bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolated metastatic extremity liposarcoma to the liver, an uncommon and transient finding
Authors: Garces Christopher A , Reith John D , Grobmyer Stephen R , Hochwald Steven N 
Published: October 2008

Abstract

Background
Extremity liposarcomas can metastasize to different areas of the body but have rarely been demonstrated to metastasize to the liver. Due to the unusual occurrence of isolated metastatic extremity liposarcoma to the liver, the optimal treatment of this condition is unknown.

Case presentation
Less than one year after resection of a myxoid/round cell liposarcoma of the left lateral calf, a 61-year-old male presented with a CT scan showing a 2 cm low-density lesion in the right lobe of the liver. The lesion tripled in size over the next few months. An extensive evaluation revealed isolated disease to the liver. The lesion was surgically removed with a right hepatic lobectomy and the pathology was consistent with metastatic myxoid/round cell liposarcoma.

Conclusion
Although extremity liposarcoma rarely metastasizes solely to the liver, the best chance at cure is with complete resection. Unfortunately, cure rates are very low in the setting of metastatic disease. As expected, the patient experienced progression of disease at sites outside of the liver 5 months after the liver resection.
Flexible Two-Phase studies for rare exposures: Feasibility, planning and efficiency issues of a new variant
Authors: Wild Pascal , Andrieu Nadine , Goldstein Alisa M , Schill Walter 
Published: October 2008

AbstractThe two-phase design consists of an initial (Phase One) study with known disease status and inexpensive covariate information. Within this initial study one selects a subsample on which to collect detailed covariate data. Two-phase studies have been shown to be efficient compared to standard case-control designs. However, potential problems arise if one cannot assure minimum sample sizes in the rarest categories or if recontact of subjects is difficult.In the case of a rare exposure with an inexpensive proxy, the authors propose the flexible two-phase design for which there is a single time of contact, at which a decision about full covariate ascertainment is made based on the proxy. Subjects are screened until the desired numbers of cases and controls have been selected for full data collection. Strategies for optimizing the cost/efficiency of this design and corresponding software are presented. The design is applied to two examples from occupational and genetic epidemiology. By ensuring minimum numbers for the rarest disease-covariate combination(s), we obtain considerable efficiency gains over standard two-phase studies with an improved practical feasibility.The flexible two-phase design may be the design of choice in the case of well targeted studies of the effect of rare exposures with an inexpensive proxy.
Questions on causality and responsibility arising from an outbreak of Pseudomonas aeruginosa infections in Norway
Authors: Iversen Bjørn G , Hofmann Bjørn , Aavitsland Preben 
Published: October 2008

AbstractIn 2002, Norway experienced a large outbreak of Pseudomonas aeruginosa infections in hospitals with 231 confirmed cases. This fuelled intense public and professional debates on what were the causes and who were responsible. In epidemiology, other sciences, in philosophy and in law there is a long tradition of discussing the concept of causality. We use this outbreak as a case; apply various theories of causality from different disciplines to discuss the roles and responsibilities of some of the parties involved. Mackie's concept of INUS conditions, Hill's nine viewpoints to study association for claiming causation, deterministic and probabilistic ways of reasoning, all shed light on the issues of causality in this outbreak. Moreover, applying legal theories of causation (counterfactual reasoning and the "but-for" test and the NESS test) proved especially useful, but the case also illustrated the weaknesses of the various theories of causation.We conclude that many factors contributed to causing the outbreak, but that contamination of a medical device in the production facility was the major necessary condition. The reuse of the medical device in hospitals contributed primarily to the size of the outbreak. The unintended error by its producer – and to a minor extent by the hospital practice – was mainly due to non-application of relevant knowledge and skills, and appears to constitute professional negligence. Due to criminal procedure laws and other factors outside the discourse of causality, no one was criminally charged for the outbreak which caused much suffering and shortening the life of at least 34 people.
Protocol of an expertise based randomized trial comparing surgical Venae Sectio versus radiological Puncture of Vena Subclavia for insertion of Totally Implantable Access Port in oncological patients
Authors: Knebel Philip , Fischer Lars , Cremonese Eva , Lopez-Benitez Ruben , Stampfl Ulrike , Radeleff Boris , Kauczor Hans-Ulrich , Büchler Markus W , Seiler Christoph M 
Published: October 2008

Abstract

Background
Totally Implantable Access Ports (TIAP) are being extensively used world-wide and can be expected to gain further importance with the introduction of new neoadjuvant and adjuvant treatments in oncology. Two different techniques for the implantation can be selected: A direct puncture of a central vein and the utilization of a Seldinger device or the surgical Venae sectio. It is still unclear which technique has the optimal benefit/risk ratio for the patient.

Design
A single-center, expertise based randomized, controlled superiority trial to compare two different TIAP implantation techniques. 100 patients will be included and randomized pre-operatively. All patients aged 18 years or older scheduled for primary elective implantation of a TIAP under local anesthesia who signed the informed consent will be included. The primary endpoint is the primary success rate of the randomized technique. Control Intervention: Venae Sectio will be employed to insert a TIAP by a surgeon; Experimental intervention: Punction of V. Subclavia will be used to place a TIAP by a radiologist. Duration of study: Approximately 10 months, follow up time: 90 days.

Organisation/Responsibility
The PORTAS 2 – Trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The Center of Clinical Trials at the Department of Surgery, University Hospital Heidelberg is responsible for design and conduct of the trial including randomization and documentation of patients' data. Data management and statistical analysis will be performed by the independent Institute for Medical Biometry and Informatics (IMBI), University of Heidelberg.

Trial Registration
The trial is registered at ClinicalTrials.gov (NCT00600444).
Mucinous breast carcinoma presenting as Paget's disease of the nipple in a man: A case report
Authors: Peschos Dimitrios , Tsanou Elena , Dallas Pavlos , Charalabopoulos Konstantinos , Kanaris Christos , Batistatou Anna 
Published: October 2008

AbstractIntroductionMale breast cancer is rare compared to its female counterpart representing less than 1% of cancer in men. Moreover, mucinous carcinoma of the male breast is an extremely rare histological subtype of malignancy. Paget's disease of the nipple is rarely observed in males.Case reportHerein, we describe a unique case of an 86 years old man with mucinous breast cancer presenting as Paget's disease of the nipple. According to the immunohistochemical evaluation the neoplastic cells were positive for estrogen (ER) and progesterone receptors (PR).ConclusionTo our best knowledge this is the first case of mucinous male breast cancer presenting as Paget's disease of the nipple.
Selective segregation of DNA strands persists in long label retaining mammary cells during pregnancy
Authors: Booth Brian W , Boulanger Corinne A , Smith Gilbert H 
Published: October 2008

Abstract
Introduction
During pregnancy the mammary epithelial compartment undergoes extreme proliferation and differentiation, facilitated by stem/progenitor cells. Mouse mammary epithelium in nonpregnant mice contains long label-retaining epithelial cells (LREC) that divide asymmetrically and retain their template DNA strands. The role of LREC during alveogenesis has not been determined.

Methods
We performed immunohistochemistry and autoradiography on murine mammary glands that had been labeled with 5-bromodeoxyuridine (5BrdU) during allometric ductal growth to investigate the co-expression of DNA label retention and estrogen receptor-α or progesterone receptor during pregnancy. A second DNA label ([3H]-thymidine) was administered during pregnancy to identify label-retaining cells (LRC), which subsequently enter the cell cycle. Use of this methodology allowed us to investigate the co-localization of 5BrdU with smooth muscle actin, CD31, cytokeratin, and desmin in periductal or peri-acinar LRC in mammary tissue from pregnant mice subsequent to a long chase period in order to identify LRC.

Results
Estrogen receptor-α positive and progesterone receptor positive cells represented approximately 30% to 40% of the LREC, which is under 1.0% of the epithelial subpopulation. Pregnancy altered the percentage of LREC expressing estrogen receptor-α. LRC situated in periductal or peri-acinar positions throughout the gland do not express epithelial, endothelial, or myoepithelial markers, and these undefined LRCs persist throughout pregnancy. Additionally, new cycling LREC ([3H]-thymidine retaining) appear during alveologenesis, and LRC found in other tissue types (for example, endothelium and nerve) within the mammary fat pad become double labeled during pregnancy, which indicates that they may also divide asymmetrically.

Conclusions
Our findings support the premise that there is a subpopulation of LREC in the mouse mammary gland that persists during alveologenesis. These cells react to hormonal cues during pregnancy and enter the cell cycle while continuing to retain, selectively, their original template DNA. In addition, nonepithelial LRC are found in periductal or peri-acinar positions. These LRC also enter the cell cycle during pregnancy. During alveologenesis, newly created label-retaining ([3H]-thymidine) epithelial cells appear within the expanding alveoli and continue to cycle and retain their original template DNA ([3H]-thymidine) strands, as determined by a second pulse of 5BrdU.
Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negativegld/gldmice
Authors: Wiede Florian , Roomberg Alicia , Cretney Erika , Lechner Anja , Fromm Phillip , Wren Leia , Smyth Mark J , Körner Heinrich 
Published: October 2008

AbstractThe generalized lymphoproliferative disorder (gld) mouse strain is characterized by severe splenomegaly/lymphadenopathy, the production of autoimmune antibodies, and the appearance of CD4/CD8-negative T cells. An additional TNF deficiency of gld/gld mice attenuates the course of the disorder through a yet-unknown mechanism. In this study, we could demonstrate that the reduced splenomegaly and lymphadenopathy in B6.gld/gld.TNF−/− mice were correlated with a decreased peripheral T cell proliferation rate and a delayed polyclonal activation. A comparative analysis of naïve T cells and memory/effector T cells showed an age-dependent difference in the T cell activation pattern in the spleen of B6.gld/gld and B6.gld/gld.TNF−/− mice. T cells from B6.gld/gld.TNF−/− spleens and lymph nodes showed significantly higher levels of CCR7 and CD62 ligand on their surface compared with B6.gld/gld mice when mice of the same age were compared. Additionally, we found an increased titer of the Th1 cytokine IFN-γ in the serum of B6.gld/gld mice, whereas the concentration of IFN-γ was markedly reduced in the serum of B6.gld/gld.TNF−/− mice. These findings support the hypothesis that increased T cell activation and proliferation in the presence of TNF contribute to the exacerbation of the gld syndrome.
Direct observations of the kinetics of migrating T cells suggest active retention by endothelial cells with continual bidirectional migration
Authors: McGettrick Helen M , Hunter Kirsty , Moss Paul A , Buckley Christopher D , Rainger G Ed , Nash Gerard B 
Published: October 2008

AbstractThe kinetics and regulatory mechanisms of T cell migration through the endothelium have not been fully defined. In experimental, filter-based assays in vitro, transmigration of lymphocytes takes hours, compared with minutes, in vivo. We cultured endothelial cell (EC) monolayers on filters, solid substrates, or collagen gels and treated them with TNF-α, IFN-γ, or both prior to analysis of lymphocyte migration in the presence or absence of flow. PBL, CD4+ cells, or CD8+ cells took many hours to migrate through EC-filter constructs for all cytokine treatments. However, direct microscopic observations of EC filters, which had been mounted in a flow chamber, showed that PBL crossed the endothelial monolayer in minutes and were highly motile in the subendothelial space. Migration through EC was also observed on clear plastic, with or without flow. After a brief settling without flow, PBL and isolated CD3+ or CD4+ cells crossed EC in minutes, but the numbers of migrated cells varied little with time. Close observation revealed that lymphocytes migrated back and forth continuously across endothelium. Under flow, migration kinetics and the proportions migrating back and forth were altered little. On collagen gels, PBL again crossed EC in minutes and migrated back and forth but showed little penetration of the gel over hours. In contrast, neutrophils migrated efficiently through EC and into gels. These observations suggest a novel model for lymphoid migration in which EC support migration but retain lymphocytes (as opposed to neutrophils), and additional signal(s) are required for onward migration.
Sex Change in the Gobiid Fish Is Mediated through Rapid Switching of Gonadotropin Receptors from Ovarian to Testicular Portion or Vice Versa
Authors: Kobayashi Yasuhisa , Nakamura Masaru , Sunobe Tomoki , Usami Takeshi , Kobayashi Tohru , Manabe Hisaya , Paul-Prasanth Bindhu , Suzuki Norio , Nagahama Yoshitaka 
Published: October 2008

Sex-changing fish Trimma okinawae can change its sex back and forth from male to female and then to male serially, depending on the social status in the harem. T. okinawae is well equipped to respond to its social status by possessing both ovarian and testicular tissues even though only one gonad remains active at one time. Here we investigated the involvement of gonadotropins in sex change by determining the changes in gonadotropin receptor (GtHR) gene expression during the onset of sex change from female to male and male to female. The expression of the GtHR was found to be confined to the active gonad of the corresponding sexual phase. During the sex-change from female to male, initially the ovary had high levels of FSHR and LHR, which eventually went up in the testicular tissue if the fish was bigger. Changing of the gonads started with switching of GtHR expression discernible within 8–12 h of the visual cue. Further in vitro culture of the transitional gonads with a supply of exogenous gonadotropin (human chorionic gonadotropin) revealed that the to-be-active gonad acquired the ability to produce the corresponding sex hormone within 1 d of the activation of GtHR. Conversely, the to-be-regressed gonad did not respond to the exogenous gonadotropin. Our findings show that the gonads of successive sex-changing fish possess the intrinsic mechanism to respond to the social cue differentially. Additionally, this location switching of GtHR expression also could substantiate the importance of the hypothalamo-pituitary-gonadotropic axis.
Gonadal sex-change in goby, in response to social cue, is mediated through a rapid switching in the expression of GtH receptors in the gonads.
Interferon-Stimulated Gene ISG12b1 Inhibits Adipogenic Differentiation and Mitochondrial Biogenesis in 3T3-L1 Cells
Authors: Li Bing , Shin Jonghyun , Lee Kichoon 
Published: October 2008

Microarray analysis was performed to find a new group of genes or pathways that might be important in adipocyte development and metabolism. Among them, a mouse interferon-stimulated gene 12b1 (ISG12b1) is expressed at a 400-fold higher level in adipocytes compared with stromal-vascular cells. It is predominantly expressed in adipose tissue among other tissues we tested. Developmentally, ISG12b1 mRNA expression was initially inhibited followed by a dramatic induction during both in vivo and in vitro adipogenic differentiation. Adenovirus-mediated overexpression of ISG12b1 inhibited adipogenic differentiation in 3T3-L1 cells as shown by decreased lipid staining with Oil-Red-O and reduction in adipogenic marker proteins including peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer-binding protein-α (C/EBPα). Our bioinformatics analysis for the predicted localization of ISG12b1 protein suggested the mitochondrial localization, which was confirmed by the colocalization of hemagglutinin-tagged ISG12b1 protein with mitochondrial marker MitoTracker. In addition, ISG12b1 protein was exclusively detected in protein extract from the fractionated mitochondria by Western blot analysis. Furthermore, overexpression of ISG12b1 in adipocytes reduced mitochondrial DNA content and gene expression of mitochondrial transcription factor A (mtTFA), nuclear respiratory factor 1 (NRF1), and cytochrome oxidase II, suggesting an inhibitory role of ISG12b1 in mitochondrial biogenesis and function. Activation of mitochondrial biogenesis and function by treatment with PPARγ and PPARα agonists in 3T3-L1 cells and cold exposure in mice induced mitochondrial transcription factors and reduced ISG12 expression. These data demonstrated that mitochondrial-localized ISG12b1 protein inhibits adipocyte differentiation and mitochondrial biogenesis and function, implying the important role of mitochondrial function in adipocyte development and associated diseases.
ISG12b1 is predominantly expressed in adipocytes and dramatically induced at the terminal stage of adipogenesis. Functionally, mitochondria-localized ISG12b1 inhibits adipogenic differentiation and mitochondria biogenesis.
Deficiency of Angiotensin Type 2 Receptor Rescues Obesity But Not Hypertension Induced by Overexpression of Angiotensinogen in Adipose Tissue
Authors: Yvan-Charvet Laurent , Massiéra Florence , Lamandé Noël , Ailhaud Gérard , Teboul Michèle , Moustaid-Moussa Naima , Gasc Jean-Marie , Quignard-Boulangé Annie 
Published: October 2008

Increased angiotensinogen (AGT) production by white adipose tissue has been related to not only obesity but also hypertension. Several studies have highlighted the importance of the angiotensin II type 2 receptor (AT2) in the regulation of blood pressure and fat mass, but the relevance of this transporter in a physiopathological model of increased AGT production, as it occurs in obesity, has not yet been investigated. We used transgenic mice that display either a deletion of AT2 (AT2 KO), an overexpression of AGT (OVEX), or both compound mutants (KOVEX). Results demonstrated that adipocyte hypertrophy and increased lipogenic gene expression induced by adipose AGT overproduction was rescued by deletion of AT2. In line with AGT overexpression, KOVEX and OVEX mice have similar increased plasma AGT levels. However, KOVEX mice display a higher blood pressure than OVEX mice. In kidney, renin expression was clearly reduced in OVEX mice, and its expression was normalized in KOVEX mice. Taken together, we demonstrated that the loss of AT2 expression was sufficient to rescue obesity induced by adipose tissue AGT overexpression and confirmed the necessary role of AT2 for the onset of obesity in this model. Furthermore, despite a reduction of adipose mass in KOVEX, AT2 deficiency caused increased renin production, further worsening the hypertension caused by AGT overexpression.
Angiotensin type 2 receptor shows antihypertensive function but promotes the angiotensin II-mediated fat mass enlargement.
Intrameal Hepatic Portal and Intraperitoneal Infusions of Glucagon-Like Peptide-1 Reduce Spontaneous Meal Size in the Rat via Different Mechanisms
Authors: Rüttimann Elisabeth B. , Arnold Myrtha , Hillebrand Jacquelien J. , Geary Nori , Langhans Wolfgang 
Published: October 2008

Peripheral administration of glucagon-like peptide (GLP)-1 reduces food intake in animals and humans, but the sites and mechanism of this effect and its physiological significance are not yet clear. To investigate these issues, we prepared rats with chronic catheters and infused GLP-1 (0.2 ml/min; 2.5 or 5.0 min) during the first spontaneous dark-phase meals. Infusions were remotely triggered 2–3 min after meal onset. Hepatic portal vein (HPV) infusion of 1.0 or 3.0 (but not 0.33) nmol/kg GLP-1 reduced the size of the ongoing meal compared with vehicle without affecting the subsequent intermeal interval, the size of subsequent meals, or cumulative food intake. In double-cannulated rats, HPV and vena cava infusions of 1.0 nmol/kg GLP-1 reduced meal size similarly. HPV GLP-1 infusions of 1.0 nmol/kg GLP-1 also reduced meal size similarly in rats with subdiaphragmatic vagal deafferentations and in sham-operated rats. Finally, HPV and ip infusions of 10 nmol/kg GLP-1 reduced meal size similarly in sham-operated rats, but only HPV GLP-1 reduced meal size in subdiaphragmatic vagal deafferentation rats. These data indicate that peripherally infused GLP-1 acutely and specifically reduces the size of ongoing meals in rats and that the satiating effect of ip, but not iv, GLP-1 requires vagal afferent signaling. The findings suggest that iv GLP-1 infusions do not inhibit eating via hepatic portal or hepatic GLP-1 receptors but may act directly on the brain.
Intrameal hepatic portal and intraperitoneal (IP) infusions of GLP-1 reduce meal size in rats, but only IP GLP-1 requires vagal afferent signaling for this effect.