bluuebunny/crossref_metadata_2025_split huggingface dataset:
A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen
Authors: Rudchenko Sergei , Scanlan Matthew , Kalantarov Gavreel , Yavelsky Victoria , Levy Chen , Estabrook Alison , Old Lloyd , Chan Gerald L , Lobel Leslie , Trakht Ilya 
Published: August 2008

Abstract

Background
We have been studying the native autoimmune response to cancer through the isolation of human monoclonal antibodies that are cancer specific from cancer patients. To facilitate this work we previously developed a fusion partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique trioma fusion partner cell line we isolated a panel of autologous human monoclonal antibodies, from both peripheral blood and lymph node lymphocytes, which are representative of the native repertoire of anti-cancer specific antibodies from breast cancer patients.

Methods
The current study employs immunocytochemistry, immunohistochemistry, Western blot analysis as well as Northern blots, Scatchard binding studies and finally SEREX analysis for target antigen identification.

Results
By application of an expression cloning technique known as SEREX, we determined that the target antigen for two monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This protein is highly expressed not only in cultured human breast cancer cells, but also in primary and metastatic tumor tissues and its overexpression appears to be cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic localization of the target protein, which is consistent with previous studies of this protein.

Conclusion
We have determined that GIPC1 is a novel breast cancer-associated immunogenic antigen that is overexpressed in breast cancer. Its role, however, in the initiation and/or progression of breast cancer remains unclear and needs further clarification.
Effect of the ethinylestradiol/norelgestromin contraceptive patch on body composition. Results of bioelectrical impedance analysis in a population of Italian women
Authors: Piccoli Antonio , Crosignani PierGiorgio , Nappi Carmine , Ronsini Salvatore , Bruni Vincenzina , Marelli Silvia ,   the Italian EVRA Contrast Study Group
Published: August 2008

Abstract
Background
As weight gain is one of the most frequently cited reasons for not using and for discontinuing hormonal contraceptives, in an open-label, single-arm, multicentre clinical study we evaluated the effect of the ethinylestradiol/norelgestromin contraceptive patch (EVRA, Janssen-Cilag International, Belgium) on body composition using bioelectrical impedance analysis (BIA).

Methods
Body weight and impedance vector components (resistance (R) and reactance (Xc), at 50 kHz frequency, Akern-RJL Systems analyzer) were recorded before entry, after 1, 3 and 6 months in 182 Italian healthy women aged 29 yr (18 to 45), and with BMI 21.8 kg/m2 (16 to 31). Total body water (TBW) was estimated with a BIA regression equation. Vector BIA was performed with the RXc mean graph method and the Hotelling's T2 test for paired and unpaired data.

Results
After 6 months body weight increased by 0.64 kg (1.1%) and TBW increased by 0.51 L (1.7%). The pattern of impedance vector displacement indicated a small increase in soft tissue hydration (interstitial gel fluid). Body composition changes did not significantly differ among groups of previous contraceptive methods. Arterial blood pressure did not significantly change over time.

Conclusion
After 6 months of treatment with the ethinylestradiol/norelgestromin contraceptive patch we found a minimal, clinically not relevant, increase in body weight less than 1 kg that could be attributed to an adaptive interstitial gel hydration. This fluctuation is physiological as confirmed by the lack of any effect on blood pressure. This could be useful in increasing women's choice, acceptability and compliance of the ethinylestradiol/norelgestromin contraceptive patch.
A novel hybrid aspirin-NO-releasing compound inhibits TNFalpha release from LPS-activated human monocytes and macrophages
Authors: Turnbull Catriona M , Marcarino Paolo , Sheldrake Tara A , Lazzarato Loretta , Cena Clara , Fruttero Roberta , Gasco Alberto , Fox Sarah , Megson Ian L , Rossi Adriano G 
Published: August 2008

AbstractBackgroundThe cytoprotective nature of nitric oxide (NO) led to development of NO-aspirins in the hope of overcoming the gastric side-effects of aspirin. However, the NO moiety gives these hybrids potential for actions further to their aspirin-mediated anti-platelet and anti-inflammatory effects. Having previously shown that novel NO-aspirin hybrids containing a furoxan NO-releasing group have potent anti-platelet effects, here we investigate their anti-inflammatory properties. Here we examine their effects upon TNFα release from lipopolysaccharide (LPS)-stimulated human monocytes and monocyte-derived macrophages and investigate a potential mechanism of action through effects on LPS-stimulated nuclear factor-kappa B (NF-κB) activation.MethodsPeripheral venous blood was drawn from the antecubital fossa of human volunteers. Mononuclear cells were isolated and cultured. The resultant differentiated macrophages were treated with pharmacologically relevant concentrations of either a furoxan-aspirin (B8, B7; 10 μM), their respective furazan NO-free counterparts (B16, B15; 10 μM), aspirin (10 μM), existing nitroaspirin (NCX4016; 10 μM), an NO donor (DEA/NO; 10 μM) or dexamethasone (1 μM), in the presence and absence of LPS (10 ng/ml; 4 h). Parallel experiments were conducted on undifferentiated fresh monocytes. Supernatants were assessed by specific ELISA for TNFα release and by lactate dehydrogenase (LDH) assay for cell necrosis. To assess NF-κB activation, the effects of the compounds on the loss of cytoplasmic inhibitor of NF-κB, IκBα (assessed by western blotting) and nuclear localisation (assessed by immunofluorescence) of the p65 subunit of NF-κB were determined.ResultsB8 significantly reduced TNFα release from LPS-treated macrophages to 36 ± 10% of the LPS control. B8 and B16 significantly inhibited monocyte TNFα release to 28 ± 5, and 49 ± 9% of control, respectively. The B8 effect was equivalent in magnitude to that of dexamethasone, but was not shared by 10 μM DEA/NO, B7, the furazans, aspirin or NCX4016. LDH assessment revealed none of the treatments caused significant cell lysis. LPS stimulated loss of cytoplasmic IκBα and nuclear translocation of the p65 NF-κB subunit was inhibited by the active NO-furoxans.ConclusionHere we show that furoxan-aspirin, B8, significantly reduces TNFα release from both monocytes and macrophages and suggest that inhibition of NF-κB activation is a likely mechanism for the effect. This anti-inflammatory action highlights a further therapeutic potential of drugs of this class.
Heterologous ectoine production in Escherichia coli: By-passing the metabolic bottle-neck
Authors: Bestvater Thorsten , Louis Petra , Galinski Erwin A 
Published: August 2008

Abstract
Transcription of the ectoine biosynthesis genes ectA, ectB and ectC from Marinococcus halophilus in recombinant Escherichia coli DH5α is probably initiated from three individual σ70/σA-dependent promoter sequences, upstream of each gene. Consequently, mRNA-fragments containing the single genes and combinations of the genes ectA and ectB or ectB and ectC, respectively, could be detected by Northern blot analysis. Under the control of its own regulatory promoter region (ectUp) a seemingly osmoregulated ectoine production was observed. In addition, aspartate kinases were identified as the main limiting factor for ectoine production in recombinant E. coli DH5α. Co-expression of the ectoine biosynthesis genes and of the gene of the feedback-resistant aspartate kinase from Corynebacterium glutamicum MH20-22B (lysC) led to markedly increased production of ectoine in E. coli DH5α, resulting in cytoplasmic ectoine concentrations comparable to those reached via ectoine accumulation from the medium.
Ectopic internal carotid artery presenting as an oropharyngeal mass
Authors: Prokopakis Emmanuel P , Bourolias Constantinos A , Bizaki Argyro J , Karampekios Spyros K , Velegrakis George A , Bizakis John G 
Published: August 2008

Abstract
Ectopic internal carotid artery (ICA) is a very rare variation. The major congenital abnormalities of the ICA can be classified as agenesis, aplasia and hypoplasia, and they can be unilateral or bilateral. Anomalies of the neck artery may be vascular neoplasms or ectopic position. Carotid angiograms provide absolute confirmation of an aberrant carotid artery, while EcoColorDoppler (ECD) gives also important information about the evaluation of carotid vassels. Nevertheless Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the neck provide spatial information about the adjacent pharyngeal anatomy and are less invasive than angiogram. Injuries to the ICA during simple pharyngeal surgical procedures can be catastrophic due to the risk of massive bleeding. We report a case of a 56 year-old male patient suffering from dysphagia associated with aberrant ICA manifesting itself as a pulsative protruding of the left lateral wall of the oropharynx.
Dorsal turning of motor corticospinal axons at the pyramidal decussation requires plexin signaling
Authors: Faulkner Regina L , Low Lawrence K , Liu Xiao-Bo , Coble Jeffrey , Jones Edward G , Cheng Hwai-Jong 
Published: August 2008

Abstract
Background
The development of the corticospinal tract (CST) in higher vertebrates relies on a series of axon guidance decisions along its long projection pathway. Several guidance molecules are known to be involved at various decision points to regulate the projection of CST axons. However, previous analyses of the CST guidance defects in mutant mice lacking these molecules have suggested that there are other molecules involved in CST axon guidance that are yet to be identified. In this study, we investigate the role of plexin signaling in the guidance of motor CST axons in vivo.

Results
Expression pattern studies show that plexin-A3, plexin-A4, and neuropilin-1 are expressed in the developing cerebral cortex when the motor CST axons originating from layer V cortical neurons are guided down to the spinal cord. By analyzing mutant mice, we show that motor CST axons that turn dorsally to cross the midline at the pyramidal decussation require plexin-A3 and plexin-A4 signaling. Although other CST guidance defects are found in neuropilin-1 mutants, this dorsal turning defect is not observed in either neuropilin-1 or neuropilin-2 mutants, suggesting that the local cues that activate plexin signaling at the dorsal turning point are membrane-bound semaphorins. Further expression pattern study and mutant analysis indicate that Sema6A is one of the local cues for motor CST axon turning at the pyramidal decussation.

Conclusion
Dorsal turning and midline crossing at the pyramidal decussation is a crucial step to properly direct CST axons into the dorsal spinal cord. We show that the signaling of plexin-A3, plexin-A4, and Sema6A is at least partially required for dorsal turning of the CST axons, while neuropilin-1 is required for proper fasciculation of the tract at midline crossing. Together with previous reports, these results demonstrate that several guidance cues are specifically utilized to regulate the dorsal turning and midline crossing of developing CST axons.
Preferential regulation of duplicated genes by microRNAs in mammals
Authors: Li Jingjing , Musso Gabriel , Zhang Zhaolei 
Published: August 2008

Abstract
Background
Although recent advances have been made in identifying and analyzing instances of microRNA-mediated gene regulation, it remains unclear by what mechanisms attenuation of transcript expression through microRNAs becomes an integral part of post-transcriptional modification, and it is even less clear to what extent this process occurs for mammalian gene duplicates (paralogs). Specifically, while mammalian paralogs are known to overcome their initial complete functional redundancy through variation in regulation and expression, the potential involvement of microRNAs in this process has not been investigated.

Results
We comprehensively investigated the impact of microRNA-mediated post-transcriptional regulation on duplicated genes in human and mouse. Using predicted targets derived from several analysis methods, we report the following observations: microRNA targets are significantly enriched for duplicate genes, implying their roles in the differential regulation of paralogs; on average, duplicate microRNA target genes have longer 3' untranslated regions than singleton targets, and are regulated by more microRNA species, suggesting a more sophisticated mode of regulation; ancient duplicates were more likely to be regulated by microRNAs and, on average, have greater expression divergence than recent duplicates; and ancient duplicate genes share fewer ancestral microRNA regulators, and recent duplicate genes share more common regulating microRNAs.

Conclusion
Collectively, these results demonstrate that microRNAs comprise an important element in evolving the regulatory patterns of mammalian paralogs. We further present an evolutionary model in which microRNAs not only adjust imbalanced dosage effects created by gene duplication, but also help maintain long-term buffering of the phenotypic consequences of gene deletion or ablation.
Cerebrovascular Disease Risk in Older Head and Neck Cancer Patients After Radiotherapy
Authors: Smith Grace L. , Smith Benjamin D. , Buchholz Thomas A. , Giordano Sharon H. , Garden Adam S. , Woodward Wendy A. , Krumholz Harlan M. , Weber Randal S. , Ang K.-Kian , Rosenthal David I. 
Published: August 2008

Purpose Cerebrovascular disease is common in head and neck cancer patients, but it is unknown whether radiotherapy increases the cerebrovascular disease risk in this population. Patients and Methods We identified 6,862 patients (age > 65 years) from the Surveillance, Epidemiology, and End Results (SEER) –Medicare cohort diagnosed with nonmetastatic head and neck cancer between 1992 and 2002. Using proportional hazards regression, we compared risk of cerebrovascular events (stroke, carotid revascularization, or stroke death) after treatment with radiotherapy alone, surgery plus radiotherapy, or surgery alone. To further validate whether treatment groups had equivalent baseline risk of vascular disease, we compared the risks of developing a control diagnosis, cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or cardiac death). Unlike cerebrovascular risk, no difference in cardiac risk was hypothesized. Results Mean age was 76 ± 7 years. Ten-year incidence of cerebrovascular events was 34% in patients treated with radiotherapy alone compared with 25% in patients treated with surgery plus radiotherapy and 26% in patients treated with surgery alone (P < .001). After adjusting for covariates, patients treated with radiotherapy alone had increased cerebrovascular risk compared with surgery plus radiotherapy (hazard ratio [HR] = 1.42; 95% CI, 1.14 to 1.77) and surgery alone (HR = 1.50; 95% CI, 1.18 to 1.90). However, no difference was found for surgery plus radiotherapy versus surgery alone (P = .60). As expected, patients treated with radiotherapy alone had no increased cardiac risk compared with the other treatment groups (P = .63 and P = .81). Conclusion Definitive radiotherapy for head and neck cancer, but not postoperative radiotherapy, was associated with excess cerebrovascular disease risk in older patients.
TREATMENT OF GIANT MIDDLE CEREBRAL ARTERY ANEURYSMS WITH A FLOW REPLACEMENT BYPASS USING THE EXCIMER LASER-ASSISTED NONOCCLUSIVE ANASTOMOSIS TECHNIQUE
Authors: van Doormaal Tristan P.C. , van der Zwan Albert , Verweij Bon H. , Han Kuo S. , Langer David J. , Tulleken Cornelis A.F. 
Published: August 2008

ABSTRACT

OBJECTIVE
To define the clinical value of the flow replacement bypass using the excimer laser-assisted nonocclusive anastomosis (ELANA) technique in the treatment of patients with a noncoilable, nonclippable giant intracranial aneurysm of the middle cerebral artery (MCA).

METHODS
Between 1999 and 2006, 22 patients with a giant intracranial aneurysm of the MCA were treated in our hospital with an ELANA flow replacement bypass and MCA occlusion. We collected data on patient characteristics, operative aspects, complications, and functional health scores using the modified Rankin Scale. Mean follow-up was 3.6 years (range, 0.2–7.7 yr).

RESULTS
We were able to construct a patent bypass in 20 (91%) of 22 patients. All 34 ELANA attempts resulted in a patent anastomosis with a strong backflow directly after ELANA catheter retraction. The patients did not need to undergo temporary occlusion in any of the ELANA constructions. Mean ± standard deviation intracranial-to-intracranial bypass flow was 53 ± 13 ml/min. MCA aneurysm treatment was attempted in all 20 patients who had a patent bypass and was successful in 19 of them. There was a fatal hemorrhagic complication in one patient (5%), a nonfatal hemorrhagic complication in three patients (14%), and a nonfatal ischemic complication in six patients (27%). At follow-up, 17 patients (77%) had a functionally favorable outcome (modified Rankin Scale score at follow-up was the same as or less than the preoperative modified Rankin Scale score). All of these patients were independent at follow-up (modified Rankin Scale score ≤2).

CONCLUSION
This study demonstrates satisfactory results in the treatment of giant MCA aneurysms with an ELANA flow replacement bypass, considering the very grave natural history and treatment complexity of these lesions. The ELANA technique is a useful tool in the treatment armamentarium of the vascular neurosurgeon.
ENDOSCOPIC ENDONASAL RESECTION OF ANTERIOR CRANIAL BASE MENINGIOMAS
Authors: Gardner Paul A. , Kassam Amin B. , Thomas Ajith , Snyderman Carl H. , Carrau Ricardo L. , Mintz Arlan H. , Prevedello Daniel M. 
Published: August 2008

ABSTRACT

OBJECTIVE
The endonasal route may be feasible for the resection of anterior cranial base tumors that abut the paranasal sinuses. There are several case reports and mixed case series discussing this approach. Other than pituitary adenomas, there is a lack of literature describing the outcomes of endonasal approaches for single-tumor types such as meningiomas.

METHODS
In this study, we describe our current endoscopic endonasal technique and demonstrate the feasibility of using it to access anterior cranial base meningiomas from the back wall of the frontal sinus to the sella and laterally to the region of the midorbit. After this discussion, which includes key technical considerations and nuances, we address safety and efficacy by reporting the outcomes of our early experience with endoscopic endonasal resection of 35 anterior cranial base meningiomas.

RESULTS
A total of 35 patients underwent endoscopic endonasal resection of anterior cranial base meningiomas from October 2002 to October 2005. Degree of resection by tumor location was as follows: 10 of the 12 (83%) patients with olfactory groove meningiomas planned for complete resection underwent gross total (seven of 12) or near-total (&gt;95%) (three of 12) resection (67% of all 15 olfactory tumors); 12 of 13 patients (92%) with tuberculum meningiomas underwent gross (11 of 13) or near (&gt;95%) (one of 13) total resection; five patients diagnosed with petroclival meningiomas had successful resection of the parasellar portion of their tumors with relief of visual symptoms (no patients underwent complete resection of their tumors via the endoscopic, endonasal approach); two giant petroclival meningiomas were debulked with 63 and 89% resection, respectively.
All patients experienced resolution or improvement of visual symptoms. No patient experienced permanent worsening of vision after surgery. Only one (3%) patient without preoperative endocrine dysfunction experienced a new, permanent pituitary deficit, diabetes insipidus. One (3%) patient experienced a new neurological deficit after experiencing a hemorrhage 3 weeks after surgery. The postoperative cerebrospinal fluid leak rate was 40% (14 of 35) and varied by tumor location. All leaks were resolved without craniotomy. There were no cases of bacterial meningitis. One patient developed a superinfection of a sterile granuloma from a sinusitis 2 years after surgery. There were two cases of deep venous thrombosis and one pulmonary embolus. There were no operative or perioperative deaths.

CONCLUSION
Cranial base meningiomas can be successfully managed via a purely endoscopic endonasal approach with acceptable morbidity and mortality rates. The extent of resection is guided by patient factors and symptoms, not by approach. This series had a high cerebrospinal fluid leak rate. With the evolution of new reconstruction techniques, these rates have been substantially reduced.
EXTENT OF SURGICAL RESECTION OF MALIGNANT ASTROCYTOMAS OF THE SPINAL CORD
Authors: McGirt Matthew J. , Goldstein Ira M. , Chaichana Kaisorn L. , Tobias Michael E. , Kothbauer Karl F. , Jallo George I. 
Published: August 2008

ABSTRACT

OBJECTIVE
The optimal management of malignant intramedullary spinal cord astrocytomas remains controversial. Although radiotherapy has become the standard of care, the relationship between extent of resection and survival remains unclear. We report the outcomes of the surgical management of 35 malignant spinal cord astrocytomas and assess the association of extent of resection with survival after aggressive resection of these tumors.

METHODS
An institutional intramedullary spinal cord tumor database (1990–2002) was reviewed to identify all patients treated for malignant astrocytomas of the spinal cord (anaplastic astrocytoma [AA] or glioblastoma multiforme [GBM]). Length of survival from surgery was charted by Kaplan-Meier plots, and association of extent of resection with survival was assessed via log rank analysis for stratified covariates and Cox proportional-hazards model for continuous covariates.

RESULTS
Twenty-seven (77%) and eight (23%) patients underwent resection of AA and GBM, respectively. Mean age was 29 ±16 years (range, 2–61 yr). Tumor involved six ± four vertebral levels. For AA cases, radical resection (no residual postoperative magnetic resonance enhancement) was achieved in 12 (44%) patients and subtotal resection (residual postoperative magnetic resonance enhancement) was achieved in 15 (56%). No GBM patients underwent radical resection (mean estimated resection, 70%). After surgery, two (6%) patients improved neurologically by modified McCormick score, 19 (54%) remained stable, and 14 (40%) declined. Median overall survival for AA patients was 72 months (85% at 1 yr; 59% at 5 yr). Median overall survival for GBM patients was 9 months (31% at 1 yr; 0% at 5 yr). Subtotal versus radical resection of AA was associated with decreased overall survival (38 versus 78% at 4 yr, P = 0.028). Postoperative tumor dissemination was associated with decreased survival (P = 0.004). When adjusting for multiple comparisons (P &lt; 0.006 needed for significance), a trend of increased survival was observed with radical resection (P = 0.023).

CONCLUSION
Neurological function can be preserved with aggressive resection of malignant intramedullary spinal astrocytomas; however, motor decline may be observed in many cases. Radical resection of AA was associated with a trend of increased overall survival in nondisseminated AA cases. Radical surgery and radiotherapy of GBM was associated with poor survival, similar to historical controls of diagnostic biopsy and radiotherapy. A markedly shorter survival may be expected in cases in which AA disseminates along the neuraxis. Biopsy alone may not provide the best outcomes for patients with malignant spinal cord tumors.