tbuckley/cabot-search huggingface dataset:
Breast Cancer Cells in Three-dimensional Culture Display an Enhanced Radioresponse after Coordinate Targeting of Integrin α5β1 and Fibronectin
Authors: Jin-Min Nam, Yasuhito Onodera, Mina J. Bissell, Catherine C. Park
Journal: Cancer Research (2010)

Tactics to selectively enhance cancer radioresponse are of great interest. Cancer cells actively elaborate and remodel their extracellular matrix (ECM) to aid in survival and progression. Previous work has shown that beta1-integrin inhibitory antibodies can enhance the growth-inhibitory and apoptotic responses of human breast cancer cell lines to ionizing radiation, either when cells are cultured in three-dimensional laminin-rich ECM (3D lrECM) or grown as xenografts in mice. Here, we show that a specific alpha heterodimer of beta1-integrin preferentially mediates a prosurvival signal in human breast cancer cells that can be specifically targeted for therapy. 3D lrECM culture conditions were used to compare alpha-integrin heterodimer expression in malignant and nonmalignant cell lines. Under these conditions, we found that expression of alpha5beta1-integrin was upregulated in malignant cells compared with nonmalignant breast cells. Similarly, we found that normal and oncofetal splice variants of fibronectin, the primary ECM ligand of alpha5beta1-integrin, were also strikingly upregulated in malignant cell lines compared with nonmalignant acini. Cell treatment with a peptide that disrupts the interactions of alpha5beta1-integrin with fibronectin promoted apoptosis in malignant cells and further heightened the apoptotic effects of radiation. In support of these results, an analysis of gene expression array data from breast cancer patients revealed an association of high levels of alpha5-integrin expression with decreased survival. Our findings offer preclinical validation of fibronectin and alpha5beta1-integrin as targets for breast cancer therapy.
Acute myeloblastic leukemia with hyperleukocytosis: Risk factors for early mortality in induction
Authors: Gerard J. Ventura, Jeane P. Hester, Terry L. Smith, Michael J. Keating
Journal: American Journal of Hematology (1988)

Eighty-five patients with acute myeloblastic leukemia (AML) presenting with hyperleukocytosis (HL) were analyzed to assess morbidity and mortality in early induction. Patients who failed to achieve remission were older and more often had pulmonary leukostasis (62% vs 23%, p = .01) and hepatomegaly (54% vs 31%, p = .06) at presentation. Thirty-seven patients (44%) did not achieve complete remission (CR); 17 (54%) died early in induction therapy, 11 directly as a result of pulmonary hemorrhage with respiratory failure, while 5 had both pulmonary hemorrhage with respiratory failure and CNS hemorrhage. Early death patients were older and more often had pulmonary leukostasis (88% vs 29%, p less than .0001), hepatomegaly (71% vs 34%, p = .01), hyperbilirubinemia (60% vs 16%, p = .01) and hypofibrinogenemia (47% vs 12%, p less than .01) at presentation. Primarily for technical reasons, preinduction leukapheresis was not employed as often in this very-high-risk group as in other patients (56% vs 82%, respectively). Thus, sufficient heterogeneity exists in patients presenting with HL to define a subset of patients at particularly high risk for early mortality. Preinduction leukapheresis applied in a prospective controlled fashion should be evaluated to assess if such treatment may decrease early mortality in this group.
Patients' Experiences With Care for Lung Cancer and Colorectal Cancer: Findings From the Cancer Care Outcomes Research and Surveillance Consortium
Authors: John Z. Ayanian, Alan M. Zaslavsky, Neeraj K. Arora, Katherine L. Kahn, Jennifer L. Malin, Patricia A. Ganz, Michelle van Ryn, Mark C. Hornbrook, Catarina I. Kiefe, Yulei He, Julie M. Urmie, Jane C. Weeks, David P. Harrington
Journal: Journal of Clinical Oncology (2010)

To assess patients' experiences with cancer care, ratings of their quality of care, and correlates of these assessments.For 4,093 patients with lung cancer and 3,685 patients with colorectal cancer in multiple US regions and health care delivery systems, we conducted telephone surveys of patients or their surrogates in English, Spanish, or Chinese at 4 to 7 months after diagnosis. The surveys assessed ratings of the overall quality of cancer care and experiences with three domains of interpersonal care (physician communication, nursing care, and coordination and responsiveness of care).English-speaking Asian/Pacific Islander patients and Chinese-speaking patients and those in worse health reported significantly worse adjusted experiences with all three domains of interpersonal care, whereas white, black, and Hispanic patients reported generally similar experiences with interpersonal care. The overall quality of cancer care was rated as excellent by 44.4% of patients with lung cancer and 53.0% of patients with colorectal cancer, and these ratings were most strongly correlated with positive experiences with coordination and responsiveness of care (Spearman rank coefficients of 0.49 and 0.42 for lung and colorectal cancer, respectively). After multivariate adjustment, excellent ratings were less common for each cancer among black patients, English-speaking Asian/Pacific Islander patients, Chinese-speaking patients, and patients reporting worse health status (all P ≤ .05).Patients' reports and ratings of care differed significantly by race, language, and health status. Efforts to improve patients' experiences with cancer care should focus on problems affecting Asian and Pacific Islander patients and those in worse health.
Is surveillance of the small bowel indicated for Lynch syndrome families?
Authors: G L ten Kate, J H Kleibeuker, F M Nagengast, M Craanen, A Cats, F H Menko, H F A Vasen
Journal: Gut (2007)

Small bowel cancer (SBC) is one of the tumours associated with Lynch syndrome (LS). To advise on screening for this tumour it is paramount to be informed about the lifetime risk. The aim of this study was to calculate the lifetime risk of SBC in LS and to identify possible risk factors.Clinical and pathological data were collected on 1496 proven or putative carriers of a mismatch repair gene mutation from 189 families. Kaplan-Meier survival analysis was used to calculate the lifetime risk and to assess potential risk factors.28 (1.9%) of the 1496 (putative) mutation carriers were identified with SBC. The median age at diagnosis was 52 years (range 23-69 years). The lifetime risk of developing SBC was 4.2%. There was no difference in risk between males and females (log rank: p = 0.2470), or between MLH1 and MSH2 mutation carriers (log rank: p = 0.2754). SBC was not observed in MSH6 mutation carriers (n = 203). The previous occurrence of colorectal cancer and a family history of SBC did not increase the risk significantly.Approximately, one out of 25 mutation carriers will develop SBC during life. No specific risk factors were identified. The risk appeared to be too low to advise screening by means of an invasive burdensome procedure like double balloon enteroscopy. However, screening by a non-invasive procedure (videocapsule endoscopy) might be considered if future studies will show its cost effectiveness. In patients with unexplained abdominal complaints and/or unexplained iron deficiency anaemia SBC should be considered.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Edwin D. Kilbourne
Journal: The Journal of Experimental Medicine (1957)

The administration of cortisone to chicken embryos infected with influenza B virus results in (a) an initial inhibition of viral synthesis and (b) an eventual increase in the final yield of virus attained. Increased yields of virus are attained regardless of the number of viral particles in the infecting inoculum or the proportion of particles which are infective. Changes in the distribution ratios of allantoic fluid and intramembrane virus are effected by cortisone only as the secondary result of reduction in viral synthesis. The manifest effect of cortisone on influenza A virus increase is inhibitory unless inocula containing relatively high proportions of inactive viral particles are used.
In vitro stimulation of pancreatic enzyme discharge by calcium.
Authors: P Layer, J Hotz, L Cherian, H Goebell
Journal: Gut (1987)

The mechanism for acute hypercalcaemia increasing pancreatic enzyme secretion is unknown. To determine if raised extracellular calcium concentrations can directly stimulate pancreatic enzyme output, we measured discharges of pulse labelled protein and chymotrypsin from isolated cat pancreatic lobules in the presence of normal and raised calcium concentrations. Incubation in 5.0 mmol/l calcium increased discharges of pulse labelled protein (four fold), chymotrypsin (2.5 fold) and amylase (2.2 fold), compared with control experiments with 2.5 mmol/l calcium (p less than 0.001). This effect was similar to the maximal effect of carbachol or caerulein. Compared with 5.0 mmol/l calcium, incubation at the higher calcium concentration of 10.0 mmol/l induced similar discharges of chymotrypsin and amylase, whereas the increase in discharge of pulse labelled protein was smaller (p less than 0.01). The effects of raised calcium were not altered by atropine. Incubation in a high calcium medium did not impair pancreatic acinar response to subsequent stimulation with carbachol, but incubation in hypothermia abolished the effects of high calcium concentrations, suggesting that increased enzyme discharge is caused by stimulation of secretion not to cell damage. These data are consistent with a direct stimulatory effect of raised extracellular calcium concentrations on pancreatic acinar cell function.
Paediatric patients with a tracheostomy: a multicentre epidemiological study
Authors: Estela Pérez-Ruiz, Pilar Caro, Javier Pérez-Frías, Maria Cols, Isabel Barrio, Alba Torrent, Maria Ángeles García, Oscar Asensio, Maria Dolores Pastor, Carmen Luna, Javier Torres, Borja Osona, Antonio Salcedo, Amparo Escribano, Isidoro Cortell, Mirella Gaboli, Alfredo Valenzuela, Elena Álvarez, Rosa Velasco, Enrique García
Journal: European Respiratory Journal (2012)

Changes in the indications for tracheostomy in children have led to the progressively greater involvement of the paediatric pulmonologist in the care of these patients. The aim of this study was to review the current profile of tracheostomised children in Spain. We undertook a longitudinal, multicentre study over 2 yrs (2008 and 2009) of all patients aged between 1 day and 18 yrs who had a tracheostomy. The study, involving 18 Spanish hospitals, included 249 patients, of whom 150 (60.2%) were &lt;1 yr of age. The main indications for the procedure were prolonged ventilation (n=156, 62.6%), acquired subglottic stenosis (n=34, 13.6%), congenital or acquired craniofacial anomalies (n=25, 10%) and congenital airway anomalies (n=24, 9.6%). The most frequent underlying disorders were neurological diseases (n=126, 50.6%) and respiratory diseases (n=98, 39.3%). Over the 2-yr study period, 92 (36.9%) children required ventilatory support, and decannulation was achieved in 59 (23.7%). Complications arose in 117 patients (46.9%). Mortality attributed to the underlying condition was 12.5% and that related directly to the tracheostomy was 3.2%. Respiratory complexity of tracheostomised children necessitates prolonged, multidisciplinary follow-up, which can often extend to adulthood.
Pirfenidone therapy for patients with progressive idiopathic pulmonary fibrosis
Authors: Franziska Ihle, Tobias Veith, Zimmermann Gregor, Wypior Gabriela, Behr Juergen, Neurohr Claus
Journal: European Respiratory Journal (2014)

Background: The aim of this observational study was to evaluate pirfenidone in patients with progressive idiopathic pulmonary fibrosis (IPF).

Methods: Patients were evaluated by repetitive pulmonary function testing (PFT) 6 months prior and minimum 6 months during pirfenidone therapy. A decrease of the Forced Vital Capacity (FVC) >5%pred. and/or a diffusing capacity for carbon monoxide (DLCO) >10%pred. was defined as IPF progression (treatment non-responder). Student's T Test was used to assessdifferences in PFT values.

Results : 31 consecutive patients (age 61±9.0years; 22male [71%]) received pirfenidone. Before the start of pirfenidone FVC%pred., DLCO and oxygen partial pressure were 59.9%pred., 33.5%pred. and 58.1 mmHg, respectively. The mean loss of FVC before the administration period did not differ significantly between responder (n=21, 68%) and non-responder (n=10; 32%; -2.18±5.78 % pred. vs. -1.73 ± 5.92%pred., p=0.843). However, at the end of the observation the FVC loss of responders was significantly less compared to non-responders (1.52±4.62%pred. vs -7.41±2.39%pred., p<0.001). Moreover, there was a significant decline of the FVC within the non-responder group (-1.73±5.92%pred. vs -7.41±2.39%pred., p=0.021). The intra-individual course of the responder group tend to increase without reaching statistical significance (-2.18±5.78%pred. vs 1.52±4.62%pred., p=0.085).

Conclusions: Our data suggest that the majority of progressive IPF patients respond to pirfenidone therapywithin the study period.
Anti-interleukin 6 receptor therapy as rescue treatment for giant cell arteritis
Authors: Christian Beyer, Roland Axmann, Enijad Sahinbegovic, Jörg H Distler, Bernhard Manger, Georg Schett, Jochen Zwerina
Journal: Annals of the Rheumatic Diseases (2011)

Treatment options for giant cell arteritis (GCA) are limited. Glucocorticoids are the mainstay of therapy, but relapses are common and often necessitate high cumulative doses of glucocorticoids.1,–,4 Interleukin 6 (IL-6) might be a key mediator of vascular inflammation in patients with GCA. Temporal artery biopsy samples show enhanced IL-6 production,5 and IL-6 levels generally correlate with disease activity.6 This prompted us to investigate the effects of anti-IL-6 receptor therapy with tocilizumab in three patients with refractory GCA.

Our first patient (79-year-old male) suffered from fever, night sweats and weight loss. Inflammation markers were elevated (C reactive protein (CRP) 168 mg/l), temporal artery biopsy showed typical histological signs and positron emission tomography (PET)/CT scans demonstrated large-vessel vasculitis (figure 1). Despite excellent initial response, we could not taper prednisone to doses less than 30 mg/day. Since methotrexate was contraindicated (chronic renal failure), we added azathioprine without clinical improvement.



Figure 1 
PET/CT scans before and after tocilizumab …
Autonomic Influences on Cardiac Function in the Newborn Lamb
Authors: S. EVANS DOWNING, THOMAS H. GARDNER, ROBERT T. SOLIS
Journal: Circulation Research (1966)

The influences of reflexly induced changes of sympathetic outflow to the heart on left ventricle contractility, heart rate, and systemic vascular resistance were studied in 26 technically successful experiments with newborn lambs ranging in age from 1 to 11 days. Reduction of brachiocephalic artery perfusion pressure was associated with a large increase of heart rate and of systemic vascular resistance. Under conditions of constant aortic pressure, heart rate and cardiac output, cephalic hypotension in most preparations induced a rapid onset of a fall of left ventricular end-diastolic pressure and an increase in the maximal rate of rise of left ventricular pressure (dp/dt max). Ventricular function curves obtained under conditions of constant aortic pressure and heart rate were shifted to the left. The average increase of stroke volume at left ventricular end-diastolic pressure of 10 cm H 2 O (SV 10 ) was 23.3%, and of dp/dt max was 30.7% in the reactive preparations. The average of the largest responses for each preparation was an increase of SV 10 of 42%, and for left ventricular dp/dt max, 48.8%. Three preparations previously subjected to carotid sinus nerve sectioning showed similar responses. No evidence for diminution of the response following parasympathetic blockade with atropine was found. In all preparations, ganglionic blockade virtually or completely eliminated the response.
The classification, functions and clinical use of different isoforms of HCG
Authors: Ulf-Håkan Stenman, Aila Tiitinen, Henrik Alfthan, Leena Valmu
Journal: Human Reproduction Update (2006)

HCG is composed of two subunits, HCGalpha and HCGbeta. During early pregnancy, HCG stimulates progesterone production in the corpus luteum, and injection of HCG is widely used to induce ovulation in assisted reproduction treatment (ART). Under experimental conditions, the free subunits have been shown to exert functions other than those of HCG, but the relevance of these remains to be determined. Intact HCG, free subunits and degraded forms of these occur in biological fluids, and determinations of these are important for diagnosis and monitoring of pregnancy, pregnancy-related disorders and several types of cancer. Development of optimal methods for the various forms has been hampered by lack of appropriate standards and expression of the concentrations of the various forms in units that are not comparable. Furthermore, the nomenclature for HCG assays is confusing and in some cases misleading. These problems can now be solved; a uniform nomenclature has been established, and new standards are available for HCG, its subunits HCGalpha and HCGbeta, the partially degraded or nicked forms of HCG and HCGbeta, and the beta-core fragment. This review describes the biochemical and biological background for the clinical use of determinations of various forms of HCG. The clinical use of HCG and studies on HCG vaccines are briefly reviewed.
The Acute Effect of Various Glycemic Index Dietary Carbohydrates on Endothelial Function in Nondiabetic Overweight and Obese Subjects
Authors: Talya Lavi, Avraham Karasik, Nira Koren-Morag, Hannah Kanety, Micha S. Feinberg, Michael Shechter
Journal: Journal of the American College of Cardiology (2009)
The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?
Authors: M A Karsdal, A C Bay-Jensen, R J Lories, S Abramson, T Spector, P Pastoureau, C Christiansen, M Attur, K Henriksen, S R Goldring, V Kraus
Journal: Annals of the Rheumatic Diseases (2013)

Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript will summarise emerging observations from cell biology, preclinical and preliminary clinical trials that elucidate interactions between the bone and cartilage components in particular. Bone and cartilage health are tightly associated. Ample evidence has been found for bone changes during progression of OA including, but not limited to, increased turnover in the subchondral bone, undermineralisation of the trabecular structure, osteophyte formation, bone marrow lesions and sclerosis of the subchondral plate. Meanwhile, a range of investigations has shown positive effects on cartilage health when bone resorption is suppressed, or deterioration of the cartilage when resorption is increased. Known bone therapies, namely oestrogens, selective oestrogen receptor modifiers (SERMs), bisphosphonates, strontium ranelate, calcitonin and parathyroid hormone, might prove useful for treating two critical tissue components of the OA joint, the bone and the cartilage. An optimal treatment for OA likely targets at least these two tissue components. The patient subgroups for whom these therapies are most appropriate have yet to be fully defined but would likely include, at a minimum, those with high bone turnover.
High-frequency representation of a single VH gene in the expressed human B cell repertoire.
Authors: A K Stewart, C Huang, B D Stollar, R S Schwartz
Journal: The Journal of Experimental Medicine (1993)

Idiotype (Id) 16/6 marks a variable (V) region structure that occurs frequently in the human immunoglobulin repertoire. The basis of the Id has been traced to a germline heavy chain gene segment, VH18/2 (VH26). To pursue the molecular basis for the frequency of Id 16/6, we have analyzed polymerase chain reaction-generated C mu, C gamma, and VH3 family V gene libraries derived from the circulating and tonsillar B cells of four normal individuals and from the B cells of two patients with active systemic lupus erythematosus (SLE). The frequency of VH18/2 in these libraries was compared with three control VH genes, VH56P1, VH21/28, and VHA57. Plaque lifts from C mu and C gamma VH cDNA libraries were screened with gene-specific oligonucleotide probes. The frequency of VH18/2 ranged from 4 to 10% of JH+ plaques (two of five times that of control VH genes). In four VH3 family-specific libraries derived from rearranged DNA, VH18/2 represented 19-33% of VH3+ plaques. Hybridizing VH18/2 plaques were 98-100% homologous to the germline VH gene; mutations when present were often in framework 3. Extensive variation was seen in the complementarity determining region 3 sequences of these rearranged V genes. The high frequency of VH18/2 expression in the B cell repertoire was confirmed by sequencing randomly picked JH+ plaques. In two patients with active SLE the frequency of use of VH18/2 was not greater than that observed in normal subjects. These results show that VH18/2 is overrepresented in the B cell repertoire of normal subjects and suggest that the immune repertoire may be dominated by relatively few V genes.
A Glimpse of Microbial Power in Preventive Medicine
Authors: George M. Weinstock
Journal: JAMA Pediatrics (2015)

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Digestive Tract Cancers in Young Adult in Tunisia: Retrospective Study About 6 Cases
Authors: Bahloul Rim, Aissi Selma, Hela Rifi, Mhamdi Intissar, Chraeit Nessrine, Ayedi Mona, Allani Bassem, Raies Henda, Mezlini Amel
Journal: Annals of Oncology (2013)
Permanent Pervenous Atrial Pacing from the Coronary Vein
Authors: DAVID H. KRAMER, ARTHUR J. MOSS
Journal: Circulation (1970)

Permanent pervenous atrial pacing from the coronary vein has been attempted in 14 patients. Several types of arrhythmias including symptomatic bradycardia, "bradytachy" syndrome, and refractory ventricular tachyarrhythmia-fibrillation have been successfully treated with pervenous atrial pacing in 10 patients for 1 to 30 mo. Longterm atrial pacing was unsuccessful in four patients; in two of these four this was due to high atrial pacing thresholds. To date there has been no evidence of pacemaker perforation or pacemaker-induced coronary vein thrombosis. It is concluded that permanent pervenous atrial pacing from the coronary vein is a reliable method of atrial pacing without resorting to thoracotomy.