bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational spectrum of APC and genotype-phenotype correlations in Greek FAP patients
Authors: Fostira Florentia , Thodi Georgia , Sandaltzopoulos Raphael , Fountzilas George , Yannoukakos Drakoulis 
Published: July 2010

Abstract

Background
Familial adenomatous polyposis, an autosomal dominant inherited disease caused by germline mutations within the APC gene, is characterized by early onset colorectal cancer as a consequence of the intrinsic phenotypic feature of multiple colorectal adenomatic polyps. The genetic investigation of Greek adenomatous polyposis families was performed in respects to APC and MUTYH germline mutations. Additionally, all available published mutations were considered in order to define the APC mutation spectrum in Greece.

Methods
A cohort of 25 unrelated adenomatous polyposis families of Greek origin has been selected. Genetic testing included direct sequencing of APC and MUTYH genes. APC gene was also checked for large genomic rearrangements by MLPA.

Results
Analysis of the APC gene performed in a Greek cohort of twenty five FAP families revealed eighteen different germline mutations in twenty families (80%), four of which novel. Mutations were scattered between exon 3 and codon 1503 of exon 15, while no large genomic rearrangements were identified.

Conclusion
This concise report describes the spectrum of all APC mutations identified in Greek FAP families, including four novel mutations. It is concluded that the Greek population is characterized by genetic heterogeneity, low incidence of genomic rearrangements in APC gene and lack of founder mutation in FAP syndrome.
Low haemoglobin predicts early mortality among adults starting antiretroviral therapy in an HIV care programme in South Africa: a cohort study
Authors: Russell Elizabeth C , Charalambous Salome , Pemba Lindiwe , Churchyard Gavin J , Grant Alison D , Fielding Katherine 
Published: July 2010

AbstractBackgroundAntiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people with HIV infection; however, mortality after the start of ART is high in resource-limited settings. We investigated risk factors for mortality among adults starting ART in a multi-clinic community programme in South Africa.MethodsCohort of adults starting ART at 27 clinics between February 2005 and June 2006, followed to 31stMarch 2007. Kaplan-Meier survival estimates were used to describe overall mortality. Shared frailty Cox regression was used to identify baseline risk factors for early mortality.ResultsAmong 1350 participants (median age 35.5 years, 60% female, median CD4 count 83/μL [interquartile range (27 - 147)], median follow-up 13.4 months), there were 185 deaths, overall mortality rate 13/100 pyrs; for 0-3, 3-9 and >9 months from ART start mortality rates were 24, 13 and 6/100 pyrs respectively. 43% of the deaths were in the first 3 months of treatment. Risk factors for mortality in univariable analysis were baseline CD4 count, viral load, haemoglobin and body mass index, in multivariable analysis adjusting for age and gender, only CD4 count and haemoglobin remained independently associated with proportional hazards not being satisfied for haemoglobin. Adjusted hazard ratios (aHR) for participants with haemoglobin <8, 8.1-9.9, >11.9(f)/12.9 (m) g/mL were 4.99, 3.05 and 0.12 respectively comparing to 10-11.9 (f)/12.9 (m)g/mL in the first 3 months of ART. aHRs for CD4 counts were 0.40, 0.38 and 0.34 for 50-99, 100-200 and >200/μL comparing to <50/μL.ConclusionsThe high mortality rate in the first 3 months underlines the need for earlier HIV diagnosis so that ART can be initiated earlier. Low haemoglobin and low CD4 count are both strong predictors of mortality, and could be used to identify individuals at high risk who might benefit from intensive case management.
Anthropometric, biochemical and clinical assessment of malnutrition in Malaysian patients with advanced cirrhosis
Authors: Tai Mei-Ling S , Goh Khean-Lee , Mohd-Taib Siti Hawa , Rampal Sanjay , Mahadeva Sanjiv 
Published: July 2010

Abstract

Background
There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies.

Methodology
A cross-sectional study of adult patients with decompensated cirrhosis was conducted. Nutritional status was assessed using standard anthropometry, serum visceral proteins and subjective global assessment (SGA).

Results
Thirty six patients (mean age 59.8 ± 12.8 years; 66.7% males; 41.6% viral hepatitis; Child-Pugh C 55.6%) with decompensated cirrhosis were recruited. Malnutrition was prevalent in 18 (50%) patients and the mean caloric intake was low at 15.2 kcal/kg/day. SGA grade C, as compared to SGA grade B, demonstrated significantly lower anthropometric values in males (BMI 18.1 ± 1.6 vs 26.3 ± 3.5 kg/m2, p < 0.0001; MAMC 19.4 ± 1.5 vs 24.5 ± 3.6 cm, p = 0.002) and females (BMI 19.4 ± 2.7 vs 28.9 ± 4.3, p = 0.001; MAMC 18.0 ± 0.9 vs 28.1 ± 3.6, p < 0.0001), but not with visceral proteins. The SGA demonstrated a trend towards more malnutrition in Child-Pugh C compared to Child-Pugh B liver cirrhosis (40% grade C vs 25% grade C, p = 0.48). Alcoholic cirrhosis had a higher proportion of SGA grade C (41.7%) compared to viral (26.7%) and cryptogenic (28.6%) cirrhosis, but this was not statistically significant.

Conclusion
Significant malnutrition in Malaysian patients with advanced cirrhosis is common. Alcoholic cirrhosis may have more malnutrition compared to other aetiologies of cirrhosis.
CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion
Authors: Johnson Erica L , Singh Rajesh , Singh Shailesh , Johnson-Holiday Crystal M , Grizzle William E , Partridge Edward E , Lillard James W 
Published: July 2010

AbstractBackgroundOvarian carcinoma (OvCa) is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells and its only natural ligand, CCL25, is largely expressed in the thymus, which involutes with age. Other than the thymus, CCL25 is expressed by the small bowel. Interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for OvCa cells. The current study shows OvCa tissue and cells significantly express CCR9, which interacts with CCL25 to support carcinoma cell migration and invasion.MethodsRT-PCR and flow cytometry techniques were used to quantify the expression CCR9 by OvCa cells. OvCa tissue microarrays (TMA) was used to confirm CCR9 expression in clinical samples. The Aperio ScanScope scanning system was used to quantify immunohistochemical staining. Cell invasion and migration assays were performed using cell migration and matrigel invasion chambers. Matrix metalloproteinase (MMP) mRNAs were quantified by RT-PCR and active MMPs were quantified by ELISA.ResultsOur results show significantly (p< 0.001) higher expression of CCR9 by mucinous adenocarcinoma, papillary serous carcinoma, and endometriod ovarian carcinoma cases, than compared to non-neoplastic ovarian tissue. Furthermore, CCR9 expression was significantly elevated in OvCa cell lines (OVCAR-3 and CAOV-3) in comparison to normal adult ovarian epithelial cell mRNA. OvCa cells showed higher migratory and invasive potential towards chemotactic gradients of CCL25, which was inhibited by anti-CCR9 antibodies. Expression of collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), and stromelysins (MMP-3, -10, and -11) by OvCa cells were modulated by CCL25 in a CCR9-dependent fashion.ConclusionsThese results demonstrate both biological significance and clinical relevance of CCL25 and CCR9 interactions in OvCa cell metastasis.
The impact of non-significant variable decelerations appearing in the latent phase on delivery mode: a prospective cohort study
Authors: Salim Raed , Garmi Gali , Nachum Zohar , Shalev Eliezer 
Published: July 2010

Abstract

Background
Variable decelerations are the most frequent fetal heart rate changes that are related to labor. The objective of the study was to estimate the impact of non-significant variable decelerations (NSV) appearing during the latent phase of labor on delivery mode and neonatal outcome.

Methods
Women at term, who were in the latent phase of labor and had a singleton pregnancy, were prospectively included. Women were divided into three groups. All had a fetal heart rate tracing with normal baseline and variability. The study group was composed of women who had in addition NSV, Category II, according to the National Institute of Child Health and Human Development categorization system. Women who had Category I tracings composed the control group. Women who had non-repetitive severe variables (SV) composed a second control group (Category II-SV). Main outcome compared was mode of delivery. Secondary outcome was cord pH. One-way analysis of variance was used to compare the continuous demographic and clinical variables of the three groups. Backwards stepwise logistic regression using significant univariables was performed to determine which predicted operative delivery. P < 0.05 was considered significant.

Results
Of 1005 women who delivered during the study period 186 had Category II- NSV tracings (study group), 76 had Category II-SV and 251 had Category I tracings. Mode of delivery and indications for operative delivery were similar between women in Category II-NSV compared to Category I. In addition mean cord pH did not differ between the two groups. Conversely, women in Category II-SV, had a higher rate of cesarean or vacuum deliveries compared to the other groups (p = 0.0001). Beside, they had a significantly higher number of neonates born with cord pH between 7.0 to 7.1 (p = 0.03).

Conclusions
Non-significant variable decelerations in early stages of labor are probably a non-ominous sign for neonatal outcome and have no impact on delivery mode.
Heterologous SH3-p85β inhibits influenza A virus replication
Authors: Zhang Dan-gui , Li Wei-zhong , Wang Ge-fei , Su Yun , Zeng Jun , Zhang Chi , Zeng Xiang-xing , Chen Xiao-xuan , Xu Yan-xuan , Li Kang-sheng 
Published: July 2010

Abstract
Phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway can support the replication of influenza A virus through binding of viral NS1 protein to the Src homology 3 (SH3) domain of p85β regulatory subunit of PI3K. Here we investigated the effect of heterologously overexpressed SH3 on the replication of different influenza A virus subtypes/strains, and on the phosphorylation of Akt in the virus-infected cells. We found that heterologous SH3 reduced replication of influenza A viruses at varying degrees in a subtype/strain-dependent manner and SH3 overexpression reduced the induction of the phosphorylation of Akt in the cells infected with PR8(H1N1) and ST364(H3N2), but not with ST1233(H1N1), Ph2246(H9N2), and Qa199(H9N2). Our results suggest that interference with the NS1-p85β interaction by heterologous SH3 can be served as a useful antiviral strategy against influenza A virus infection.
Predictive relevance of HOXB13 protein expression for tamoxifen benefit in breast cancer
Authors: Jerevall Piiha-Lotta , Jansson Agneta , Fornander Tommy , Skoog Lambert , Nordenskjöld Bo , Stål Olle 
Published: July 2010

Abstract
Introduction
The HOXB13:IL17BR index has been identified to predict clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer. Further studies have shown that HOXB13 in particular can indicate benefit of prolonged tamoxifen treatment. Patients with high-expressing tumors did not benefit from prolonged treatment, suggesting that HOXB13 might be involved in tamoxifen resistance. No studies have been made regarding the HOXB13 protein levels in breast cancer. The aim of our study was to investigate whether tamoxifen benefit can be correlated to different levels of HOXB13 protein expression.

Methods
We used immunohistochemistry to analyze protein levels of HOXB13 in tumor samples from 912 postmenopausal node-negative breast cancer patients randomized to adjuvant tamoxifen therapy or no endocrine treatment.

Results
Tamoxifen-treated patients with estrogen receptor-positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival (DRFS) (hazard ratio = 0.38, 95% confidence interval = 0.23 to 0.60, P = 0.000048). However, for patients with a high or intermediate HOXB13 tumor expression, tamoxifen did not prolong the DRFS compared with the untreated patients (hazard ratio = 0.88, 95% confidence interval = 0.47 to 1.65, P = 0.69). Interaction between HOXB13 expression and benefit from tamoxifen was statistically significant for DRFS (P = 0.035). No prognostic value could be ascribed to HOXB13 among systemically untreated patients.

Conclusions
A high HOXB13 expression was associated with decreased benefit from tamoxifen, which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment.
Standardized intensive care unit management in an anhepatic pig model: new standards for analyzing liver support systems
Authors: Thiel Christian , Thiel Karolin , Etspueler Alexander , Schenk Thomas , Morgalla Matthias H , Koenigsrainer Alfred , Schenk Martin 
Published: July 2010

Abstract
Introduction
Several anhepatic pig models were developed in the past. Most models suffer from short anhepatic survival times due to insufficient postoperative intensive care unit (ICU) management. The aim of this study was to analyze anhepatic survival time under standardized intensive care therapy in a pig model.

Methods
Eight pigs underwent total hepatectomy after Y-graft interposition between the infrahepatic vena cava and the portal vein to the suprahepatic vena cava. An intracranial probe was inserted for intracranial pressure (ICP) monitoring. Animals received pressure-controlled ventilation under deep narcosis. Vital parameters were continuously recorded. Urinary output, blood gas analysis, haemoglobin, hematocrit, serum electrolytes, lactate, and glucose were monitored hourly, and creatinine, prothrombin time, international normalised ratio, and serum albumin were monitored every 8 hours. Sodium chloride solution 0.9%, hydroxyethyl starch 6%, fresh frozen plasma, and erythrocyte units were used for volume substitution, and norepinephrine was used to prevent severe hypotension. Serum electrolytes and acid-base balance were corrected as required. Antibiotic prophylaxis with ceftriaxon was given daily, as well as furosemide, to maintain diuresis.

Results
Postoperative survival was 100% after 24 hours, with a maximum survival of 73 (mean, 58 ± 4) hours. Haemodynamic parameters such as heart rate, mean arterial pressure, and pulse oximetry remained stable during surgical procedures and following anhepatic status due to ICU therapy until escalating at time of death. Deteriorating pulmonary function could be stabilized by increasing oxygen concentration, positive end-expiratory pressure, and maximal airway pressure. Furosemide was used to maintain diuresis until renal failure occurred. ICP started at 15-17 mmHg and increased continuously up to levels of 41-43 mmHg at time of death. All animals died as a result of multiple-organ failure.

Conclusions
Using standardized intensive care management after total hepatectomy, we were able to prolong anhepatic survival over 58 hours without the use of liver support systems. The survival benefit of liver support systems in previous animal studies should be reevaluated against our model.
Ligand-Independent Antiapoptotic Function of Estrogen Receptor-β in Lung Cancer Cells
Authors: Zhang GuangFeng , Yanamala Naveena , Lathrop Kira L. , Zhang Lin , Klein-Seetharaman Judith , Srinivas Harish 
Published: July 2010

Abstract
Recent studies have demonstrated the presence of estrogen receptor (ER)β in the mitochondria in various cell types and tissues, but the exact function of this localization remains unclear. In this study, we have examined the function of mitochondrial ERβ in non-small-cell lung cancer (NSCLC) cells. Down-regulation of ERβ by short hairpin RNA constructs sensitized NSCLC cells to various apoptosis-inducing agents such as cisplatin, taxol, and etoposide. The increased growth inhibition and induction of apoptosis in ERβ-knockdown cells was observed irrespective of estrogen treatment, suggesting a ligand-independent role of ERβ in regulating the intrinsic apoptotic pathway. Further, ERβ from the mitochondrial fraction physically interacted with the proapoptotic protein Bad, in a ligand-independent manner. Glutathione-S-transferase pull-down assays and molecular modeling studies revealed that the DNA-binding domain and hinge region of ERβ, and the BH3 domain of Bad were involved in these interactions. Further investigations revealed that ERβ inhibited Bad function by disrupting Bad-Bcl-XL and Bad-Bcl-2 interactions. Reintroduction of ERβ in the mitochondria of ERβ knockdown cells reversed their sensitivity to cisplatin. Overall, our results demonstrate a ligand-independent role of ERβ in regulating apoptosis, revealing a novel function for ERβ in the mitochondria.
Secondary care treatment of patients with varicose veins in National Health Service England: at least how it appeared on a National Health Service website
Authors: Lim C S , Gohel M S , Shepherd A C , Davies A H 
Published: July 2010

Objectives This study aimed to assess the trends and regional variations in secondary care treatment of patients with varicose veins in National Health Service (NHS) England based on data published by the Hospital Episode Statistics which was freely and readily available to the public and health-care policy-makers. Methods Hospital Episode Statistics data for patients being treated for varicose veins, and UK Statistics Authority population estimates in all 28 Strategic Health Authorities (SHAs) in England from 2002 to 2006 were retrieved and analysed. Results Between 2002 and 2006 there was a 20% overall reduction (46,190–37,135) in the total number of varicose vein procedures performed in NHS England per year. The number of varicose vein procedures performed per 100,000 population per year varied significantly across the SHAs ( P < 0.0001). Similarly, significant regional variations were also noted in the frequency of primary procedures of greater and small saphenous vein ( P < 0.0001). During this time, injection sclerotherapy was only performed in 15 (53.6%) SHAs. The annual proportion of varicose vein procedures performed as daycases had increased from 56% to 64% during the period. Conclusion From 2002 to 2006 there was an overall reduction in the total number of varicose vein procedures performed in NHS England with major regional variations.
IgG4-Bestimmungen gegen Nahrungsmittel werden nicht zur Diagnostik empfohlen: Positionspapier der European Academy of Allergology and Clinical Immunology (EAACI)1 / Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force report
Authors: Stapel Steven O. , Asero Ricardo , Ballmer-Weber Barbara K. , Knol Edward F. , Strobel Stephan , Vieths Stefan , Kleine-Tebbe Jörg 
Published: July 2010

Zusammenfassung
Serologische Tests zur Immunglobulin-G4-(IgG4-) Bestimmung gegen Nahrungsmittel werden weiterhin für die Diagnose einer nahrungsmittelbedingten Überempfindlichkeit beworben. Da viele Patienten ohne diagnostische Bestätigung eines kausalen Zusammenhanges davon überzeugt sind, dass ihre Symptome mit der Nahrungsmittelzufuhr zusammenhängen, stellen Tests auf nahrungsmittelspezifisches IgG4 einen wachsenden Markt dar. Die Bestimmung von IgG4 im Blut gegen verschiedene Nahrungsmittel wird anhand eines umfangreichen Screenings auf Hunderte von Nahrungsmitteln mit Enzymimmunoassays (EIA) und Radioallergosorbenttests (RAST) bei Kleinkindern, Jugendlichen und Erwachsenen durchgeführt. Viele Serumproben zeigen allerdings positive IgG4-Ergebnisse ohne korrespondierende klinische Symptome. In Verbindung mit dem Mangel an überzeugenden Hinweisen auf histaminfreisetzende Eigenschaften von IgG4 beim Menschen und dem Fehlen jeglicher kontrollierter Studien zum diagnostischen Wert der IgG4-Bestimmung bei Nahrungsmittelallergie rechtfertigen diese Befunde nicht die Hypothese, dass nahrungsmittelspezifisches IgG4 Reaktionen einer Nahrungsmittelüberempfindlichkeit auslöst. Im Gegensatz zu den kritisierten Hypothesen ist die Anwesenheit von IgG4 gegen Nahrungsmittel ein Hinweis auf die wiederholte Exposition des Organismus gegenüber den Nahrungsmittelbestandteilen, die als Fremdproteine vom Immunsystem erkannt worden sind. Vor-handenes IgG4 sollte keineswegs als Auslöser für eine Überempfindlichkeit angesehen werden, sondern als Indikator für immunologische Toleranz, die auf aktivierten regulatorischen T-Zellen beruht. Zusammenfassend zeigt nahrungsmittelspezifisches IgG4 keine (drohende) Nahrungsmittelallergie oder -unverträglichkeit an, sondern stellt eine physiologische Reaktion des Immunsystems nach Kontakt mit Nahrungsmittelbestandteilen dar. Daher wird die Bestimmung von IgG4 gegen Nahrungsmittel als irrelevant für die Labordiagnostik einer Nahrungsmittelallergie oder -intoleranz angesehen und sollte bei Symptomen, die im Zusammenhang mit der Nahrungsaufnahme auftreten, nicht durchgeführt werden.
Testalternativen zum Tuberkulin-Hauttest / Alternative assays to the tuberculin skin test
Authors: Meier Thomas , Enders Martin 
Published: July 2010

Zusammenfassung
Der Tuberkulin-Hauttest (THT) wird seit über einem Jahrhundert zum indirekten Nachweis einer Infektion mit Erregern der Tuberkulose eingesetzt. Seit wenigen Jahren stehen nun mit den Interferon-γ-release-assays (IGRAs) alternative Blutteste für das klinische Labor zur Verfügung. Die beiden IGRAs T-SPOT.TB und QuantiFERON-TB Gold in-Tube zeigen im Vergleich zum THT bei mindestens vergleichbarer Sensitivität eine deutlich höhere Spezifität. Ein wesentlicher Vorteil der IGRAs ist, dass sie im Gegensatz zum THT nicht durch eine BCG-Impfung im Sinne eines falsch-positiven Ergebnisses beeinflusst werden. Die IGRAs stellen einen bedeutenden Fortschritt in der Diagnostik der latenten Tuberkulose dar und ermöglichen eine zuverlässigere Indikationsstellung der Chemoprävention bei Umgebungsuntersuchungen. Bei Verdacht auf das Vorliegen einer aktiven Tuberkulose sind die mikrobiologischen und molekularbiologischen Nachweismethoden weiterhin vorrangig. Jedoch können die IGRAs das Methodenspektrum zur Diagnostik der pulmonalen und extrapulmonalen Tuberkulose sinnvoll ergänzen.
Lipoprotein-assoziierte Phospholipase A2: ein neuer Marker für kardiovaskuläre Erkrankungen / Lipoprotein-associated phospholipase A2: a novel marker of cardiovascular diseases
Authors: Siekmeier Rüdiger , Grammer Tanja B. , Scharnagl Hubert , Stojakovic Tatjana , König Wolfgang , März Winfried 
Published: July 2010

Zusammenfassung
Aufgrund von Erkenntnissen der letzten Jahre wird die Atherosklerose heute auch als eine entzündliche Erkrankung gesehen. Die hochsensitive Bestimmung des C-reaktiven Proteins (hsCRP) wird bereits seit einigen Jahren dazu herangezogen, zusätzliche Informationen zum individuellen kardiovaskulären Risiko zu gewinnen. Weniger bekannt ist die Bestimmung der Lipoprotein-assoziierten Phospholipase A2 (Lp-PLA2), die vor allem spezifische Aussagen zur Stabilität der atherosklerotischen Plaque, dem pathologischen Korrelat der Atherosklerose ermöglichen soll.