bluuebunny/crossref_metadata_2025_split huggingface dataset:
C-kit Expression in Canine Mucosal Melanomas
Authors: Newman S. J. , Jankovsky J. M. , Rohrbach B. W. , LeBlanc A. K. 
Published: August 2011

The c-kit receptor is responsible for transmission of promigration signals to melanocytes; its downregulation may be involved in malignant progression of human melanocytic neoplasms. Expression of this receptor has not been examined in normal or neoplastic melanocytes from dogs. In this study, 14 benign dermal and 61 malignant mucosal melanocytic tumors were examined for c-kit (KIT) expression. Sites of the mucosal melanomas were gingiva (not further specified; n = 30), buccal gingiva ( n = 6), soft palate ( n = 4), hard palate ( n = 5), tongue ( n = 7), lip ( n = 6), and conjunctiva ( n = 3). Melan A was expressed in all 14 dermal melanocytomas and in 59 of 61 (96.7%) tumors from oral or conjunctival mucosa, confirming melanocytic origin. C-kit receptor expression was strong and diffuse throughout the cytoplasm in all 14 dermal melanocytomas and was identified in basilar mucosal melanocytes over submucosal neoplasms (27 of 61, 44.3%), junctional (neoplastic) melanocytes (17 of 61, 27.9%), and, less commonly, neoplastic melanocytes of the subepithelial tumors (6 of 61, 9.8%). KIT expression anywhere within the resected melanomas correlated with significantly longer survival. These results suggest that c-kit receptor expression may be altered in canine melanomas and may have potential as a prognostic indicator for mucosal melanomas.
Intramuscular Transplantation of Muscle-Derived Stem Cells Accelerates Skeletal Muscle Healing After Contusion Injury via Enhancement of Angiogenesis
Authors: Ota Shusuke , Uehara Kenji , Nozaki Masahiro , Kobayashi Tetsuo , Terada Satoshi , Tobita Kimimasa , Fu Freddie H. , Huard Johnny 
Published: August 2011

Background: Muscle contusions are common muscle injuries. Although these injuries are capable of healing, incomplete functional recovery often occurs. Muscle-derived stem cells (MDSCs) are likely derived from blood vessel cells and have a multilineage differentiation potential. Purpose: The aims of this study are (1) to find optimal timing of MDSC transplantation to enhance muscle healing by stimulating muscle regeneration and preventing scar tissue (fibrosis) formation after skeletal muscle contusion injury, and (2) to investigate the role of angiogenesis in the muscle-healing process after MDSC transplantation. Study Design: Controlled laboratory study. Methods: Muscle-derived stem cells were injected directly into injured tibialis anterior muscles of mice at various time points (1, 4, and 7 days) after the muscle contusion injury. Muscle regeneration, angiogenesis, and fibrosis formation were evaluated by histology and real-time polymerase chain reaction analysis, and functional recovery was measured by physiologic testing. Results: Transplantation of MDSCs at 4 days after injury significantly promoted angiogenesis, which was induced by high levels of vascular endothelial growth factor expression at week 1, and significantly increased muscle regeneration and muscle strength by week 2, when compared with the other groups. A decrease in fibrosis formation was observed at week 4, when compared with the other groups, after the transplantation of MDSCs at 4 and 7 days after injury. Conclusion: Intramuscular injection of MDSCs at 4 days after injury improved and accelerated skeletal muscle healing by increasing angiogenesis and decreasing scar tissue formation. Clinical Relevance: These findings could contribute to the development of biologic treatments to aid in muscle healing after muscle injury.
Functional magnetic resonance imaging correlates of cognitive performance in patients with a clinically isolated syndrome suggestive of multiple sclerosis at presentation: an activation and connectivity study
Authors: Forn C , Rocca MA , Valsasina P , Boscá I , Casanova B , Sanjuan A , Ávila C , Filippi M 
Published: August 2011

Background/Objective: To assess whether abnormalities on functional magnetic resonance imaging (fMRI) are related to cognitive function in patients at presentation with clinically isolated syndrome (CIS) suggestive of multiple sclerosis. Methods: Eighteen patients with CIS and 15 healthy controls (HCs) performed an adapted fMRI version of the Paced Auditory Serial Addition Test (PASAT). According to their PASAT performance, CIS patients were divided into two groups: 10 with a low PASAT performance (<1 SD from the mean value of HCs) were considered ‘cognitive impairment’ (CI); eight patients were defined as ‘cognitively preserved’ (CP). Between-group differences in the patterns of brain activations and effective connectivity were assessed. Results: During PASAT, compared to HCs, CIS patients showed increased activations of the bilateral inferior parietal lobe (IPL), bilateral precuneus, bilateral middle frontal gyrus (MFG), left anterior cingulate cortex (ACC), left claustrum, right thalamus and right caudate nucleus. When CIS patients were analyzed, the CI group had a more significant activation of the bilateral IPL than HCs and CP patients. Compared to CP patients, they also had more significant recruitment of the right superior parietal lobe, right cerebellum, left MFG and left ACC. The analysis of effective connectivity showed stronger connections between several regions of the right hemisphere involved in working memory function in CI patients versus CP and HC. Conclusions: During performance of the PASAT, CIS patients show abnormalities in the patterns of cortical recruitment and connectivity related to the level of their cognitive impairment.
Functional human regulatory T cells fail to control autoimmune inflammation due to PKB/c-akt hyperactivation in effector cells
Authors: Wehrens Ellen J. , Mijnheer Gerdien , Duurland Chantal L. , Klein Mark , Meerding Jenny , van Loosdregt Jorg , de Jager Wilco , Sawitzki Birgit , Coffer Paul J. , Vastert Bas , Prakken Berent J. , van Wijk Femke 
Published: August 2011

AbstractDuring the last decade research has focused on the application of FOXP3+ regulatory T cells (Tregs) in the treatment of autoimmune disease. However, thorough functional characterization of these cells in patients with chronic autoimmune disease, especially at the site of inflammation, is still missing. Here we studied Treg function in patients with juvenile idiopathic arthritis (JIA) and observed that Tregs from the peripheral blood as well as the inflamed joints are fully functional. Nevertheless, Treg-mediated suppression of cell proliferation and cytokine production by effector cells from the site of inflammation was severely impaired, because of resistance to suppression. This resistance to suppression was not caused by a memory phenotype of effector T cells or activation status of antigen presenting cells. Instead, activation of protein kinase B (PKB)/c-akt was enhanced in inflammatory effector cells, at least partially in response to TNFα and IL-6, and inhibition of this kinase restored responsiveness to suppression. We are the first to show that PKB/c-akt hyperactivation causes resistance of effector cells to suppression in human autoimmune disease. Furthermore, these findings suggest that for a Treg enhancing strategy to be successful in the treatment of autoimmune inflammation, resistance because of PKB/c-akt hyperactivation should be targeted as well.
Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients
Authors: Cibeira Maria Teresa , Sanchorawala Vaishali , Seldin David C. , Quillen Karen , Berk John L. , Dember Laura M. , Segal Adam , Ruberg Frederick , Meier-Ewert Hans , Andrea Nancy T. , Sloan J. Mark , Finn Kathleen T. , Doros Gheorghe , Blade Joan , Skinner Martha 
Published: August 2011

Abstract
Previous studies have suggested that, in patients with AL amyloidosis treated with high-dose melphalan and autologous stem-cell transplantation (HDM/SCT), the greatest benefit is seen in those patients achieving a hematologic complete response (CR). We analyzed a series of 421 consecutive patients treated with HDM/SCT at a single referral center and compared outcomes for patients with and without CR. Treatment-related mortality was 11.4% overall (5.6% in the last 5 years). By intention-to-treat analysis, the CR rate was 34% and the median event-free survival (EFS) and overall survival (OS) were 2.6 and 6.3 years, respectively. Eighty-one patients died within the first year after HDM/SCT and were not evaluable for hematologic and organ response. Of 340 evaluable patients, 43% achieved CR and 78% of them experienced an organ response. For CR patients, median EFS and OS were 8.3 and 13.2 years, respectively. Among the 195 patients who did not obtain CR, 52% achieved an organ response, and their median EFS and OS were 2 and 5.9 years, respectively. Thus, treatment of selected AL patients with HDM/SCT resulted in a high organ response rate and long OS, even for those patients who did not achieve CR.
Extranodal dissemination of non-Hodgkin lymphoma requires CD47 and is inhibited by anti-CD47 antibody therapy
Authors: Chao Mark P. , Tang Chad , Pachynski Russell K. , Chin Robert , Majeti Ravindra , Weissman Irving L. 
Published: August 2011

AbstractNon-Hodgkin lymphoma (NHL) presents as both localized and disseminated disease with spread to secondary sites carrying a worse prognosis. Although pathways driving NHL dissemination have been identified, there are few therapies capable of inhibiting them. Here, we report a novel role for the immunomodulatory protein CD47 in NHL dissemination, and we demonstrate that therapeutic targeting of CD47 can prevent such spread. We developed 2 in vivo lymphoma metastasis models using Raji cells, a human NHL cell line, and primary cells from a lymphoma patient. CD47 expression was required for Raji cell dissemination to the liver in mouse xenotransplants. Targeting of CD47 with a blocking antibody inhibited Raji cell dissemination to major organs, including the central nervous system, and inhibited hematogenous dissemination of primary lymphoma cells. We hypothesized that anti-CD47 antibody-mediated elimination of circulating tumor cells occurred through phagocytosis, a previously described mechanism for blocking anti-CD47 antibodies. As predicted, inhibition of dissemination by anti-CD47 antibodies was dependent on blockade of phagocyte SIRPα and required macrophage effector cells. These results demonstrate that CD47 is required for NHL dissemination, which can be therapeutically targeted with a blocking anti-CD47 antibody. Ultimately, these findings are potentially applicable to the dissemination and metastasis of other solid tumors.
Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia
Authors: Schwind Sebastian , Marcucci Guido , Kohlschmidt Jessica , Radmacher Michael D. , Mrózek Krzysztof , Maharry Kati , Becker Heiko , Metzeler Klaus H. , Whitman Susan P. , Wu Yue-Zhong , Powell Bayard L. , Baer Maria R. , Kolitz Jonathan E. , Carroll Andrew J. , Larson Richard A. , Caligiuri Michael A. , Bloomfield Clara D. 
Published: August 2011

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.
Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group
Authors: Eichenauer Dennis A. , Fuchs Michael , Pluetschow Annette , Klimm Beate , Halbsguth Teresa , Böll Boris , von Tresckow Bastian , Nogová Lucia , Borchmann Peter , Engert Andreas 
Published: August 2011

Abstract
Nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) accounts for ∼ 5% of Hodgkin lymphoma cases. The disease is characterized by a strong CD20 expression on the malignant cells and a more indolent clinical course compared with classic HL. Anti-CD20 antibody treatment has shown clinical activity in relapsed NLPHL. In this phase 2 trial, we investigated rituximab in newly diagnosed stage IA NLPHL patients. Four weekly applications at 375 mg/m2 were given. Among the 28 evaluable patients, overall response rate was 100%, 24 patients (85.7%) achieved complete remission, and 4 (14.3%) achieved partial remission. At a median follow-up of 43 months, overall survival was 100%; progression-free survival at 12, 24, and 36 months was 96.4%, 85.3%, and 81.4%, respectively. No grade 3 or 4 toxicity was observed. Although treatment results with rituximab appear inferior compared with radiotherapy and combined-modality approaches in early-stage patients, investigation of anti-CD20 antibody-based combinations in NLPHL is warranted. This study was registered at www.clinicaltrials.gov as #NCT00346684.
Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease
Authors: Kim Han-Joon , Jeon Beom S , Lee Won Yong , Lee Myoung Chong , Kim Jae Woo , Kim Jong-Min , Ahn Tae-Beom , Cho Jinwhan , Chung Sun Ju , Grieger Frank , Whitesides John , Boroojerdi Babak 
Published: August 2011

Abstract

Background
A recent trial involving predominantly Caucasian subjects with Parkinson Disease (PD) showed switching overnight from an oral dopaminergic agonist to the rotigotine patch was well tolerated without loss of efficacy. However, no such data have been generated for Korean patients.

Methods
This open-label multicenter trial investigated PD patients whose symptoms were not satisfactorily controlled by ropinirole, at a total daily dose of 3 mg to 12 mg, taken as monotherapy or as an adjunct to levodopa. Switching treatment from oral ropinirole to transdermal rotigotine was carried out overnight, with a dosage ratio of 1.5:1. After a 28-day treatment period, the safety and tolerability of switching was evaluated. Due to the exploratory nature of this trial, the effects of rotigotine on motor and nonmotor symptoms of PD were analyzed in a descriptive manner.

Results
Of the 116 subjects who received at least one treatment, 99 (85%) completed the 28-day trial period. Dose adjustments were required for 11 subjects who completed the treatment period. A total of 76 treatment-emergent adverse events (AEs) occurred in 45 subjects. No subject experienced a serious AE. Thirteen subjects discontinued rotigotine prematurely due to AEs. Efficacy results suggested improvements in both motor and nonmotor symptoms and quality of life after switching. Fifty-two subjects (46%) agreed that they preferred using the patch over oral medications, while 31 (28%) disagreed.

Conclusions
Switching treatment overnight from oral ropinirole to transdermal rotigotine patch, using a dosage ratio of 1.5:1, was well tolerated in Korean patients with no loss of efficacy.

Trial registration
This trial is registered with the ClincalTrails.gov Registry (NCT00593606).
Dicer and miRNA in relation to clinicopathological variables in colorectal cancer patients
Authors: Stratmann Johannes , Wang Chao-Jie , Gnosa Sebastian , Wallin Åsa , Hinselwood David , Sun Xiao-Feng , Zhang Hong 
Published: August 2011

Abstract

Background
Dicer is aberrantly expressed in several types of cancers. Applying real-time PCR, we detected the expression of Dicer mRNA in normal mucosa (n = 162), primary colorectal cancer (CRC) (n = 162) and liver metastasis (n = 37), and analysed the relationship between Dicer expression and clinicopathological features. We also correlated the expression of Dicer mRNA to the miRNA expression of miR-141, miR-200a, miR-200b, mir-200c and miR-429 in liver metastases.

Methods
RT-PCR and qPCR were used to analyse the Dicer expression in normal mucosa, primary tumour and liver metastasis by using the High Capacity cDNA Reverse Transcription Kit and TaqMan™® Gene Expression assays for Dicer and GAPDH. RT-PCR and qPCR were used to detect miRNA expression in liver metastases by utilizing TaqMan® MicroRNA Reverse Transcription Kit and TaqMan® miRNA Assays. Statistical analyses were performed with STATISTICA.

Results
Dicer expression in rectal cancer (3.146 ± 0.953) was higher than in colon cancer (2.703 ± 1.204, P = 0.018). Furthermore the Dicer expression was increased in primary tumours (3.146 ± 0.952) in comparison to that in normal mucosa from rectal cancer patients (2.816 ± 1.009, P = 0.034) but this is not evident in colon cancer patients. Dicer expression in liver metastases was decreased in comparison to that of either normal mucosa or primary tumour in both colon and rectal cancers (P < 0.05). Patients with a high Dicer expression in normal mucosa had a worse prognosis compared to those with a low Dicer expression, independently of gender, age, tumour site, stage and differentiation (P < 0.001, RR 3.682, 95% CI 1.749 - 7.750). In liver metastases, Dicer was positively related to miR-141 (R = 0.419, P = 0.015).

Conclusion
Dicer is up-regulated in the early development of rectal cancers. An increased expression of Dicer mRNA in normal mucosa from CRC patients is significantly related to poor survival independently of gender, age, tumour site, stage and differentiation.
Non-invasive algorithm for bowel motility estimation using a back-propagation neural network model of bowel sounds
Authors: Kim Keo-Sik , Seo Jeong-Hwan , Song Chul-Gyu 
Published: August 2011

Abstract

Background
Radiological scoring methods such as colon transit time (CTT) have been widely used for the assessment of bowel motility. However, these radiograph-based methods need cumbersome radiological instruments and their frequent exposure to radiation. Therefore, a non-invasive estimation algorithm of bowel motility, based on a back-propagation neural network (BPNN) model of bowel sounds (BS) obtained by an auscultation, was devised.

Methods
Twelve healthy males (age: 24.8 ± 2.7 years) and 6 patients with spinal cord injury (6 males, age: 55.3 ± 7.1 years) were examined. BS signals generated during the digestive process were recorded from 3 colonic segments (ascending, descending and sigmoid colon), and then, the acoustical features (jitter and shimmer) of the individual BS segment were obtained. Only 6 features (J

1, 3

, J

3, 3

, S

1, 2

, S

2, 1

, S

2, 2

, S

3, 2
), which are highly correlated to the CTTs measured by the conventional method, were used as the features of the input vector for the BPNN.

Results
As a results, both the jitters and shimmers of the normal subjects were relatively higher than those of the patients, whereas the CTTs of the normal subjects were relatively lower than those of the patients (p < 0.01). Also, through k-fold cross validation, the correlation coefficient and mean average error between the CTTs measured by a conventional radiograph and the values estimated by our algorithm were 0.89 and 10.6 hours, respectively.

Conclusions
The jitter and shimmer of the BS signals generated during the peristalsis could be clinically useful for the discriminative parameters of bowel motility. Also, the devised algorithm showed good potential for the continuous monitoring and estimation of bowel motility, instead of conventional radiography, and thus, it could be used as a complementary tool for the non-invasive measurement of bowel motility.
Possible linkages between the inner and outer cellular states of human induced pluripotent stem cells
Authors: Saito Shigeru , Onuma Yasuko , Ito Yuzuru , Tateno Hiroaki , Toyoda Masashi , Hidenori Akutsu , Nishino Koichiro , Chikazawa Emi , Fukawatase Yoshihiro , Miyagawa Yoshitaka , Okita Hajime , Kiyokawa Nobutaka , Shimma Yohichi , Umezawa Akihiro , Hirabayashi Jun , Horimoto Katsuhisa , Asashima Makoto 
Published: August 2011

Abstract

Background
Human iPS cells (hiPSCs) have attracted considerable attention for applications to drug screening and analyses of disease mechanisms, and even as next generation materials for regenerative medicine. Genetic reprogramming of human somatic cells to a pluripotent state was first achieved by the ectopic expression of four factors (Sox2, Oct4, Klf4 and c-Myc), using a retrovirus. Subsequently, this method was applied to various human cells, using different combinations of defined factors. However, the transcription factor-induced acquisition of replication competence and pluripotency raises the question as to how exogenous factors induce changes in the inner and outer cellular states.

Results
We analyzed both the RNA profile, to reveal changes in gene expression, and the glycan profile, to identify changes in glycan structures, between 51 cell samples of four parental somatic cell (SC) lines from amniotic mesodermal, placental artery endothelial, and uterine endometrium sources, fetal lung fibroblast (MRC-5) cells, and nine hiPSC lines that were originally established. The analysis of this information by standard statistical techniques combined with a network approach, named network screening, detected significant expression differences between the iPSCs and the SCs. Subsequent network analysis of the gene expression and glycan signatures revealed that the glycan transfer network is associated with known epitopes for differentiation, e.g., the SSEA epitope family in the glycan biosynthesis pathway, based on the characteristic changes in the cellular surface states of the hiPSCs.

Conclusions
The present study is the first to reveal the relationships between gene expression patterns and cell surface changes in hiPSCs, and reinforces the importance of the cell surface to identify established iPSCs from SCs. In addition, given the variability of iPSCs, which is related to the characteristics of the parental SCs, a glycosyltransferase expression assay might be established to define hiPSCs more precisely and thus facilitate their standardization, which are important steps towards the eventual therapeutic applications of hiPSCs.