tbuckley/cabot-search huggingface dataset:
Controlling Major Cellular Processes of Human Mesenchymal Stem Cells using Microwell Structures
Authors: Xun Xu, Weiwei Wang, Karl Kratz, Liang Fang, Zhengdong Li, Andreas Kurtz, Nan Ma, Andreas Lendlein
Journal: Advanced Healthcare Materials (2014)

Directing stem cells towards a desired location and function by utilizing the structural cues of biomaterials is a promising approach for inducing effective tissue regeneration. Here, the cellular response of human adipose‐derived mesenchymal stem cells (hADSCs) to structural signals from microstructured substrates comprising arrays of square‐shaped or round‐shaped microwells is explored as a transitional model between 2D and 3D systems. Microwells with a side length/diameter of 50 μm show advantages over 10 μm and 25 μm microwells for accommodating hADSCs within single microwells rather than in the inter‐microwell area. The cell morphologies are three‐dimensionally modulated by the microwell structure due to differences in focal adhesion and consequent alterations of the cytoskeleton. In contrast to the substrate with 50 μm round‐shaped microwells, the substrate with 50 μm square‐shaped microwells promotes the proliferation and osteogenic differentiation potential of hADSCs but reduces the cell migration velocity and distance. Such microwell shape‐dependent modulatory effects are highly associated with Rho/ROCK signaling. Following ROCK inhibition, the differences in migration, proliferation, and osteogenesis between cells on different substrates are diminished. These results highlight the possibility to control stem cell functions through the use of structured microwells combined with the manipulation of Rho/ROCK signaling.
Are US flu death figures more PR than science?
Authors: Peter Doshi
Journal: BMJ (2005)

US data on influenza deaths are a mess. The Centers for Disease Control and Prevention (CDC) acknowledges a difference between flu death and flu associated death yet uses the terms interchangeably. Additionally, there are significant statistical incompatibilities between official estimates and national vital statistics data. Compounding these problems is a marketing of fear—a CDC communications strategy in which medical experts “predict dire outcomes” during flu seasons.

The CDC website states what has become commonly accepted and widely reported in the lay and scientific press: annually “about 36 000 [Americans] die from flu” (www.cdc.gov/flu/about/disease.htm) and “influenza/pneumonia” is the seventh leading cause of death in the United States (www.cdc.gov/nchs/fastats/lcod.htm). But why are flu and pneumonia bundled together? Is the relationship so strong or unique to warrant characterising them as a single cause of death?

David Rosenthal, director of Harvard University Health Services, said, “People don't necessarily die, per se, of the [flu] virus—the viraemia. What they die of is a secondary pneumonia. So many of these pneumonias are not viral pneumonias but secondary [pneumonias].” But Dr Rosenthal agreed that the flu/pneumonia relationship was not unique. For instance, a recent study ( JAMA 2004;292: 1955-60) found that stomach acid suppressing drugs are associated with a higher risk of community …
131. Recombinant Adeno-Associated Virus 2-Mediated Transfer of the Human Superoxide-Dismutase Gene Does Not Confer Radioresistance on HeLa Cervical Carcinoma Cells
Authors: Marlon R. Veldwijk, Carsten Herskind, Stephanie Laufs, W. Jens Zeller, Stefan Fruehauf, Frederik Wenz
Journal: Molecular Therapy (2005)

Top of pageAbstract
Introduction: The success rate of any therapeutic approach depends on the therapeutic window, which can be increased by either raising the resistance of the normal tissue without protecting the tumor cells or by sensitizing the tumor cells but not the normal cells. Two promising candidate genes for normal tissue protection against radiation-induced damage may be the copper-zinc (CuZnSOD) and manganese superoxide-dismutase genes (MnSOD). The recombinant adeno-associated virus 2 (rAAV-2) offers attractive advantages over other vector systems: low immunogenicity, ability to infect dividing and non-dividing tissues and a low chance of insertional mutagenesis, due to extra-chromosomal localization. We report the production of novel rAAV-2-SOD vectors and the investigation of their modulating effects on HeLa-RC cells after irradiation.

Material and methods: rAAV-2 vectors were cloned containing the human CuZnSOD or MnSOD as transgene and vector stocks were produced. In the initial experiments human cervix carcinoma (HeLa-RC) cells were chosen for their susceptibility to rAAV-2. On day 0, cells were seeded and transduced with the rAAV-2-SOD vectors. On day 3, cells were harvested, irradiated (1-8 Gy) and reseeded in different assays (FACS, SOD, MTT and colony assays). Furthermore, a proliferation assay was performed on SOD-transduced cells which were incubated with the superoxide radical-generating substance paraquat for 96 hours, in order to show the functionality of the SOD vectors.

Results: Although >70% of all cells expressed SOD, significant amounts of SOD protein were detected and the superoxide-detoxifying function of SOD could be shown, no radioprotective effect of SOD was observed after transduction of HeLa-RC cells.

Conclusions: Novel rAAV-2-SOD vectors that could be produced at high titer, were able to efficiently infect cells and express functional SOD. The absence of a radioprotective effect in the HeLa-RC cancer cells indicates an additional safety feature and suggests that rAAV-mediated MnSOD overexpression might contribute to increasing the therapeutic index when applied for normal tissue protection. AAV-SOD radioprotection studies on normal tissue cells are currently in progress.
Prioritization of Biomarker Targets in Human Umbilical Cord Blood: Identification of Proteins in Infant Blood Serving as Validated Biomarkers in Adults
Authors: Nicole Hansmeier, Tzu-Chiao Chao, Lynn R. Goldman, Frank R. Witter, Rolf U. Halden
Journal: Environmental Health Perspectives (2012)

Early diagnosis represents one of the best lines of defense in the fight against a wide array of human diseases. Umbilical cord blood (UCB) is one of the first easily available diagnostic biofluids and can inform about the health status of newborns. However, compared with adult blood, its diagnostic potential remains largely untapped.Our goal was to accelerate biomarker research on UCB by exploring its detectable protein content and providing a priority list of potential biomarkers based on known proteins involved in disease pathways.We explored cord blood serum proteins by profiling a UCB pool of 12 neonates with different backgrounds using a combination of isoelectric focusing and liquid chromatography coupled with matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) and by comparing results with information contained in metabolic and disease databases available for adult blood.A total of 1,210 UCB proteins were identified with a protein-level false discovery rate of ~ 5% as estimated by naïve target-decoy and MAYU approaches, signifying a 6-fold increase in the number of UCB proteins described to date. Identified proteins correspond to 138 different metabolic and disease pathways and provide a platform of mechanistically linked biomarker candidates for tracking disruptions in cellular processes. Moreover, among the identified proteins, 38 were found to be approved biomarkers for adult blood.The results of this study advance current knowledge of the human cord blood serum proteome. They showcase the potential of UCB as a diagnostic medium for assessing infant health by detection and identification of candidate biomarkers for known disease pathways using a global, nontargeted approach. These biomarkers may inform about mechanisms of exposure-disease relationships. Furthermore, biomarkers approved by the U.S. Food and Drug Administration for screening in adult blood were detected in UCB and represent high-priority targets for immediate validation.
Liver Abscess: Rose Bengal I 131 Hepatic Photoscan in Diagnosis and Management
Authors: Bernard M. Schuman, Melvin A. Block, William R. Eyler, Lucille DuSault
Journal: JAMA (1964)

Seven consecutive patients with liver abscess recovered because of early confirmation of the diagnosis and guided drainage procedures made possible by the Rose Bengal I 131 (RIRB) liver photoscan. High mortality associated with abscess of the liver has, in large part, been related to the difficulty in establishing an early diagnosis. Now, information regarding the presence, location, size, and number of abscesses is available from anterior and lateral hepatic photoscans. With this demonstration it is possible to choose the most expeditious route for evacuation of the cavity. During therapy, liver scans provide objective evidence of the size of the residual lesion.
Viability and primary culture of rat hepatocytes after hypothermic preservation: The superiority of the leibovitz medium over the university of wisconsin solution for cold storage
Authors: Marie-gwenaëlle Poullain, Alain Fautrel, Claire Guyomard, Christophe Chesne, Luc Grislain, André Guillouzo
Journal: Hepatology (1992)

Hepatocytes isolated from adult rat livers were hypothermically preserved for 24 or 48 hr before being plated under conventional culture conditions. They were stored either in the Leibovitz medium, a cell culture medium with and without polyethylene glycol (PEG), a compound known to suppress ischemia-induced cell swelling, or in the University of Wisconsin solution, the most effective solution for cold organ preservation. After 24 or 48 hr of storage at 4.5° C in Leibovitz medium, cell viability and adherence efficiency to plastic dish, were only slightly reduced, whereas University of Wisconsin hepatocytes had a decreased viability and (especially after 48-hr storage) lost their adhesion ability; they did not survive in vitro. The metabolic competence of hepatocytes maintained in Leibovitz medium was retained over the 3 days of culture, as shown by low extracellular levels of the membrane-bound and cytosolic hepatic enzymes, as well as by intracellular glutathione content, albumin secretion rate and several phase I and phase II drug metabolic reactions very close to those found with fresh hepatocytes maintained under similar culture conditions. Addition of polyethylene glycol to the Leibovitz medium resulted in slightly higher viability and function of hepatocytes after cold storage. These results clearly demonstrate that viability of a transplanted liver does not correlate with long-term in vitro viability of isolated hepatocytes after hypothermic preservation in University of Wisconsin solution. They also suggest that nutritional and energy substrates as found in the Leibovitz medium are probably required to define a suitable solution for cold preservation of isolated parenchymal cells. The findings with Leibovitz medium favor the conclusion that hypothermically preserved hepatocytes could be used for various metabolic studies and for the treatment of liver insufficiency. (Hepatology 1992;15:97-106).
Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats☆☆☆★★★
Authors: J PENE, A DESROCHES, L PARADIS, B LEBEL, M FARCEA, C NICODEMUS, H YSSEL, J BOUSQUET
Journal: Journal of Allergy and Clinical Immunology (1998)
Treatment of Anorexia nervosa by the Integration of Behavior Therapy and Psychotherapy
Authors: Jeffrey L. Geller
Journal: Psychotherapy and Psychosomatics (1975)

Anorexia nervosa has been approached by a variety of therapeutic regimens. These regimens have addressed themselves to either the underlying psychological problems or the eating disorder. By integrating behavior therapy and psychotherapy, the author proposes a treatment plan which addresses both problems simultaneously. Psychotherapy and behavior therapy are theoretically integrable; their integration produces a treatment consistent with the dynamics underlying anorexia nervosa; and this treatment produces, during a relatively short hospital stay, rapid weight gain and a foundation for continued psychotherapy. The case of a 22-year-old female is presented which describes the treatment by the proposed integrated model with documentation of the results at discharge and at 3 months and 1 year follow-up.
Classification and management of allergic rhinitis patients in general practice during pollen season
Authors: H. Van Hoecke, N. Vastesaeger, L. Dewulf, L. Sys, P. Van Cauwenberge
Journal: Allergy (2006)

Background: Allergic rhinitis (AR) represents a major challenge in primary care. The Allergic Rhinitis and its Impact on Asthma (ARIA) group proposed a new classification for AR and developed evidence‐based guidelines for the management of this disease. We conducted this study to further characterize the classes of AR described by ARIA, and to evaluate whether the management of AR in general practice is in accordance with the ARIA guidelines. Methods: During the pollen season of 2003, 95 Belgian general practitioners (GPs) enrolled 804 patients who presented with symptoms of AR. For each patient, a questionnaire comprising the clinical presentation and management was completed. Results: In 64% of the patients, AR was classified as intermittent and in 36% as persistent. Persistent rhinitis caused more discomfort than intermittent rhinitis. Only 50% of the patients had ever undergone allergy testing. Among them, 51% were allergic to both seasonal and perennial allergens. Eighty‐two per cent of the persistent rhinitics were allergic to at least one seasonal allergen and 72% of the intermittent rhinitics to at least one perennial allergen. When compared strictly with the ARIA recommendations, 49% of the patients with mild and/or intermittent AR were overtreated, whereas about 30% of those with moderate/severe persistent rhinitis were undertreated. Conclusion: This study confirms that the previous classification of AR into ‘seasonal’ and ‘perennial’ is not satisfactory and that intermittent and persistent AR are not equivalent to seasonal and perennial AR respectively. Furthermore, persistent rhinitis has been shown to be a distinct disease entity. Further efforts are required to disseminate and implement evidence‐based diagnostic and treatment guidelines for AR in primary care practice.
Combined Immunochemotherapy With Reduced Whole-Brain Radiotherapy for Newly Diagnosed Primary CNS Lymphoma
Authors: Gaurav D. Shah, Joachim Yahalom, Denise D. Correa, Rose K. Lai, Jeffrey J. Raizer, David Schiff, Renato LaRocca, Barbara Grant, Lisa M. DeAngelis, Lauren E. Abrey
Journal: Journal of Clinical Oncology (2007)

Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) after CR.Thirty patients (17 women; median age, 57 years; median Karnofsky performance score, 70) were treated with five to seven cycles of induction chemotherapy (rituximab, MTX, procarbazine, and vincristine [R-MPV]) as follows: day 1, rituximab 500 mg/m2; day 2, MTX 3.5 gm/m2 and vincristine 1.4 mg/m2. Procarbazine 100 mg/m2/d was administered for 7 days with odd-numbered cycles. Patients achieving CR received dose-reduced WBRT (23.4 Gy), and all others received standard WBRT (45 Gy). Two cycles of high-dose cytarabine were administered after WBRT. CSF levels of rituximab were assessed in selected patients, and prospective neurocognitive evaluations were performed.With a median follow-up of 37 months, 2-year overall and progression-free survival was 67% and 57%, respectively. Forty-four percent of patients achieved a CR after five or fewer cycles, and 78% after seven cycles. The overall response rate was 93%. Nineteen of 21 CR patients received the planned 23.4 Gy WBRT. The most commonly observed grade 3 to 4 toxicities included neutropenia (43%), thrombocytopenia (36%), and leukopenia (23%). No treatment-related neurotoxicity has been observed.The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support. Additional cycles of R-MPV nearly doubled the CR rate. Reduced-dose WBRT was not associated with neurocognitive decline, and disease control to date is excellent.
Recent Developments in Low-Level Lead Exposure and Intellectual Impairment in Children
Authors: Karin Koller, Terry Brown, Anne Spurgeon, Len Levy
Journal: Environmental Health Perspectives (2004)

In the last decade children's blood lead levels have fallen significantly in a number of countries, and current mean levels in developed countries are in the region of 3 Mu g/dL. Despite this reduction, childhood lead poisoning continues to be a major public health problem for certain at-risk groups of children, and concerns remain over the effects of lead on intellectual development in infants and children. The evidence for lowered cognitive ability in children exposed to lead has come largely from prospective epidemiologic studies. The current World Health Organization/Centers for Disease Control and Prevention blood level of concern reflects this and stands at 10 Mu g/dL. However, a recent study on a cohort of children whose lifetime peak blood levels were consistently less than 10 Mu g/dL has extended the association of blood lead and intellectual impairment to lower levels of lead exposure and suggests there is no safety margin at existing exposures. Because of the importance of this finding, we reviewed this study in detail along with other recent developments in the field of low-level lead exposure and children's cognitive development. We conclude that these findings are important scientifically, and efforts should continue to reduce childhood exposure. However, from a public health perspective, exposure to lead should be seen within the many other risk factors impacting on normal childhood development, in particular the influence of the learning environment itself. Current lead exposure accounts for a very small amount of variance in cognitive ability (1-4%), whereas social and parenting factors account for 40% or more.
Analgesia and the acute abdomen.
Authors: I D Fraser
Journal: BMJ (1979)

Obstetric anaesthetic and analgesic services in Wales SIR,-We agree with Dr D J Bowen and his colleagues (20 October, p 1002) that epidural analgesia should be available in every consultant obstetric unit as part of the pain relief service.However, there are considerable logistic difficulties to overcome in imple- menting this policy, such as the size and location of the unit and, not least, a shortage of trained anaesthetists.Unless the service can be safely offered mortality and morbidity are inevitable.It will take time to achieve this aim and our survey in Wales showed that the present deficiencies are substantial.We believed that our suggestions might go some way towards improving the situation.Dr Bowen and his colleagues are puzzled because we stated that there were few medical indications for epidural block and feel that breech deliveries, pre-eclamptic toxaemia, forceps deliveries, etc, are indications.However, there are no controlled trials to support their views.
Clinical diagnoses reached in patients undergoing combined ambulatory ph and impedance monitoring for symptoms suspected to be secondary to reflux disease refractory to acid suppression
Authors: J. W. Winter, F. Moroni, R. Gillespie, S. Thomson, C. Buchanan
Journal: Gut (2011)

<h3>Introduction</h3> Since August 2007 we have employed combined ambulatory pH and impedance monitoring in the investigation of patients with symptoms thought attributable to gastro-oesophageal reflux refractory to acid suppression. The aim of this study was to retrospectively analyse clinical data in patients who had undergone this investigation and ascertain the diagnoses reached. <h3>Methods</h3> Information on patients undergoing combined ambulatory pH and impedance monitoring between August 2007 and August 2010 was obtained from the database at our GI physiology unit. Case records were then identified to ascertain the diagnoses reached in each case. Information obtained from the impedance studies included acid exposure time, frequency of acid and weakly acid reflux events and symptom association probability. <h3>Results</h3> 57 patients underwent combined ambulatory pH and impedance monitoring over this time period. Case records were available for 52/57 patients. 51/52 underwent oesophageal manometry, 22/52 had upper GI endoscopy and 7/52 had scintigraphic measurement of gastric emptying. Following global assessment of the results of investigations 10/52 (19%) patients were found to have refractory reflux disease. 28/52 (54%) were judged to have functional symptoms, 4/52 had aerophagy, 4/52 gastroparesis, 3/52 oesophageal motility disorders, 2/52 hypersensitive oesophagus and 1/52 eosinophilic oesophagitis. 6/10 patients with refractory reflux disease agreed to surgical referral. 2 have since had fundoplication, 1 awaits fundoplication and 3 await surgical review. <h3>Conclusion</h3> In this retrospective and uncontrolled cohort, use of combined ambulatory pH and impedance monitoring helped diagnose reflux refractory to acid suppression in 19% of patients investigated. Only 12% of patients having this investigation were referred for surgical management of reflux disease. Over half of patients investigated had no evidence of organic disease to account for their symptoms. Prospective studies are required to identify factors which will improve selection of patients for this investigation.
Prostate-Specific Antigen Improves the Ability of Clinical Stage and Biopsy Gleason Sum to Predict the Pathologic Stage at Radical Prostatectomy in the New Millennium
Authors: Felix K.-H. Chun, Alberto Briganti, Andrea Gallina, Georg C. Hutterer, Shahrokh F. Shariat, Elie Antebie, Jochen Walz, Claus G. Roehrborn, Andrea Salonia, Patrizio Rigatti, Fred Saad, Hartwig Huland, Francesco Montorsi, Markus Graefen, Pierre I. Karakiewicz
Journal: European Urology (2007)
THE HISTOLOGICAL SIGNS OF RESISTANCE TO A TRANSMISSIBLE SARCOMA OF THE FOWL
Authors: Peyton Rous, James B. Murphy
Journal: The Journal of Experimental Medicine (1912)

1. The living tissue of the chicken sarcoma, when implanted in susceptible hosts, survives, proliferates, and thus gives rise apparently to the whole of the new tumor. The histological findings about the graft do not suggest any other origin for the growth. 2. In fowls with a natural or acquired resistance, a very striking series of phenomena takes place about the graft or the established growth. They are referable to the presence of the living neoplastic cells and are essentially similar to those already described in mammals. 3. The lymphocyte has an association with the processes of resistance in the fowl, similar to, but more marked than that observed in mammals. 4. Resistance of the host does not constitute for the chicken tumor a differential means whereby the extrinsic agent present in the growth can be observed to engender it. In general, it may be stated that, when the new host is so unfavorable to the transplanted sarcoma cells as to cause their death, no tumor develops. 5. The activity of the extrinsic agent is negligible as affecting the interpretation of the phenomena about grafts of the avian sarcoma in resistant and susceptible hosts. They are referable to the presence of the transplanted cells. 6. The appearance or non-appearance of a specific, supporting, and vascularizing reaction in the host tissues cannot be looked upon as determining the fate of grafts of the chicken sarcoma. The same seems to be true of mammalian neoplasms.
Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia
Authors: A Hochhaus, S G O'Brien, F Guilhot, B J Druker, S Branford, L Foroni, J M Goldman, M C Müller, J P Radich, M Rudoltz, M Mone, I Gathmann, T P Hughes, R A Larson
Journal: Leukemia (2009)