tbuckley/cabot-search huggingface dataset:
AB0005 F1 Hybrid of NZW and Fcg Riib-Deficient B6 Mice Developed Phenotype Conversion from Rheumatoid Arthritis to Murine Lupus
Authors: H. Amano, T. Kaneko, Q. Lin, K. Shinya, K. Nishikawa, S. Hirose, Y. Takasaki
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> FcγRIIB negatively regulates BCR-mediated activation signals. We previously established an FcγRIIB-deficient B6-congenic mouse strain (KO1) by gene targeting in 129-derived embryonic stem cells followed by backcrossing to B6 mice. KO1 spontaneously developed pathology of rheumatoid arthritis (RA) with autoantibody production and pannus formation leading to joint destruction. <h3>Objectives</h3> To analyse the phenotypic change of KO1 by crossing with lupus prone New Zealand White (NZW) mice, we established the F1 hybrid of KO1 and NZW mice. Also we analysed (KO1 x NZW) F2 mice to see the sharing loci contributing to disease phenotypes. <h3>Methods</h3> We analysed the (KO1 x NZW) F1 mice and (KO1 x NZW) F2 mice. Serum levels of RF, IgG antibodies against double-stranded DNA and chromatin were measured using ELISA. The severity of renal disease was monitored by biweekly testing for proteinuria. Histopathological examination was also performed. <h3>Results</h3> The F1 hybrid of these mice developed glomerulonephritis with the high incidence of positive anti- double-stranded DNA and chromatin antibodies. They did not develop the phenotype of RA, but developed lupus phenotype associated with the inflammatory infiltration in salivary glands as observed in Sjögren syndrome. In the progeny of (KO1 x NZW) F2 mice, RA, SLE, and Sjögren syndrome developed independently or overlapped in an individual mouse. We found that the B6-derived locus located in the centromeric region on chromosome 12 was significantly associated with all these disease phenotypes, suggesting that this locus may play a role in common process shared by these diseases. <h3>Conclusions</h3> Phenotypic specificity of murine autoimmune disorder depends on the genetic factors sharing RA, SLE, and Sjögren syndrome. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6071
Plasma Neurotransmitters and Functional Illness
Authors: Fuad Lechin, Bertha van der Dijs, Marcel E. Lechin
Journal: Psychotherapy and Psychosomatics (1996)

Although the concept of functional illness has blurred boundaries, some consensus exists on its understanding among clinicians. In short, it is easier to conceive than to define functional illness. Semantic and conceptual discussion concerning this issue have been endless. Many links exist that connect brain and body (mind and organs, psyche and soma). Amongst them, neurotransmitters, released by peripheral neurons and some glandular cells (adrenal, enterochromaffm cells, mast cells), are diverted into the bloodstream. Although neurotransmitters cannot cross the blood-brain barrier, basic and clinical research has progressively established the relationship between central and peripheral neurochemical activities. Hence, it is possible to obtain some approach to the central profile through the measurement of circulating neurotransmitters. However, this approach is more reliable if we can measure all circulating factors and, in addition, test the responses to different kinds of challenges (stressors, drugs, etc.). All diseases (somatic, psychiatric and psychosomatic) present some kind of plasma neurotransmitter disturbance; however, only in some has the whole abnormal profile been established. Technical difficulties as well as expensive procedures have interfered with the generalization of this research area. In the present review article, we summarize data quoted from current scientific literature reporting exhaustive research in this area.
P08.22 * THE ROLE OF CYBERKNIFE FOR PITUITARY METASTASES
Authors: R. Nomura, K. Sato, I. Suzuki
Journal: Neuro-Oncology (2014)

BACKGROUND: Pituitary metastases are found in 1.0-26.7% of cancer patients at autopsy. But clinically very rare. We evaluate the efficacy and safety of CyberKnife treatment in the management of metastatic cancer to the pituitary grand. PATIENTS 13 pituitary metastases (male 6, female 7). Age 47y-69y (median 53y). KPS ≧70. No previous irradiation. METHODS: Treatment system: CyberKnife (G3 or G4), Planning system: On target, Multiplan (Accuray), Calculation model: Ray tracing, Inverse algorithm, Immobilaization: thermoplastic mask, Image: CECT 1mm in thickness + MRI Gd T1WI 1-3mm in thickness, PTV = CTV = GTV, Verification: TLS (Target locating system), 6 axis correction. TREATMENT PROTOCOL: Marginal dose: D95PTV ≧ 95%, iso-dose line 80% (goal), Fractions: tumor size, adjacent to OAR (organs at risk), Tolerable dose of optic appratus: 12Gy (SRS), 21Gy (3fr.), 25Gy (5fr.), 28Gy (7fr.). Tumor volume (PTV): 0.5-18.2 cc (median 2.8 cc), Primary origin: Breast 5, Lung 2, Others 6. Clinical symptom: visual disturbance 11 (85%), diabetes insipidus 5 (38%), diplopia 1 (7.7%), asymptomatic 1 (7.7%). Marginal dose: 18-35 Gy (median 23Gy). RESULTS: Follow up periods 4-31months. Progression free survival: 81.8% (@6m), 63.6% (@12m), 54.5% (@24m). Overall survival: 92.3% (@3m), 84.6% (@6m), 67.3% (@12m), 25.6% (@24m). Maximum dose for optic apparatus BED2 (Gy): 84-229 Gy (median 98.3Gy). Only 1 case became entirely blind 12 months after CyberKnife for 6 months until her death, despite tumor reduction. In this case, maximum dose for optic apparatus BED2 (Gy) was 229 Gy (highest). CONCLUSION: These preliminary results seem to indicate that CyberKnife SRT is a safe, effective and palliative treatment for most patients with pituitary metastasis. To prevent radiation induced optic neuropathy, maximum dose for optic apparatus BED2 (Gy) is under 126 Gy (single dose equivalent: 15Gy). Its safety and efficacy remain to be observed in long-term follow up.
Minimal Residual Disease in <i>NPM1</i>-Mutated AML
Authors: Michael J. Burke
Journal: New England Journal of Medicine (2016)

One of the most important discoveries in the treatment of acute leukemia is that the presence of minimal residual disease is an independent prognostic factor for the duration of remission and survival. This is particularly true for patients with acute lymphoblastic leukemia.1,2 The identification of minimal residual disease at the end of induction therapy, at the end of consolidation therapy, or before allogeneic hematopoietic stem-cell transplantation in patients with acute lymphoblastic leukemia is associated with a significantly worse outcome than is the absence of minimal residual disease at the same time point.13The presence of minimal residual disease . . .
Oolong tea is useful for lens cleansing in transnasal small-caliber esophagogastroduodenoscopy
Authors: Y. Komazawa, Y. Amano, M. Yuki, H. Fukuhara, T. Mishiro, T. Mishiro, T. Shizuku, Y. Kinoshita
Journal: Endoscopy (2009)

See also: Commentaire de travail de Y. Komazawa et al., pp. 104Endoscopy 2010; 42(02): 183-183DOI: 10.1055/s-0031-1291834
Endoscopic ultrasound-guided fine needle aspiration diagnosis of a focal fatty mass in the pancreas
Authors: Luca Barresi, Ilaria Tarantino, Dario Ligresti, Rosa Liotta, Gabriele Curcio, Antonino Granata, Caruso Settimo, Mario Traina
Journal: Endoscopy (2014)

Focal fatty masses of the pancreas, which include focal fatty infiltration, lipoma, and liposarcoma, are rare entities [1]. A well-differentiated lipogenic liposarcoma can mimic a benign lesion on radiologic examination and only cytohistology can resolve the doubt [2].
Reduced Sensitivity of Lymphocyte Beta-Adrenergic Receptors in Patients with Endogenous Depression and Psychomotor Agitation
Authors: J. John Mann, Richard P. Brown, James P. Halper, John A. Sweeney, James H. Kocsis, Peter E. Stokes, John P. Bilezikian
Journal: New England Journal of Medicine (1985)

It has been suggested that there are altered levels of norepinephrine or other neurotransmitters at functionally important receptors in patients with depressive disorders. This hypothesis is difficult to study in the human central nervous system. However, noradrenergic function can be assessed indirectly with peripheral-blood lymphocytes used as a model of the beta-adrenergic receptor complex. We found that drug-free inpatients with endogenous depression had lower isoproterenol-stimulated cyclic AMP levels in intact lymphocytes than did healthy control subjects (3.9 +/- 0.5 vs. 7.4 +/- 1.0 pmol per 10(6) cells, P less than 0.01). The density and affinity of beta-adrenergic receptors were similar in controls and depressed subjects (beta-receptor number, 5.4 +/- 0.7 and 5.3 +/- 0.8 fmol per 10(6) cells; binding affinity, 106 +/- 7.6 vs. 99.2 +/- 11.4 pM, respectively). When the depressed patients were subdivided by psychomotor manifestations, binding characteristics were indistinguishable among the subgroups. However, a significant reduction in beta-adrenergic responsiveness was observed in patients with psychomotor agitation, as compared with controls (2.6 +/- 0.5 vs. 7.4 +/- 1.0 pmol per 10(6) cells, P less than 0.01), but not in patients with psychomotor retardation (5.8 +/- 1.1 pmol per 10(6) cells, P less than 0.05). Thus, the desensitization of beta-adrenergic receptors was correlated more closely with the severity of psychomotor agitation than with the overall severity of depression.
P149Role of the mevalonate pathway in myocardial postconditioning
Authors: G Szucs, Z Murlasits, C Csonka, P Ferdinandy
Journal: Cardiovascular Research (2014)

We have previously reported that chronic oral treatment with the HMG-CoA reductase inhibitor lovastatin shows cardioprotection but interacts with the cardioprotective effect of postconditioning and that farnesol, a key intermediate of the mevalonate pathway, is cardioprotective possibly via enhancement of protein geranylgeranylation. Here we studied the interaction of the HMG-CoA reductase inhibitor atorvastatin and farnesol with postconditioning.
Persistent Intense MIBG Activity in the Liver Caused by Prior Radiation
Authors: Jigang Yang, Ion Codreanu, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2014)

The positive predictive value of MIBG scintigraphy in the evaluation of neuroblastoma is very high, and false-positive findings are rare. We present here persistently elevated MIBG activity in the liver caused by external beam radiation, which could be misinterpreted as malignant involvement if history and prior studies were not carefully correlated.
Abstract 2871: JNK1-phosphorylation of Bcl-2 is essential for adenoviral-induced autophagic cell death in glioma cells
Authors: Sarah R. Klein, Sujan Piya, Erin J. White, Hong Jiang, W.K.Alfred Yung, Candelaria Gomez-Manzano, Juan Fueyo
Journal: Cancer Research (2011)

Abstract Purpose: Delta-24-RGD is a highly selective and potent oncolytic adenovirus that is currently being tested in a clinical trial for patients with malignant gliomas. The mechanism of oncolysis for Delta-24-RGD is defined as autophagic cell death, yet the signal transduction and molecular interactions responsible remain uncharacterized. Methods: Utilizing JNK1- and JNK2-null mouse embryonic fibroblasts, we analyzed the involvement of JNK in Bcl-2 phosphorylation and degradation, and adenoviral-induced autophagy. Mutations at the phosphorylation sites of Bcl-2 were employed to determine which are necessary for release of Beclin 1, degradation of Bcl-2, and induction of autophagy by adenovirus. Results: In this report, we reveal that activation of c-Jun N-terminal kinase 1 (JNK1) is required to initiate and maintain autophagy induced by wild-type and Delta-24-RGD adenoviruses in the host cell. In addition, JNK1-dependent phosphorylation of Bcl-2 at serine 87 (but not serine 70) and subsequent inhibition of Bcl-2:Beclin 1 heterodimerization is necessary for autophagy to occur in infected cells. Upon phosphorylation and release from Beclin 1, Bcl-2 is degraded by the proteosome. Finally, the activation of JNK leads to its translocation to the nucleus and results in the transcription of autophagy-related (ATG) genes for the maintenance of autophagy, as yet undocumented in mammalian cells. Conclusion: Adenoviruses have thus evolved a highly complex mechanism of regulating autophagy which differs from the typical cellular stress response that may be exploited in the treatment of gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2871. doi:10.1158/1538-7445.AM2011-2871
Abstract 5228: Do cancer cells undergo phenotypic switching? The case for imperfect cancer stem cell markers.
Authors: Stefano Zapperi, Caterina Anna Maria Laporta
Journal: Cancer Research (2013)

Abstract The identification of cancer stem cells in vivo and in vitro relies on specific surface markers that should allow to sort cancer cells in phenotypically distinct subpopulations. Experiments report that sorted cancer cell populations after some time tend to express again all the original markers, leading to the hypothesis of phenotypic switching, according to which cancer cells can transform stochastically into cancer stem cells. Here we explore an alternative explanation based on the hypothesis that markers are not perfect and are thus unable to identify all cancer stem cells. Our analysis is based on a mathematical model for cancer cell proliferation that takes into account phenotypic switching, imperfect markers and error in the sorting process. Our conclusion is that the observation of reversible expression of surface markers after sorting does not provide sufficient evidence in support of phenotypic switching. Citation Format: Stefano Zapperi, Caterina Anna Maria Laporta. Do cancer cells undergo phenotypic switching? The case for imperfect cancer stem cell markers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5228. doi:10.1158/1538-7445.AM2013-5228 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Adenocarcinoid tumor of the rectum: a rare finding in a patient with recurrent fistulizing perianal Crohn’s disease
Authors: Stephanie Judd, Edi Levi, Suhag Patel, Fadi Antaki
Journal: Endoscopy (2013)

Malignancy in patients with Crohn's colitis is well described; however, adenocarcinoid tumor associated with Crohn's disease is very rare with only four cases reported in the literature [1]. This is the first reported case of an adenocarcinoid tumor arising in a fistulous tract.
THU0087 Influence of Sex and HLA B27 on Enthesis in Early Spondyloarthritis. an Ultrasound Study:
Authors: I. Monjo Henry, C. Castillo-Gallego, D. Peiteado, S. Falcao, E. Martín Mola, E. de Miguel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Spondyloarthritis (SpA) is a group of disorders that are characterized by inflammatory involvement of the enthesis and the adjacent bone. The importance of enthesis has increased over the last years as a result of their inclusion in the recent developed Assessment of SpondyloArthritis International Society (ASAS) new classification criteria for axial and peripheral SpA. Ultrasound is superior to clinical examination for detecting early signs of enthesitis and enthesopathy and improve the knowledge about enthesis pathology. The positivity of HLA B27 has a strong association with ankylosing spondylitis and male sex is associated with X-Rays progression, but today there is few information about presence and progression of entheseal lesions in SpA. <h3>Objectives</h3> To evaluate the influence of HLA B27 and gender on ultrasound enthuses affectation and progression in early spondyloarthritis. <h3>Methods</h3> Longitudinal, prospective, blinded ultrasound study in patients diagnosed with early spondyloarthritis that fulfilled ASAS classification criteria. All patients underwent ultrasound MASEI index at baseline, at 6 and 12 months. Inter-reader ICC was 0,83. <h3>Results</h3> One hundred and forty-six early SpA patients (68 females and 78 males) were examined. HLA B27 positive was present in 32% of the male patients and 16.51% of the female patients. The diagnostics, according to the order of frequency were: non-radiological spondyloarthritis (65.83%), psoriatic arthritis (17%), ankylosing spondylitis (8.33%), spondyloarthritis associated with intestinal inflammatory disease (4.17%) and reactive arthritis (4.17%). The mean ASDAS value during the first visit was 2.39 (high activity). Baseline mean visual analogic scale for pain and patient global disease assessment were 5.15±2.5 and 2.98±1.56, respectively. The mean BASFI was 2.37±2.1. The baseline mean (range) BASDAI, ASDAS, ESR and CRP measurements were 4.60±2.07, 2.41±1.17, 15.0±16.99 mm/h and 8.67±16.98 mg/l, respectively. As shown in the table, the male patients scored higher in the MASEI index during the first visit and at the 12-month visit, reaching statistical significance in both global indices and in almost all elemental lesions explored. When we analyse HLA B27 positive patients, the only significance in the MASEI index was found at the 12-month visit, and at the basal visit and the 12-month visit for thickness. After analyzing the data we estimates that the highest score in this ultrasound index was mainly influenced by the male and the positivity of HLA B27 was probably due to the greater frequency of males in this group (66.04%). <h3>Conclusions</h3> Male gender determines a higher enthesis involvement in early spondyloarthritis while the HLA B27 seems to have a less pathogenic fact. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4444
Abstract 1827: HnRNP I interacts with lncRNA UCA1 and regulates its stability.
Authors: Jianguo Huang, Yin-Yuan Mo
Journal: Cancer Research (2013)

Abstract Background: The human genome also makes a large number of non-coding RNAs including long non-coding RNAs (lncRNAs) and microRNAs in addition to protein-coding genes. While microRNAs are well characterized, little is known about lncRNAs. Emerging evidence has implicated lncRNAs in gene regulation; and they are often aberrantly expressed in a variety of human diseases, in particular cancer. The heterogeneous nuclear ribonucleoprotein I (hnRNP I) is a member of the large hnRNP family and has been implicated in mRNA splicing, stability and translational regulation of certain RNA transcripts. During screening for lncRNA-interacted proteins, we identified hnRNP I as a binding partner for UCA1. However, it remains unclear how hnRNP I interacts with UCA1 and whether such an interaction impacts UCA1-mediated cell growth and responsiveness to anti-cancer drugs. Methods: To determine cell growth and response to doxorubicin, we performed MTT assays as well as cell counting assays. Protein levels from treated cells were analyzed by western blot. Real-time RT-PCR was used to determine relative expression of genes. Interaction between hnRNP I and UCA1 was confirmed by RNA co-immunoprecipitation and RNA pulldown. RNA stability was determined by treating MCF-7 cells with actinomycin D, followed by real-time RT-PCR. hnRNP I was knock down by transient transfection of hnRNP I siRNAs. Results: We found that UCA1 induced proliferation and increased resistance to doxorubicin in MCF-7 cells. RNA pulldown assays revealed that UCA1 RNA directly interacted with hnRNP I. This interaction was further confirmed by RNA immunoprecipitation by hnRNP I antibody. Real-time RT-PCR revealed that knockdown of hnRNP I by RNAi reduced the level of UCA1 in MCF-7 cells and it also repressed the induction of UCA1 by doxorubicin. Further experiments suggested that hnRNP I impacts the UCA1 stability. We showed that half-life of UCA1 was about 12 h but was decreased to about 6 h in the presence of hnRNP I siRNAs. We further showed that the phosphorylated form of hnRNA I, predominantly in the cytoplasm, was a major form that interacts with UCA1. Conclusion: Taken together, these results suggest that hnRNP I plays a role in regulation of the stability of UCA1. Since previous work implicates the involvement of UCA1 in tumor cell growth and chemoresistance, a better understanding of the underlying mechanism will provide new insight of targeting UCA1 in cancer therapy. Citation Format: Jianguo Huang, Yin-Yuan Mo. HnRNP I interacts with lncRNA UCA1 and regulates its stability. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1827. doi:10.1158/1538-7445.AM2013-1827
P17.51 * FUNCTIONAL PREDICTION OF MITOCHONDRIAL DNA MUTATIONS IN GLIOBLASTOMA MULTIFORME
Authors: R. E. Lloyd, K. Keatley, D. J. Littlewood, W. V. Holt, S. C. Higgins, Q. An, H. L. Fillmore, G. J. Pilkington, J. E. McGeehan
Journal: Neuro-Oncology (2014)

Gliobastoma multiforme (GBM) is the most common adult primary brain tumour. It is highly malignant with fewer than half of patients surviving for over one year following diagnosis. One reason for this is its highly heterogeneous nature, which renders the current standard-of-care treatment of surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy inadequate. Altered metabolism is a hallmark of cancer compared to non-cancer cells and central to this are mitochondria, which contain their own multi-copy circular DNA (mtDNA). At the heart of every mitochondrion is a collection of five large protein machines known as the respiratory chain (RC). The RC consists of approximately 70 subunits. MtDNA-encodes thirteen of the core catalytic subunits that form the RC. Variations in mtDNA can therefore directly affect metabolism and contribute to the pathology of numerous human diseases, including cancer. The acquisition of TMZ-resistance and decreased overall survival in GBM patients has been linked to altered RC activity but the contribution of mtDNA variations to this remains unexplored. To address this we have employed a novel dual approach for (1) discovering and (2) predicting the function of mtDNA variations in GBM patients using a combination of long PCR and next generation sequencing and 3D structural analysis, respectively. We have generated a set of 10 high quality mtDNAs each from GBM-biopsy derived cells with a mean depth of coverage per nucleotide of over 22,000. This enabled a total of 193 mtDNA variations to be detected, including those present at less than 1% heteroplasmy. Twenty five of these variations caused non-synonymous amino acid substitutions (AAS) in mtDNA-encoded Complex III and IV proteins. Using 3D structural analysis, we predict that 8 of these are highly likely to be functional, occurring in RC active sites, substrate/drug binding pockets and protein-protein interaction regions. The latter class will affect the assembly and stability of the RC complexes. All functional candidates were absent from the non-neoplastic astrocytic control, and mining the human mtDNA database revealed the majority never, or very rarely, occur in healthy subjects. Long PCR and next generation sequencing provides a high throughput, cost effective and sensitive method for detecting mtDNA variations in GBM. While 3D structural analysis reveals considerable insight into the functional role of mtDNA variations, including how they could affect metabolism and contribute to the differential survival and chemosensitivity of individual patients. This study forms an important first step towards determining the functional and clinical significance of mtDNA variations in GBM. The next step will be to validate the functional and clinical significance of the candidate variations so that better predictors of outcomes and more personalised therapies can be developed for patients in the future.