tbuckley/cabot-search huggingface dataset:
A Multitargeted, Metronomic, and Maximum-Tolerated Dose “Chemo-Switch” Regimen is Antiangiogenic, Producing Objective Responses and Survival Benefit in a Mouse Model of Cancer
Authors: Kristian Pietras, Douglas Hanahan
Journal: Journal of Clinical Oncology (2004)

A transgenic mouse model has revealed parameters of the angiogenic switch during multistep tumorigenesis of pancreatic islets, and demonstrated efficacy of antiangiogenic therapies. Pericytes have been revealed as functionally important for tumor neovasculature, using kinase inhibitors targeting their platelet-derived growth factor receptors (PDGFRs). Additionally, vascular endothelial growth factor receptor (VEGFR) inhibitors and metronomic chemotherapy show modest benefit against early- but not late-stage disease.Seeking to improve efficacy against otherwise intractable end-stage pancreatic islet tumors, two receptor tyrosine kinase inhibitors, imatinib and SU11248, were used to disrupt PDGFR-mediated pericyte support of tumor endothelial cells in concert with maximum-tolerated dose (MTD) or metronomic chemotherapy and/or VEGFR inhibition.Imatinib, despite equivocal efficacy as monotherapy, reduced pericyte coverage of tumor vessels and enhanced efficacy in combination with metronomic chemotherapy or VEGFR inhibition. A regimen involving all three was even better. MTD using cyclophosphamide caused transitory regression, but then rapid regrowth, in contrast to metronomic cyclophosphamide plus imatinib, which produced stable disease. The MTD regimen elicited apoptosis of tumor cells but not endothelial cells, whereas the other regimens increased endothelial cell apoptosis concordant with efficacy. A "chemo-switch" protocol, involving sequential MTD and then metronomic chemotherapy, overlaid with multitargeted inhibition of PDGFR and VEGFR, gave complete responses and unprecedented survival advantage in this model.This study demonstrates a potentially tractable clinical strategy in a stringent preclinical model, wherein standard-of-care chemotherapy is followed by a novel maintenance regimen: PDFGR is targeted to disrupt pericyte support, while metronomic chemotherapy and/or VEGFR inhibitors target consequently sensitized endothelial cells, collectively destabilizing pre-existing tumor vasculature and inhibiting ongoing angiogenesis.
Two Tiers of Physicians in France
Authors: Paul C. Sorum
Journal: JAMA (1998)

5 The 40% to 50% of the medical students who, at the end of medical school, pass the rigorous entrance exami- nation to the internat (the residency track to train specialists) have higher status than those who enter the generalist track (the residanat). Specialists also spend a longer time in resi- dency training than do generalists (4-5 years as opposed to 2.5 years), earn more money when they enter practice, and have the possibility of becoming academic physicians. Most of the clinical training of medical students and residents, even of future generalists, occurs within university hospitals and to a lesser extent nonuniversity hospitals under the tutelage of specialists and subspecialists. Except for the recent require- ment for residents in the generalist track to spend 4 to 6 months in a generalist's private office, 6 French physicians have not started to move training into ambulatory settings. Generalists, who comprise 50% of all physicians and 60% of private practitioners, 3(p109) dominate primary care in France. Few specialists provide primary care, unlike in the United States and Germany. 7 Primary care physicians seldom take care of their hospitalized patients; this care is provided by specialists or subspecialists, who are either private practition- ers or salaried hospital employees (including the teaching fac- ulty in the university medical centers). The specialists and subspecialists in the hospital are not consultants, therefore, but rather assume full control. In this way, the French medical system is similar to those of England, Germany, and Italy. 4,7,8
Giant Sternal Condrosarcoma
Authors: Augustin Pirvu, Oana Pop, Julie Villa, Linda Sakhri, Anne Claire Toffart
Journal: Journal of Thoracic Oncology (2012)

A 57-year-old man, without any medical history, was referred to our department for a giant presternal mass (Fig.1). The tumor was known for 5 years. The computed tomography showed a heterogeneous structure, infiltrating the sternal insertions of both pectoralis major muscles (Fig 2). The Tc 90 whole body scintigraphy shows a single lesion in the middle of sternum.FIGURE 2Computed tomography scan: bulky tumor mass in the presternal soft tissue with maximum diameter of 25.8/30.3 cm (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT) After a negative search for metastasis, we performed a radical resection. The pathologic examination reveals a chondrosarcoma, with intense necrosis and hemorrhage. The tumor invades the cartilages and bone tissue of the sternum and of two adjacent ribs cartilages. The resection margins do not show signs of neoplasic infiltration. Today, the patient is without recurrence, 3 years after surgery. Chest wall tumors are complex conditions requiring a interdisciplinary discussion.1Kachroo P Pak PS Sandha HS et al.Single-institution, multidisciplinary experience with surgical resection of primary chest wall sarcomas.J Thorac Oncol. 2012; 7: 552-558Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar
Examination of Young Children with Acute Appendicitis
Authors: R. Strang
Journal: BMJ (1950)

CASE 2This patient, aged 29, was at the 15th week of her third pregnancy when admitted here on March 31, 1949, having been ill with meningitis for ten days.Her cerebrospinal fluid was clear and showed protein 120 mg.% ; cells 147 (all lymphocytes);
The basement membrane zone of the nail
Authors: R.D. SINCLAIR, F. WOJNAROWSKA, I.M. LEIGH, R.P.R. DAWBER
Journal: British Journal of Dermatology (2006)

The anatomy of the epidermis, dermis and subcutaneous tissues of the nail apparatus is distinct from that of non-appendageal skin. Apart from the demonstration of the longitudinal configuration of the dermal-epidermal junction of the nail bed, there have been no studies of the composition of the basement membrane zone of the nail apparatus. We obtained three human accessory digits, including one thumb, all of which had been amputated for cosmetic reasons, and were without known pathology. Specimens were stained with a battery of monoclonal and polyclonal antibodies which target normal basement membrane zone antigens, and studied by indirect immunoflourescence. This study demonstrated that the four distinct regions of the nail, namely the proximal nail fold, the nail matrix, the nail bed and the hyponychium expressed all the target antigens found in the normal non-appendageal basement membrane. In particular, there was normal expression of the epidermal-associated antigens, the 220-and 180-kDa bullous pemphigoid antigens, and the α6β4 integrin. There was also normal expression of the lamina lucida antigens LH39, GB3 and laminin. It is of interest that the dermal-associated components, namely the 285-kDa linear IgA antigen, the extracellular matrix glycoproteins chondroitin sulphate, type VII collagen and its closely associated proteins, and the poorly characterized antigen for LH24 and LH39 were all normally expressed.Fibronectin, which is not a normal basement membrane zone component, was diffusely expressed in the extracellular matrix, but did not accentuate the basement membrane zone. LHF2, an antibody raised against tenascin, which shows weak positive staining at the tips of dermal papillae in normal skin (unpublished data) diffusely stained the extracellular matrix and the tips of the dermal papillae of the nail matrix and hyponychium, but did not stain the basement membrane of the nail bed. These findings show that despite the numerous distinct features of epidermis, dermis and subcutis of the nail apparatus, the basement membrane zone has virtually identical antigen expression to that of the dermal-epidermal junction elsewhere. The difference in LHF2 expression in the nail bed most likely reflects the different shape of the nail bed basement membrane, which is arranged in longitudinal folds.
Hospital Characteristics and Mortality Rates
Authors: Arthur J. Hartz, Henry Krakauer, Evelyn M. Kuhn, Mark Young, Steven J. Jacobsen, Greer Gay, Larry Muenz, Myron Katzoff, R. Clifton Bailey, Alfred A. Rimm
Journal: New England Journal of Medicine (1989)

Abstract The Health Care Financing Administration (HCFA) publishes hospital mortality rates each year. We undertook a study to identify characteristics of hospitals associated with variations in these rates. To do so, we obtained data on 3100 hospitals from the 1986 HCFA mortality study and the American Hospital Association's 1986 annual survey of hospitals. The mortality rates were adjusted for each hospital's case mix and other characteristics of its patients. The mortality rate for all hospitalizations was 116 per 1000 patients. Adjusted mortality rates were significantly higher for for-profit hospitals (121 per 1000) and public hospitals (120 per 1000) than for private not-for-profit hospitals (114 per 1000; P<0.0001 for both comparisons). Osteopathic hospitals also had an adjusted mortality rate that was significantly higher than average (129 per 1000; P<0.0001). Private teaching hospitals had a significantly lower adjusted mortality rate (108 per 1000) than private nonteaching hospitals (116 per 1000; P<0.0001). Adjusted mortality rates were also compared for hospitals in the upper and lower fourths of the sample in terms of certain hospital characteristics. The mortality rates were 112 and 121 per 1000 for the hospitals in the upper and lower fourths, respectively, in terms of the percentage of physicians who were board-certified specialists (P<0.0001), 112 and 120 per 1000 for occupancy rate (P<0.0001), 113 and 120 per 1000 for payroll expenses per hospital bed (P<0.0001), and 113 and 119 per 1000 for the percentage of nurses who were registered (P<0.0001). (N Engl J Med 1989; 321: 1720–5.)
Workers' health protection still poor two years after factory collapse in Bangladesh
Authors: J. Clark
Journal: BMJ (2015)

Two years after the Rana Plaza catastrophe that left over 1100 mostly women garment workers dead and more than 2500 injured, a new report has said that improvements promised by the government and companies have not been enough to improve the working conditions, rights, and health of workers.

The eight storey building outside Dhaka, Bangladesh, which housed several clothing factories supplying global brands such as Benetton, Primark, and Walmart, collapsed on 24 April 2013 in one of the world’s worst industrial disasters.

The charity Human Rights Watch released the report on 22 April in Dhaka, detailing the experiences of garment workers, which included verbal abuse, physical assault, and threats of sexual violence.1 The workers, the vast majority of whom are women, are denied breaks to use the toilet and often do not have …
Abstract 2492: Protein phosphatase PP6 regulates the sensitivity of glioblastoma cells to radiation
Authors: Ying Shen, Xin Fei, Yongbin Wang, Xianming Kong, Yongming Qiu, Jun Mi
Journal: Cancer Research (2011)

Abstract Glioblastoma is one of most aggressive primary tumors. The average survival time of GBM patients is 12 months; moreover, GBM is highly resistant to radiotherapy and chemotherapy, so, how to increase the sensitivity of GBM cells to radiotherapy is still a challenging to all oncologists. Our study demonstrate serine/threonine protein phosphatase PP6 is associated with the radioresistance of glioblastoma (GBM) cells, and the expression level of PP6c (PP6 catalytic subunit) is highly correlated with the survival time of GBM patients (R2 = -0.7). Lentiviruses-mediated PP6c knocking down increases the radiosensitivity of glioblastoma in xenografted mouse model, and prolong the survival time of tumor-bearing mouse; while the overexpression of PP6c decreases the radiosensitivity of glioblastoma and shortens the survival time of tumor-bearing mouse. Our data also show the PP6 is complexed with DNA-PK by the co-immunoprecipitation assay, the siRNA knock-down of PP6c inhibits DNA damage-induced DNA-PK activation and DNA-repair capacity, and sensitized the U251, T98G, U87 three cell lines to radiation in vitro. These results strongly suggest PP6 is a therapeutic target for radiosensitization. Key Words: DNA-PK, PP6, ubiquitination, radiosensitivity, GBM Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2492. doi:10.1158/1538-7445.AM2011-2492
Rapamycin, anti-aging, and avoiding the fate of Tithonus
Authors: Arlan Richardson
Journal: Journal of Clinical Investigation (2013)

The discovery that rapamycin increased the lifespan of mice was recognized by Science as one of the top 10 scientific breakthroughs of 2009. In addition to increasing lifespan, Neff and colleagues show that while rapamycin improves several functions/pathologies that change with age, it has little effect on the majority of the physiological and structural parameters they evaluated. What do these data tell us about the ability of rapamycin to delay aging and improve quality of life, i.e., prevent the fate of Tithonus?
A memorable book: From magic to science
Authors: J. Pollert
Journal: BMJ (1997)

I graduated in Prague, Czechoslovakia, in 1939 one month before the Czech capital was occupied by the Nazis. I was lucky to escape to Palestine, where I joined the Czechoslovak Army, later to be transferred to the Royal Army Medical Corps. In order to acquaint myself with the British pharmacopoeia—somewhat different from the central European one—I looked up in the hospital's small library a textbook of clinical pharmacology. It was …
Reentrant excitation around a fixed obstacle in uniform anisotropic ventricular myocardium.
Authors: J Brugada, L Boersma, C J Kirchhof, V V Heynen, M A Allessie
Journal: Circulation (1991)

BACKGROUND The purpose of this study was to investigate the role of tissue anisotropy and dispersion of refractoriness on initiation of reentrant ventricular tachycardia (VT). METHODS AND RESULTS A ring of perfused uniform anisotropic ventricular epicardium in Langendorff-perfused rabbit hearts was created by an endocardial freezing technique. High-resolution mapping (248 channels) was used to analyze epicardial activation of the left ventricle. One to three premature beats were induced at a total of 272 points in 17 experiments (16 different points around the ring in each experiment). Reentrant VT could be initiated at 43 of the 272 points tested. The cycle length of VT was stable and ranged from 128 to 198 msec (mean, 161 +/- 19 msec). Correlation between conduction velocity and the angle between the circulating activation wave and epicardial fiber orientation showed that in segments of the ring where conduction was perpendicular to the fiber axis, mean conduction velocity was 25 +/- 5 cm/sec compared with 60 +/- 7 cm/sec when conduction was parallel to the fiber orientation. Analysis of the site of unidirectional conduction block showed that in 41 of 43 cases, block occurred while the impulse was propagating parallel to the fiber orientation. Measurement of the refractory periods at either side of the line of unidirectional block showed that only in 12 of 43 cases did block occur while the impulse was propagating into an area with a longer (more than 10 msec) refractory period. CONCLUSIONS In uniform anisotropic ventricular myocardium, reentrant VT is initiated because lowering the stimulating efficacy of the depolarization wave by premature beats leads to preferential conduction block parallel to the fiber orientation.
Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes
Authors: Kenneth L. Scott, Cristina Nogueira, Timothy P. Heffernan, Remco van Doorn, Sabin Dhakal, Jason A. Hanna, Chengyin Min, Mariela Jaskelioff, Yonghong Xiao, Chang-Jiun Wu, Lisa A. Cameron, Samuel R. Perry, Rhamy Zeid, Tamar Feinberg, Minjung Kim, George Vande Woude, Scott R. Granter, Marcus Bosenberg, Gerald C. Chu, Ronald A. DePinho, David L. Rimm, Lynda Chin
Journal: Cancer Cell (2011)
Increase of Gi alpha in human hearts with dilated but not ischemic cardiomyopathy.
Authors: M Böhm, P Gierschik, K H Jakobs, B Pieske, P Schnabel, M Ungerer, E Erdmann
Journal: Circulation (1990)

In myocardial membranes from hearts with dilated cardiomyopathy (DCM), there was a 37% increase of the Gi alpha-protein as measured by 32P-ADP-ribosylation of a approximately 40 kDa pertussis toxin substrate. Immunoblotting techniques also showed increased amounts of Gi alpha in DCM. In hearts with ischemic cardiomyopathy (ICM), Gi alpha was not altered compared with nonfailing myocardium (NF). Basal and Gpp(NH)p-stimulated adenylate cyclase activity was reduced in DCM but not in ICM. The number of beta-adrenoceptors was similarly reduced both in DCM and ICM compared with NF. Alterations of m-cholinoceptors or A1-adenosine receptors did not occur. Consistently, "indirect" negative inotropic effects of the m-cholinoceptor agonist carbachol and the A1-adenosine receptor agonist R-PIA were not different in ICM, DCM, and nonfailing myocardium. In ICM and DCM, there was a marked reduction of the positive inotropic responses to isoprenaline and milrinone. However, there was a further reduction in DCM compared with ICM. It is concluded that the increase of Gi alpha is accompanied by a reduction of basal and guanine-nucleotide-stimulated adenylate cyclase activity. Alterations of m-cholinoceptors and A1-adenosine receptors do not appear to be involved. The further decrease of the positive inotropic effects of isoprenaline and milrinone in DCM provides evidence that the increase of Gi alpha is functionally relevant in DCM but not ICM and hence might contribute to the reduced effects of endogenous catecholamines and exogenous cAMP-dependent positive inotropic agents in the former but not the latter condition.
THE WOODBRIDGE TREATMENT OF TYPHOID FEVER.
Authors: W. BAYARD SHIELDS
Journal: JAMA (1896)

A good deal of attention has been paid to articles which have appeared at various times in the last few years in theJournal of the American Medical Associationby Dr. J. E Woodbridge, of Youngstown, Ohio, one of the trustees of theAssociation, in regard to his treatment of typhoid fever. This treatment is according to a method based on the inhibitory influence which antiseptics frequently administered have on the typhoid bacilli in the intestinal canal, checking their activity, hence preventing the rapid and abundant development of toxins, the absorption of which into the system produces the grave nervous troubles so frequently seen in this disease. That the absorption of the toxins formed by the destructive and putrefactive action of the typhoid bacilli is the cause of the nervous symptoms in this disease seems beyond a doubt in my mind, and not, as has been assumed by Liebermeister, to
Functional defects in NOD2 signaling in experimental and human Crohn disease
Authors: Daniele Corridoni, Kristen O Arseneau, Fabio Cominelli
Journal: Gut Microbes (2014)

Increasing evidence suggests that a deficit in innate immunity may play a causative role in the pathogenesis of inflammatory bowel disease. The most compelling support for this hypothesis comes from the genetic association of Crohn disease (CD) with carriage of polymorphisms within the NOD2 gene, which represent the most frequent genetic defect in CD. Our findings suggest that SAMP1/YitFc mice, which develop CD-like ileitis in the absence of NOD2 genetic mutations, fail to respond to MDP administration by displaying decreased innate cytokine production and impaired bacterial clearance before the onset of disease. This provides evidence that dysregulated NOD2 signaling, genetic or functional in nature, predisposes to chronic intestinal inflammation, and supports a new paradigm that CD may occur from a deficit in innate immunity as opposed to an overly aggressive immune response. This new paradigm could lead to potential development of new preventative or therapeutic modalities for patients with CD.
The Precision Medicine Initiative
Authors: Euan A. Ashley
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro.
Authors: S Markowicz, E G Engleman
Journal: Journal of Clinical Investigation (1990)

Interest in human dendritic cells (DC) has been heightened recently by the discovery that this cell type is a primary target of the human immunodeficiency virus, the causative agent of AIDS. DC are bone marrow-derived cells with an extraordinarily potent ability to promote the immunological activity of T lymphocytes. Unfortunately, since DC constitute less than 0.5% of peripheral blood mononuclear cells and die within a few days of their isolation, they are not readily accessible to study. We report here that granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine with well-recognized effects on granulocyte and macrophage maturation, profoundly affects the morphology and viability of DC isolated from peripheral blood. GM-CSF not only promotes DC survival but also induces DC differentiation to mobile, reversibly adherent cells with long-branched projections. DC cultured in GM-CSF survive for up to 6 wk and retain their ability to stimulate the proliferation of T cells in allogeneic and autologous mixed leukocyte reactions.
ENFORCEMENT OF MEDICAL LAWS DEPENDENT ON AN ORGANIZED PROFESSION.
Authors: T. J. HAPPEL
Journal: JAMA (1901)

The question of medical legislation has been an open one for a time sufficiently long for thinking men of the profession to have become thoroughly conversant with it, but every member of an examining board soon becomes aware of the fact that many physicians in states having good laws by which to regulate the practice of medicine, know practically nothing about them. In some cases a few of the best men of the profession openly oppose medical legislation, laying down the broad proposition that every man should be allowed to do as he pleases in this free land of ours, employing if he wishes any one claiming to be a practitioner of medicine regardless of qualifications. Others take the position that the possession of a diploma from a medical college in so-called good standing and the registration of this diploma should be the only requirement demanded of them, taking the