prothrombin activity, previous history of cholangitis, stone location) predicted poor late results, but the risk for patients with bilateral stones to develop late complications was 7.2 times higher than for those with unilateral disease.

Non‐Oriental PIHL is a rare disease, and the patients’ characteristics are similar to those of patients with Oriental PIHL. We believe that personalized treatment based on the presentation of the disease led to the high incidence of good late results in this series.
Patient‐controlled Dietary Schedule Improves Clinical Outcome after Gastrectomy for Gastric Cancer
Authors: Hirao Motohiro , Tsujinaka Toshimasa , Takeno Atsushi , Fujitani Kazumasa , Kurata Miki
Published: June 2005

Although studies have shown that early oral feeding after abdominal surgery is feasible, the optimal dietary schedule has not been established. This study was conducted prospectively to compare the clinical outcome of patient‐controlled dietary schedule with that of conventional dietary schedule after gastric resection for early cancer. Patients in the patient‐controlled diet (PC) group (n = 53) received a solid diet on demand; patients in the conventional regimen (CR) group (n = 50) received a solid diet from postoperative day (POD) 10. All patients underwent distal gastrectomy for early gastric cancer. A liquid diet was tolerated by the PC group on POD 2, and a solid diet was taken on POD 6 after gastrectomy, earlier than in the CR group. The postoperative hospital stay was 18.5 ± 5.9 days (10–40) in the PC group, versus 21.7 ± 8.8 days (14–57) in the CR group (p = 0.02). Patients in the PC group had a higher daily oral intake of calories on POD 10 than those in the CR group (p = 0.02). Changes in body weight and serum albumin during the postoperative period and after discharge, and the incidence of complications and variances from clinical pathways did not show significant differences between the two groups. The PC schedule was feasible after distal gastrectomy for early gastric cancer. It improved the clinical outcome, with a shorter postoperative hospital stay and a higher oral energy intake on early phase, compared with the CR schedule. Moreover, the PC approach was useful for establishing the optimal dietary schedule and improving the clinical pathway.
Comparison of Surgical Techniques for Treatment of Benign Toxic Multinodular Goiter
Authors: Alimoglu Orhan , Akdag Murat , Sahin Mustafa , Korkut Cagatay , Okan Ismail , Kurtulmus Neslihan
Published: June 2005

Controversy remains regarding the best surgical approach for toxic multinodular goiter (MNG). The aim of this study was to evaluate the results of various thyroid operations for managing toxic MNG. A group of 100 patients with toxic MNG were divided into three groups and managed with total thyroidectomy (TT; group I, n‐17), near‐total thyroidectomy (NTT; group II, n = 48), or bilateral subtotal thyroidectomy (BST; group III, n = 35). Patients were compared with regard to age, gender, surgical operations, complications, thyroid hormone status, duration of hospitalization, and the reoperation rate for incidentally found thyroid carcinomas. There were 14 men (14%) and 86 women (86 %) with a mean age of 47.03 ± 13.56 years (range 19–77 years). After the operation two patients had a hematoma, and one patient had a seroma. Four patients had unilateral vocal cord paralysis, and one had permanent paralysis. Moreover, 18 patients had transient and 2 patients permanent hypocalcemia. There was no significant difference between the groups regarding complications (p < 0.05). Permanent hypothyroidism was achieved in all patients in group I and 44 patients (92 %) in group II, whereas in group III only 10 (29%) patients had hypothyroidism. Conversely, hyperthyroidism, both subclinical and clinical, was noted only in group III (12 patients, 34 %) during follow‐up. We think that TT and NTT are safe, effective approaches in the treatment of toxic MNG, preventing recurrence of thyrotoxicosis and reoperation for incidentally found thyroid cancers. The complication rates for TT and NTT were similar to that for BST. Hence these operation should be considered for patients referred for surgical treatment of toxic MNG.
Primary Closure of the Common Duct over Endonasobiliary Drainage Tubes
Authors: Wani Mehmood A. , Chowdri Nisar A. , Naqash Sameer H. , Wani Nazir A.
Published: June 2005

The T‐tube remains the standard method of intraductal drainage after open choledochotomy for choledocholithiasis. We studied the use of an endonasobiliary drainage (ENBD) tube as an alternative to the T‐tube for postoperative intraductal drainage. A series of 20 patients with documented choledocholithiasis in whom endoscopic methods of stone retrieval failed to clear the common bile duct (CBD) were selected for the study. All patients had ENBD tubes placed preoperatively at endoscopic retrograde cholangiopancreaticography and then were subjected to open choledocholithotomy with primary closure of the choledochotomy over the ENBD. The age of the patients in the study group ranged from 18 to 75 years. Three patients (15%) had acute cholangitis at the time of surgery. Stones were confirmed at surgery in 85% of the patients, and the size of the CBD was found to range from 1.0 to 2.3 cm. All 20 patients underwent closure of the common duct over an ENBD tube without any difficulty. None of the patients experienced biliary complications such as bile leaks, biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. No patient had any residual stone as documented by postoperative cholangiograms. Abdominal drains remained in place for 2 to 4 days, and the ENBD tubes were removed between days 6 and 8. The length of the postoperative hospital stay varied from 7 to 15 days, with 65% of the patients going home before postoperative day 8.
Ultrasonographically and Anatomopathologically Detectable Node Metastases in the Lateral Compartment as Indicators of Worse Relapse‐free Survival in Patients with Papillary Thyroid Carcinoma
Authors: Ito Yasuhiro , Tomoda Chisato , Uruno Takashi , Takamura Yuuki , Miya Akihiro , Kobayashi Kaoru , Matsuzuka Fumio , Kuma Kanji , Miyauchi Akira
Published: June 2005

The recent prevalence of ultrasonography has made it easier to detect lymph node metastasis in the lateral compartment of patients with thyroid carcinoma. In this study, we investigated the prognostic impact of lateral node metastasis preoperatively detectable by ultrasonography (US) and metastasis diagnosed by pathology examination but not detected on preoperative US [anatomopathologically (AP)‐detectable metastasis] in 560 patients with papillary carcinoma >1 cm in diameter, who underwent thyroidectomy with modified radical neck dissection at our hospital. Patients with US‐detectable metastasis (US+ patients) showed a significantly worse relapse‐free survival (RFS) rate than those with no metastasis (US−/AP− patients) or AP‐detectable metastasis (US−/AP+ patients) regardless of tumor size. Furthermore, the RFS of US‐/AP+ patients with tumors >2 cm was worse than that of US−/AP− patients with tumors >2 cm or US−/AP+ patients with tumors measuring 1.1–2.0 cm. There was no significant difference in RFS between US−/AP+ and US−/AP− patients with tumors measuring 1.1–2.0 cm. These findings suggest that US‐detectable lateral metastasis predicts a worse RFS for patients regardless of tumor size, and AP‐detectable metastasis affects the RFS of patients with tumors >2 cm.
Intra‐abdominal and Retroperitoneal Lymphangiomas in Pediatric and Adult Patients
Authors: Goh Brian K. P. , Tan Yu‐Meng , Ong Hock‐Soo , Chui Chan‐Hon , Ooi London L.P.J. , Chow Pierce K.H. , E.L. Tan. Carolyn , Wong Wai‐Keong
Published: June 2005

Intra‐abdominal and retroperitoneal lymphangiomas are a rare, congenital malformations of the lymphatics, which are found predominantly in children. The aim of this study is to evaluate the clinical features of this tumor, highlighting the differences in adults and pediatric patients. We also evaluate the preoperative diagnosis, radiological features, surgical treatment, and outcome of this rare condition. Between 1990 and 2004, 14 patients who underwent surgical resection of an intra‐abdominal lymphangioma were reviewed retrospectively. There were five pediatric patients between fetal age and 17 years of age and nine adults between 31 and 62 years of age. Overall, females outnumbered males in the series, with a male‐to‐female ratio of 3:4. However, males predominated in the pediatric age group with a male‐to‐female ratio of 1.5:1. The clinical presentation of children was more acute ranging from 3 days to 2 months. In adults, four patients were asymptomatic, and the remaining five had symptom duration ranging from 2 weeks to a year. The lymphangiomas occurred in the mesentery (n = 4), retroperitoneum (n = 4), omentum (n = 3), pancreas (n = 2), and spleen (n = 1). All the patients underwent total surgical resection with or without organ resection, and there were no recurrences at a median follow‐up of 2 years (range; 3 months–13 years). This series demonstrates that abdominal lymphangiomas have a male preponderance and present more acutely in pediatric patients, whereas in adults, female patients predominate and the history is more chronic.
Perforated Peptic Ulcer Treated by Simple Closure and Helicobacter Pylori Eradication
Authors: Rodríguez‐Sanjuán Juan C. , Fernández‐Santiago Roberto , García Rosa A. , Trugeda Soledad , Seco Isabel , de Torre Fernando la , Naranjo Angel , Gómez‐Fleitas Manuel
Published: June 2005

Simple closure followed by Helicobacter pylori (Hp) eradication has become the most used procedure in perforated ulcer treatment. However, its efficacy and safety are still to be determined. To assess recurrence and re‐perforation rates, and as a secondary objective, to analyze Hp infection rates in perforated ulcer patients and controls, we conducted a prospective study. Ninety‐two consecutive patients (ages: 19–96 years) were operated on between 1996 and 2002, and treated by simple closure followed by Hp eradication and NSAID avoidance. The data were prospectively collected in a database. Hp infection was diagnosed in 68 patients (73.9%). Thirty‐four patients (37%) consumed nonsteroidal anti‐inflammatory drugs (NSAIDs), and 23 (25%) had both Hp infection and NSAID antecedents. The perforation was gastric in 4 cases and pre‐pyloric, pyloric or duodenal in 88. There were postoperative complications in 24 patients (26%) and 4 patients died (4.3%). Hp eradication was shown in 46 patients. There was clinical ulcer recurrence in 4 (4.3%); in 3 of them recurrence manifested as re‐perforation, all in gastric locations. Overall relapse and re‐perforation 1‐year crude rates were 6.1% and 4.1%, respectively. Crude rates for non‐gastric ulcer recurrence were 0 at 1 year and 2.6% at 2 years and for non‐gastric ulcer re‐perforation rates were 0 at 1 and 2 years. This therapeutic strategy is associated with a low rate of recurrence and no re‐perforations in case of duodenal, pyloric, or pre‐pyloric perforated ulcers, but it is not acceptable for perforated gastric ulcers.
Elective Inguinal Hernia Repair with Mesh: Is there a Need for Antibiotic Prophylaxis? — A Review
Authors: Biswas Seema
Published: June 2005

Although it is widely accepted that antibiotic prophylaxis is indicated in elective mesh repair of inguinal hernia, the evidence for its value has been controversial. A recent Cochrane meta‐analysis showed that there is insufficient data overall to demonstrate a clear advantage of prophylaxis and illustrated the classic problem in evidence‐based medicine where a lack of evidence in support of an intervention may be interpreted as a reason not to implement it. This review of the literature evaluates the evidence for the effectiveness of intravenous antibiotics as prophylaxis in inguinal hernia repair with mesh. Pubmed and Embase searches revealed seven trials of antibiotic prophylaxis in mesh repair of inguinal hernia. The quality of the evidence and the limitations of the seven trials are discussed. Analysis of these seven trials adds to the Cochrane meta‐analysis of Sanchez‐Manuel and Seco‐Gil. Only two of the trials support the use of antibiotic prophylaxis, and those were the only double‐blind randomized controlled trials reviewed. In evidence‐based medicine the absence of evidence in clear support of an intervention (as in this review, where only two of the seven trials support the use of antibiotic prophylaxis) may be taken as reason not to implement the intervention. It is possible, however, that what is needed to clarify the issue are further randomized controlled trials, rigorously performed and recruiting significantly larger numbers of patients.
Emergency Major Abdominal Surgery in Patients over 85 Years of Age
Authors: Zerbib Ph. , Kulick J. F. , Lebuffe G. , Khoury‐Helou A. , Plenier I. , Chambon J. P.
Published: June 2005

The aim of this retrospective study was to evaluate the outcome and prognostic parameters of patients over 85 years of age undergoing major abdominal emergency surgery. The medical records of 45 consecutive patients aged over 85 years who underwent major abdominal emergency surgery between May 1999 and November 2001 were reviewed. The mean patient age was 88 years. Eight patients were American Society of Anesthesiologists (ASA) IV or V, 21 were ASA III, and 16 were ASA I or II. We performed 38 median and 7 right subcostal laparotomies. Perioperative mortality was 26.6% (3 times higher than that of the overall population at the same age). Perioperative complications occured in 29.5% of patients. Ten patients returned home after surgery, of whom 70% remained alive at the end of the study. Twenty‐three left the hospital for a long‐term care institution or post‐acute care unit: of these 20% remained alive at the end of the study. Among ASA I or II patients, 43.7% remained alive at the end of the study, although 18.7% died within 1 month of the surgery. Among ASA III, IV, or V patients, only 17.2% remained alive at the end of the study, and 34.5% died within 1 month of the surgery. None of patients classified as ASA IV or V survived for more than 6 month after surgery. With an overall mortality rate of about 30%, and with the clear correlation between increased mortality and higher ASA scores, the place of palliative treatment must remain a major consideration for patients in this age group classified ASA III or higher. When surgery is performed, early return home, should be encouraged.
Dopamine‐secreting Pheochromocytomas: In Search of a Syndrome
Authors: Dubois Luc A. , Gray Daryl K.
Published: June 2005

Pheochromocytomas rarely produce dopamine as the only catecholamine. Two cases are reported here, and a review of the literature was conducted. Unlike norepinephrine‐and epinephrine‐secreting tumors, dopamine‐secreting pheochromocytomas lack a classic clinical presentation and are often asymptomatic. Urinary and serum metabolites cannot be relied on to make the diagnosis, and serum or urine dopamine levels (or both) must be measured when dealing with a potential pheochromocytoma. Dopamine‐secreting tumors are less likely to enhance with metaiodobenzylguanidine (MIBG) scanning and may benefit from the use of positron emission tomography. Treatment is en bloc surgical excision; but unlike other pheochromocytomas, α‐blockade is not indicated as it may lead to hypotension and cardiovascular collapse. Metyrosine is a medication that can be useful for preoperative control of symptoms from these tumors. The function of metyrosine is to block dopamine synthesis; it has no α‐blocking effect. This medication is an option for controlling symptoms but should not be used routinely in these patients. The prognosis for patients with these tumors is worse than for those with an epinephrine‐ and norepinephrine‐secreting tumor. Because of their asymptomatic nature, dopamine‐secreting pheochromocytomas tend to be detected later and are more likely to be malignant at the time of diagnosis.
Arterial Reconstruction during Pancreatoduodenectomy in Patients with Celiac Axis Stenosis—Utility of Doppler Ultrasonography
Authors: Nara Satoshi , Sakamoto Yoshihiro , Shimada Kazuaki , Sano Tsuyoshi , Kosuge Tomoo , Takahashi Yuh , Onaya Hiroaki , Yamamoto Junji
Published: June 2005

Celiac axis stenosis is found at an incidence of 2%–24% in the general population. During pancreatoduodenectomy in patients with celiac axis stenosis, division of the gastroduodenal artery from the common hepatic artery may cause acute ischemia of the upper abdominal organs, such as the liver, stomach, or spleen. Under these circumstances, the clinical indications of arterial reconstruction remain controversial. Between 1994 and 2003, seven patients with celiac axis stenosis (n = 4) or occlusion (n = 3) underwent pancreatoduodenectomy at our hospital. Arterial reconstruction, including division of the median arcuate ligament, was conducted in two patients; the replaced right hepatic artery was preserved in one patient, and no vascular refinement was undertaken in the remaining four of the seven patients. In two of the four patients without arterial reconstruction or preservation, the serum levels of liver enzymes were markedly elevated (> 800 IU/l) on postoperative day 1, and these patients subsequently developed liver abscesses. Two patients who underwent arterial reconstruction and three patients who showed no decrease in intrahepatic arterial flow under Doppler ultrasonography after clamping of the gastroduodenal artery developed no ischemic complications. Although our experience is limited, when intraoperative Doppler ultrasonography indicates a decrease in the hepatic arterial signals, we believe that reconstruction of the hepatic artery will be necessary to minimize ischemic complications in the liver in patients with celiac axis stenosis.
Influence of Surgery‐related Factors on Quality of Life after Esophageal or Cardia Cancer Resection
Authors: Viklund Pernilla , Lindblad Mats , Lagergren Jesper
Published: June 2005

Knowledge of how factors related to esophageal cancer resection affect long‐term quality of life after surgery is scarce, and no population‐based studies are available. Therefore, we conducted a Swedish nationwide, prospective, population‐based study of how esophageal surgery–related factors influence quality of life 6 months postoperatively. The Swedish Esophageal and Cardia Cancer register (SECC‐register) encompasses 174 hospital departments (97%). Microscopically radically operated patients responded to a validated written questionnaire assessing quality of life. The basic questionnaire (QLQ‐C30) and the esophagus‐specific module (OES‐24) were developed by the European Organization for Research and Treatment of Cancer. The Mann‐Whitney test, the Jonckheere‐Terpstras test, and logistic regression were used in statistical analyses. Among 100 included patients, the occurrence of surgery‐related complications was the main predictor of reduced global quality of life 6 months after surgery (p for trend = 0.03). This effect remained after adjustment for potential confounding variables. Except for anastomotic strictures, each of the predefined complications—i.e., anastomotic leakage, infections, cardiopulmonary complications, and operative technical complications—contributed to decreased quality‐of‐life scores. Other potentially relevant factors—e.g. degree of lymph node dissection, resection margins, operative blood loss or duration, and hospital type—did not significantly affect quality of life. In conclusion, any measures that can reduce the risk of major surgery–related complications can decrease the negative impact on quality of life after esophageal cancer surgery. More population‐based studies are warranted, however.
Selecting the Number of Classes Under Latent Class Regression: A Factor Analytic Analogue
Authors: Huang Guan-Hua
Published: June 2005

Recently, the regression extension of latent class analysis (RLCA) model has received much attention in the field of medical research. The basic RLCA model summarizes shared features of measured multiple indicators as an underlying categorical variable and incorporates the covariate information in modeling both latent class membership and multiple indicators themselves. To reduce complexity and enhance interpretability, one usually fixes the number of classes in a given RLCA. Often, goodness of fit methods comparing various estimated models are used as a criterion to select the number of classes. In this paper, we propose a new method that is based on an analogous method used in factor analysis and does not require repeated fitting. Two ideas with application to many settings other than ours are synthesized in deriving the method: a connection between latent class models and factor analysis, and techniques of covariate marginalization and elimination. A Monte Carlo simulation study is presented to evaluate the behavior of the selection procedure and compare to alternative approaches. Data from a study of how measured visual impairments affect older persons’ functioning are used for illustration.
Establishment and characterization of endothelial cell lines from the aorta of miniature pig for the study of xenotransplantation
Authors: Kim Donghee , Kim Jae Young , Koh Hyun Sook , Lee Jung Pyo , Kim Young Tae , Kang Hee Jung , Hwang Woo Suk , Kim Yoon Berm , Lee Jung Sang , Ahn Curie
Published: June 2005

Pig endothelial cells are the first cells to interact with human immune components after organ xenotransplantation, which is a procedure currently considered to be the best treatment option for end‐stage organ failure. It is, therefore, essential to study the mechanisms of molecular interaction between pig endothelial cells and human immune components, in order to overcome xenograft rejection. The aim of this study was to establish immortalized pig aortic endothelial cell lines, in order to facilitate future in vitro studies of human anti‐pig immune responses. Endothelial cell lines were established following the transfection of primary endothelial cells isolated from the aortas of the Minnesota miniature pig with plasmid pRNS‐1 carrying genes for neomycin resistance and the SV40 large T antigen. The immortalized cell lines showed a relatively rapid doubling time (17.6 h) and the endothelial cell phenotype, as indicated by the formation of typical cobblestone monolayers and by the constitutive expression of PECAM‐1 and the von Willebrand factor. Flow cytometric analysis demonstrated the constitutive expression of SLA class I and CD86, whereas the expression of E‐selectin and SLA class II was only induced after stimulation with human TNF‐α and pig IFN‐γ, respectively. On the other hand, no CD80 expression was detected in the primary cells or cell lines in the presence or absence of either human TNF‐α or pig IFN‐γ. A vigorous human T cell proliferation against these cell lines was observed in the mixed lymphocyte—endothelial cell culture. These results suggest that pig endothelial cells, immortalized by the introduction of SV40 T, retain their original characteristics, except for the acquired property of immortalization, and that they may be useful for future in vitro studies of xenogeneic human anti‐pig immune responses.
In vitro hematopoietic differentiation of human embryonic stem cells induced by co‐culture with human bone marrow stromal cells and low dose cytokines
Authors: Wang Jian , Zhao Hui‐Ping , Lin Ge , Xie Chang‐Qing , Nie Dong‐Song , Wang Qi‐Ru , Lu Guang‐Xiu
Published: June 2005

Human embryonic stem (hES) cells randomly differentiate into multiple cell types during embryoid body (EB) development and limited studies have focused on directed hematopoietic differentiation. Here, we report that the treatment of hES cells during EBs development with a combination of low dose hematopoietic cytokines, including stem cell factor (SCF), Flt‐3 ligand, vascular endothelial growth factor (VEGF) and human bone marrow stromal cells (hBMSCs), generated cell clusters that contained 8.81% KDR‐positive hemangioblasts, 9.94% CD34‐positive hematopoietic stem cells and 25.7% CD45‐positive mature hematopoietic cells, and expressed hematopoietic genes such as KDR, stem cell leukemia (scl) and runt‐related transcription factor 1 (Runx1). We provide the first evidence for the role of the cytokine—hBMSCs combination in promoting hematopoietic differentiation of hES cells, and thus provide the potential for generation of hematopoietic cells, as well as for understanding early developmental events that govern the initiation of hematopoiesis in humans.
Gene transfection and expression in a primary culture of mammary epithelial cells isolated from lactating sows
Authors: Sun Y.L. , Lin C.S. , Chou Y.C.
Published: June 2005

Porcine mammary epithelial cells (PMECs) were isolated from lactating sow mammary glands and cultured on a matrix gel. Primary culture cells expressed significant amounts of the specific marker cytokeratin as determined by immunohistochemistry, and exhibited mammary‐specific functions, such as transcription of α‐lactalbumin, β‐casein and β‐lactoglobulin genes. They also formed mammospheres when the medium was supplemented with lactogenic hormones. The PMECs were used to study gene transfer and expression in vitro. A gene encoding enhanced green fluorescent protein (EGFP) was used as a reporter and two constructs were investigated, pEGFP‐N1 (a vector constructed with a CMV promoter followed by the EGFP gene) and pGB562/GFP (a mammary gland‐specific expression vector with regulatory sequences from the goat β‐casein gene linked to EGFP). The efficiency of DNA transfer into the cultured PMECs was about 20–30%. GFP expression in the pGB562/GFP‐transfected PMECs was markedly stimulated by prolactin supplements in the medium. The established PMECs maintained optimal gene expression from 1 to 20 passages and appeared to provide an efficient and convenient system for assessing the expression of transgenes containing mammary gland‐specific promoters.
Protective effect of ginkgo biloba against gossypol‐induced apoptosis in human lymphocytes
Authors: Ergun Ufuk , Yurtcu Erkan , Ergun Mehmet Ali
Published: June 2005

Ginkgo biloba (EGb 761) is a well‐defined plant extract that directly scavenges hydroxyl radicals. It is a potent antioxidant that inhibits apoptosis in cultured cells and is effective in treating mild‐to‐moderate dementia in Alzheimer patients. Apoptosis is an active process of cell destruction and it plays an important role in pathological processes. The aim of this study is to investigate the anti‐apoptotic effect of EGb 761 in gossypol‐treated human lymphocytes. Pretreatment of lymphocytes with 10 μg/ml EGb 761 for 30 min or 1 h decreased the percentage of apoptosis to 17.5% and 20%, respectively. EGb 761 treatment (25–150 μg/ml) decreased the level of apoptosis to a plateau between 8 and 10% of the control values. We conclude that EGb 761 reduces gossypol‐induced apoptosis in human lymphocytes.
A daily process design study of attentional pain control strategies in the self‐management of cancer pain
Authors: Buck Rhiannon , Morley Stephen
Published: June 2005

This study investigated the use of attentional control strategies in the self‐management of pain using daily process design methodology. Twenty six cancer patients with pain completed diaries 3 times daily for 10 days. Diaries incorporated measures of pain intensity, affect, coping, coping efficacy, and the novelty and predictability of pain, and participants completed a cross‐sectional measure of catastrophizing. At the across‐person level, focusing on pain was associated with increased negative affect, and the use of pain focusing strategies was positively correlated with experiencing pain that was novel in its location or quality. Distractions that were interesting, important and pleasant were positively correlated with positive affect, perceptions of control over pain and ability to decrease pain. Over‐prediction of pain was positively correlated with catastrophizing, and negatively correlated with perceptions of control over and ability to decrease pain. The within‐person analysis (ARIMA modelling) showed that catastrophizing moderated the effects of pain focusing strategies, novel pain and over‐predictions of pain. Meta‐analysis of the ARIMA models revealed that the within‐person effects of using attentional strategies did not generalize across the sample. These findings indicated that the effects of distraction strategies are influenced by their motivational‐affective significance rather than the frequency with which they are used, and provided further evidence that the threat value of pain influences the way in which people cope with their pain. Theoretical and clinical implications are discussed.
Lacosamide displays potent antinociceptive effects in animal models for inflammatory pain
Authors: Stöhr Thomas , Krause Eva , Selve Norma
Published: June 2005

Lacosamide is a functionalized amino acid which was initially synthesized as an antiepileptic drug. In addition to its broad anti‐seizure activity, lacosamide was shown to display efficacy in animal models for neuropathic pain and is currently in phase III clinical development for the treatment of epilepsy and neuropathic pain. In order to further profile its antinociceptive properties, the effects of lacosamide on inflammatory pain in the formalin test, the carrageenan model and the adjuvant‐induced arthritis model were investigated.

For the formalin test, mice received an intraplantar injection of formalin and the subsequent licking response was measured over 45 min. Lacosamide was administered 30 min before formalin. For the carrageenan model, mechanical and thermal hyperalgesia were assessed 3 h following an intraplantar injection of carrageenan. Lacosamide was administered to rats 30 min before pain threshold measurements. For the adjuvant‐induced arthritis test rats received intraplantar injections of Freund's complete adjuvant into the right hindpaw which lead to the development of arthritic symptoms in all animals tested for antinociception. On day 11 after arthritis induction, mechanical hyperalgesia was assessed by the modified Randall Selitto paw pressure test following acute treatment with lacosamide.

Lacosamide dose‐dependently attenuated mechanical hyperalgesia following carrageenan injection and in rats suffering from Freund's complete adjuvant‐induced arthritis. Moreover, thermal hyperalgesia induced by carrageenan as well as the formalin‐induced licking response were dose‐dependently attenuated by lacosamide.

These results suggest lacosamide may be active against various forms of acute and chronic inflammatory pain in humans.
TNF‐α enhances phenotypic and functional maturation of human epidermal Langerhans cells and induces IL‐12 p40 and IP‐10/CXCL‐10 production
Authors: Berthier-Vergnes Odile , Bermond Fabienne , Flacher Vincent , Massacrier Catherine , Schmitt Daniel , Péguet-Navarro Josette
Published: June 2005

Dendritic cells (DC) play a central role in immunity/tolerance decision, depending on their activation/maturation state. TNF‐α is largely produced in the skin under inflammatory conditions. However, it still remains to be defined how TNF‐α modulates the activation status of human LC, the most specialized DC controlling skin immunity. Here, we reported that fresh immature LC, highly purified from healthy human skin and exposed for two days to TNF‐α under serum‐free conditions, expressed up‐regulated level of co‐stimulatory molecules (CD40, CD54, CD86), maturation markers (CD83, DC‐LAMP), CCR7 lymph node homing receptor, and down‐regulated Langerin level, in a dose‐dependent manner. This mature phenotype is closely associated with enhanced LC allostimulatory capacity. Furthermore, TNF‐α significantly increased the number of viable LC and decreased their spontaneous apoptosis. More importantly, TNF‐α induced LC to produce both IFN‐gamma‐inducible‐protein IP‐10/CXCL10, a Th1‐attracting chemokine and IL‐12 p40. Bioactive IL‐12 p70 was never detected, even after additional CD40 stimulus. The results implicate LC as an effective target through which TNF‐α may up‐ or down‐regulate the inflammatory skin reactions.
RETRACTED: Role of the PDK1–PKB–GSK3 pathway in regulating glycogen synthase and glucose uptake in the heart
Authors: Mora Alfonso , Sakamoto Kei , McManus Edward J. , Alessi Dario R.
Published: June 2005

In order to investigate the importance of the PDK1–PKB–GSK3 signalling network in regulating glycogen synthase (GS) in the heart, we have employed tissue specific conditional knockout mice lacking PDK1 in muscle (mPDK1−/−), as well as knockin mice in which the protein kinase B (PKB) phosphorylation site on glycogen synthase kinase‐3α (GSK3α) (Ser21) and GSK3β (Ser9) is changed to Ala. We demonstrate that in hearts from mPDK1−/− or double GSK3α/GSK3β knockin mice, insulin failed to stimulate the activity of GS or induce its dephosphorylation at residues that are phosphorylated by GSK3. We also establish that in the heart, both GSK3 isoforms participate in the regulation of GS, with GSK3β playing a more prominent role. This contrasts with skeletal muscle where GSK3β is the major regulator of insulin‐induced GS activity. Despite the inability of insulin to stimulate glycogen synthesis in hearts from the mPDK1−/− or double GSK3α/GSK3β knockin mice, these animals possessed normal levels of cardiac glycogen, demonstrating that total glycogen levels are regulated independently of insulin's ability to stimulate GS in the heart and that mechanisms such as allosteric activation of GS by glucose‐6‐phosphate and/or activation of GS by muscle contraction, could operate to maintain normal glycogen levels in these mice. We also demonstrate that in cardiomyocytes derived from the mPDK1−/− hearts, although the levels of glucose transporter type 4 (GLUT4) are increased 2‐fold, insulin failed to stimulate glucose uptake, providing genetic evidence that PDK1 plays a crucial role in enabling insulin to promote glucose uptake in cardiac muscle.
Sp1 elements in SULT2B1b promoter and 5′‐untranslated region of mRNA: Sp1/Sp2 induction and augmentation by histone deacetylase inhibition
Authors: Lee Young C. , Higashi Yuko , Luu Chu , Shimizu Chikara , Strott Charles A.
Published: June 2005

The steroid/sterol sulfotransferase gene (SULT2B1) encodes for two isozymes of which one (SULT2B1b) sulfonates cholesterol and is selectively expressed in skin. The human SULT2B1 gene contains neither a TATAAA nor a CCAAT motif upstream of the coding region for SULT2B1b; however, this area is GC‐rich. Of five Sp1 elements identified two had regulatory activity utilizing immortalized human keratinocytes: one element is located above the ostensible transcription initiation site, whereas the other is located within the 5′‐untranslated region of the SULT2B1b mRNA. Sp1 and Sp2 transcription factors identified by supershift analyses induced reporter gene activity, an effect markedly augmented by histone deacetylase inhibition.
Purification and functional reconstitution of the human Wilson copper ATPase, ATP7B
Authors: Portmann Reto , Solioz Marc
Published: June 2005

Wilson disease is a disorder of copper metabolism, due to inherited mutations in the Wilson copper ATPase gene ATP7B. To purify and study the function of the ATPase, the enzyme was truncated by five of the six metal binding domains and endowed with an N‐terminal histidine‐tag for affinity purification. This construct, Δ1–5WNDP, was able to functionally complement a yeast strain defective in its native copper ATPase CCC2. Δ1–5WNDP was purified by Ni‐affinity chromatography and reconstituted into proteoliposomes. This allowed, for the first time, the functional study of the Wilson ATPase in a purified, reconstituted system.
Cooperative effect of hydrophobic and electrostatic forces on alcohol‐induced α‐helix formation of α1‐acid glycoprotein
Authors: Nishi Koji , Komine Yoshio , Sakai Norifumi , Maruyama Toru , Otagiri Masaki
Published: June 2005

α1‐Acid glycoprotein (AGP) is a serum glycoprotein that mainly binds basic drugs. Previous reports have shown that AGP converts from a β‐sheet to an α‐helix upon interaction with biomembranes. In the current studies, we found that alkanols, diols, and halogenols all induce this conformational change. Increased length and bulkiness of the hydrocarbon group and the presence of a halogen atom promoted this conversion, whereas the presence of a hydroxyl group inhibited it. Moreover, the effect was dependent on the hydrophobic and electrostatic properties of the alcohols. These results indicate that, in a membrane environment, hydrophobic and electrostatic factors cooperatively induce the transition of AGP from a β‐sheet to an α‐helix.
Disulfide‐bond formation in the H+‐pyrophosphatase of Streptomyces coelicolor and its implications for redox control and enzyme structure
Authors: Mimura Hisatoshi , Nakanishi Yoichi , Maeshima Masayoshi
Published: June 2005

Redox control of disulfide‐bond formation in the H+‐pyrophosphatase of Streptomyces coelicolor was investigated using cysteine mutants expressed in Escherichia coli. The wild‐type enzyme, but not a cysteine‐less mutant, was reversibly inactivated by oxidation. To determine the residues involved in oxidative inactivation, different cysteine residues were replaced. Analysis with a cysteine‐modifying reagent revealed that the formation of a disulfide bond between cysteines 253 and 621 was responsible for enzyme inactivation. This result suggests that residues in different cytoplasmic loops are close to each other in the tertiary structure. Both cysteine residues are conserved in K+‐independent (type II) H+‐pyrophosphatases.
Expression of pro‐apoptotic Bfk isoforms reduces during malignant transformation in the human gastrointestinal tract
Authors: Dempsey Clare E. , Dive Caroline , Fletcher Daniel J. , Barnes Frances A. , Lobo Alan , Bingle Colin D. , Whyte Moira K.B. , Renshaw Stephen A.
Published: June 2005

Reduced expression of pro‐apoptotic Bcl‐2 family proteins has been described in many gastrointestinal cancers, and may play a role in tumourigenesis. The human homologue of the pro‐apoptotic Bcl‐2 protein, Bfk, is predominantly expressed in tissues of the gastrointestinal tract. In colon, four alternatively spliced isoforms were identified; of which two are pro‐apoptotic when overexpressed. In the transition from normal tissue to tumour, pro‐apoptotic Bfk isoform expression is substantially reduced in up to 80% of tumours isolated from the human gastrointestinal tract (8/10 colonic tumours and 26/37 of all gastrointestinal tumours) compared to 3/117 tumours from outside the gastrointestinal tract. These data suggest that pro‐apoptotic isoforms of Bfk may help to protect against the development of human gastrointestinal malignancy.
Hsp27‐2D‐gel electrophoresis is a diagnostic tool to differentiate primary desminopathies from myofibrillar myopathies
Authors: Clemen Christoph S. , Fischer Dirk , Roth Udo , Simon Stéphanie , Vicart Patrick , Kato Kanefusa , Kaminska Anna M. , Vorgerd Matthias , Goldfarb Lev G. , Eymard Bruno , Romero Norma B. , Goudeau Bertrand , Eggermann Thomas , Zerres Klaus , Noegel Angelika A. , Schröder Rolf
Published: June 2005

Small heat shock proteins prevent abnormal protein folding and accumulation. We analyzed the expression of hsp27 and αB‐crystallin in skeletal muscle specimens of patients with desminopathies, plectinopathies, myotilinopathy, and other myofibrillar myopathies by means of differential centrifugation, 2D‐gel electrophoresis, Western blotting, and mass spectrometry. Hsp27‐P82 and ‐P15 as well as αB‐crystallin‐P59 and ‐P45 are the major serine phosphorylation isoforms in normal and diseased human skeletal muscle. 2D‐gel‐electrophoresis revealed spots of hsp27 in a range of pH 5.3–6.4 in samples of all skeletal muscle specimens, except for the seven desminopathies. They indicated a shift of the main hsp27‐spot to alkaline pH degrees, which may help to differentiate primary desminopathies from other myopathies with structural pathology of the desmin cytoskeleton.
Phospho‐STAT5 accumulation in nuclear fractions from vitamin A‐deficient rat liver
Authors: Murray Michael , Butler Alison M. , Fiala-Beer Eva , Su Gloria M.
Published: June 2005

The growth hormone (GH)‐responsive cytochrome P450 (CYP) 2C11 is down‐regulated in vitamin A‐deficient (VAD) rat liver. This study assessed the impact of a VAD diet on the hepatic Janus kinase‐Signal Transducers and Activators of Transcription (JAK‐STAT) system that mediates GH signalling. Nuclear tyrosine‐ and serine‐phosphorylated STAT5 accumulated in VAD liver, whereas nuclear JAK2 tyrosine kinase and SHP‐1 phosphatase were decreased. Tyrosine‐phosphorylated SHP‐1 was decreased to 36 ± 14% of control (P
< 0.01), indicating its impaired activation in VAD liver. Episodic GH pulses increased nuclear phospho‐STAT5, especially in control liver, but nuclear phospho‐JAK2 and phospho‐SHP‐1 were not restored. CYP2C11 protein and testosterone 16α‐hydroxylation were decreased in VAD liver to 67 ± 16% and 76 ± 19% of control, and were further decreased by GH to 32 ± 8% and 30 ± 14% of control. Thus, hypo‐responsiveness of JAK‐STAT in VAD liver is associated with impaired nuclear phospho‐STAT dephosphorylation.
The properties of the mitochondrial megachannel in mitoplasts from human colon carcinoma cells are not influenced by Bax
Authors: Campello Silvia , Marchi Umberto De , Szabò Ildikò , Tombola Francesco , Martinou Jean-Claude , Zoratti Mario
Published: June 2005

This paper explores the relationship between Bax and the mitochondrial permeability transition pore (PTP). Isolated human colon tumor (HCT116) Bax− mitochondria exposed to recombinant Bax exhibited a slow, cyclosporin A‐sensitive swelling, but only at [Bax] >
200 nM. The amount of Bax incorporated was much higher than that found in organelles isolated from HCT116 Bax+ staurosporine‐ or etoposide‐treated apoptotic cells, casting doubts on the significance of the putative PT induction for apoptosis. Bax did not influence the electrophysiological properties of an approximately 1 nS channel ascribed to the Ca2+‐dependent mitochondrial permeability transition pore. These observations indicate that the PTP is independent of Bax.
Comparison of replicative senescence and stress‐induced premature senescence combining differential display and low‐density DNA arrays
Authors: Pascal Thierry , Debacq-Chainiaux Florence , Chrétien Aline , Bastin Coralie , Dabée Anne-France , Bertholet Vincent , Remacle José , Toussaint Olivier
Published: June 2005

Human diploid fibroblasts (HDFs) exposed to subcytotoxic stress display many features of senescence. Using differential display RT‐PCR, gene expression of HDFs in premature senescence induced by tert‐butylhydroperoxide or ethanol and in replicative senescence was compared to gene expression of HDFs at early cumulative population doublings. Thirty genes of known function were identified from the 265 differentially displayed cDNA fragments. A customized low‐density array allowed to confirm the relative level of the corresponding 30 transcripts. We found differential expression of genes coding for proteins implicated namely in growth arrest (PTEN, IGFBP‐3, LRP‐1 and CAV1), senescent morphogenesis (TGF‐β1 and LOXL2) and iron metabolism (TFR and FTL).
Multiple Plexiform Schwannoma of the Hand and Forearm: A Long-Term Follow-Up
Authors: TALWALKAR S. C. , CUTLER L. , STILWELL J. H.
Published: June 2005

We present a case report to illustrate the differential diagnosis and management of a multiple plexiform schwannoma involving the main nerve trunks of the upper limb in a 4 year-old boy. The tumour was diagnosed by MRI scan and histological examination. A 12 year follow-up is presented in which, despite multiple recurrences, the condition has been controlled by surgical means and the limb salvaged.
The Safest Location for Steroid Injection in the Treatment of Carpal Tunnel Syndrome
Authors: RACASAN O. , DUBERT TH.
Published: June 2005

Steroid injections are routinely performed for carpal tunnel syndrome. Direct needle injury of the median nerve is the major complication of these injections. The safest location of the injection remains controversial. The purpose of this study is to define safe guidelines to avoid nerve injury. The distances between the Median nerve, Palmaris Longus, Flexor Carpi Ulnaris and Flexor Carpi Radialis tendons were measured preoperatively, 1 cm proximal to the distal wrist crease in 93 endoscopic carpal tunnel releases. We found that the median nerve extended ulnarly beyond the Palmaris Longus tendon in 82 hands (88%). It is concluded that the median nerve is at risk if the injection is performed within 1 cm on either the ulnar or radial side of the Palmaris Longus tendon. More ulnarly, there is risk to the ulnar pedicle. The safest location is to inject through the FCR tendon.