tbuckley/cabot-search huggingface dataset:
Update on the dementia spectrum of depression
Authors: V O Emery, T E Oxman
Journal: American Journal of Psychiatry (1992)

The primary focus of this review is to examine the usual dichotomy between depressive dementia as functional and reversible and degenerative dementia as organic and irreversible.The authors propose viewing depression, cognitive impairment, and degenerative dementia as intersecting continua. They define five prototypical groups along these continua: 1) major depression without depressive dementia, 2) depressive dementia, 3) degenerative dementia without depression, 4) depression of degenerative dementia, and 5) independent co-occurrence of degenerative dementia and depression. Clinical, neuropsychological, and neurobiological studies comparing these groupings were identified by a computerized literature search covering the past 20 years. References were selected for review if they compared at least two groups. Degenerative dementia was limited to the Alzheimer type.No studies clearly included all five of the prototypical groups. There are methodological problems with each type of research reviewed, but the consensus of the research is that severe cognitive impairment of depression is associated with a variety of organic abnormalities. Depending on the length of follow-up, depressive dementia may not be as reversible as previously thought.The continuum viewpoint encourages longitudinal clinical follow-up for early detection and alleviation of incipient depressive and dementing symptoms. Hypotheses of overlapping pathophysiological mechanisms rather than differential diagnosis become an important research focus. The authors discuss three different types of relationships for future research: 1) interactions, 2) consequences of disease or treatment, and 3) necessary but not sufficient pathophysiology.
Interobserver variability of clinical scores in hidradenitis suppurativa is low
Authors: K. Sartorius, H. Killasli, J. Heilborn, G.B.E. Jemec, J. Lapins, L. Emtestam
Journal: British Journal of Dermatology (2010)

Background Hidradenitis suppurativa (HS) is a chronic recurrent disease with scars and sinus tract formation that causes substantial impact on quality of life. For evaluation of HS and treatment results, a scoring system for disease severity (Hidradenitis Suppurativa Score, HSS) has been proposed. Objectives To describe the interobserver reliability of the HSS and further to document its correlation with risk factors and other measures of disease severity. Methods Sixty-one consecutive patients with HS, referred to a clinical centre with special interest in the disease, were scored according to the HSS protocol: eight patients by four dermatologists together, 23 patients by all four observers independently and 30 patients by a single observer. Interobserver variability in HSS between the four observers was investigated in the group of 23 patients. Patients' reports of weight and height, smoking habits etc., were collected, as well as Dermatology Life Quality Index (DLQI) questionnaires. Results The interobserver concordance of HSS was 0·95. Median (interquartile range, IQR) HSS for all patients was 40 (18–73); women 39 (16–68); men 60·5 (30–95). Median (IQR) HSS for nonsmokers was 26 (12–65); former smokers 30 (10–56); smokers 44 (26–108). Median (IQR) HSS for normal weight patients was 12 (10–30); overweight 43 (25–58); obese 51 (24–95). Mean ± SD DLQI for all patients was 11·3 ± 8·6. Conclusions HSS is simple to use and shows low interobserver variability. The score correlates with suggested risk factors, indicating that it reflects a valid estimation of disease severity.
Fas triggers an alternative, caspase-8–independent cell death pathway using the kinase RIP as effector molecule
Authors: Nils Holler, Rossana Zaru, Olivier Micheau, Margot Thome, Antoine Attinger, Salvatore Valitutti, Jean-Luc Bodmer, Pascal Schneider, Brian Seed, Jürg Tschopp
Journal: Nature Immunology (2000)
Abstract 5792: Lower Ankle-Brachial Index Associated With Lipid-Rich Coronary Plaques in Patient Underwent Elective Coronary Intervention: Integrated Backscatter Ultrasound Analysis
Authors: Tadayuki Uetani, Tetsuya Amano, Yusaku Shinbo, Ayako Kunimura, Soichiro Kumagai, Kiminobu Yokoi, Ken Harada, Tomohiro Yoshida, Bunichi Kato, Masataka Kato, Nobuyuki Marui, Michio Nanki, Hideo Izawa, Tatsuaki Matsubara, Hideki Ishii, Toyoaki Murohara
Journal: Circulation (2009)

Background Association between low Ankle Brachial Index (ABI) and cardiovascular events were demonstrated. The aim of this study is to evaluate association between ABI and coronary plaque radiofrequency characterization by integrated backscatter ultrasound (IB-IVUS). Methods From Jan.2006 to Dec. 2008 Total of 189 consecutive patients who underwent elective PCI following ABI measurements and IB-IVUS analysis were enrolled. The Color coded maps of tissue characteristics of each 1mm slice of target lesions were constructed and volume of each plaque components (calcification, fibrous and lipid core) was calculated. And percentage of lipid volume in the target lesion (% lipid; volume of lipid core/total plaque volume) was calculated. Results ABI significantly correlated with lipid volume of target lesion (r= −0.19, p&lt;0.05), but did not correlate with fibrous volume (r=0.09, P=0.2)(Figure ). ABI (r= −0.18, p&lt;0.01) and HDL-cholesterol (r= −0.14, p&lt;0.05) inversely correlated with %lipid. There was no significant association between %lipid and other clinical factors (age, gender, conventional risk factors, blood pressure, lipid-profile and HbA1c). In multiple regression analysis, ABI significantly associated with %lipid after adjusting for age, gender, prior revascularization of PAD (bypass surgery or angioplasty), systolic BP, LDL-cholesterol, HDL-cholesterol, triglyceride and HbA1c. Conclusion Our present findings provide the first evidence that decrease of ABI may be associated with progression of lipid-rich coronary plaques. After adjustment of other clinical factors, ABI independently associated with lipid-rich coronary plaque of coronary stenosis.
990. Transduction of Pancreatic Islets with Pseudotyped Adeno-Associated Virus: Effect of Viral Capsid
Authors: Nan Zhang, Nathalie Clement, Haojiang Zhang, Dongmei Chen, Shuang Fu, Michael Linden, Jonathan S. Bromberg
Journal: Molecular Therapy (2004)

Recombinant adeno-associated viral (rAAV) vectors currently show promise for islet gene therapy. In the presence of complementing AAV2 Rep proteins, AAV2 genomes can be pseudotyped with other serotype capsids to assemble infectious virions. Using this pseudotyping strategy, AAV2 genomes carrying the GFP reporter gene were encapsidated into AAV1, AAV2, and AAV5 capsids. The utility of cross-packaged AAV1, AAV2, and AAV5 capsid-mediated transduction to murine and human pancreatic islets was evaluated. These pseudotyped rAAV vectors all showed some ability to transduce both human and murine pancreatic islets. The transduction efficiency of rAAV vector was dependent on the cross-packaged capsid. Pseudotyped rAAV2/1 based vectors transduced murine islets at greater efficiency than either rAAV2/2 or rAAV2/5 vectors. For human islet transduction, the rAAV2/2 vector was more efficient than rAAV2/1 or rAAV2/5 vectors. The vector capsids permit species specific transduction. rAAV2/2 transduced human islets more efficiently than murine islets, while rAAV2/1 transducted murine islets more efficiently than human islets. Pseudotyped rAAV transduced islet grafts maintained normal function in vitro, reversed diabetes in vivo, and expressed transgenic product persistently in vivo. These studies provide a methodologic framework for evaluating the function of pseudotyped rAAV.
Broadening the diagnosis of bipolar disorder: benefits vs. risks
Authors: STEPHEN M. STRAKOWSKI, DAVID E. FLECK, MARIO MAJ
Journal: World Psychiatry (2011)

There is considerable debate over whether bipolar and related disorders that share common signs and symptoms, but are currently defined as distinct clinical entities in DSM-IV and ICD-10, may be better characterized as falling within a more broadly defined "bipolar spectrum". With a spectrum view in mind, the possibility of broadening the diagnosis of bipolar disorder has been proposed. This paper discusses some of the rationale for an expanded diagnostic scheme from both clinical and research perspectives in light of potential drawbacks. The ultimate goal of broadening the diagnosis of bipolar disorder is to help identify a common etiopathogenesis for these conditions to better guide treatment. To help achieve this goal, bipolar researchers have increasingly expanded their patient populations to identify objective biological or endophenotypic markers that transcend phenomenological observation. Although this approach has and will likely continue to produce beneficial results, the upcoming DSM-IV and ICD-10 revisions will place increasing scrutiny on psychiatry's diagnostic classification systems and pressure to re-evaluate our conceptions of bipolar disorder. However, until research findings can provide consistent and converging evidence as to the validity of a broader diagnostic conception, clinical expansion to a dimensional bipolar spectrum should be considered with caution.
Abstract 744: Effective use of MDK/Midkine and MEK inhibitor to treat KRas mutated pulmonary adenocarcinoma cells
Authors: Takuya Fukazawa, Yutaka Maeda, Naomasa Ishida, Tomoki Yamatsuji, Munenori Takaoka, Minoru Haisa, Nagio Takigawa, Jeffery Whitsett, Yoshio Naomoto
Journal: Cancer Research (2014)

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Although a platinum-doublet regimen has become the standard of care, the benefit is modest and the 5-year survival rate has remained essentially unchanged over the past 3 decades. Recently, several molecular alterations have been defined as “driver mutations,“ such as mutations in epidermal growth factor receptor (EGFR), KRas, chimeric tyrosine kinases involving ALK, RET, ROS1. And molecular targeting therapies for lung adenocarcinoma, targeting mutant EGFR or ALK, RET and ROS1 fusions, limit non-tumor toxicity and extend survival time compared to the conventional chemotherapies. However, there is no effective molecularly targeted therapy for mutant KRas-driven lung adenocarcinoma, the most frequent type of lung adenocarcinoma in the Caucasian population. Therefore, specific therapies that target various lung tumor types are desperately needed. Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. We have previously reported that a MDK inhibitor: iMDK suppresses non-small cell lung cancer expressing MDK in vitro and in vivo without harming normal cells. Importantly, iMDK inhibits the PI3 kinase / Akt pathway and induces apoptosis in MDK expressing non-small cell lung cancer cells. In the present study, we have investigated the combination effect of iMDK and a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD0325901. The combination treatment of iMDK and PD0325901 more effectively suppressed cell viability and colony formation, increased caspase-3 activity and induced apoptosis than those of single use in H441 and H2009 pulmonary adenocarcinoma cells harboring a G12 KRas mutation. Here, we describe the efficacy of the use of iMDK and PD0325901 for patients with inoperable advanced lung cancer including pulmonary adenocarcinoma harboring KRas mutations. Citation Format: Takuya Fukazawa, Yutaka Maeda, Naomasa Ishida, Tomoki Yamatsuji, Munenori Takaoka, Minoru Haisa, Nagio Takigawa, Jeffery Whitsett, Yoshio Naomoto. Effective use of MDK/Midkine and MEK inhibitor to treat KRas mutated pulmonary adenocarcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 744. doi:10.1158/1538-7445.AM2014-744
Iatrogenic lymphoproliferative disorder
Authors: Kamyar Nader, Danielle Smith Behrens, Chady Abboud Leon, Roland Schwarting, Andres Ferber
Journal: American Journal of Hematology (2014)

A 69-year-old male with rheumatoid arthritis, on methotrexate and plaquenil, presented with palpable right axillary lymphadenopathy. This was associated with progressive dyspnea, weight loss, and night-sweats for one-month duration. On examination, there was a 2 × 2 cm nontender lymph node on the right axillary. Positron emission tomography-computed tomography (PET-CT) illustrated diffuse hypermetabolic lymphadenopathy with moderate pericardial effusion (Image 1). Patient had a right axillary excisional biopsy that confirmed Diffuse Large B-Cell Lymphoma, which positively stained for Epstein–Barr virus encoded RNA (EBER) on in-situ-hybridization. Bone marrow biopsy was normal. A diagnosis of IIIB other iatrogenic immunodeficiency associated lymphoproliferative disorder (OIIA-LPD) was given and decided to hold methotrexate. After 6 weeks of withdrawal, the symptoms resolved along with his lymphadenopathy on PET-CT (Image 2). Patients with rheumatoid arthritis have a risk of developing LPDs with or without methotrexate. However, further immunosuppression with methotrexate and reactivation of Epstein–Barr virus is postulated to be a possible culprit in lymphomagenesis, given that withdrawal of methotrexate correlates with regression of disease in many cases 1-7. Patient currently remains in complete remission.
Abstract 1795: Small molecule SBI-601 inhibits Siah1/2 ubiquitin ligases, attenuates HIF1α expression and growth of melanoma and prostate cancer cells
Authors: Yongmei Feng, Tal Varsano, Hampton Sessions, Michael Davies, Greg Roth, Ze'ev Ronai
Journal: Cancer Research (2014)

Abstract The ubiquitin ligases Siah1/2 have been implicated in the control of key cellular pathways, including hypoxia (through the control of prolyl hydroxylase 1/3 stability), mitochondrial fission (through the control of AKAP121 stability) and Ras/Raf signaling (through its control of Sprouty 2 stability). Expression or activity of Siah1/2 is upregulated in number of cancer types and correspondingly, inhibition of Siah1/2 effectively attenuates growth of prostate, melanoma, lung and pancreatic tumors. To identify possibly Siah1/2 inhibitors, we have performed a HTS screen using affinity selection-mass spectrometry (AS-MS). Using a select set of 32,000 drug-like molecules in mass-encoded mixtures of 400 compounds per assay well, we identified 36 distinct clusters of structurally related scaffolds that demonstrate high-binding affinity to full-length bacterially produced purified and active Siah2. Of those, 9 out of 21 closely related analogs were evaluated in functional assays. One compound, SBI-0640601, showed potent and reproducible inhibition of Siah2, as measured by the reduction in HIF1α levels and activity, measured by HRE-Luciferase assays in both melanoma and prostate cancer cultures. SBI-0640601 is a natural product known as betulonic acid (BA) and is one of a family of triterpenoid natural medicinal products derived from birch trees (genera Betula). Independent binding studies (differential scanning calorimetry) confirmed that SBI-0640601 binds to full-length bacterially produced Siah2 and to a RING domain-deleted version of Siah1. In vitro, SBI-0640601 attenuated the binding of PHD3 to Siah2, in keeping with the observation that ubiquitination of most substrates requires binding to the Siah2 substrate-binding domain. SBI-0640601 inhibited growth of melanoma and prostate cancer cells in 2D and 3D cultures. Further, SBI-0640601 effectively attenuated neuroendocrine differentiation phenotype in adenocarcinoma cells, consistent with the effect seen upon inhibition of Siah1/2 expression. RPPA analysis identified that SBI-0640601 effectively attenuates AMPK and mTOR signaling pathways, in addition to affecting MAPK signaling. Overall, SBI-0640601 appears to inhibit key processes previously shown to be regulated by Siah1/2, holding promise for further assessment in preclinical setting. Note: This abstract was not presented at the meeting. Citation Format: Yongmei Feng, Tal Varsano, Hampton Sessions, Michael Davies, Greg Roth, Ze'ev Ronai. Small molecule SBI-601 inhibits Siah1/2 ubiquitin ligases, attenuates HIF1α expression and growth of melanoma and prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1795. doi:10.1158/1538-7445.AM2014-1795
Böbrek Taşı Hastalığının İkincil Yollarla Önlenmesi İçin Diyet, Sıvı Alımı veya İlave Maddeler: Randomize Çalışmaların Meta-Analizi ve Sistematik Bir Derleme
Authors: Howard A. Fink a, Joseph W. Akornor, Pranav S. Garimella, Rod MacDonald, Andrea Cutting, Indulis R. Rutks, Manoj Monga, Timothy J. Wilt
Journal: European Urology (2009)
Immunisation: the views of parents and health professionals in Ireland
Authors: S Cotter, F Ryan, H Hegarty, T. J McCabe, E Keane
Journal: Eurosurveillance (2003)

A knowledge, attitude and practice study on vaccinations was undertaken among Irish parents and healthcare professionals between May and August 2001. Parents expressed fear of vaccine side effects, mistrust of health services, and felt poorly informed on the vaccination issues. According to group discussions, health professionals felt they lack time and user-friendly materials to properly inform the parents.
The relationship between comorbidities and systemic inflammation in patients with COPD
Authors: Ali Kocabas, Gulsum Tezcagirir, Gulsah Seydaoglu, Ezgi Ozyilmaz
Journal: European Respiratory Journal (2011)

Objectives:  Although the effect of comorbidities on morbidity and mortality of COPD is better understood, the discussion about the role of systemic inflammation on development of comorbidities is going on. We aimed to investigate the relationship between systemic inflammation and comorbidities in patients with COPD.   Methods:  Comorbidities, systemic and local inflammation markers were investigated in 50-stable COPD patients and 42-healthy adults who admitted to our out-patient clinic. Venous blood samples for markers of systemic inflammation (CRP,fibrinogen,AAT, TNF-α, sTNF-R, IL-1, IL-6, IL-8, neutrophils,lymphocytes,eosinophils) and induced sputum samples for local inflammation markers (TNF-α, IL-6, neutrophils, lymphocytes, eosinophils) were examined.   Results:  At least one comorbidity was determined in 80% of patients with COPD and 47.6% in the controls. The depression, cachexia, pulmonary hypertension and prevalence of coronary artery disease in patients with COPD were higher than the controls (p   Conclusion:  The observed comorbidities in COPD is closely related to systemic inflammation however we think that the exact mechanism of each comorbidity needs to be further investigated.
The impact of new technologies in medicine
Authors: A. Berger
Journal: BMJ (1999)

<h3>Summary</h3> Obesity and excess body fat contribute to both the risk for and progression of several prevalent neurologic conditions. While obesity treatment is not generally considered part of the job description of the neurologist, we summarize the evidence for this important relationship, and describe ways that being mindful of diet and lifestyle factors in the neurologic patient can yield dividends for patient outcomes.
SIGNIFICANCE OF HEMOPTYSIS IN APPARENTLY INACTIVE PULMONARY TUBERCULOSIS
Authors: R CHARR
Journal: Annals of Internal Medicine (1954)

Article1 September 1954SIGNIFICANCE OF HEMOPTYSIS IN APPARENTLY INACTIVE PULMONARY TUBERCULOSISROBERT CHARR, M.D., F.A.C.P.ROBERT CHARR, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-41-3-479 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDoes hemoptysis in patients with apparently inactive pulmonary tuberculosis mean relapse of tuberculosis? If not, what other pulmonary diseases are the causes? How frequently is the hemoptysis unexplained? What is the usual outcome? With these questions in mind, the present study was carried out.MATERIAL STUDIED AND FINDINGSThe clinical material studied consisted of 123 patients, 54 men and 69 women. In all of these patients the tuberculosis had been considered inactive for the past five to 20 years. Twenty-one—11 women and 10 men—had hemoptysis. Of the total, in 13 the hemoptysis could not be explained. The roentgenologic examination of...Bibliography1. Sokoloff MJ: Hemoptysis in stabilized tuberculosis, Presented at the meeting of Eastern Section, American Trudeau Society, October 31, 1952. Google Scholar2. O'Keefe J: Personal communication. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*Received for publication January 22, 1954. (Presented at the Regional Meeting, American College of Physicians, January 15, 1954, Philadelphia.)From the Department of Medicine, Jefferson Medical College, and the Division of Medicine, Pennsylvania Hospital, Philadelphia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byZur Ätiologie und Krankheitskoinzidenz bei wiederholten LungenblutungenPrimary Pulmonary Carcinoma Associated with Active Pulmonary Tuberculosis 1 September 1954Volume 41, Issue 3Page: 479-486KeywordsHospital medicinePulmonary diseases ePublished: 1 December 2008 Issue Published: 1 September 1954 PDF downloadLoading ...
994. Gene Knockdown in Mice by Using Lentiviral Vectors Expressing Small Interfering RNA
Authors: Oded Singer, Masahito Ikawa, Nien Hoong, Greg Campbell, Inder M. Verma
Journal: Molecular Therapy (2004)

Top of pageAbstract
Many approaches have been described recently for generating loss-of-function phenotypes in eukaryotic systems using RNAi. Use of RNAi by means of long dsRNAs (>50bp) is limited in mammalian cells due to the induction of a nonspecific inhibitory response resulting from the interferon pathway. This limitation was overcome by the finding that small interfering RNAs (siRNAs) can specifically silence genes in mammalian cells without activating the nonspecific interferon pathway. We have designed lentiviral vectors expressing siRNAs to knock down the expression of specific genes. We have previously shown that a lentiviral vector capable of expressing siRNA specific for GFP (siGFP) was able to silence GFP expression in TgGFP mice upon transduction of fertilized mouse embryos. We have found that transgenesis of mouse embryos can be achieved both by zona pellucida removal prior to transduction and by microinjection of lentivirus particles under the intact zona layer. Efficiency of transgenesis was high using both methods, up to 80% and 100% respectively. However, survival of the treated embryos was low in the case of zona removal techniques (10-20%), compared to 40-60% for microinjection. We are currently using transgenesis by lentiviral vectors expressing small interfering RNAs to generate knockdown mice to study functional genomics.
Abstract 619: Non Invasive Assessment of Plaque Imaging in Non Culprit Artery of Acute Coronary Syndrome by Cardiac Magnetic Resonance
Authors: Yasuyo Taniguchi, Takeshi Ishimoto, Shinichiro Yamada, Kazuo Mizutani, Sachiyo Iwata, Katsunori Okajima, Akira Shimane, Masahiro Kumada, Tomofumi Takaya, Manabu Kanda, Yasue Tsukishiro, Tatsushi Tagashira, Takatoshi Hayashi, Teishi Kajiya
Journal: Circulation (2009)