bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion
Authors: Fujioka Masayuki , Hayakawa Kazuhide , Mishima Kenichi , Kunizawa Ai , Irie Keiichi , Higuchi Sei , Nakano Takafumi , Muroi Carl , Fukushima Hidetada , Sugimoto Mitsuhiko , Banno Fumiaki , Kokame Koichi , Miyata Toshiyuki , Fujiwara Michihiro , Okuchi Kazuo , Nishio Kenji 
Published: November 2009

Abstract
Reperfusion after brain ischemia causes thrombus formation and microcirculatory disturbances, which are dependent on the platelet glycoprotein Ib–von Willebrand factor (VWF) axis. Because ADAMTS13 cleaves VWF and limits platelet-dependent thrombus growth, ADAMTS13 may ameliorate ischemic brain damage in acute stroke. We investigated the effects of ADAMTS13 on ischemia-reperfusion injury using a 30-minute middle cerebral artery occlusion model in Adamts13−/− and wild-type mice. After reperfusion for 0.5 hours, the regional cerebral blood flow in the ischemic cortex was decreased markedly in Adamts13−/− mice compared with wild-type mice (P < .05), which also resulted in a larger infarct volume after 24 hours for Adamts13−/− compared with wild-type mice (P < .01). Thus, Adamts13 gene deletion aggravated ischemic brain damage, suggesting that ADAMTS13 may protect the brain from ischemia by regulating VWF-platelet interactions after reperfusion. These results indicate that ADAMTS13 may be a useful therapeutic agent for stroke.
Granzyme B is not required for regulatory T cell–mediated suppression of graft-versus-host disease
Authors: Cai Sheng F. , Cao Xuefang , Hassan Anjum , Fehniger Todd A. , Ley Timothy J. 
Published: November 2009

AbstractRegulatory T (Treg) cells can suppress a wide variety of immune responses, including antitumor and alloimmune responses. The mechanisms by which Treg cells mediate their suppressive effects depend on the context of their activation. We previously reported that granzyme B is important for Treg cell–mediated suppression of antitumor immune responses. We therefore hypothesized that granzyme B may likewise be important for suppression of graft-versus-host disease (GVHD). We found that allogeneic mismatch induces the expression of granzyme B in mixed lymphocyte reactions and in a model of graft-versus-host disease (GVHD). However, wild-type and granzyme B–deficient Treg cells were equally able to suppress effector T (Teff) cell proliferation driven by multiple stimuli, including allogeneicantigen-presenting cells. Surprisingly, adoptive transfer of granzyme B–deficient Treg cells prevented GVHD lethality, suppressed serum cytokine production in vivo, and prevented target organ damage. These data contrast strikingly with our previous study, which demonstrated that granzyme B plays a nonredundant role in Treg cell–mediated suppression of antitumor responses. Taken together, these findings suggest that targeting specific Treg cell–suppressive mechanisms, such as granzyme B, may be therapeutically beneficial for segregating GVHD and graft-versus-tumor immune responses.
Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 Nuclear Bodies
Authors: Rajan Prabhakar , Dalgliesh Caroline , Bourgeois Cyril F , Heiner Monika , Emami Kaveh , Clark Emma L , Bindereif Albrecht , Stevenin James , Robson Craig N , Leung Hing Y , Elliott David J 
Published: November 2009

Abstract

Background
Active pre-mRNA splicing occurs co-transcriptionally, and takes place throughout the nucleoplasm of eukaryotic cells. Splicing decisions are controlled by networks of nuclear RNA-binding proteins and their target sequences, sometimes in response to signalling pathways. Sam68 (Src-associated in mitosis 68 kDa) is the prototypic member of the STAR (Signal Transduction and Activation of RNA) family of RNA-binding proteins, which regulate splicing in response to signalling cascades. Nuclear Sam68 protein is concentrated within subnuclear organelles called SLM/Sam68 Nuclear Bodies (SNBs), which also contain some other splicing regulators, signalling components and nucleic acids.

Results
We used proteomics to search for the major interacting protein partners of nuclear Sam68. In addition to Sam68 itself and known Sam68-associated proteins (heterogeneous nuclear ribonucleoproteins hnRNP A1, A2/B1 and G), we identified hnRNP L as a novel Sam68-interacting protein partner. hnRNP L protein was predominantly present within small nuclear protein complexes approximating to the expected size of monomers and dimers, and was quantitatively associated with nucleic acids. hnRNP L spatially co-localised with Sam68 as a novel component of SNBs and was also observed within the general nucleoplasm. Localisation within SNBs was highly specific to hnRNP L and was not shared by the closely-related hnRNP LL protein, nor any of the other Sam68-interacting proteins we identified by proteomics. The interaction between Sam68 and hnRNP L proteins was observed in a cell line which exhibits low frequency of SNBs suggesting that this association also takes place outside SNBs. Although ectopic expression of hnRNP L and Sam68 proteins independently affected splicing of CD44 variable exon v5 and TJP1 exon 20 minigenes, these proteins did not, however, co-operate with each other in splicing regulation of these target exons.

Conclusion
Here we identify hnRNP L as a novel SNB component. We show that, compared with other identified Sam68-associated hnRNP proteins and hnRNP LL, this co-localisation within SNBs is specific to hnRNP L. Our data suggest that the novel Sam68-hnRNP L protein interaction may have a distinct role within SNBs.
Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MRgene
Authors: Kanda Kyoko , Nozu Kandai , Yokoyama Naoki , Morioka Ichiro , Miwa Akihiro , Hashimura Yuya , Kaito Hiroshi , Iijima Kazumoto , Matsuo Masafumi 
Published: November 2009

Abstract

Background
Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR), but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations.

Methods and Results
We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products.

Conclusion
mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.
Placental malaria among HIV-infected and uninfected women receiving anti-folates in a high transmission area of Uganda
Authors: Newman Patrick M , Wanzira Humphrey , Tumwine Gabriel , Arinaitwe Emmanuel , Waldman Sarah , Achan Jane , Havlir Diane , Rosenthal Philip J , Dorsey Grant , Clark Tamara D , Cohan Deborah 
Published: November 2009

Abstract

Background
HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS) and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP). TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women.

Methods
This was a cross sectional study comparing the prevalence of placental malaria between HIV-infected women prescribed TS and HIV-uninfected women prescribed intermittent preventive therapy with sulphadoxine-pyrimethamine (IPT-SP) in a high malaria transmission area in Uganda. Placental blood was evaluated for malaria using smear and PCR.

Results
Placentas were obtained from 150 HIV-infected women on TS and 336 HIV-uninfected women on IPT-SP. The proportion of HIV-infected and HIV-uninfected women with placental malaria was 19% vs. 26% for those positive by PCR and 6% vs. 9% for those positive by smear, respectively. Among all infants, smear+ placental malaria was most predictive of low birth weight (LBW). Primigravidae were at higher risk than multigravidae of having placental malaria among HIV-uninfected, but not HIV-infected, women. Adjusting for gravidity, age, and season at the time of delivery, HIV-infected women on TS were not at increased risk for placental malaria compared to HIV-uninfected women on IPT-SP, regardless of the definition used.

Conclusion
Prevalence of placental malaria was similar in HIV-infected women on TS and HIV-uninfected women on IPT-SP. Nonetheless, while nearly all of the women in this study were prescribed anti-folates, the overall risk of placental malaria and LBW was unacceptably high. The population attributable risk of placental malaria on LBW was substantial, suggesting that future interventions that further diminish the risk of placental malaria may have a considerable impact on the burden of LBW in this population.
Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines
Authors: Bredholt Therese , Dimba Elizabeth AO , Hagland Hanne R , Wergeland Line , Skavland Jørn , Fossan Kjell O , Tronstad Karl J , Johannessen Anne C , Vintermyr Olav K , Gjertsen Bjørn T 
Published: November 2009

Abstract

Background
An organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity.

Results
Khat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation.

Conclusion
Khat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.
Sutureless technique to support anastomosis during thoracic aorta replacement
Authors: Apostolakis Efstratios E , Leivaditis Vassilios N , Anagnostopoulos Constantinos 
Published: November 2009

Abstract

Background
In aortic replacement procedures the aortic wall and Teflon strips form a double layer, with the use of continuous sutures. Surgical glues may or may not be used to enhance the durability of the anastomoses. In this technical report a modification of the aortic stumps preparation is devised.
The technique reduces substantially the preparation time of the aortic stumps by the use of ligation clips and a surgical sealant.

Technique
Suturing is the standard method for the aortic-teflon double-layer formation prior to Dacron anastomosis. In this study, instead of suturing, 5-6 ligation clips are primarily applied on the exterior of the double layer to facilitate proper cooptation. Secondarily, in order to fuse the two layers together, a sealant is injected in between the Teflon and aortic wall. Thus each stump is delivered quickly sutureless for the Dacron anastomosis.
Between January 2003 and March 2009 this modified operative technique was performed in 14 cases (group A) with a mean age of 50 ± 16 years. This was contrasted against 24 controls (group B), with a mean age of 40 ± 28 years, treated with the conventional method, where only continuous sutures were used during the anastomosis. All patients were cases of ascending aorta replacement and/or aortic hemi-arch replacement, for acute aortic dissection or aortic dilatation.

Results
The pure anastomosis time (stump preparation and Dacron connection) was shortened by approximately 25 minutes depending on surgeon's experience. The anastomosis blood-loss was also significantly reduced in the sutureless group A, as evident by the dry operative field and the limited use of blood products, post-prosthetic graft anastomosis. This reflected to a faster post-operative recovery, faster extubation and fewer complications. At a mean follow-up of 21 ± 7 days, there were no post-operative deaths being related to acute aortic dissection or rupture of the anastomotic site.

Conclusion
Aortic replacement with the combination of ligation clips and a surgical sealant vs. sutures alone allows easy manipulations of the aorta and adaptation of the diameters, thus optimizing aortic operational timings and hemostasis. Moreover, it prevents blood loss and aortic wall trauma from multiple sutures.
Fibrin glue in the treatment of anal fistula: a systematic review
Authors: Cirocchi Roberto , Farinella Eriberto , La Mura Francesco , Cattorini Lorenzo , Rossetti Barbara , Milani Diego , Ricci Patrizia , Covarelli Piero , Coccetta Marco , Noya Giuseppe , Sciannameo Francesco 
Published: November 2009

AbstractBackgroundNew sphincter-saving approaches have been applied in the treatment of perianal fistula in order to avoid the risk of fecal incontinence. Among them, the fibrin glue technique is popular because of its simplicity and repeatability. The aim of this review is to compare the fibrin glue application to surgery alone, considering the healing and complication rates.MethodsWe performed a systematic review searching for published randomized and controlled clinical trials without any language restriction by using electronic databases. All these studies were assessed as to whether they compared conventional surgical treatment versus fibrin glue treatment in patients with anal fistulas, in order to establish both the efficacy and safety of each treatment. We used Review Manager 5 to conduct the review.ResultsThe healing rate is higher in those patients who underwent the conventional surgical treatment (P = 0,68), although the treatment with fibrin glue gives no evidence of anal incontinence (P = 0,08). Furthermore two subgroup analyses were performed: fibrin glue in combination with intra-adhesive antibiotics versus fibrin glue alone and anal fistula plug versus fibrin glue. In the first subgroup there were not differences in healing (P = 0,65). Whereas in the second subgroup analysis the healing rate is statistically significant for the patients who underwent the anal fistula plug treatment instead of the fibrin glue treatment (P = 0,02).ConclusionIn literature there are only two randomized controlled trials comparing the conventional surgical management versus the fibrin glue treatment in patients with anal fistulas. Although from our statistical analysis we cannot find any statistically significant result, the healing rate remains higher in patients who underwent the conventional surgical treatment (P = 0,68), and the anal incontinence rate is very low in the fibrin glue treatment group (P = 0,08). Anyway the limited collected data do not support the use of fibrin glue. Moreover, in our subgroup analysis the use of fibrin glue in combination with intra-adhesive antibiotics does not improve the healing rate (P = 0.65), whereas the anal fistula plug treatment compared to the fibrin glue treatment shows good results (P = 0,02), although the poor number of patients treated does not lead to any statistically evident conclusion. This systematic review underlines the need of new RCTs upon this issue.
False positive diagnosis of malignancy in a case of cryptogenic organising pneumonia presenting as a pulmonary mass with mediastinal nodes detected on fluorodeoxyglucose-positron emission tomography: a case report
Authors: Ponnuswamy Aravind , Mediratta Neeraj , Lyburn Iain D , Finnerty James P 
Published: November 2009

Abstract

Introduction
We report the case of a patient with positive findings on a lung emission tomography/computed tomography (PET/CT) scan, with possible contra lateral mediastinal involvement, which strongly suggested an inoperable lung carcinoma. The lung mass proved to be a cryptogenic organising pneumonia. While the latter has previously been shown to be PET/CT positive, mediastinal involvement simulating malignant spread has not been previously reported.

Case presentation
A 50-year-old Caucasian woman presented with a history of unproductive cough and was found to have a mass in the right upper lobe as shown on chest X-ray and a computed tomography scan. A subsequent PET/CT scan showed strong uptake in the right upper lobe (maximum standard uptake values (SUVmax) 9.6) with increased uptake in the adjacent mediastinum and contralateral mediastinal nodes. Surgical resection and mediastinoscopy revealed cryptogenic organising pneumonia, with enlarged reactive mediastinal lymph nodes.

Conclusion
The case illustrates the limits of PET/CT scanning as a diagnostic tool, and emphasizes the importance of obtaining histological confirmation of malignant diseases whenever possible.
Anastomotic leak management after a low anterior resection leading to recurrent abdominal compartment syndrome: a case report and review of the literature
Authors: Toutouzas Kostas , Kleidi Eleftheria S , Drimousis Panagiotis G , Balla Margarita , Papanikolaou Metaxia N , Larentzakis Andreas , Theodorou Dimitrios , Katsaragakis Stylianos 
Published: November 2009

Abstract

Introduction
Low anterior resection is usually the procedure of choice for rectal cancer, but a series of complications often accompany this procedure. This case report describes successful management of an intricate anastomotic leak after a low anterior resection.

Case presentation
A 66-year-old Caucasian man was admitted to our hospital and diagnosed with a low rectal adenocarcinoma. He underwent a low anterior resection but subsequently developed fecal peritonitis due to an anastomotic leak. He was operated on again but developed abdominal compartment syndrome, multi-organ failure and sepsis. He was aggressively treated in the intensive care unit and in the operating room. Overall, the patient underwent four laparotomies and stayed in the intensive care unit for 75 days. He was discharged after 3 months of hospitalization.

Conclusion
Abdominal compartment syndrome may present as a devastating complication of damage control laparotomy. Prompt recognition and goal-directed management are the cornerstones of treatment.
Intradiscal injection of simvastatin retards progression of intervertebral disc degeneration induced by stab injury
Authors: Zhang Huina , Wang Lin , Park Jun Beom , Park Paul , Yang Victor C , Hollister Scott J , La Marca Frank , Lin Chia-Ying 
Published: November 2009

Abstract
Introduction
Earlier work indicates that the cholesterol-lowering drug, simvastatin, is anabolic to chondrogenic expression of rat intervertebral disc (IVD) cells, which suggests a potential role for simvastatin in IVD regeneration. In this study, we expand on our earlier work to test the effectiveness of simvastatin on disc degeneration utilizing a rat tail disc degeneration model.

Methods
30 rats that underwent 21 G needle-puncture at rat tail discs were injected with simvastatin-loaded poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG) gel (5 mg/ml) or vehicle control at 4 weeks after needle injury. All animals were sacrificed 2 weeks after simvastatin injection. Bone morphogenetic protein-2 (BMP-2), aggrecan, collagen type II, and collagen type I messenger ribonucleic acid (mRNA) expression in the rat nucleus pulposus (NP) were measured by real-time polymerase chain reaction (PCR). In vivo magnetic resonance imaging (MRI) was performed to monitor changes in disc degeneration. Rat discs were also assessed by histology using hematoxylin and eosin (H&E) and safranin O staining. In addition, the NP weight, glycosaminoglycan (sGAG) and DNA content were also measured.

Results
A single dose of simvastatin loaded in thermo-sensitive PEG-PLGA-PEG gel injected into the NP had the trend to increase aggrecan expression and sGAG content, and significantly increased mRNA levels of BMP-2, collagen type II, and the differentiation index (the ratio of collagen type II to collagen type I). The decreased NP weight, T2 intensity, as well as MRI index in the rat tail discs induced by needle puncture were significantly reversed after 2 weeks of simvastatin treatment. In addition, simvastatin treatment also improved histological changes induced by needle puncture.

Conclusions
A single injection of simvastatin loaded in PEG-PLGA-PEG gel into rat tail discs had the potential to retard or regenerate the degenerative disc.
Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells
Authors: Jiménez-Gómez Gema , Gómez-Perales Jesús L , Ramos-Amaya Ana , González-García Inés , Campos-Caro Antonio , Brieva José A 
Published: November 2009

Abstract
This study focuses on the regulation of Ig gene variability and the rules and limits of the adaptability of IGHV genes from human plasma cells.
Systemic antigen-induced PCs are generated in inductive lymphoid tissues. Some of them are selected to travel through the circulation and finally, to home onto BM niches. BM PCs show prolonged survival and secrete high-affinity antibodies. In this study, human PCs were isolated from tonsil, blood, and BM, their IGHV3 and IGHV6 genes were sequenced, and their SHM were evaluated. The SHM analysis reveals the existence of a maturational gradient in these genes, as demonstrated by a progressive increase in the frequency of total and R mutations and total and NC aa changes following the direction: tonsil → blood → BM. The ratio of R to S mutations in the CDR1 and -2, but not in the FRs, increases from tonsil to blood and BM; this parameter reaches a maximum threshold when more than 10 mutations/sequence occur. Further analyses indicate that CDR1 and CDR2 SHM followed different strategies to provide appropriate amino acid changes, but both exhibited maximal resistance to incorporating drastic molecular alterations in the BM PCs. Finally, all of the findings are similar in IGHV3 and IGHV6 sequences, indicating that they reflect general rules imposed by in vivo antigen selection.