tbuckley/cabot-search huggingface dataset:
Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts.
Authors: M G Klug, M H Soonpaa, G Y Koh, L J Field
Journal: Journal of Clinical Investigation (1996)

This study describes a simple approach to generate relatively pure cultures of cardiomyocytes from differentiating murine embryonic stem (ES) cells. A fusion gene consisting of the alpha-cardiac myosin heavy chain promoter and a cDNA encoding aminoglycoside phosphotransferase was stably transfected into pluripotent ES cells. The resulting cell lines were differentiated in vitro and subjected to G418 selection. Immunocytological and ultrastructural analyses demonstrated that the selected cardiomyocyte cultures (> 99% pure) were highly differentiated. G418 selected cardiomyocytes were tested for their ability to form grafts in the hearts of adult dystrophic mice. The fate of the engrafted cells was monitored by antidystrophin immunohistology, as well as by PCR analysis with primers specific for the myosin heavy chain-aminoglycoside phosphotransferase transgene. Both analyses revealed the presence of ES-derived cardiomyocyte grafts for as long as 7 wk after implantation, the latest time point analyzed. These studies indicate that a simple genetic manipulation can be used to select essentially pure cultures of cardiomyocytes from differentiating ES cells. Moreover, the resulting cardiomyocytes are suitable for the formation of intracardiac grafts. This selection approach should be applicable to all ES-derived cell lineages.
(36) Granuloma annulare
Authors: W.F.G. Tucker, S.S. Bleehen
Journal: British Journal of Dermatology (1986)

Journal Article (36) Granuloma annulare Get access W.F.G. Tucker, Drs, W.F.G. Tucker, Drs Search for other works by this author on: Oxford Academic Google Scholar S.S. Bleehen S.S. Bleehen Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Pages 82–85, https://doi.org/10.1111/j.1365-2133.1986.tb07731.x Published: 01 July 1986
Pretransplantation hepatitis C virus quasispecies may be predictive of outcome after liver transplantation
Authors: Shawn J. Pelletier, Daniel P. Raymond, Traves D. Crabtree, Julia C. Iezzoni, Robert G. Sawyer, Young S. Hahn, Timothy L. Pruett
Journal: Hepatology (2000)

The evolution of hepatitis C virus (HCV) envelope variation was studied using a liver-transplant model to evaluate the role of HCV quasispecies for hepatocyte infection. Twelve HCV polymerase chain reaction (PCR)-positive liver-transplant recipients (6 with posttransplantation biochemical hepatitis and 6 without hepatitis [controls]) were prospectively evaluated and underwent detailed quasispecies analysis of pre- and postoperative serum samples. HCV amino acid sequence diversity and complexity at the first hypervariable region (HVR1) of the second envelope protein (E2) was correlated with outcome. Recurrence of HCV-induced allograft injury was defined by persistently elevated serum alanine transaminase (ALT) levels. The major variant (sequences >10% of all clones) of recipients with hepatitis accounted for a significantly smaller percent of all preoperative clones compared with controls (41% +/- 6% vs. 69% +/- 8%; P <.015). Recipients with hepatitis had an increased number of pretransplantation major variants (2.5 +/- 0.3 vs. 1.1 +/- 0.2; P <.006). Eighty-three percent of controls had a predominant variant (accounting for >50% of clones) compared with 17% of those with recurrence (P <.05). These differences did not persist postoperatively. In addition, recipients without a pretransplantation predominant variant demonstrated an increased allograft fibrosis score (2.3 +/- 0.3 vs. 0.5 +/- 0.3; P <.015) at 181 to 360 days posttransplantation compared with those in whom a predominant variant was present. Increased HCV envelope complexity may act as a stronger antigenic stimulus or improve hepatocyte receptor binding and lead to allograft hepatitis and fibrosis. Although pretransplantation differences in HCV quasispecies did not persist postoperatively, pretransplantation quasispecies may be a predictor of HCV-induced hepatitis and graft fibrosis after liver transplantation.
Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin
Authors: Thierry Poynard, John McHutchison, Michael Manns, Rob P. Myers, Janice Albrecht
Journal: Hepatology (2003)

Liver fibrosis and activity indexes were validated in patients infected by hepatitis C virus (HCV) nontreated and treated by interferon. The aim was to validate their usefulness as surrogate markers of histologic features using the data of a randomized trial of combination peginterferon alfa–2b and ribavirin. Three hundred fifty–two patients who had had 2 interpretable liver biopsies and stored serum sample before and after treatment were selected. Two hundred eight patients received peginterferon alfa–2b 1.5 mcg per kg and ribavirin and 144 patients interferon alfa–2b 3 MU three times a week and ribavirin for 48 weeks. A fibrosis and an activity index combining 5 and 6 biochemical markers were assessed at baseline and at end of follow–up (24 weeks after treatment). The biochemical markers have significant predictive values both for the diagnosis of fibrosis and for activity. For the diagnosis of bridging fibrosis and/or moderate necroinflammatory activity, the area under the receiver operating characteristics curve of the activity index was 0.76 ± 0.03 at baseline and 0.82 ± 0.02 at end of follow–up. A cutoff of activity index at 0.30 (range, 0.00–1.00) had 90% sensitivity and 88% positive predictive value for the diagnosis of bridging fibrosis or moderate necroinflammatory activity. Sensitivity analyses with biopsy specimens of size greater than 15 mm suggest that a part of discordances between biochemical markers and histology were due to biopsy specimen sampling error. In conclusion, these biochemical markers of fibrosis and activity could be used as surrogate markers for liver biopsy in patients with chronic hepatitis C, both for the initial evaluation and for follow–up.
Saponins modulate the intracellular trafficking of protein toxins
Authors: Alexander Weng, Mayank Thakur, Benedicta von Mallinckrodt, Figen Beceren-Braun, Roger Gilabert-Oriol, Burkard Wiesner, Jenny Eichhorst, Stefan Böttger, Matthias F. Melzig, Hendrik Fuchs
Journal: Journal of Controlled Release (2012)
Memory Loss—When Is It Alzheimer Disease?
Authors: C. Munro Cullum
Journal: JAMA (1998)

Because the group of individuals older than 85 years is now the fastest growing segment of our society, it is critical for physicians to enhance their familiarity with the changes in memory associated with normal aging and to be able to identify the early signs of abnormal mental decline. Great progress has been made in the past few years in the ability to differentiate normal aging-related memory changes from the impairments associated with dementia, including Alzheimer disease (AD). Reassuring the patient with memory complaints who does not show evidence of a dementing disease on formal examination is important and gratifying. The early identification of a dementing disease is equally important to provide optimal care and plan for the future.
An Interesting View
Authors: Roland Talanow, Sankaran Shrikanthan, Donald R. Neumann
Journal: Clinical Nuclear Medicine (2010)

This is a 54-year-old female patient with a history of ulcerative colitis. She underwent proctocolectomy and end ileostomy in the 1970s, and now presented with pain around the end of her stoma. The area was biopsied and the pathology report showed an invasive moderately differentiated adenocarcinoma with mucinous features. Subsequently, a PET-CT was performed for initial treatment strategy examination. PET-CT, including volume rendering, demonstrated increased FDG uptake within the stoma site as well as within a loop of bowel traversing through the ostomy tract (maximal SUV is 5.9 and 6.6, respectively). This case is of particular interest, because (1) a volume-rendered PET (only PET—without CT) of such a lesion has not been shown in the literature, (2) this scenario (primary cancer to the stoma detected by PET) is rarely encountered, and (3) these volume-rendered images are useful tools for demonstration of disease sites to clinicians.
Successful liaison between the health team and social workers in Blackburn, West Lothian.
Authors: B McKinstry
Journal: BMJ (1987)

Many forms of liaison between social workers and primary health care workers have been described.' 2 In Blackburn for the past 10 years we have held weekly meetings for all the health professionals who work in our health centre, members of the area social work team, and the local officer of the Royal Scottish Society for Prevention ofCruelty to Children.We thought we should take stock of the value of the meetings and look at how our workload and the type of work have changed over the 10 years.Until the 1960s Blackburn was a small mining town.The building of a large truck manufacturing plant nearby led to a large influx of people, mainly from the Glasgow conurbation.They were housed in high rise, flat roofed accommodation, which quickly became damp and uninhabitable.Over the past eight years the plant wound down its operations and has now closed, leaving Blackburn with one of the highest unemployment rates in Britain: >25%.Until last year large tracts of the town consisted of boarded up buildings and a few occupied flats, many of which have now been razed to the ground or converted to good, well insulated accom- modation.The town also includes West Lothian's "homeless accommodation," where families who have been made homeless owing to domestic violence, rents arrears, or other causes are housed for up to three months while they await new homes.Blackburn has more than its fair share of social problems, and it is in this atmosphere that Dr W Gilmour, our former senior partner, started the weekly meetings.
CLINICAL USES OF 2,3-DIMERCAPTOPROPANOL (BAL). VII. THE TREATMENT OF ARSENICAL DERMATITIS WITH PREPARATIONS OF BAL
Authors: W. T. Longcope, John A. Luetscher, M. M. Wintrobe, Val Jäger
Journal: Journal of Clinical Investigation (1946)

The development of 2,3-dimercaptopropanol (British Anti-Lewisite, BAL) by Peters, Stocken, and Thompson (1) has made available a potent antidote for arsenical poisoning.Study of the chemical combination of arsenic with sensitive en- zymes and cells indicated that the arsenic could, under certain circumstances, be removed from the cells, and that enzymes could be reactivated by the action of BAL (1, 2).BAL administered to ani- mals exerted both protective and therapeutic ef- fects against local and systemic injury by toxic arsenicals (1, 2).These observations strongly suggested that BAL might be useful in arsenical poisoning in man, and cautious trials were ini- tiated in this hospital at the end of 1942. METHODSPatients were admitted to a special ward which was in part arranged for the care of civilians employed at Edgewood Arsenal, under contract between the Johns Hopkins Hospital and the U. S. Employees Compensation Com- mission, and in cooperation with the Chemical Warfare Service.A detailed clinical study was made of these patients both before and after the administration of BAL.BAL was given by inunction in 1 to 10 per cent ointment (3) and later by intramuscular injection in 5 to 10 per cent solution in peanut oil containing benzyl benzoate (4).Dosage was at first varied and rather small because of the lack of information on the therapeutic and toxic ef- fects of BAL.Arsenic in the urine was determined by the method of Magnuson and Watson (5) in the laboratory of Dr. H. Eagle.Chemical analyses of the blood were made under the direction of Dr. Mary Buell.RESULTS
Krzysztof B. Stengert, MD, PhD
Authors: Hanne M. Jensen
Journal: JAMA (1988)

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The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways
Authors: Megan S. Lim, Mary L. Carlson, David K. Crockett, G. Chris Fillmore, David R. Abbott, Olaotan F. Elenitoba-Johnson, Sheryl R. Tripp, George Z. Rassidakis, L. Jeffrey Medeiros, Philippe Szankasi, Kojo S. J. Elenitoba-Johnson
Journal: Blood (2009)
Treating Tumors With a Vaccinia Virus Expressing IFNβ Illustrates the Complex Relationships Between Oncolytic Ability and Immunogenicity
Authors: Liang-Chuan S Wang, Rachel C Lynn, Guanjun Cheng, Edward Alexander, Veena Kapoor, Edmund K Moon, Jing Sun, Zvi G Fridlender, Stuart N Isaacs, Stephen H Thorne, Steven M Albelda
Journal: Molecular Therapy (2011)

Since previous work using a nonreplicating adenovirus-expressing mouse interferon-β (Ad.mIFNβ) showed promising preclinical activity, we postulated that a vector-expressing IFNβ at high levels that could also replicate would be even more beneficial. Accordingly a replication competent, recombinant vaccinia viral vector-expressing mIFNβ (VV.mIFNβ) was tested. VV.mIFNβ-induced antitumor responses in two syngeneic mouse flank models of lung cancer. Although VV.mIFNβ had equivalent in vivo efficacy in both murine tumor models, the mechanisms of tumor killing were completely different. In LKRM2 tumors, viral replication was minimal and the tumor killing mechanism was due to activation of immune responses through induction of a local inflammatory response and production of antitumor CD8 T-cells. In contrast, in TC-1 tumors, the vector replicated well, induced an innate immune response, but antitumor activity was primarily due to a direct oncolytic effect. However, the VV.mIFNβ vector was able to augment the efficacy of an antitumor vaccine in the TC-1 tumor model in association with increased numbers of infiltrating CD8 T-cells. These data show the complex relationships between oncolytic viruses and the immune system which, if understood and harnessed correctly, could potentially be used to enhance the efficacy of immunotherapy. Since previous work using a nonreplicating adenovirus-expressing mouse interferon-β (Ad.mIFNβ) showed promising preclinical activity, we postulated that a vector-expressing IFNβ at high levels that could also replicate would be even more beneficial. Accordingly a replication competent, recombinant vaccinia viral vector-expressing mIFNβ (VV.mIFNβ) was tested. VV.mIFNβ-induced antitumor responses in two syngeneic mouse flank models of lung cancer. Although VV.mIFNβ had equivalent in vivo efficacy in both murine tumor models, the mechanisms of tumor killing were completely different. In LKRM2 tumors, viral replication was minimal and the tumor killing mechanism was due to activation of immune responses through induction of a local inflammatory response and production of antitumor CD8 T-cells. In contrast, in TC-1 tumors, the vector replicated well, induced an innate immune response, but antitumor activity was primarily due to a direct oncolytic effect. However, the VV.mIFNβ vector was able to augment the efficacy of an antitumor vaccine in the TC-1 tumor model in association with increased numbers of infiltrating CD8 T-cells. These data show the complex relationships between oncolytic viruses and the immune system which, if understood and harnessed correctly, could potentially be used to enhance the efficacy of immunotherapy.
Prospective Study of Prostate Tumor Angiogenesis and Cancer-Specific Mortality in the Health Professionals Follow-Up Study
Authors: Lorelei A. Mucci, Anna Powolny, Edward Giovannucci, Zhiming Liao, Stacey A. Kenfield, Rulong Shen, Meir J. Stampfer, Steven K. Clinton
Journal: Journal of Clinical Oncology (2009)

Purpose Tumor growth requires the development of independent vascular networks that are often primitive in morphology and function. We examined whether microvessel morphology contributes to the considerable biologic heterogeneity of prostate cancer. Methods We evaluated microvessel morphology as a predictor of prostate cancer mortality among 572 men in the Health Professionals Follow-Up Study diagnosed with cancer during 1986 to 2000. We immunostained prostatectomy tumor block sections for endothelial marker CD34 and assessed microvessel density, vessel size (area and diameter), and irregularity of vessel lumen using image analysis. Proportional hazards models were used to assess microvessel density and morphology in relation to lethal prostate cancer. Results Poorly differentiated tumors exhibited greater microvessel density, greater irregularity of the vessel lumen, and smaller vessels. During 20 years of follow-up, 44 men developed bone metastases or died of cancer. Men with tumors exhibiting the smallest vessel diameter, based on quartiles, were 6.0 times more likely (95% CI, 1.8 to 20.0) to develop lethal prostate cancer. Men with the most irregularly shaped vessels were 17.1 times more likely (95% CI, 2.3 to 128) to develop lethal disease. Adjusting for Gleason grade and prostate-specific antigen levels did not qualitatively change the results. Microvessel density was not linked to cancer-specific mortality after adjusting for clinical factors. Conclusion Aggressive tumors form vessels that are primitive in morphology and function, with consequences for metastases. Vascular size and irregularity reflect the angiogenic potential of prostate cancer and may serve as biomarkers to predict prostate cancer mortality several years after diagnosis.
Haemodynamic consequences of arterial replacement with a synthetic graft
Authors: R. F APPLEYARD, L. R SAUVAGE
Journal: Cardiovascular Research (1986)

Because of structural differences between a synthetic graft and the natural artery, a graft would be expected to alter the haemodynamics of the vessel which is bypassed. To examine this, a segment of the lower descending thoracic aorta in six calves was removed and replaced with a Dacron graft. The gradients in pressure and flow across this segment were calculated from simultaneous measurements of pressure and flow made at both ends. From these, the longitudinal (Zl) and transverse (Zt) impedance of the segment was computed. In three animals pressure and flow were measured in the ascending aorta so that the systemic input impedance (Zi) could also be computed. Neither the magnitude nor phase of Zl was affected by the graft. However, the magnitude of Zt was approximately five times higher at all frequencies above DC following insertion of the graft. The characteristic impedance (Zo) was computed from Zl and Zt. Zo for the aortic segment remained approximately constant between 20 and 40 Pa·s·cm−3 for the first 10 harmonics. In contrast, Zo for the graft was strongly frequency dependent, and progressively increased in magnitude up through the tenth harmonic. The input impedance at the entrance to the segment (Zx was strongly influenced by Zo. As a result, the higher frequency components of Zx were increased following insertion of the graft. In spite of these local changes in impedance, Zi was not affected by the graft. This was probably due to effective filtering by the healthy, compliant aorta left intact between the graft and the left ventricle.
Cost effectiveness of detecting Barrett's cancer.
Authors: T A Wright, M R Gray, A I Morris, I T Gilmore, A Ellis, H L Smart, M Myskow, J Nash, R J Donnelly, A N Kingsnorth
Journal: Gut (1996)

BACKGROUND: Screening Barrett9s oesophagus is controversial owing to a large variation in the reported incidence of neoplastic change and lack of evidence that screening improves tumour prognosis. AIMS: To determine the incidence of Barrett9s cancer, its cost of detection, and stage of disease at time of diagnosis. PATIENTS AND METHODS: Data from our surveillance programme have been reviewed to assess the incidence of malignant change, tumour stage at diagnosis, and the cost per cancer detected. RESULTS: 166 patients had annual endoscopic surveillance. Six patients (five men) developed cancer-an incidence of one cancer per 59 male and 167 female patient-years of follow up. The screened group had a significantly earlier stage than a control group of unscreened cancers (p &lt; 0.05). The cost of detecting one cancer was Pounds 14 868 for men and Pounds 42 084 for women. CONCLUSIONS: The cost of screening for Barrett9s cancer is high but may be justified on the basis of the high incidence of detecting early stage disease.
Why a theory of human nature cannot be based on the distinction between universality and variability: Lessons from anthropology
Authors: Rita Astuti, Maurice Bloch
Journal: Behavioral and Brain Sciences (2010)

We welcome the critical appraisal of the database used by the behavioral sciences, but we suggest that the authors' differentiation between variable and universal features is ill conceived and that their categorization of non-WEIRD populations is misleading. We propose a different approach to comparative research, which takes population variability seriously and recognizes the methodological difficulties it engenders.
Personalized treatment of hepatitis B
Authors: Anna S. Lok
Journal: Clinical and Molecular Hepatology (2015)

There are seven approved drugs for treatment of hepatitis B. Professional guidelines provide a framework for managing patients but these guidelines should be interpreted in the context of the individual patient's clinical and social circumstances. Personalized management of hepatitis B can be applied based on prediction of the individual patient's risk of cirrhosis and hepatocellular carcinoma to guide the frequency and intensity of monitoring and urgency of treatment. It can also be applied to decisions regarding when to start treatment, which drug to use, and when to stop based on the individual patient's disease characteristics, preference, comorbidities and other mitigating circumstances. Keywords: Hepatitis B virus; Chronic hepatitis B; Management; Personalized medicine
Massive elevation of procalcitonin plasma levels in the absence of infection in kidney transplant patients treated with pan-T-cell antibodies
Authors: R. Sabat, C. Höflich, W.D. Döcke, F. Kern, H.-D. Volk, M. Oppert, B. Windrich, C. Rosenberger, P. Reinke, J. Kaden
Journal: Intensive Care Medicine (2001)