bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Granule Secretion Continuously Prevents Intratumor Hemorrhage
Authors: Ho-Tin-Noé Benoit , Goerge Tobias , Cifuni Stephen M. , Duerschmied Daniel , Wagner Denisa D. 
Published: August 2008

Abstract
Cancer is associated with a prothrombogenic state capable of platelet activation. Platelets, on the other hand, can support angiogenesis, a process involved in the progression of tumor growth and metastasis. However, it is unclear whether platelet/tumor interactions substantially contribute to tumor physiology. We investigated whether platelets stabilize tumor vessels and studied the underlying mechanisms. We induced severe acute thrombocytopenia in mice bearing s.c. Lewis lung carcinoma or B16F10 melanoma. Intravital microscopy revealed that platelet depletion led to a rapid destabilization of tumor vessels with intratumor hemorrhage starting as soon as 30 min after induction of thrombocytopenia. Using an inhibitor of glycoprotein Ibα (GPIbα) and genetically engineered mice with platelet adhesion defects, we investigated the role of platelet adhesion receptors in stabilizing tumor vessels. We found that a single defect in either GPIbα, von Willebrand factor, P-selectin, or platelet integrin activation did not lead to intratumor hemorrhage. We then compared the ability of transfused resting and degranulated platelets to prevent intratumor hemorrhage. Whereas resting platelets prevented thrombocytopenia-induced tumor bleeding, circulating degranulated platelets did not. This suggests that the prevention of intratumor hemorrhage by platelets relies on the secretion of the content of platelet granules. Supporting this hypothesis, we further found that thrombocytopenia dramatically impairs the balance between propermeability and antipermeability factors in tumor-bearing animals, in particular depleting blood of angiopoietin-1 and serotonin. Our results show a crucial contribution of platelets to tumor homeostasis through continuous prevention of severe intratumor hemorrhage and consequent cell death. The study also suggests platelet function as a reasonable target for specific destabilization of tumor vessels. [Cancer Res 2008;68(16):6851–8]
Glycogen Synthase Kinase-3 Inhibition Induces Glioma Cell Death through c-MYC, Nuclear Factor-κB, and Glucose Regulation
Authors: Kotliarova Svetlana , Pastorino Sandra , Kovell Lara C. , Kotliarov Yuri , Song Hua , Zhang Wei , Bailey Rolanda , Maric Dragan , Zenklusen Jean Claude , Lee Jeongwu , Fine Howard A. 
Published: August 2008

Abstract
Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, is involved in diverse cellular processes ranging from nutrient and energy homeostasis to proliferation and apoptosis. Its role in glioblastoma multiforme has yet to be elucidated. We identified GSK3 as a regulator of glioblastoma multiforme cell survival using microarray analysis and small-molecule and genetic inhibitors of GSK3 activity. Various molecular and genetic approaches were then used to dissect out the molecular mechanisms responsible for GSK3 inhibition–induced cytotoxicity. We show that multiple small molecular inhibitors of GSK3 activity and genetic down-regulation of GSK3α/β significantly inhibit glioma cell survival and clonogenicity. The potency of the cytotoxic effects is directly correlated with decreased enzyme activity–activating phosphorylation of GSK3α/β Y276/Y216 and with increased enzyme activity inhibitory phosphorylation of GSK3α S21. Inhibition of GSK3 activity results in c-MYC activation, leading to the induction of Bax, Bim, DR4/DR5, and tumor necrosis factor-related apoptosis-inducing ligand expression and subsequent cytotoxicity. Additionally, down-regulation of GSK3 activity results in alteration of intracellular glucose metabolism resulting in dissociation of hexokinase II from the outer mitochondrial membrane with subsequent mitochondrial destabilization. Finally, inhibition of GSK3 activity causes a dramatic decrease in intracellular nuclear factor-κB activity. Inhibition of GSK3 activity results in c-MYC–dependent glioma cell death through multiple mechanisms, all of which converge on the apoptotic pathways. GSK3 may therefore be an important therapeutic target for gliomas. Future studies will further define the optimal combinations of GSK3 inhibitors and cytotoxic agents for use in gliomas and other cancers. [Cancer Res 2008;68(16):6643–51]
Quantitative Control of Adaptive Cardiac Hypertrophy by Acetyltransferase p300
Authors: Wei Jian Qin , Shehadeh Lina A. , Mitrani James M. , Pessanha Monica , Slepak Tatiana I. , Webster Keith A. , Bishopric Nanette H. 
Published: August 2008

Background—Acetyltransferase p300 is essential for cardiac development and is thought to be involved in cardiac myocyte growth through MEF2- and GATA4-dependent transcription. However, the importance of p300 in the modulation of cardiac growth in vivo is unknown.Methods and Results—Pressure overload induced by transverse aortic coarctation, postnatal physiological growth, and human heart failure were associated with large increases in p300. Minimal transgenic overexpression of p300 (1.5- to 3.5-fold) induced striking myocyte and cardiac hypertrophy. Both mortality and cardiac mass were directly related to p300 protein dosage. Heterozygous loss of a single p300 allele reduced pressure overload–induced hypertrophy by ≈50% and rescued the hypertrophic phenotype of p300 overexpressers. Increased p300 expression had no effect on total histone deacetylase activity but was associated with proportional increases in p300 acetyltransferase activity and acetylation of the p300 substrates histone 3 and GATA-4. Remarkably, a doubling of p300 levels was associated with the de novo acetylation of MEF2. Consistent with this, genes specifically upregulated in p300 transgenic hearts were highly enriched for MEF2 binding sites.Conclusions—Small increments in p300 are necessary and sufficient to drive myocardial hypertrophy, possibly through acetylation of MEF2 and upstream of signals promoting phosphorylation or nuclear export of histone deacetylases. We propose that induction of myocardial p300 content is a primary rate-limiting event in the response to hemodynamic loading in vivo and that p300 availability drives and constrains adaptive myocardial growth. Specific reduction of p300 content or activity may diminish stress-induced hypertrophy and forestall the development of heart failure.
The Relation of El Niño–Southern Oscillation (ENSO) to Winter Tornado Outbreaks
Authors: Cook A. R. , Schaefer J. T. 
Published: August 2008

Abstract
Winter tornado activity (January–March) between 1950 and 2003 was analyzed to determine the possible effect of seasonally averaged sea surface temperatures in the equatorial Pacific Ocean, the ENSO phase, on the location and strength of tornado outbreaks in the United States. Tornado activity was gauged through analyses of tornadoes occurring on tornado days (a calendar day featuring six or more tornadoes within the contiguous United States) and strong and violent tornado days (a calendar day featuring five or more tornadoes rated F2 and greater within the contiguous United States). The tornado days were then stratified according to warm (37 tornado days, 14 violent days), cold (51 tornado days, 28 violent days), and neutral (74 tornado days, 44 violent days) winter ENSO phase. It is seen that during winter periods of neutral tropical Pacific sea surface temperatures, there is a tendency for U.S. tornado outbreaks to be stronger and more frequent than they are during winter periods of anomalously warm tropical Pacific sea surface temperatures (El Niño). During winter periods with anomalously cool Pacific sea surface temperatures (La Niña), the frequency and strength of U.S. tornado activity lies between that of the neutral and El Niño phase. ENSO-related shifts in the preferred location of tornado activity are also observed. Historically, during the neutral phase, tornado outbreaks typically occurred from central Oklahoma and Kansas eastward through the Carolinas. During cold phases, tornado outbreaks have typically occurred in a zone stretching from southeastern Texas northeastward into Illinois, Indiana, and Michigan. During anomalously warm phases activity was mainly limited to the Gulf Coast states, including central Florida. The data are statistically and synoptically analyzed to show that they are not only statistically significant, but also meteorologically reasonable.
Results of Arthroscopic Iliopsoas Tendon Release in Competitive and Recreational Athletes
Authors: Anderson Scott A. , Keene James S. 
Published: August 2008

Background An arthroscopic iliopsoas tendon release will alleviate painful snapping of the tendon. One question that remains is whether athletes can return to sports after this procedure. This study presents the results of 5 competitive and 10 recreational athletes who had an arthroscopic release of their iliopsoas tendon. Hypothesis Athletes can return to full participation in their sport after an arthroscopic iliopsoas tendon release. Study Design Case series; Level of evidence, 4. Methods Fifteen athletes (2 college, 3 high school, 10 recreational) with painful snapping hips and no pain relief after anesthetic magnetic resonance arthrography had an ultrasound evaluation of their iliopsoas tendon and an anesthetic injection into the Psoas bursa. In all 15 patients, the injection relieved their hip pain, and in 10 patients, real-time imaging demonstrated snapping of the tendon. All hips were assessed with Byrd's 100-point hip scoring system before the release and at 1.5,3,6, and 12 months after surgery. Results Preoperative hip scores averaged 41 and 44 points for the competitive and recreational athletes, respectively. After surgery, the 2 groups used crutches for 4 weeks, and had 6-week scores that averaged 87 and 63 points. At 6 months, their scores averaged 94 and 98 points, and at 12 months, 96 and 97 points, and none had recurrence of their snapping or pain. All 15 athletes returned to full participation in their sport at an average of 9 months after surgery. Conclusion A return to college, high school, and recreational sports can be expected after an arthroscopic release of the iliopsoas tendon.
Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura
Authors: Neunert Cindy E. , Buchanan George R. , Imbach Paul , Bolton-Maggs Paula H. B. , Bennett Carolyn M. , Neufeld Ellis J. , Vesely Sara K. , Adix Leah , Blanchette Victor S. , Kühne Thomas 
Published: August 2008

AbstractControversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP). Drug treatment is usually administered to prevent severe hemorrhage, although the definition and frequency of severe bleeding are poorly characterized. Accordingly, the Intercontinental Childhood ITP Study Group (ICIS) conducted a prospective registry defining severe hemorrhage at diagnosis and during the following 28 days in children with ITP. Of 1106 ITP patients enrolled, 863 were eligible and evaluable for bleeding severity assessment at diagnosis and during the subsequent 4 weeks. Twenty-five children (2.9%) had severe bleeding at diagnosis. Among 505 patients with a platelet count less than or equal to 20 000/mm3 and no or mild bleeding at diagnosis, 3 (0.6%), had new severe hemorrhagic events during the ensuing 28 days. Subsequent development of severe hemorrhage was unrelated to initial management (P = .82). These results show that severe bleeding is uncommon at diagnosis in children with ITP and rare during the next 4 weeks irrespective of treatment given. We conclude that it would be difficult to design an adequately powered therapeutic trial aimed at demonstrating prevention of severe bleeding during the first 4 weeks after diagnosis. This finding suggests that future studies of ITP management should emphasize other outcomes.
Newly identified patterns of Pax2 expression in the developing mouse forebrain
Authors: Fotaki Vassiliki , Price David J , Mason John O 
Published: August 2008

Abstract
Background
The availability of specific markers expressed in different regions of the developing nervous system provides a useful tool for the study of mouse mutants. One such marker, the transcription factor Pax2, is expressed at the midbrain-hindbrain boundary and in the cerebellum, spinal cord, retina, optic stalk, and optic chiasm. We recently described a group of diencephalic cells that express Pax2 as early as embryonic day (E) 10.5, and become part of the eminentia thalami by E11.5. The discovery of this previously undescribed cell population prompted us to examine Pax2 protein expression in the developing mouse forebrain in more detail.

Results
We determined the expression pattern of Pax2 in the forebrain of wild type mouse embryos between E10.5 and postnatal day (P) 15. Pax2 expression was detected in the septum of the basal forebrain, hypothalamus, eminentia thalami and in the subfornical organ. To evaluate Pax2 as a marker for septal cells, we examined Pax2 expression in Pax6Sey/Seymutants, which have an enlarged septum. We found that Pax2 clearly marks a population of septal cells equivalent to that seen in wild types, indicating its utility as a marker of septal identity. These cells did not express the GABAergic marker calbindin nor the cholinergic marker choline acetyltransferase and were not detectable after P15.

Conclusion
Pax2 is expressed in populations of cells within the developing septum, hypothalamus, and eminentia thalami. It seems especially useful as a marker of the telencephalic septum, because of its early, strong and characteristic expression in this structure. Further, its expression is maintained in the enlarged septum of Pax6Sey/Seymutants.
CCL5 regulation of mucosal chlamydial immunity and infection
Authors: Sakthivel Senthilkumar K , Singh Udai P , Singh Shailesh , Taub Dennis D , Igietseme Joseph U , Lillard James W 
Published: August 2008

AbstractBackgroundFollowing genital chlamydial infection, an early T helper type 1 (Th1)-associated immune response precedes the activation and recruitment of specific Th1 cells bearing distinct chemokine receptors, subsequently leading to the clearance ofChlamydia. We have shown that CCR5, a receptor for CCL5, is crucial for protective chlamydial immunity. Our laboratory and others have also demonstrated that CCL5 deficiencies found in man and animals can increase the susceptibility and progression of infectious diseases by modulating mucosal immunity. These findings suggest the CCR5-CCL5 axis is necessary for optimal chlamydial immunity. We hypothesized CCL5 is required for protective humoral and cellular immunity againstChlamydia.ResultsThe present study revealed that CCR5 and CCL5 mRNAs are elevated in the spleen, iliac lymph nodes (ILNs), and genital mucosa followingChlamydia muriduramchallenge. Antibody (Ab)-mediated inhibition of CCL5 during genital chlamydial infection suppressed humoral and Th1 > Th2 cellular responses by splenic-, ILN-, and genital mucosa-derived lymphocytes. Antigen (Ag)-specific proliferative responses of CD4+T cells from spleen, ILNs, and genital organs also declined after CCL5 inhibition.ConclusionThe suppression of these responses correlated with delayed clearance ofC. muriduram, which indicate chlamydial immunity is mediated by Th1 immune responses driven in part by CCL5. Taken together with other studies, the data show that CCL5 mediates the temporal recruitment and activation of leukocytes to mitigate chlamydial infection through enhancing adaptive mucosal humoral and cellular immunity.
Lymphotoxin-alpha polymorphisms and presence of cancer in 1,536 consecutive autopsy cases
Authors: Takei Kako , Ikeda Shinobu , Arai Tomio , Tanaka Noriko , Muramatsu Masaaki , Sawabe Motoji 
Published: August 2008

AbstractBackgroundLymphotoxin-alpha (LTA) is a pro-inflammatory cytokine with anti-tumor activity. The objective of this study was to determine whetherLTApolymorphisms influence the presence of cancer.MethodsLTApolymorphisms C804A (rs1041981, T60N) and T495C (rs2229094, C13R) were determined in 1,536 consecutive autopsy cases and were registered in the Japanese single-nucleotide polymorphisms (SNPs) for geriatric research (JG-SNP) Internet database. Tumors were systematically reviewed, pathologically confirmed, and assessed in relation toLTAgenotype.ResultsThe study population consisted of 827 males and 709 females, with a mean age of 80 years. Altogether, we studied 606 subjects without cancer and 930 subjects with cancer of the stomach (n = 183), lung (n = 164), colon or rectum (n = 143), or other sites. The presence of cancer was higher in males than in females. The C804A and T495C polymorphisms were associated with cancer in males (CA + AA: CC, adjusted OR = 0.72, 95% CI = 0.53 – 0.99; TC + CC: TT, adjusted OR = 1.45, 95% CI = 1.04 – 2.02; respectively) but not in females. In males, the C804A polymorphism was associated with lung cancer (CA + AA: CC, adjusted OR = 0.60, 95% CI = 0.37 – 0.97), whereas the T495C polymorphism was associated with gastric cancer (TC + CC: TT, adjusted OR = 1.68, 95% CI = 1.06 – 2.65).ConclusionWe found some evidence of an association betweenLTApolymorphisms and cancer risk in elderly Japanese men. Further studies in larger populations should examine this hypothesis.
Cost effectiveness of chest pain unit care in the NHS
Authors: Oluboyede Yemi , Goodacre Steve , Wailoo Allan ,   the ESCAPE Research Team
Published: August 2008

Abstract

Background
Acute chest pain is responsible for approximately 700,000 patient attendances per year at emergency departments in England and Wales. A single centre study of selected patients suggested that chest pain unit (CPU) care could be less costly and more effective than routine care for these patients, although a more recent multi-centre study cast doubt on the generalisability of these findings.

Methods
Our economic evaluation involved modelling data from the ESCAPE multi-centre trial along with data from other sources to estimate the comparative costs and effects of CPU versus routine care. Cost effectiveness ratios (cost per QALY) were generated from our model.

Results
We found that CPU compared to routine care resulted in a non-significant increase in effectiveness of 0.0075 QALYs per patient and a non-significant cost decrease of £32 per patient and thus a negative incremental cost effectiveness ratio. If we are willing to pay £20,000 for an additional QALY then there is a 70% probability that CPU care will be considered cost-effective.

Conclusion
Our analysis shows that CPU care is likely to be slightly more effective and less expensive than routine care, however, these estimates are surrounded by a substantial amount of uncertainty. We cannot reliably conclude that establishing CPU care will represent a cost-effective use of health service resources given the substantial amount of investment it would require.
Excision of sympathetic ganglia and the rami communicantes with histological confirmation offers better early and late outcomes in Video assisted thoracoscopic sympathectomy
Authors: Rathinam Sridhar , Nanjaiah Prakash , Sivalingam Sivakumar , Rajesh Pala B 
Published: August 2008

Abstract

Background
Video-Assisted Thoracoscopic Sympathectomy (VATS) is an established minimally invasive procedure for thoracic sympathetic blockade in patients with hyperhidrosis, facial flushing and intractable angina. Various techniques using clips, diathermy and excision are used to perform sympathectomy. We present our technique of excision of the sympathetic chain with histological proof and the analysis of the early and late outcomes.

Methods
We evaluated 200 procedures in 100 consecutive patients, who underwent Video Assisted Thoracoscopic Sympathectomy by a single surgeon in our centre between September 1996 to March 2007. All patients had maximum medical therapy prior to surgery and were divided into 3 groups based on indications, Group 1(hyperhidrosis: 48 patients), Group 2 (facial flushing: 26 patients) and Group 3(intractable angina: 26 patients). The demography and severity of symptoms for each group were analysed. The endpoints were success rate, 30 day mortality, complications and patient's satisfaction.

Results
99 patients had bilateral VATS sympathectomy and 1 had unilateral sympathectomy. The conversion rate to open was 1(1%). All patients had successful removal of ganglia proven histologically with no perioperative mortality in our series. The complications included pneumothorax (5%), acute coronary syndrome (2%), transient Horner's syndrome (1%), transient paraesthesia (1%), wound infection (4%), compensatory hyperhidrosis (18%), residual flushing (3%) and wound pain (5%). There were five late deaths in the intractable angina group at a mean follow up of 36.7 months. Overall success rates of abolishing the symptoms were 96.3%, 87.5% and 95.2% for Group 1, 2 and 3 respectively.

Conclusion
Excision of the sympathetic chain with histological confirmation during VATS sympathectomy is a safe and effective method in treating hyperhidrosis, facial flushing and intractable angina with good long term results and satisfaction.
Hematemesis, a very rare presentation of solid pseudo-papillary tumors of the pancreas: a case report
Authors: Apostolidis Stylianos , Papavramidis Theodossis S , Zatagias Akis , Michalopoulos Antonis , Papadopoulos Vassilis N , Paramythiotis Daniel , Harlaftis Nick 
Published: August 2008

Abstract

Introduction
Solid pseudo-papillary tumors of the pancreas are rare and typically present in young female patients. They are slowly growing masses that may attain large size, and are of low malignant potential. Surgical resection is usually curative.

Case presentation
A 71-year-old woman presented to the emergency department with an episode of hematemesis but was otherwise hemodynamically stable. Emergency gastroscopy revealed a bleeding mass projecting to the duodenum. Fluid, blood and electrolyte resuscitation followed. Computed tomography revealed a small mass in the head of the pancreas. A Whipple operation was performed. Pathology revealed a solid pseudo-papillary tumor. The postoperative course of the patient was uneventful and no recurrence was present a year after the operation.

Conclusion
In our case, the most noteworthy observations concern the small size of the tumor, the age of the patient and the presenting symptom. However, pancreaticoduodenectomy in a 71-year-old woman is a major effort and should only be undertaken by centers and surgeons experienced in complex hepatobiliary surgery. Furthermore, the unique nature of this case reminds every clinician that each patient has to be considered separately and with extreme caution.