tbuckley/cabot-search huggingface dataset:
First successful reduction of clinical allergenicity of food by genetic modification:<i>Mal d 1</i>-silenced apples cause fewer allergy symptoms than the wild-type cultivar
Authors: A. E. J. Dubois, G. Pagliarani, R. M. Brouwer, B. J. Kollen, L. O. Dragsted, F. D. Eriksen, O. Callesen, L. J. W. J. Gilissen, F. A. Krens, R. G. F. Visser, M. J. M. Smulders, B. J. Vlieg-Boerstra, B. J. Flokstra-de Blok, W. E. van de Weg
Journal: Allergy (2015)

Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals.We performed oral food challenges in 21 apple-allergic individuals with Elstar apples which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual analogue scale (VAS).Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges with these downregulated apple lines produced significantly less intense maximal symptoms to the first dose (Vmax1) than with Elstar (Vmax1 Elstar 3.0 mm vs 0.0 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm vs 0.2 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043). Only one subject (5%) remained symptom-free when challenged with the Elstar apple, whereas 43% did so with e-DR1 and 63% with e-DR2.These data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 gene expression in the fruit and reduction of symptoms when these apples are ingested by allergic subjects. Approximately half of the subjects developed no symptoms whatsoever, and virtually all subjects wished to consume the apple again in the future.
A memorable patient: The danger of a high C
Authors: G. Ingram
Journal: BMJ (2000)

While about to take blood, I noticed a thin scar running along the left elbow of my elderly patient in exactly the place I would have liked to venesect him. I asked him how he got the scar and was bemused by the reply: “That is from when I broke my neck playing the ‘Tiger Rag.’ I questioned him further. The events occurred in 1945, when he was posted to Burma. Shortly before the war ended, he was travelling …
Abstract 671: CD38-specific engineered toxin body: Therapeutic potential for multiple myeloma
Authors: Sangeetha Rajagopalan, Brigitte Brieschke, Garrett L. Robinson, Jennifer Erdman, William Null, Jack P. Higgins, Erin K. Willert
Journal: Cancer Research (2014)

Abstract Multiple myeloma is a malignancy of plasma cells that accounts for 10% of all hematological cancers. Current treatments for multiple myeloma include immunomodulatory agents, protease inhibitors and chemotherapies and, while these therapies are often initially effective, most patients experience relapse. New therapeutics are urgently required. CD38 is a transmembrane glycoprotein absent on most resting leukocytes but expressed on lymphoid malignancies, including multiple myeloma and lymphoma, making it an attractive target for directed therapy. Recent clinical trials with antibodies to CD38 have shown promise in multiple myeloma. While these antibodies rely on the recruitment of an immune response for cytotoxicity, we have developed an engineered toxin body (ETB) comprising a CD38 binding scFv and a de-immunogenized form of Shiga-like Toxin A (MT-4001) capable of specifically recognizing and directly killing CD38 expressing cells. Our results show that MT-4001 is a promising targeted therapeutic agent against CD38 positive cancer cells and is currently under further development. Citation Format: Sangeetha Rajagopalan, Brigitte Brieschke, Garrett L. Robinson, Jennifer Erdman, William Null, Jack P. Higgins, Erin K. Willert. CD38-specific engineered toxin body: Therapeutic potential for multiple myeloma. [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 671. doi:10.1158/1538-7445.AM2014-671
Viral lower respiratory tract infection in infants and young children
Authors: J B M van Woensel
Journal: BMJ (2003)

Viruses are the most common cause of lower respiratory tract disease in infants and young children and are a major public health problem in this age group. The novel variant of coronavirus that is associated with the worldwide outbreak of severe acute respiratory syndrome and human metapneumovirus, a recently identified new respiratory pathogen, have stressed the continuing importance of viral respiratory infections over the whole age spectrum.

Costs attributable to viral lower respiratory tract infections in both outpatient and inpatient settings are an important burden on national healthcare budgets.1 Each year approximately 3% of all children less than 1 year of age need to be admitted to hospital with moderate or severe viral lower respiratory tract infection.2 This review gives an update of viral lower respiratory tract infection in infants and young children, with special emphasis on treatment and prevention.

We gathered information from our own experience and by reading relevant literature on viral respiratory infections in infants and children obtained by searching Medline and the Cochrane database. Much literature is available on the topic, so we based our review on well designed major observational studies, controlled trials, and systematic reviews. We consulted the websites of the World Health Organization and the Centers for Disease Control for the most recent information on severe acute respiratory syndrome.

A great variety of viruses can cause lower respiratory tract disease in children—for example, respiratory syncytial virus, influenza viruses, parainfluenza viruses, rhinovirus, adenovirus, and the recently identified human metapneumovirus.3,w1,w2 Although most respiratory viral infections occur throughout the year, seasonal variation (in a worldwide comparable pattern) is obvious for certain viruses, such as respiratory syncytial virus and influenza virus (figure).



Epidemiology of respiratory syncytial virus, influenza A, adenovirus, and parainfluenza virus in the Netherlands, 1997-2003



### Respiratory syncytial virus and influenza viruses

Worldwide, respiratory syncytial virus is …
573. Investigation into the Frequency of Post-Integrative Gene Silencing Using a Non-Selective Sleeping Beauty Transposition System
Authors: Brian S. Garrison, Stephen R. Yant, Jacob G. Mikkelsen, Mark A. Kay
Journal: Molecular Therapy (2005)

The Sleeping Beauty (SB) transposon represents an important vehicle for in vivo gene delivery because it can stably integrate into the genomes of mammalian cells. Although SB is the most efficient non-viral integrating system described to date, all previous estimations of SB's integrative potential have relied on the use of antibiotic selection schemes. Previous work in other integrating systems (e.g. retroviruses) has demonstrated significant post-integrative gene silencing, leading us to investigate how genomic integration influences transposon expression in human cells. To do this we devised a new strategy to monitor SB integration that is not dependent on transgene expression. We constructed a single plasmid (pT/RSV-YFP.CMV-SB) containing both a YFP-marked transposon and a separate transposase expression cassette (external to the transposon), then transfected the plasmid into HeLa cells. Shortly thereafter, cells were single-cell sorted by FACS to generate approximately 100 clonal cell lines. After 8 weeks of growth (>50 cell divisions) 30% of the cell lines continue to show stable transgene expression, as determined by fluorescence microscopy and FACS analyses. We have screened these cell lines for the presence of transposon sequences by both PCR and Southern blot analyses, using various restriction enzymes to determine (i) the copy number and (ii) the molecular forms of the transposable element. Results indicate approximately 50% of the total cell lines contain an integrated transposon sequence(s), of which roughly 20% show little or no YFP expression. Our early results, based upon Hpa II (a methylation sensitive restriction enzyme) cleavage of genomic DNA, suggested the lack of YFP expression was not due to DNA methylation but to some other regulatory system. However, more recent data (including the use of the methylation specific McrBC enzyme) indicates that some of the integrated transposons do in fact become methylated over time. Possibly related, most individual cell lines show heterogeneous YFP levels throughout the cell population. Using aphidicolin (a cell cycle inhibitor) we determined that the varied YFP expression is not cell cycle dependent. We are continuing to explore post-integrative gene expression/silencing using a variety of approaches including a detailed analysis of how CpG concentration within the transposon expression cassette affects long-term gene expression. Overall, our transposon clones are proving to be an important new reagent to investigate the mechanism(s) by which integrating genetic elements (e.g. transposons and retroviruses) are silenced by the host cell, and should further our understanding of transcriptional silencing of integrating gene transfer vectors.
The laying on of hands
Authors: Benji Perin
Journal: Annals of Internal Medicine (2015)

Ad Libitum7 July 2015The laying on of handsBenji PerinBenji PerinFrom University of Washington School of Medicine, Seattle, Washington.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-0292 Audio Reading - “The laying on of hands” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The laying on of hands," by B. Perin. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It's not what you think.No deep breath; and exhaleA warm, wise touch following your belly as it recedesLike shore break sliding home to ocean over stones and sandNo—I'm thinking of something else entirely.Do you ever listen to your heart at night before falling asleepAnd see it beating, beating, beating?It makes me worry how it never gets a rest.Well, the way I see it, when my patient's organsPut in for sick pay and retirement one after another—kidneys, lungs, blood vesselsThe heart was finally like, “f— it, I'm out.”Would that it were the heart of a young man... Author, Article, and Disclosure InformationAffiliations: From University of Washington School of Medicine, Seattle, Washington.Current Author Address: Benji Perin, University of Washington School of Medicine; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The laying on of hands” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The laying on of hands," by B. Perin. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 7 July 2015Volume 163, Issue 1Page: 31KeywordsBlood vesselsHeartKidneysLungsRibsSweatThoraxTouch ePublished: 7 July 2015 Issue Published: 7 July 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 4107: Efficient delivery of dietary compound modulates mcp-1 in murine prostate cancer cells
Authors: Manoj K. Mishra, James A. Stokes, Amanee Salaam, Elijah Nyairo, Udai Singh, Derrick Dean
Journal: Cancer Research (2014)

Abstract Monocyte chemo-attractant protein (MCP-1) is a chemokine, which recruits monocytes, neutrophils, and lymphocytes in response to trauma and proinflammatory cytokines such as TNF-α. MCP-1 generally is not expressed in healthy individuals, but in response to various stressful stimuli it gets up-regulated, which in turn contributes to increased inflammation. MCP-1 has been implicated in mediating apoptosis by producing a proapoptotic protein designated MCP-induced protein (MCPIP). Resveratrol (RES), a polyphenolic compound found in the skin of red fruits, exhibits anti-inflammatory, anti-oxidative, anti-cancer, and anti-proliferative characteristics. In this study, we hypothesized that the functionalization of RES with detonated nano-diamond (DND, hereafter called fDND) will enhance the effective delivery of RES to tumor cell and impact the modulation of molecular mechanisms in murine prostate cancer (PCa) cells. This hypothesis was tested on mouse PCa cell lines, derived from transgenic adenocarcinoma of mouse prostate (TRAMP), in C57/B6 mice. Interestingly, TRAMP-C1 and TRAMP-C2 form tumor while TRAMP-C3 fails to develop tumor. TRAMP cells were treated with different concentrations of fDND at different time points and analyzed for underlying cellular and molecular mechanisms such as cell viability/proliferation, mitochondrial membrane potential, cytokines and growth factors production. The initial results indicate that the fDND significantly induce molecular signatures in TRAMP-C3 cells in comparison with TRAMPC1 and C2. Interestingly, the level of MCP-1 was significant elevated in TRAMP C1 and C2 cells. Thus, suggesting a major role of MCP-1 in the regulation of cancer progression and clearance. This data also suggest that the functionality of dietary compounds can be enhanced by conjugating or functionalizing them with DND, which can be used as a therapeutic carrier. Citation Format: Manoj K. Mishra, James A. Stokes, Amanee Salaam, Elijah Nyairo, Udai Singh, Derrick Dean. Efficient delivery of dietary compound modulates mcp-1 in murine 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 4107. doi:10.1158/1538-7445.AM2014-4107
The Enhancing Effect (or Actively Acquired Tolerance) and the Histocompatibility-2 Locus in the Mouse&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: George D. Snell
Journal: JNCI Journal of the National Cancer Institute (1954)

The Enhancing Effect (or Actively Acquired Tolerance) and the Histocompatibility-2 Locus in the Mouse Get access George D. Snell George D. Snell Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 665–677, https://doi.org/10.1093/jnci/15.3.665 Published: 01 December 1954
Abstract 12877: Malnutrition Assessed by Geriatric Nutritional Index Provides the Additional Long-Term Prognostic Information to Renal Dysfunction in Patients Admitted for Acute Decompensated Heart Failure
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Satoh, Masahiro Seo, Masatake Fukunami
Journal: Circulation (2014)

Backgrounds: Renal dysfunction has emerged as one of the most potent prognostic indicators in patients with heart failure. Hospitalization for acute decompensated heart failure (ADHF) isassociated with a high mortality after discharge. Malnutrition is also associated with poor outcome in ADHF pts. However, there is no information available on the long-term prognostic significance of malnutrition, relating to renal dysfunction in ADHF patients. Methods and Results: We studied 305 consecutive ADHF patients discharged with survival. Nutritional status was evaluated by Geriatric Nutritional Risk Index (GNRI) calculated as follows: 14.89 x serum albumin (g/dl) + 41.7 x body mass index/22. During a follow-up period of 4.2±3.2 yrs, 69 patients had cardiovascular death (CVD). At multivariate Cox analysis, GNRI at discharge (p=0.003) and estimated glomerular filtration rate (GFR) (p=0.03) were significantlyassociated with CVD, independently of systolic blood pressure, serum sodium level and prior heart failure hospitalization. Receiver-operator curve analysis revealed that GNRI of 88 was a fair discriminator for CVD (AUC 0.698 (95%CI 0.628-0.768), p&lt;0.0001). In patients with renal dysfunction defined as low GFR (&lt;the median value:54.5ml/min/1.73m 2 ), CVD was significantly more frequently observed in pts with than without low GNRI &lt;88 (52% vs 26%, p&lt;0.0001, the adjusted hazard ratio (HR):2.7 (95%CI 1.5-4.8)). Furthermore, in group without renal dysfunction, pts with low GNRI had the significantlyincreased risk, compared to those with high GNRI&gt;88 (28% vs 6%, p&lt;0.0001, the adjusted HR:4.7 (95%CI 1.6-13.4)). Conclusion: Malnutrition Assessed by Geriatric Nutritional Index provides the long-term prognostic information in patients admitted for acute decompensated heart failure, irrespective of renal dysfunction.
Intensive therapy followed by bone marrow transplantation for patients with acute lymphocytic leukemia in second or subsequent remission: determination of prognostic factors (a report from the University of Minnesota Bone Marrow Transplantation Team)
Authors: WG Woods, ME Nesbit, NK Ramsay, W Krivit, TH Kim, A Goldman, PB McGlave, JH Kersey
Journal: Blood (1983)
DSM-III and DSM-III-R diagnoses of autism
Authors: F R Volkmar, J Bregman, D J Cohen, D V Cicchetti
Journal: American Journal of Psychiatry (1988)

The authors examined the reliability, sensitivity, and specificity of DSM-III and DSM-III-R criteria for autism in relation to each other and to clinical diagnoses in 114 children and adults (52 diagnosed by clinicians' best judgment as autistic and 62 as nonautistic but developmentally disordered). They used a standard, structured coding scheme to evaluate each patient. The reliability of specific criteria was generally high. Although DSM-III criteria were highly specific, they were less sensitive; the reverse was true for DSM-III-R. The authors conclude that the diagnostic concept of autism in DSM-III-R appears to have been substantially broadened.
Congenital tracheal diverticle with delayed symptoms
Authors: Tamara Svobodová, Jarmila Turzöková, Robert Lischke, Petr Pohunek
Journal: European Respiratory Journal (2013)

We discuss a case of a girl who presented at the age of 10 years with atypical musical wheezing during forced breathing. She had positive sensitization to pollens, house dust mites and cat and was treated for allergy and mild asthma with budesonide and antihistamines. As the wheezing was not typical for asthma, she underwent further diagnostics.  Spirometry was normal, bronchoscopy and imaging found a communicating tracheal diverticle of the size 17 x 10 x 8 mm. As the girl was otherwise asymptomatic, we have opted for a conservative management.  Wheezing disappeared and the patient was completely asymptomatic until 18 years of age when she started to suffer from expiratory wheezing and dyspnea during exercise. Spirometry revealed obstruction of the large airways during expiration. CT confirmed the diverticle of the same size and shape as described before. A wide communication with trachea was described. On bronchoscopy the orifice of the diverticle was found to be closing as a valve with air trapping in the diverticle during forced breathing and coughing with enlargement of the diverticle and bulging of the posterior wall of the trachea. During coughing and forced breathing the tracheal lumen was almost closing.  The diverticle was removed by thoracic surgeon from the neck approach and the 5 mm wide orifice closed using part of the diverticle wall. Histology confirmed normal tracheal epithelium. Since the surgery the girl is completely symptom free.  This case shows a possible difference in imaging and bronchoscopy, especially in breathing related variable conditions.   Supported by the project (Ministry of Health) for conceptual development of research organization 00064203 (University Hospital Motol, Prague,Czech Republic) .
Abstract 2708: Development of allosteric regulators of the dimerization domains of the plasminogen-related growth factor family for the treatment of pancreatic cancer
Authors: Kevin J. Church, Leen Kawas, Joseph Harding, Malte Lang, Michelle McMicheal
Journal: Cancer Research (2014)

Abstract The plasminogen-related family of growth factors includes the hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP), both of which normally mediate a variety of cellular behaviors including proliferation, survival, and migration. A major contributor to the formation and persistence of various cancers is the dysregulation of these growth factor systems. Overexpression of the HGF receptor, c-Met, is common in many cancers including pancreatic cancer, and is associated with poor prognosis. Dysregulation of this system often leads to tumorigenesis and induction of various malignant phenotypes including increased proliferation, survival, migration, and invasion. In order to activate c-Met, HGF must first undergo an activation step in which it forms an HGF homodimer. Small molecule antagonists with homology to a putative “hinge” region within the HGF sequence have been developed that bind to HGF and allosterically block dimerization, therefore inhibiting c-Met signaling. Norleual [Nle-Tyr-Ile-ψ-(CH2-NH2)3-4-His-Pro-Phe] has previously been shown to inhibit HGF dimerization and HGF-dependent c-Met activation. We have assessed the ability of Norleual to block HGF dimerization and activation of c-Met within pancreatic cancer cells. Similar to the HGF/c-Met system, over-activation of the closely related MSP/Ron (MSP receptor) growth factor system has been identified as a critical contributor to pancreatic cancer progression. Due to overall high sequence homology between HGF and MSP, including the putative “hinge” region, we have hypothesized that MSP must also dimerize in order to efficiently activate the Ron receptor, and that this activation step can be targeted by “hinge” region homologs. Our results indicate that MSP naturally forms dimers and incubation with Norleual and similar “hinge” region antagonists inhibits dimerization. Further, we have demonstrated that MSP dimerization may be biologically significant and inhibition of dimerization suppresses MSP-dependent cell signaling and cell behaviors. The ultimate goal of this work is to develop a dual inhibitor capable of suppressing both the HGF and MSP growth factor systems, and further assess the therapeutic potential of these inhibitors for treatment of pancreatic cancer. Citation Format: Kevin J. Church, Leen Kawas, Joseph Harding, Malte Lang, Michelle McMicheal. Development of allosteric regulators of the dimerization domains of the plasminogen-related growth factor family for the treatment of pancreatic cancer. [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 2708. doi:10.1158/1538-7445.AM2014-2708