bluuebunny/crossref_metadata_2025 huggingface dataset:
Alkali–silica reactivity of some common rock types. A global petrographic atlas
Authors: Fernandes Isabel , Broekmans Maarten A. T. M. , Nixon Philip , Sims Ian , dos Anjos Ribeiro Maria , Noronha Fernando , Wigum Børge
Published: April 2013

The correct identification of potentially alkali–silica reactive aggregates is important for the prevention of alkali–silica reaction (ASR) in concrete. Although a number of standards for assessment of concrete aggregate by petrography are available, distinction of potentially deleterious from innocuous rock types can be problematic. The application of geological nomenclature alone is insufficient, as the geological history and hence mineralogical texture of a given rock type may strongly influence its performance in concrete. One of the goals of RILEM TC 219-ACS is to develop a worldwide photo atlas as a guide for petrographers in the identification of the mineral compositions and textures that are characteristic of alkali-reactive rocks. The atlas is based on micrographs of rock types recognized as potentially deleterious by field performance and/or laboratory expansion testing. It is intended to serve as an independent reference work and aims to unify rock terminology so as to improve the petrographic characterization of aggregates. The mission of RILEM, the International Union of Laboratories and Experts in Construction Materials, Systems and Structures (Réunion Internationale des Laboratoires et Experts des Matériaux), is to advance scientific knowledge in the field of construction. Its Technical Committee TC 219-ACS focuses on alkali reactions and their effects on concrete.
Cell volume and monovalent ion transporters: their role in cell death machinery triggering and progression
Authors: Orlov Sergei N. , Platonova Alexandra A. , Hamet Pavel , Grygorczyk Ryszard
Published: April 2013

Cell death is accompanied by the dissipation of electrochemical gradients of monovalent ions across the plasma membrane that, in turn, affects cell volume via modulation of intracellular osmolyte content. In numerous cell types, apoptotic and necrotic stimuli caused cell shrinkage and swelling, respectively. Thermodynamics predicts a cell type-specific rather than an ubiquitous impact of monovalent ion transporters on volume perturbations in dying cells, suggesting their diverse roles in the cell death machinery. Indeed, recent data showed that apoptotic collapse may occur in the absence of cell volume changes and even follow cell swelling rather than shrinkage. Moreover, side-by-side with cell volume adjustment, monovalent ion transporters contribute to cell death machinery engagement independently of volume regulation via cell type-specific signaling pathways. Thus, inhibition of Na+-K+-ATPase by cardiotonic steroids (CTS) rescues rat vascular smooth muscle cells from apoptosis via a novel Na+i-K+i-mediated, Ca2+i-independent mechanism of excitation-transcription coupling. In contrast, CTS kill renal epithelial cells independently of Na+-K+-ATPase inhibition and increased [Na+]i/[K+]i ratio. The molecular origin of [Na+]i/[K+]i sensors involved in the inhibition of apoptosis as well as upstream intermediates of Na+i/K+i-independent death signaling triggered by CTS remain unknown.
Lesion in the lateral cerebellum specifically produces overshooting of the toe trajectory in leading forelimb during obstacle avoidance in the rat
Authors: Aoki Sho , Sato Yamato , Yanagihara Dai
Published: April 2013

During locomotion, stepping over an obstacle under visual guidance is crucial to continuous safe walking. Studies of the role of the central nervous system in stepping movements have focused on cerebral cortical areas such as the primary motor cortex and posterior parietal cortex. There is speculation that the lateral cerebellum, which has strong anatomical connections with the cerebral cortex, also plays a key role in stepping movements over an obstacle, although this function of the lateral cerebellum has not yet been elucidated. Here we investigated the role of the lateral cerebellum during obstacle avoidance locomotion in rats with a lateral cerebellar lesion. A unilateral lesion in the lateral cerebellum did not affect limb movements during overground locomotion. Importantly, however, the lesioned animals showed overshooting of the toe trajectory specific to the leading forelimb ipsilateral to the lesion when stepping over an obstacle, and the peak toe position, in which the toe is maximally raised during stepping, shifted away from the upper edge of the obstacle. Recordings of EMG activity from elbow flexor and extensor muscles suggested that the overshooting toe trajectory in the ipsilateral leading forelimb possibly resulted from sustained elbow flexion and delayed elbow extension following prolonged activity of the biceps brachii. These results suggest that the lateral cerebellum specifically contributes to generating appropriate toe trajectories in the ipsilateral leading forelimb and to controlling related muscle activities in stepping over an obstacle, especially when accurate control of the distal extremity is achieved under visual guidance.
IL-17–Mediated M1/M2 Macrophage Alteration Contributes to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws
Authors: Zhang Qunzhou , Atsuta Ikiru , Liu Shiyu , Chen Chider , Shi Shihong , Shi Songtao , Le Anh D.
Published: April 2013

Purpose: Osteonecrosis of the jaw (ONJ) is emerging as one of the important complications in cancer patients treated with antiresorptive agents. This study explored the potential role of interleukin (IL)-17–mediated M1/M2 macrophage alterations in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Experimental Design: The expression of IL-17 and M1 and M2 macrophage markers at the local mucosal site of human BRONJ lesions was examined by immunofluorescence studies. BRONJ-like disease was induced in C57BL/6 mice and multiple myeloma-burdened mice by intravenous injection of zoledronate to evaluate the correlation of elevated IL-17 levels with changes in M1 and M2 macrophage phenotypes and the therapeutic effects of blocking IL-17 on pathogenesis of BRONJ-like disease.

Results: Increased T-helper (TH)17 cells and IL-17 cytokine correlate with an increase in M1/M2 macrophages ratio at the local mucosal site of both murine and human BRONJ lesion. Convincingly, in mice burdened with multiple myeloma, a combination of elevated suprabasal level and drug-induced IL-17 activity augmented the incidence of BRONJ; both systemic increase of IL-17 and disease severity could be reversed by adoptive transfer of ex vivo expanded M2 macrophages. Targeting IL-17 via specific neutralizing antibodies or a small inhibitory molecule, laquinimod, significantly decreased M1/M2 ratio and concomitantly suppressed BRONJ-like condition in mice. Mechanistically, IL-17 enhanced IFN-γ–induced M1 polarization through augmenting STAT-1 phosphorylation while suppressing IL-4–mediated M2 conversion via inhibiting STAT-6 activation.

Conclusions: These findings have established a compelling linkage between activated IL-17–mediated polarization of M1 macrophages and the development of BRONJ-like conditions in both human disease and murine models. Clin Cancer Res; 19(12); 3176–88. ©2013 AACR.
CRM1 and BRAF Inhibition Synergize and Induce Tumor Regression in BRAF-Mutant Melanoma
Authors: Salas Fragomeni Roberto A. , Chung Hye Won , Landesman Yosef , Senapedis William , Saint-Martin Jean-Richard , Tsao Hensin , Flaherty Keith T. , Shacham Sharon , Kauffman Michael , Cusack James C.
Published: April 2013

Resistance to BRAF inhibitor therapy places priority on developing BRAF inhibitor-based combinations that will overcome de novo resistance and prevent the emergence of acquired mechanisms of resistance. The CRM1 receptor mediates the nuclear export of critical proteins required for melanoma proliferation, survival, and drug resistance. We hypothesize that by inhibiting CRM1-mediated nuclear export, we will alter the function of these proteins resulting in decreased melanoma viability and enhanced BRAF inhibitor antitumoral effects. To test our hypothesis, selective inhibitors of nuclear export (SINE) analogs KPT-185, KPT-251, KPT-276, and KPT-330 were used to induce CRM1 inhibition. Analogs PLX-4720 and PLX-4032 were used as BRAF inhibitors. Compounds were tested in xenograft and in vitro melanoma models. In vitro, we found CRM1 inhibition decreases melanoma cell proliferation independent of BRAF mutation status and synergistically enhances the effects of BRAF inhibition on BRAF-mutant melanoma by promoting cell-cycle arrest and apoptosis. In melanoma xenograft models, CRM1 inhibition reduces tumor growth independent of BRAF or NRAS status and induces complete regression of BRAF V600E tumors when combined with BRAF inhibition. Mechanistic studies show that CRM1 inhibition was associated with p53 stabilization and retinoblastoma protein (pRb) and survivin modulation. Furthermore, we found that BRAF inhibition abrogates extracellular signal–regulated kinase phosphorylation associated with CRM1 inhibition, which may contribute to the synergy of the combination. In conclusion, CRM1 inhibition impairs melanoma survival in both BRAF-mutant and wild-type melanoma. The combination of CRM1 and BRAF inhibition synergizes and induces melanoma regression in BRAF-mutant melanoma. Mol Cancer Ther; 12(7); 1171–9. ©2013 AACR.
Potential Role of mTORC2 as a Therapeutic Target in Clear Cell Carcinoma of the Ovary
Authors: Hisamatsu Takeshi , Mabuchi Seiji , Matsumoto Yuri , Kawano Mahiru , Sasano Tomoyuki , Takahashi Ryoko , Sawada Kenjiro , Ito Kimihiko , Kurachi Hirohisa , Schilder Russell J. , Testa Joseph R. , Kimura Tadashi
Published: April 2013

The goal of this study was to examine the role of mTOR complex 2 (mTORC2) as a therapeutic target in ovarian clear cell carcinoma (CCC), which is regarded as an aggressive, chemoresistant histologic subtype. Using tissue microarrays of 98 primary ovarian cancers [52 CCCs and 46 serous adenocarcinomas (SAC)], activation of mTORC2 was assessed by immunohistochemistry. Then, the growth-inhibitory effect of mTORC2-targeting therapy, as well as the role of mTORC2 signaling as a mechanism for acquired resistance to the mTOR complex 1 (mTORC1) inhibitor RAD001 in ovarian CCC, were examined using two pairs of RAD001-sensitive parental (RMG2 and HAC2) and RAD001-resistant CCC cell lines (RMG2-RR and HAC2-RR). mTORC2 was more frequently activated in CCCs than in SACs (71.2% vs. 45.7%). Simultaneous inhibition of mTORC1 and mTORC2 by AZD8055 markedly inhibited the proliferation of both RAD001-sensitive and -resistant cells in vitro. Treatment with RAD001 induced mTORC2-mediated AKT activation in RAD001-sensitive CCC cells. Moreover, increased activation of mTORC2–AKT signaling was observed in RAD001-resistant CCC cells compared with the respective parental cells. Inhibition of mTORC2 during RAD001 treatment enhanced the antitumor effect of RAD001 and prevented CCC cells from acquiring resistance to RAD001. In conclusion, mTORC2 is frequently activated, and can be a promising therapeutic target, in ovarian CCCs. Moreover, mTORC2-targeted therapy may be efficacious in a first-line setting as well as for second-line treatment of recurrent disease developing after RAD001-treatment. Mol Cancer Ther; 12(7); 1367–77. ©2013 AACR.
Bioactive Lipids S1P and C1P Are Prometastatic Factors in Human Rhabdomyosarcoma, and Their Tissue Levels Increase in Response to Radio/Chemotherapy
Authors: Schneider Gabriela , Bryndza Ewa , Abdel-Latif Ahmed , Ratajczak Janina , Maj Magdalena , Tarnowski Maciej , Klyachkin Yuri M. , Houghton Peter , Morris Andrew J. , Vater Axel , Klussmann Sven , Kucia Magdalena , Ratajczak Mariusz Z.
Published: April 2013

Evidence suggests that bioactive lipids may regulate pathophysiologic functions such as cancer cell metastasis. Therefore, we determined that the bioactive lipid chemoattractants sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) strongly enhanced the in vitro motility and adhesion of human rhabdomyosarcoma (RMS) cells. Importantly, this effect was observed at physiologic concentrations for both bioactive lipids, which are present in biologic fluids, and were much stronger than the effects observed in response to known RMS prometastatic factors such as stromal derived factors-1 (SDF-1/CXCL12) or hepatocyte growth factor/scatter factor (HGF/SF). We also present novel evidence that the levels of S1P and C1P were increased in several organs after γ-irradiation or chemotherapy, which indicates an unwanted prometastatic environment related to treatment. Critically, we found that the metastasis of RMS cells in response to S1P can be effectively inhibited in vivo with the S1P-specific binder NOX-S93 that is based on a high-affinity Spiegelmer. These data indicate that bioactive lipids play a vital role in dissemination of RMS and contribute to the unwanted side effects of radio/chemotherapy by creating a prometastatic microenvironment. Mol Cancer Res; 11(7); 793–807. ©2013 AACR.
Karyological individualities in nonhuman primates and their potential inheritance
Authors: Chiarelli B.
Published: April 2013

The peculiarities of the chromosomes among different primate species are considered useful for paternity tests. This type of information is required for sociological studies and specifically for studying the mechanisms of group organization in nature.
Syllable Structure and Dorsal Friction in German
Authors: Simpson Adrian
Published: April 2013

Phonemic phonological accounts of the fricatives [ç], [x] and [Ӽ] in German must either introduce an arbitrary piece of morphological information into the phonology, or set up a controversial phoneme of open juncture. An alternative account is proposed which avoids both of these problems. I provide a phonological analysis which employs an explicit syllable structure and a phonetic interpretation of this structure is given in terms of the exponency statements of a Firthian prosodic phonology.
Hints to the Diagnosis of Mixed Acinar-Endocrine Carcinoma on Pancreatic Fine-Needle Aspiration: Avoiding a Potential Diagnostic Pitfall
Authors: Sullivan Peggy S. , Clebanoff Jennifer L. , Hirschowitz Sharon L.
Published: April 2013

Background: Mixed acinar-endocrine carcinoma (MAEC) is a rare mixed tumor of the pancreas defined by both acinar and endocrine cell differentiation. Case: We present 2 cases of MAEC initially diagnosed as pancreatic endocrine neoplasm on fine-needle aspiration. Both patients were male, aged 51 and 75 years, and presented with 16-mm and 6-mm pancreatic masses, respectively. Aspirates showed loose aggregates and dispersed single plasmacytoid cells with moderate nuclear size variation, slightly irregular nuclear contours, fine to coarsely granular chromatin, occasional prominent nucleoli, and scant to moderate finely granular cytoplasm. Rare mitotic figures and pyknotic forms were noted in one of the cases. Endocrine differentiation was confirmed by immunocytochemistry which led to an initial diagnosis of pancreatic endocrine neoplasm. Trypsin and lipase immunocytochemistry were later obtained, confirming a component of acinar cell differentiation. Findings were confirmed on surgical excision. Conclusion: Because of their potentially more aggressive clinical course and different therapeutic implications, MAECs are an important consideration in the differential diagnosis of pancreatic neoplasms. Certain cytomorphologic features and immunocytochemical markers of acinar cell differentiation may be helpful in raising the possibility of MAEC on cytology.
Wake-Up Stroke: Incidence, Risk Factors and Outcome of Acute Stroke during Sleep in a Japanese Population. Takashima Stroke Registry 1988-2003
Authors: Turin Tanvir Chowdhury , Kita Yoshikuni , Rumana Nahid , Nakamura Yasuyuki , Takashima Naoyuki , Ichikawa Masaharu , Sugihara Hideki , Morita Yutaka , Hirose Kunihiko , Okayama Akira , Miura Katsuyuki , Ueshima Hirotsugu
Published: April 2013

Characterization of the time of stroke onset has been plagued by the problem of determining the time of the onset of events that are detected when the patient awakens. Our aim was to evaluate the characteristics, risk factors and acute fatality associated with wake-up stroke. Data was obtained from Takashima Stroke Registry covering approximately 55,000 residents in central Japan. During the period 1988-2003, information about the situation at stroke onset was available for 897 cerebral infarction (CI) and 335 intracerebral hemorrhage (ICH) events. Differences in characteristics and outcome between stroke during sleep and stroke while awake were explored. Among CI and ICH cases, 9.7 and 11.9% suffered from stroke during sleep, respectively. Hypertension and experiencing a severe event were associated with stroke during sleep among CI. Smoking and experiencing a severe event were associated with stroke during sleep and a drinking history reduced the chance of stroke during sleep among ICH. Acute fatality risks did not differ between stroke during sleep and stroke while awake among both CI and ICH cases. About 1 in 10 stroke patients had an onset of stroke during sleep. Hypertensive, smoker and clinically more severely affected patients had a higher prevalence of stroke during sleep. There were no differences between the 2 groups with respect to acute-case fatality.
Do Novel Psychoactive Substances Displace Established Club Drugs, Supplement Them or Act as Drugs of Initiation? The relationship between Mephedrone, Ecstasy and Cocaine
Authors: Moore Karenza , Dargan Paul I. , Wood David M. , Measham Fiona
Published: April 2013

Background/Aims: To assess whether novel psychoactive substances (NPS) displace established club drugs, supplement them or act as drugs of initiation via a study of the relationship between mephedrone, ecstasy pills, cocaine and MDMA powder amongst club-goers considered to be ‘early adopters' of psychostimulant/club drug trends. Methods: In situ surveys were conducted with 308 customers in two south London gay dance clubs across 3 weekend nights in July 2010 to assess the prevalence and patterns of self-reported use of a range of illegal drugs and NPS. Results: Mephedrone was added to existing drug repertoires amongst those surveyed and acted to supplement more established club drugs including ecstasy pills, cocaine and MDMA powder, rather than replacing or displacing those drugs. Conclusion: This survey suggests that NPS are likely to be added to drug repertoires, particularly amongst experienced users with consequent health risks for individuals and resource implications for services. This study points to a complex relationship between NPS and illegal drug availability, purity and regulatory control, one which is increasingly important to understand given the global emergence of NPS and the challenges they present to existing supply, demand and harm reduction strategies.
Spindle Epithelial Tumor with Thymus-Like Differentiation: A Case Report and Review of Literature
Authors: Misra R.K. , Mitra Shaila , Yadav Rajesh , Bundela Alpana
Published: April 2013

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare type of thyroid tumor with fewer than 35 reported cases available in the literature so far, most of them having been diagnosed histologically after resection. The tumor is believed to be derived from branchial-pouch or thymic remnants, occurring in young adults, predominantly in males, with a male:female ratio 1.8:1. Case: A 14-year-old girl presented with a nodular mass in her right thyroid that had been present for 1 year. Ultrasonological study revealed a heterogeneous solid mass (2.5 × 1.5 × 1.5 cm) in the right lobe of the thyroid. Fine-needle aspiration (FNA) smears were highly cellular and comprised of predominantly dissociated uniform spindle cells with naked oval nuclei along with some aggregates and groups. Occasional islands of epithelial cells were also present. Cytologically, the spindle cells had bland nuclear chromatin, with very scanty mitotic figures. Upon examination of the FNA smears, a provisional diagnosis of SETTLE was suggested along with a request for an incisional biopsy to rule out another differential diagnosis of medullary carcinoma thyroid. On the resected tissue specimen, diagnosis was histologically confirmed to be SETTLE. Immunohistochemical study revealed a strong and diffuse positivity for high-molecular-weight keratin and vimentin, and negativity for thyroglobulin, calcitonin, S-100 protein, desmin, chromogranin and synaptophysin. Conclusion: Cytologically, SETTLE can safely be considered, especially if spindle elements are observed along with the occasional group of epithelial cells in FNA smears from the thyroid of young adults. It can help in the preoperative recognition of lesions based on distinctive cytomorphological features and immunohistochemical characteristics, allowing a more sound therapeutic approach because these patients can present with delayed metastasis.
The Effectiveness of the Liquid-Based Preparation Method in Cerebrospinal Fluid Cytology
Authors: Argon Asuman , Uyaroğlu Mehmet Ali , Nart Deniz , Veral Ali , Kitapçıoğlu Gül
Published: April 2013

Objectives: Since malignant cells were first detected in the cerebrospinal fluid (CSF), numerous methods have been used for CSF examination. The cytocentrifugation and liquid-based cytology (LBC) methods are two of these. We aimed to investigate whether the results from the LBC method were different from the results of the cytological diagnosis of the CSF materials that were prepared using the cytocentrifugation method. Materials and Methods: A retrospective analysis was conducted using the pathological records of 3,491 (cytocentrifugation on 1,306 and LBC on 2,185) cytological specimens of CSF which were diagnosed over a 4-year period between January 2007 and December 2011. The Fisher exact test was used to compare the results of the LBC and cytocentrifugation methods. Results: While there was a noticeable decrease in nondiagnostic diagnosis and a slight decrease in suspicious diagnosis, there was an increase in malignant and benign diagnosis with the LBC method in comparison to the centrifugation method. Statistically, the decrease in nondiagnostic diagnosis was considered significant (p < 0.0001). Discussion: The LBC method seems like a better option than the cytocentrifugation method, because of many preparatory, screening and diagnostic advantages, especially in pathology departments where materials come from far away and large volumes are examined.
Bone Marrow-Derived Mesenchymal Stem Cells Promote Hepatic Regeneration after Partial Hepatectomy in Rats
Authors: Li Dong-Liang , He Xiu-Hua , Zhang Shi-An , Fang Jian , Chen Feng-Sui , Fan Jing-Jing
Published: April 2013

Objectives: Our goal was to study the ability of mesenchymal stem cells (MSCs) to stimulate liver regeneration after partial hepatectomy in rats. Methods: MSCs were isolated from bone marrow and cultured in vitro. Their characteristics were analyzed by flow cytometry. After 70% partial hepatectomy, Sprague-Dawley rats were randomly divided into three groups: a control group that was injected with saline, animals that received bone marrow-derived MSCs (BM-MSCs) by tail vein injection (the BM-MSC-TV group) and animals that received BM-MSCs by portal vein injection (the BM-MSC-PV group). The injected BM-MSCs were traced by labeling with 4′,6-diamidino-2-phenylindole, and cell proliferations were determined by immunohistochemical staining with Ki-67 and 5-bromo-2′-deoxyuridine. Results: After the third passage, the cultured BM-MSCs had a fibroblast-like morphology and expressed high levels of stem cell markers CD29 and CD90. The levels of albumin rose significantly in the BM-MSC-TV and BM-MSC-PV groups compared with the control group. The number of 4′,6-diamidino-2-phenylindole-positive liver cells in the BM-MSC-PV group was significantly higher than in the BM-MSC-TV group. The levels of Ki-67 and 5-bromo-2′-deoxyuridine were significantly higher in the BM-MSC-TV and the BM-MSC-PV groups than in the controls. Conclusion: Taken together, these results indicate that BM-MSC injections enhance liver regeneration after partial hepatectomy in rats.
Left Ventricular Assist Devices: From the Bench to the Clinic
Authors: Lee Sangjin , Fukamachi Kiyotaka , Golding Leonard , Moazami Nader , Starling Randall C.
Published: April 2013

The development of ventricular assist devices (VADs) over the past 5 decades as therapy for advanced heart failure (HF) has been extraordinary. Since the original VAD design by Michael DeBakey in the early 1960s, numerous devices for mechanical circulatory support have been engineered, assessed in preclinical studies, applied to human patients in large multicenter clinical trials, and now, select devices are Food and Drug Administration-approved therapy for advanced HF patients. This review highlights select examples of durable VADs from the engineering aspect of design and conception to experimental studies and clinical application underscoring the remarkable progression of such technology to now becoming the standard of care for many advanced HF patients.
Narrowband Ultraviolet B Interferes with Gene Expression in the Peripheral Blood T Cells of Patients with Psoriasis
Authors: Li Junqin , Hou Ruixia , Yang Yuanwen , Liu Ruifeng , Zhao Xincheng , Li Xinhua , Yin Guohua , An Peng , Wang Yong , Zhang Kaiming
Published: April 2013

Background: Psoriasis pathogenesis and development are closely related to abnormal T cell activity. Narrowband ultraviolet B (NB-UVB) treatment markedly improves skin lesions in psoriasis. Objectives: To investigate differential gene expression in psoriasis and to understand the possible mechanisms of NB-UVB therapy for psoriasis. Methods: The mRNA expression profiles and differentially expressed genes from peripheral blood T cells of psoriatic patients before and after NB-UVB treatment were examined using RNA sequencing and validated by real-time reverse-transcription polymerase chain reaction. Results: A total of 129 genes were differentially expressed in the peripheral blood T cells of psoriatic patients: 83 genes were downregulated and 46 were upregulated in psoriatic patients compared to those of healthy subjects. These genes were enriched in intracellular membrane-bound organelles, membrane-bound organelles and the nucleus, and are involved in the cell cycle, apoptosis, inflammation and other processes. These changes are reversed in psoriatic patients with good clinical outcomes following NB-UVB treatment. Conclusion: NB-UVB treatment has beneficial effects on local psoriatic lesions, possibly due to its effect on peripheral blood T cell gene expression.
Overexpression of MicroRNA-1 Improves the Efficacy of Mesenchymal Stem Cell Transplantation after Myocardial Infarction
Authors: Huang Feng , Li Mei-Ling , Fang Zhen-Fei , Hu Xin-Qun , Liu Qi-Ming , Liu Zhen-Jiang , Tang Liang , Zhao Yan-Shu , Zhou Sheng-Hua
Published: April 2013

Background: The aim of this research was to study whether transplantation of mesenchymal stem cells (MSCs) overexpressing microRNA-1 into mouse infarcted myocardium can enhance cardiac myocyte differentiation and improve cardiac function efficiently. Methods: Eight-week-old female C57BL/6 mice underwent ligation of the left coronary artery to produce models of myocardial infarction. The ligated animals were randomly divided into 4 groups (20 in each). One week later, they were intramyocardially injected at the heart infarcted zone with microRNA-1-transduced MSCs (MSCmiR-1 group), mock-vector-transduced MSCs (MSCnull group), MSCs (MSC group) or medium (PBS group). At 4 weeks post-transplantation, transthoracic echocardiographic assessment, histological evaluation and Western blot were performed. Results: The transplanted MSCs were able to differentiate into cardiomyocytes in the infarcted zone. Cardiac function in the MSC, MSCnull and MSCmiR-1 groups was significantly improved compared to the PBS group (p < 0.01 or p < 0.001). However, treatment of MSCs expressing microRNA-1 was more effective for cardiac repair and improved cardiac function more efficiently by enhancing cell survival and cardiac myocyte differentiation compared to the MSC group or the MSCnull groups (p < 0.05 or p < 0.01, respectively). Conclusions: Transplantation of microRNA-1-transfected MSCs was more conducive to repair of infarct injury and improved heart function by enhancing transplanted cells survival and cardiomyogenic differentiation.
Molecular Pathways and Cellular Metabolism in Colorectal Cancer
Authors: Hagland Hanne R. , Berg Marianne , Jolma Ingunn W. , Carlsen Arne , Søreide Kjetil
Published: April 2013

Colorectal cancer (CRC) is, for sporadic forms, most strongly related to lifestyle factors. The epidemic of obesity and physical inactivity has great impact on disease patterns. Likewise, an altered metabolism has consequences at the cellular and molecular level with implications for cancer initiation and growth. Understanding the genetic hallmarks of cancers has improved over the years and now also includes cancer metabolic reprogramming. The initiation of cancer through genetic instability, including chromosomal instability, microsatellite instability and epigenetic silencing through the CpG island methylator phenotype follows pathways with distinct clinical, pathological, and genetic characteristics. These can potentially be used for molecular classification and comprehensive tumor profiling for improved diagnostics, prognosis and treatment in CRC. For one, epidermal growth factor receptor-directed treatment now considerably prolongs survival in metastatic disease, but defining the true responders from non-responders has emerged as complex. Further, the use of both non-steroidal anti-inflammatory drugs including cyclooxygenase-2 inhibitors is associated with a decreased incidence of adenoma and reduced mortality rate of CRC. This review gives a brief yet updated overview of the current understanding of CRC as a genetic and molecular disease with potential for clinical pathways of prevention, improved prediction and better prognosis in the future.
Reproducibility of Regional DEXA Examinations of Abdominal Fat and Lean Tissue
Authors: Tallroth Kaj , Kettunen Jyrki A. , Kujala Urho M.
Published: April 2013

Objective: The aim of this study was to develop and test the validity of a new repeatable method to delimit abdominal areas for follow-up of fat mass (FM) and lean tissue mass (LM) in DEXA examinations. Methods: 37 male volunteers underwent two DEXA examinations. Total body FM and LM measurements and corresponding abdominal measurements in a carefully defined region were calculated from the first scan. After repositioning of the subjects and a second scan, the delimited region was copied and the abdominal tissues re-calculated. Results: The mean LM of the abdominal area was 2.804 kg (SD 0.556), and the mean FM was 1.026 kg (SD 0.537). The intra-class correlation coefficient for the repeated abdominal LM, FM, and LM/FM ratio measurements was 0.99. The mean difference (bias) for the repeated abdominal LM measurements was -13 g (95% confidence interval (CI) -193.0 to 166.8), and for the repeated abdominal FM measurements it was -35 g (95% CI -178.9 to 108.5). Conclusions: The results indicate that regional DEXA is a sensitive method with excellent reproducibility in the measurements of the abdominal fat and lean tissues. The method may serve as a useful tool for evaluation and follow-up of various dietary and training programmes.
Warthin Tumor with Signet-Ring Cell Features as a Pitfall in Salivary Gland Cytopathology
Authors: Bellevicine Claudio , Iaccarino Antonino , Malapelle Umberto , Troncone Giancarlo
Published: April 2013

Background: Warthin tumor (WT) is a common parotid lesion reliably diagnosed by fine-needle aspiration (FNA). Worrisome metaplastic changes may occur in WT. Their interpretation as mucoepidermoid carcinoma represents a diagnostic pitfall. Moreover, WT and mucoepidermoid carcinoma may coexist, making this distinction difficult. So it is worthwhile to report unusual WT features. We describe a WT with signet-ring cells (SRCs). Case: A 61-year-old male presenting with a 3.6-cm right parotid gland mass underwent FNA with rapid on-site evaluation. DiffQuik-stained smears showed groups of oncocytic cells with abundant granular cytoplasm in a background rich with debris, foamy macrophages and lymphoid cells. SRCs were observed on Papanicolaou-stained smears prepared from a second pass. A WT with SRC features was diagnosed. Histology revealed a WT with post-FNA infarctual changes. Conclusion: To avoid false-positive diagnoses, the cytopathologist should be aware that SRC features may occur in WT. The concomitant presence of oncocytes and SRCs is useful to correctly diagnose this unusual WT variant.
Infective Endocarditis with Symptomatic Cerebral Complications: Contribution of Cerebral Magnetic Resonance Imaging
Authors: Goulenok T. , Klein I. , Mazighi M. , Messika-Zeitoun D. , Alexandra J.F. , Mourvillier B. , Laissy J.P. , Leport C. , Iung B. , Duval X. ,   and the IMAGE study group
Published: April 2013

Background: Cerebral complications are well-identified causes of morbidity and mortality in patients with infective endocarditis (IE). Few studies have analysed the impact of brain magnetic resonance imaging (MRI) in IE patients with neurological manifestations. Objectives: The aims of this study were to assess the MRI contribution to the management of patients with IE neurological manifestations and to compare cerebral CT and MRI findings. Material and Methods: Patients with definite or probable IE and neurological manifestations were prospectively enrolled from 2005 to 2008, in a university hospital (Bichat Claude Bernard Hospital, Paris). Clinical and radiological characteristics and echocardiographic findings were systematically recorded. Brain MRI with angiography was performed and compared to available CT scans. The contribution of MRI results to cerebral involvement staging and to therapeutic plans was evaluated. Results: Thirty patients, 37-89 years old, were included. Nineteen suffered from pre-existing heart disease. Blood cultures were positive in 29 cases and the main micro-organisms were streptococci (n = 14) and staphylococci (n = 13). The IE was mainly located on mitral (n = 15) and aortic valves (n = 13). Neurological events were strokes (n = 12), meningitis (n = 5), seizures (n = 1), impaired consciousness (n = 11) and severe headache (n = 1). MRI findings included ischaemic lesions (n = 25), haemorrhagic lesions (n = 2), subarachnoid haemorrhage (n = 5), brain abscess (n = 6), mycotic aneurysm (n = 7), vascular occlusion (n = 3) and cerebral microbleeds (n = 17). In 19/30 cases, neurological manifestations were observed before the diagnosis of IE. MRI was more sensitive than CT scan in detecting both clinically symptomatic cerebral lesions (100 and 81%, respectively) and additional asymptomatic lesions (50 and 23%, respectively). Therapeutic plans were modified according to MRI results in 27% of patients: antibiotherapy regimen modifications in 7% (switch for molecules with high cerebral diffusion) and surgical plan modifications in 20% (indication of valvular replacement due to the embolic nature of the vegetations revealed by MRI or postponement of surgery due to haemorrhagic lesions). None of the 16/30 (51%) operated-on patients experienced postoperative neurological worsening. In-hospital death occurred in 4 patients. Conclusion: In patients with IE neurological manifestations, MRI revealed a broader involvement of the brain (type and number of lesions) than indicated by clinical signs and/or CT scan. With a better disease staging of neurological manifestations, MRI brain imaging may help in patient management and the decision-making process especially for cardiac surgery indication and timing of valve replacement.
Isolated Lacunar Infarct: An Early Clinical Presentation of CADASIL?
Authors: Carra-Dallière C. , Ayrignac X. , Renard D. , Menjot de Champfleur N. , Tourniaire P. , Mine M. , Labauge P.
Published: April 2013

No abstract available 
Can Breast Nipple Fluid Collected with Automated Aspiration and Preserved in Based-Liquid Solution Improve the Cytological Samples?
Authors: Filassi José Roberto , Zonta Marco Antonio , Trinconi Angela , Calvagno Daniele , Velame de Oliveira Fernada , Ricci Marcos Desidério , Baracat Edmund , Longatto-Filho Adhemar
Published: April 2013

Objective: Samples from breast nipples collected with the automated HALO™ Mamo Cito Test were studied in order to evaluate the cellularity for the diagnosis of breast cancer. Study Design: One hundred and fifty-nine asymptomatic women were prospectively examined. Women younger than 18 years, pregnant or lactating women, and women with a history of breast cancer, with previous radio- or chemotherapy and with nipple piercing were excluded from the study. Nipple samples from both breasts were collected. Results: In 107 (34.96%) of the 306 samples of nipple discharge analyzed by optical microscopy, adequate cellularity was observed after the HALO procedure. Cytological findings, previously categorized according to the National Health Service Breast Screening Program (NHSBSP), were grouped as unsatisfactory, benign, suspected for malignancy, and malignant. Of the cellular breast samples, 97.19% (104/107) were classified as benign, and 2.81% (3/107) were classified as suspicious for malignancy. In 199 cases there were samples without cells (65.03%). Most of the cells observed were easily recognized as well-preserved and adequately stained macrophages. None of the women reported discomfort with the nipple aspiration procedure. Conclusions: The results discussed here encouraged us to use samples collected automatically in routine procedures.
Negative Chronotropic Effects and Coronary Ischaemic Abnormalities Following Thalidomide Therapy
Authors: Ali Ali , Hothi Sandeep S. , Thompson Andrew , Malik Nadim
Published: April 2013

The severe teratogenic side effects of thalidomide led to its well-publicized withdrawal in the 1970s, but as it is cautiously being reintroduced into clinical use, new adverse effects are being described. A 65-year-old male with multiple myeloma received chemotherapy which included cyclophosphamide, thalidomide and dexamethasone. Whilst on this treatment he experienced severe chest pain leading to an acute hospital admission complicated by significant bradycardia with sinus pauses of 7 s, necessitating temporary right ventricular pacing. Despite correction of the bradycardia with temporary pacing, he experienced further episodes of chest pain, during which an ECG (with the pacemaker briefly switched off) showed ST elevation in the inferior leads along with runs of non-sustained ventricular tachycardia. Emergency coronary angiography demonstrated unobstructed coronary arteries. Due to ST elevation in the absence of flow-limiting coronary disease his presentation was presumed to be due to intermittent coronary artery spasm. He was started on sustained-release nifedipine without any beta-blockers and further thalidomide therapy was omitted. On this pharmacological therapy, over a period of 24 months, there were no further recurrences of any cardiac symptoms. To our knowledge there have been no previous reports of coronary artery spasm associated with the use of thalidomide. The precise mechanism remains undefined, with several plausible hypothetical pathways which we discuss. We discuss various mechanisms including autonomic, autocoid and paracrine modes of action that may underlie cardiac side effects of thalidomide. We report coronary spasm in addition to bradycardia as cardiac side effects that cardiologists and oncologists need to be alert to.
Characterization of the Relaxant Response to Taurine in Rat Corpus Cavernosum
Authors: Dalaklioglu-Tasatargil S.
Published: April 2013

The aim of this study was to evaluate the relaxant effect of taurine, one of the most commonly employed dietary supplements, in rat corpus cavernosum (CC), and to further investigate the contribution of possible underlying mechanisms. Strips of CC were suspended in an organ bath system for isometric tension studies. Taurine (10-80 mmol/l) produced a concentration-dependent relaxation response in rat CC. Endothelial removal did not cause a significant inhibition of the relaxation response to taurine. Incubation of endothelium-denuded CC strips with the nonselective potassium channel blocker tetraethylammonium (10 mmol/l), the ATP-sensitive potassium (KATP) channel blocker glibenclamide (10 μmol/l), the inward rectifier potassium (Kir) channel inhibitor barium chloride (30 μmol/l), and the large conductance calcium-activated potassium channel inhibitor iberiotoxin (0.1 μmol/l) significantly inhibited the relaxant responses to taurine. However, taurine-induced relaxation was not inhibited by the voltage-dependent potassium channel inhibitor 4-aminopyridine (1 mmol/l). On the other hand, taurine (20 mmol/l, 30 min) inhibited both intracellular and extracellular calcium-dependent contraction in CC strips. These findings suggest that taurine induced relaxation of CC via an endothelium-independent pathway. The activation of KATP channels, Kir channels and calcium channels is thought to play an important role in endothelium-independent relaxation of CC, but other direct effects on calcium dynamics may also contribute to its relaxant effect.
Mycobacterium tuberculosis-Induced Neutrophil Extracellular Traps Activate Human Macrophages
Authors: Braian Clara , Hogea Valentin , Stendahl Olle
Published: April 2013

Neutrophils activated by Mycobacterium tuberculosis (Mtb) form neutrophil extracellular traps (NETs), containing DNA and several biologically active cytosolic and granular proteins. These NETs may assist in the innate immune defense against different pathogens. We investigated whether the NET-forming neutrophils mediate an activating signal to macrophages during the early multicellular inflammatory reaction and granuloma formation. Mtb-induced NETs were found to be reactive oxygen species dependent and phagocytosis dependent. A neutrophil elastase inhibitor also delayed NET formation. However, NET formation occurred independently of Mtb-induced apoptosis. We observed close interactions between macrophages and Mtb-activated neutrophils, where macrophages bound and phagocytosed NETs. Significant secretion of the cytokines interleukin (IL)-6, tumor necrosis factor-α, IL-1β and IL-10 were detected from macrophages cocultured with NETs from Mtb-activated but not phorbol myristate acetate-activated neutrophils. NETs binding heat shock protein 72 (Hsp72) or recombinant Hsp72 were able to trigger cytokine release from macrophages. Only Mtb-induced NETs contained Hsp72, suggesting that these NETs can transfer this danger signal to adjacent macrophages. We propose that Hsp72 sequestered in NETs plays an important role in the interaction between neutrophils and macrophages during the early innate immune phase of an Mtb infection. The immunomodulatory role of NETs and proteins derived from them may influence not only chronic inflammation during tuberculosis but also immune regulation and autoimmunity.
Cisplatin plus Capecitabine as First-Line Chemotherapy for Recurrent or Metastatic Head and Neck Squamous Cell Cancer: Experience Outside of a Trial Setting
Authors: McPartlin A.J. , Mais K. , Barker C. , Swindell R. , Mitchell K. , Sykes A. , Lee L. , Yap B. , Slevin N.J.
Published: April 2013

Purpose: Cisplatin/5-fluorouracil (5-FU) is an accepted palliative chemotherapy treatment for head and neck squamous cell carcinoma, improving quality of life but not overall survival. Capecitabine in place of 5-FU removes the morbidity of an infusional regime with potential benefit in patient well-being. This study looks at outcomes for cisplatin plus capecitabine (PX) outside of a trial setting. Methods: Consecutive patients receiving this treatment in a single centre were retrospectively analysed. Cisplatin (mean dose 75 mg/m2) was given on day 1 of a 3-week cycle and capecitabine (mean dose 808 mg/m2 twice daily) on days 1-14, for up to 6 cycles. Results: Sixty-five patients (median age 58.6 years) received a median of 4 cycles of chemotherapy. The overall response rate was 30.7%, with a median overall survival of 7.3 months. Treatment was well tolerated with a 10.7% grade 3 and a 1.5% grade 4 neutropenia rate, with no other grade 4 toxicities. One patient died of neutropenic sepsis whilst on treatment. Twenty-seven percent of patients stopped treatment early due to chemotherapy-related side effects. Conclusion: PX is well tolerated outside the trial setting with outcomes similar to historical published literature. Ease of administration and benefit to patient convenience make it an attractive alternative to standard palliative treatment.
Introduction of Hypothermia for Neonates with Perinatal Asphyxia in the Netherlands and Flanders
Authors: Groenendaal Floris , Casaer Alexandra , Dijkman Koen P. , Gavilanes Antonio W.D. , de Haan Timo R. , ter Horst Henk J. , Laroche Sabine , Naulaers Gunnar , Rijken Monique , van Straaten Henrica L.M. , Steiner Katerina , Swarte Renate M.C. , Zecic Alexandra , Zonnenberg Inge A. ,   and the Dutch-Flemish Working Group on Neonatal Neurology
Published: April 2013

Background: Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database. Objectives: The aim of this study was to analyse complications and outcome after implementation. Methods: Data were retrieved from an online database to which all centres had contributed. Results: In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials. Conclusions: The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials.