tbuckley/cabot-search huggingface dataset:
Anti-GD3 Chimeric sFv-CD28/T-Cell Receptor ζ Designer T Cells for Treatment of Metastatic Melanoma and Other Neuroectodermal Tumors
Authors: Agnes S.Y. Lo, Qiangzhong Ma, David L. Liu, Richard P. Junghans
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The aims of this study are to compare antitumor activities of two generations of GD3-specific chimeric antigen receptors (CAR) in human primary T lymphocytes in vitro and to evaluate the antitumor efficacy of using a combination of systemic infusion of interleukin-2 (IL2) and designer T cells to eradicate subcutaneous established GD3+ melanoma in nude mice. Experimental Design: Antitumor activities were compared for two generations of designer T cells, the progenitor first-generation with immunoglobulin T-cell receptor (TCR) with Signal 1 and the second-generation designer T cells with Signal 1+2. Osmotic IL2 pumps were used to deliver the maximum tolerated dose of IL2 to enhance the antitumor effects of designer T cells on subcutaneous established melanoma in nude mice. Results: Melanoma is associated with high expression of ganglioside GD3, which has been targeted with modest effect in antibody therapies. We previously showed that an anti-GD3 CAR (sFv-TCRζ) will recruit T cells to target this non–T-dependent antigen, with potent killing of melanoma cells. Here, we report the addition of a CD28 costimulation domain to create a second-generation CAR, called Tandem for two signals. We show that this Tandem sFv-CD28/TCRζ receptor on T cells confers advantages of improved cytokine secretion, cytotoxicity, proliferation, and clonal expansion on tumor contact versus the same CAR without costimulation. In an adoptive transfer model using established melanoma tumors, designer T cells with CD28 showed a 50% rate of complete remissions but only where IL2 was supplemented. Conclusions: As a reagent for clinical development, the second-generation product is shown to have superior properties to warrant its preference for clinical designer T-cell immunotherapy for melanoma and other tumors. Systemic IL2 was required for optimal activity in an established tumor model. Clin Cancer Res; 16(10); 2769–80. ©2010 AACR.
Doctors need a “sea change” in their attitude to <i>C difficile</i>
Authors: Adrian O'Dowd
Journal: BMJ (2007)

An NHS trust could face criminal charges over failures in its infection control measures that contributed to the deaths of 90 patients.

Every NHS trust in England will now get a copy of a damning report into failures at the Maidstone and Tunbridge Wells NHS Trust in Kent as a precautionary measure to highlight mistakes that occurred there. The Healthcare Commission, England's health watchdog, has just published its report after an investigation into outbreaks of Clostridium difficile at the trust's hospitals between April 2004 and September 2006.

The Healthcare Commission said that there were “significant failings” at the trust and that of 345 deaths it considered as part of its review 90 were “definitely …
A STUDY OF IRON-INDUCED LIVER DAMAGE
Authors: C. L. Witzleben, N. J. Chaffey
Journal: The Journal of Experimental Medicine (1962)

The nature of short term iron-induced liver damage and its effect on the hepatic damage induced by other toxins have been studied by the use of histochemical techniques. The results suggest that a reduction of effective available sulfhydryl groups is a critical hepatotoxic property of storage iron. A reduction of glucose-6-phosphatase, consistently found in iron-loaded animals, demonstrates the sensitivity of the microsomes to the presence of storage iron. The mitochondria appear to be less sensitive, but may be affected under certain conditions. The results suggest that in order for simultaneously acting liver insults to result in additive damage, the mechanisms by which they act must have a critical and relatively specific relationship.
Cardiac Device Infection—or Not
Authors: Larry M. Baddour
Journal: Circulation (2010)

T remendous gains in our understanding of cardiovascular implantable electronic device (CIED) infection were achieved over the past decade.2][3] This observation was somewhat unanticipated in view of the generalized incorporation of strict infection control and prevention practices during the perioperative period of device placement and the routine use of preoperative antibiotic administration as surgical site prophylaxis that characterize the current practice.From data generated from epidemiological and case-control analyses, [3][4][5] we now recognize that much of the increasing rate of CIED infection is likely multifactorial in cause and involves both host-and device-related factors.These include device placement in older and sicker patients and the implantation of more "hardware" (leads), which can require a longer intervention time.
Conjunctival Melanomas Harbor <i>BRAF</i> and <i>NRAS</i> Mutations—Response
Authors: Klaus G. Griewank, Henrike Westekemper, Bastian Schilling, Elisabeth Livingstone, Tobias Schimming, Antje Sucker, Uwe Hillen, Klaus-Peter Steuhl, Lisa Zimmer, Dirk Schadendorf
Journal: Clinical Cancer Research (2013)

In our recently published study ([1][1]), we describe genetic similarities between conjunctival and cutaneous melanoma and propose that the treatment rationale for patients with metastasized conjunctival melanoma should be adapted to that for metastasized cutaneous melanoma. Weber and colleagues ([2
Simple presentation of test accuracy may lead to inflated disease probabilities
Authors: L. M Bachmann
Journal: BMJ (2003)

EDITOR—We found that conveying information on the accuracy of tests in non-technical language improved doctors' ability to estimate disease probabilities accurately.1 We investigated whether doctors might misuse such non-technical presentation when considering the probability of endometrial cancer in a patient with positive results on transvaginal ultrasonography.

View this table:

Distributions of attributed likelihood ratios in three groups given different summaries of information on diagnostic accuracy



We presented 263 general practitioners in Switzerland with a pre-test probability of 10%, information that …
Angiotensin II Receptor Subtypes in the Skeletal Muscle Vasculature of Patients With Severe Congestive Heart Failure
Authors: Slawomir L. Malendowicz, Pierre V. Ennezat, Marco Testa, Laura Murray, Edmund H. Sonnenblick, Todd Evans, Thierry H. LeJemtel
Journal: Circulation (2000)

Background —Vascular remodeling occurs in the skeletal muscle of patients with severe congestive heart failure (CHF); this remodeling is mediated in part by increased activity of the renin-angiotensin system. Animal models suggest that in the vasculature, angiotensin II receptor type 2 (AT2-R) expression may be upregulated in pathological states associated with vascular remodeling. The therapeutic effects of an AT1-R antagonist may, therefore, be in part due to increased plasma angiotensin II levels, which stimulate AT2-R. However, whether AT2-R is expressed in the skeletal muscle vasculature of patients with severe CHF is unknown. Methods and Results —The steady-state transcript levels of the AT1-R and AT2-R genes were analyzed by reverse transcription–polymerase chain reaction in RNA samples prepared from the skeletal muscle of 12 patients with severe CHF (V̇O 2 &lt;10 mL · kg −1 · min −1 ) and 5 age-matched healthy subjects who underwent vastus lateralis biopsies. Human fetal skeletal muscle RNA served as a positive control for the expression of AT1-R and AT2-R gene transcripts. Transcripts from the AT1-R gene were detected readily in all samples. In contrast, transcripts from the AT2-R gene were only detected in fetal skeletal muscle samples and could not be detected in the skeletal muscle vasculature of healthy subjects or that of CHF patients, who were treated with either angiotensin-converting enzyme inhibitors or AT1-R antagonists. Conclusions —The AT2-R gene is not expressed in the skeletal muscle of patients with CHF. In the absence of detectable AT2-R gene transcripts, the AT2-R pathway is unlikely to contribute to the effects of AT1-R antagonists on the skeletal muscle vasculature in patients with severe CHF.
Intensive Lifestyle Changes for Reversal of Coronary Heart Disease
Authors: Dean Ornish
Journal: JAMA (1998)

The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year.To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease.Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design.Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography.Two tertiary care university medical centers.Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years.Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events.Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]).More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.
The role of leukotriene receptor antagonists in asthma
Authors: A. Low
Journal: Thorax (2011)

This study assessed the effectiveness of a leukotriene receptor antagonist (LTRA) in two pragmatic randomised controlled trials over a 2-year period in primary care practices across the UK. The first trial compared LTRAs with inhaled glucocorticoids as the first-line treatment in asthma. …
Newer Aspects of Diabetic Microangiopathy
Authors: J Berkman, H Rifkin
Journal: Annual Review of Medicine (1966)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Global gene expression profiling confirms the molecular fidelity of primary tumor-based orthotopic xenograft mouse models of medulloblastoma
Authors: Xiumei Zhao, Zhigang Liu, Litian Yu, Yujing Zhang, Patricia Baxter, Horatiu Voicu, Sivashankarappa Gurusiddappa, Joseph Luan, Jack M. Su, Hon-chiu Eastwood Leung, Xiao-Nan Li
Journal: Neuro-Oncology (2012)

We previously showed that primary tumor-based orthotopic xenograft mouse models of medulloblastoma replicated the histopathological phenotypes of patients' original tumors. Here, we performed global gene expression profiling of 11 patient-specific xenograft models to further determine whether the xenograft tumors were molecularly accurate during serial subtransplantations in mouse brains and whether they represented all the molecular subtypes of medulloblastoma that were recently described. Analysis of the transcriptomes of 9 pairs of matched passage I xenografts and patients' tumors revealed high correlation coefficients (r(2) > 0.95 in 5 models, > 0.9 in 3 models, and > 0.85 in 1 model) and only identified 69 genes in which expressions were altered (FDR = 0.0023). Subsequent pair-wise comparisons between passage I, III, and V xenografts from the 11 models further showed that no dramatic alterations were introduced (r(2) > 0.9 in 8 models and > 0.8 in 3 models). The genetic abnormalities of each model were then identified through comparison with control RNAs from 5 normal cerebella and 2 fetal brains. Hierarchical clustering using 3 previously published molecular signatures showed that our models span the whole spectrum of molecular subtypes, including SHH (n = 2), WNT (n = 2), and the most recently identified group C (n = 4) and group D (n = 3). In conclusion, we demonstrated that the 11 orthotopic medulloblastoma xenograft models were molecularly faithful to the primary tumors, and our comprehensive collection of molecularly distinct animal models should serve as a valuable resource for the development of new targeted therapies for medulloblastoma.
Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke
Authors: Marie Carlén, Konstantinos Meletis, Christian Göritz, Vladimer Darsalia, Emma Evergren, Kenji Tanigaki, Mario Amendola, Fanie Barnabé-Heider, Maggie S Y Yeung, Luigi Naldini, Tasuku Honjo, Zaal Kokaia, Oleg Shupliakov, Robert M Cassidy, Olle Lindvall, Jonas Frisén
Journal: Nature Neuroscience (2009)
Diagnostic value of performing chest x-rays in patients presenting with recent-onset arthritis
Authors: J K de Vries-Bouwstra, T W J Huizinga, L N Willems, A H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2011)

<b>Objectives</b> To develop reference values and centile charts for respiratory rate based on age and body temperature, and to determine how well these reference values can predict the presence of lower respiratory tract infections (LRTI) in children with fever. <b>Design</b> Prospective observational study. <b>Participants </b>Febrile children aged at least 1 month to just under 16 years (derivation population, n=1555; validation population, n=671) selected from patients attending paediatric emergency departments or assessment units in hospitals. <b>Setting</b> One hospital in the Netherlands in 2006 and 2008 (derivation population); one hospital in the Netherlands in 2003-05 and one hospital in the United Kingdom in 2005-06 (validation population). <b>Intervention</b> We used the derivation population to produce respiratory rate centile charts, and calculated 50th, 75th, 90th, and 97th centiles of respiratory rate at a specific body temperature. Multivariable regression analysis explored associations between respiratory rate, age, and temperature; results were validated in the validation population by calculating diagnostic performance measures, z scores, and corresponding centiles of children with diagnoses of pneumonic LRTI (as confirmed by chest radiograph), non-pneumonic LRTI, and non-LRTI. <b>Main outcome measure</b> Age, respiratory rate (breaths/min) and body temperature (°C), presence of LRTI. <b>Results</b> Respiratory rate increased overall by 2.2 breaths/min per 1°C rise (standard error 0.2) after accounting for age and temperature in the model. We observed no interactions between age, temperature, and respiratory rates. Age and temperature dependent cut-off values at the 97th centile were more useful for ruling in LRTI (specificity 0.94 (95% confidence interval 0.92 to 0.96), positive likelihood ratio 3.66 (2.34 to 5.73)) than existing respiratory rate thresholds such as Advanced Pediatrics Life Support values (0.53 (0.48 to 0.57), 1.59 (1.41 to 1.80)). However, centile cut-offs could not discriminate between pneumonic LRTI and non-pneumonic LRTI. <b>Conclusions</b> Age specific and temperature dependent centile charts describe new reference values for respiratory rate in children with fever. Cut-off values at the 97th centile were more useful in detecting the presence of LRTI than existing respiratory rate thresholds.
Van Gogh Had Meniere's Disease and Not Epilepsy
Authors: I. Kaufman Arenberg
Journal: JAMA (1990)

We intend to correct the historical error that Vincent Van Gogh's medical problems resulted from epilepsy plus madness, a diagnosis made during his life but for which no rigid criteria are apparent. Review of 796 personal letters to family and friends written between 1884 and his suicide in 1890 reveals a man constantly in control of his reason and suffering from severe repeated attacks of disabling vertigo, not a seizure disorder. His own diagnosis of epilepsy was made from the written diagnosis by Dr Peyron, the physician at the asylum of St Remy (France), wherein on May 9, 1889, Van Gogh voluntarily committed himself to the asylum for epileptics and lunatics. However, the clinical descriptions in his letters are those of a person suffering from Meniere's disease, not epilepsy. The authors point out that Prosper Meniere's description of his syndrome (an inner-ear disorder) was not well known when Van Gogh died and that it often was misdiagnosed as epilepsy well into the 20th century. (<i>JAMA</i>. 1990;264:491-493)
A Clinical Syndrome and EEG-Sleep Changes Associated with Amino Acid Deprivation
Authors: BOYD K. LESTER, RAUL E. CHANES, PAUL T. CONDIT
Journal: American Journal of Psychiatry (1969)

Sleep studies and psychiatric examinations were made on three patients with inoperable malignancies whose illnesses were being managed with an experimental low phenylalanine-tyrosine diet. There was a systematic reduction of REM sleep, supporting the findings of Jouvet suggesting that norepinephrine (a metabolic product of phenylalanine and tyrosine) has a role in the maintenance of REM sleep. The patients developed a reversible clinical syndrome manifested by indifference to their environment, lethargy, and impairment of long-term memory.
The epidermal growth factor receptor mediates allergic airway remodelling in the rat
Authors: M. Tamaoka, M. Hassan, T. McGovern, D. Ramos-Barbón, T. Jo, Y. Yoshizawa, B. Tolloczko, Q. Hamid, J. G. Martin
Journal: European Respiratory Journal (2008)

The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia. To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat). Brown Norway rats were sensitised to OVA and challenged three times at 5-day intervals to evoke airway remodelling. The effects of an epidermal growth factor (EGF) receptor inhibitor, AG1478, and a cysteinyl leukotriene-1 receptor antagonist, montelukast, on epithelial and airway smooth muscle (ASM) cell proliferation in vivo in response to repeated OVA challenge were tested. Three challenges with leukotriene (LT)D 4 were given, to examine their effects on remodelling with and without AG1478 pretreatment. OVA challenges caused ASM hyperplasia, with an increase in mass, epithelial cell proliferation and goblet cell proliferation. AG1478 prevented the changes, as did montelukast. Multiple OVA challenges increased heparin-binding EGF-like growth factor but not EGF expression by airway epithelium. LTD 4 reproduced the changes in remodelling induced by OVA and this was blocked by AG1478. Allergen-induced airway epithelial and airway smooth muscle remodelling is mediated by cysteinyl leukotrienes via the cysteinyl leukotriene-1 receptor with downstream effects on the epidermal growth factor receptor axis.
Circulating Progenitor Cells Can Be Reliably Identified on the Basis of Aldehyde Dehydrogenase Activity
Authors: Thomas J. Povsic, Katherine L. Zavodni, Francine L. Kelly, Shoukang Zhu, Pascal J. Goldschmidt-Clermont, Chunming Dong, Eric D. Peterson
Journal: Journal of the American College of Cardiology (2007)
Neural Progenitor Cell Lines Inhibit Rat Tumor Growth <b> <i>in Vivo</i> </b>
Authors: Karin Staflin, Gabriella Honeth, Suzanne Kalliomäki, Christian Kjellman, Klaus Edvardsen, Magnus Lindvall
Journal: Cancer Research (2004)

Abstract Current therapies for gliomas often fail to address their infiltrative nature. Conventional treatments leave behind small clusters of neoplastic cells, resulting in eventual tumor recurrence. In the present study, we have evaluated the antitumor activity of neural progenitor cells against gliomas when stereotactically injected into nucleus Caudatus of Fisher rats. We show that the rat neural progenitor cell lines HiB5 and ST14A, from embryonic hippocampus and striatum primordium, respectively, are able to prolong animal survival and, in 25% of the cases, completely inhibit the outgrowth of N29 glioma compared with control animals. Delayed tumor outgrowth was also seen when HiB5 cells were inoculated at the site of tumor growth 1 week after tumor inoculation or when a mixture of tumor cells and HiB5 cells were injected s.c. into Fisher rats. HiB5 cells were additionally coinoculated together with two alternative rat gliomas, N32 and N25. N32 was growth inhibited, but rats inoculated with N25 cells did not show a prolonged survival. To evaluate the possibility of the involvement of the immune system in the tumor outgrowth inhibition, we show that HiB5 cells do not evoke an immune response when injected into Fisher rats. Furthermore, the rat neural progenitor cells produce all transforming growth factor β isotypes, which could explain the observed immunosuppressive nature of these cells. Hence, some neural progenitor cells have the ability to inhibit tumor outgrowth when implanted into rats. These results indicate the usefulness of neural stem cells as therapeutically effective cells for the treatment of intracranial tumors.
Elevated Levels of Circulating Procoagulant Microparticles in Patients With Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia
Authors: Bénédicte Hugel, Gérard Socié, Thi Vu, Florence Toti, Eliane Gluckman, Jean-Marie Freyssinet, Marie-Lorraine Scrobohaci
Journal: Blood (1999)
PURE CULTIVATION OF SPIROCHÆTA REFRINGENS
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1912)

A strain of Spirochoeta refringens has been obtained in pure culture, and its morphological and cultural characteristics have been studied. The strain possessed no pathogenicity for rabbits or monkeys. It probably belongs to the genus Treponema, but it is easily differentiated from Treponema pallidum, Treponema microdentium, and Treponema macrodentium. Its relation to Spirochoeta balanitidis and Spirochoeta buccalis is still undetermined.
Some doctors left in charge of 400 patients at night, study shows
Authors: A. O'Dowd
Journal: BMJ (2010)

Doctors providing medical cover at night are sometimes left in charge of as many as 400 patients, report findings released from an as yet unpublished study.

Figures from the Royal College of Physicians study found large variations in the provision of medical cover in hospitals at night in terms of number of patients and the seniority of the doctor in charge.

The college and doctors’ leaders have both called for urgent action as they said the figures raised grave concerns about how patient safety could be guaranteed in all cases.

The full study will be published in Clinical Medicine , the college’s own journal, in August, but …