tbuckley/cabot-search huggingface dataset:
Re: Brain and Other Central Nervous System Cancers: Recent Trends in Incidence and Mortality
Authors: C. B. Schechter
Journal: JNCI Journal of the National Cancer Institute (1999)

Background: During the 1980s, the incidence of primary malignant brain and other central nervous system tumors (hereafter called brain cancer) was reported to be increasing among all age groups in the United States, while mortality was declining for persons younger than 65 years. We analyzed these data to provide updates on incidence and mortality trends for brain cancer in the United States and to examine these patterns in search of their causes. Methods: Data on incidence, overall and according to histology and anatomic site, and on relative survival were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for 1975 through 1995. Mortality data were obtained from the National Center for Health Statistics. Medicare procedure claims from the National Cancer Institute’s SEER‐Medicare database were used for imaging trends. Statistically significant changes in incidence trends were identified, and annual percent changes were computed for log linear models. Results/ Conclusions: Rates stabilized for all age groups during the most recent period for which SEER data were available, except for the group containing individuals 85 years of age or older. Mortality trends continued to decline for the younger age groups, and the steep increases in mortality seen in the past for the elderly slowed substantially. Patterns differed by age group according to the site and grade of tumors between younger and older patients. During the last decade, use of computed tomography scans was relatively stable for those 65‐74 years old but increased among those 85 years old or older. Implications: Improvements in diagnosis and changes in the diagnosis and treatment of elderly patients provide likely explanations for the observed patterns in brain cancer trends. [J Natl Cancer Inst 1999;91:1382‐90]
Use of Alternative Sweeteners in Diabetic Diet
Authors: Phyllis A Crapo
Journal: Diabetes Care (1988)

Alternative sweeteners are widely advocated and used. However, there is insufficient scientific information to determine whether alternative sweeteners are of value in the management of diabetes, either in improving dietary adherance or in contributing to the achievement or maintenance of a lower body weight. Each of the available sweeteners has advantages and disadvantages; no one is preferred. Recommendations about alternative-sweetener use should be tailored to the specific dietary and life-style patterns of the individual.
Engineered Fusokine GIFT4 Licenses the Ability of B Cells to Trigger a Tumoricidal T-cell Response
Authors: Jiusheng Deng, Shala Yuan, Andrea Pennati, Jordan Murphy, Jian Hui Wu, David Lawson, Jacques Galipeau
Journal: Cancer Research (2014)

Engineered chimeric cytokines can generate gain-of-function activity in immune cells. Here, we report potent antitumor activity for a novel fusion cytokine generated by N-terminal coupling of GM-CSF to IL4, generating a fusokine termed GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL4 receptors on the cell surface and displayed a pan-STAT hyperphosphorylation associated with acquisition of a distinct phenotype and function described to date. In C57BL/6J mice, administration of GIFT4 expanded endogenous B cells and suppressed the growth of B16F0 melanoma cells. Furthermore, B16F0 melanoma cells engineered to secrete GIFT4 were rejected immunologically in a B-cell-dependent manner. This effect was abolished when GIFT4-expressing B16F0 cells were implanted in B-cell-deficient mice, confirming a B-cell-dependent antitumor effect. Human GIFT4-licensed B cells primed cytotoxic T cells and specifically killed melanoma cells in vitro and in vivo. Taken together, our results demonstrated that GIFT4 could mediate expansion of B cells with potent antigen-specific effector function. GIFT4 may offer a novel immunotherapeutic tool and define a previously unrecognized potential for B cells in melanoma immunotherapy.
Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial
Authors: Michel Azizi, Marc Sapoval, Philippe Gosse, Matthieu Monge, Guillaume Bobrie, Pascal Delsart, Marco Midulla, Claire Mounier-Véhier, Pierre-Yves Courand, Pierre Lantelme, Thierry Denolle, Caroline Dourmap-Collas, Hervé Trillaud, Helena Pereira, Pierre-François Plouin, Gilles Chatellier
Journal: The Lancet (2015)
Pathogenesis of congenital alkalosis with diarrhea
Authors: Frederick A. Bieberdorf, Phillip Gorden, John S. Fordtran
Journal: Journal of Clinical Investigation (1972)

Using a triple-lumen constant perfusion system, we have studied ileal electrolyte transport in a patient with congenital alkalosis with diarrhea and made the following observations. First, chloride cannot be transported against electrochemical gradients, but can be readily absorbed or secreted down electrochemical gradients. Second, chloride secretion down an electrochemical gradient can be increased by raising lumen bicarbonate concentration. Third, sodium absorption does occur against electrochemical gradients and is associated with hydrogen ion secretion. Fourth, electrical potential difference (PD) between lumen and blood is near zero when lumen sodium concentration is 140 mEq/liter. Fifth, a normal sodium diffusion potential is present. Sixth, potassium is transported passively in response to electrochemical gradients. The ileal electrolyte transport disorder of congenital alkalosis with diarrhea can be simulated exactly in normal subjects perfused with a solution in which chloride is replaced with poorly absorbable sulfate and phosphate. These results can be explained by postulating a single defect in the double ion exchange model (sodium-hydrogen, chloride-bicarbonate) previously proposed for normal ileal transport: i.e., normal sodium-hydrogen exchange, but a chloride-bicarbonate exchange that is incapable of transporting chloride against an electrochemical gradient, yet continues to transport anions passively. In contrast, the results appear incompatible with the concept of ileal electrogenic sodium transport.
The peritoneal environment in endometriosis
Authors: E Oral, D L Olive, A Arici
Journal: Human Reproduction Update (1996)

The local environment of peritoneal fluid (PF) surrounding the endometriotic implant is immunologically dynamic and links the reproductive and immune systems. Peritoneal fluid contains a variety of free floating cells, including macrophages, mesothelial cells, lymphocytes, eosinophils and mast cells. Macrophages are attracted to the peritoneal environment more abundantly than any other cell type. These scavengers promote cellular growth and viability through secretion of growth factors and cytokines. It is now becoming evident that cytokines play an important role in reproduction at various levels, including gamete function, fertilization and embryo development, implantation and postimplantation survival of the conceptus. Peritoneal fluid has been shown to affect negatively ovum capture by the fimbria, sperm survival, spermatozoon-oocyte interaction and embryonic development. We have recently identified the presence of two pro-inflammatory chemoattractant cytokines for monocyte/macrophages (MCP-1) and for granulocytes (interleukin-8, IL-8) in the PF. Concentrations of both IL-8 and MCP-1 are not only elevated in PF of women with endometriosis compared to those without endometriosis, but they are related to the severity of the disease. Over the past 70 years, at least a dozen theories have been proposed to explain the histogenesis and aetiology of endometriosis. It appears that the aetiology is multifactorial, and today a composite theory of retrograde menstruation with implantation of endometrial fragments in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted explanation for peritoneal endometriosis.
CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab
Authors: E. Mahe, V. Descamps, M. Grossin, S. Fraitag, B. Crickx
Journal: British Journal of Dermatology (2003)

Journal Article CD30+ T‐cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab Get access E. Mahé, E. Mahé Departments of Dermatology and Dr Emmanuel Mahé. E‐mail: emmanuel.mahe@bch.ap‐hop‐paris.fr Search for other works by this author on: Oxford Academic Google Scholar V. Descamps, V. Descamps Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar M. Grossin, M. Grossin Pathology, Bichat‐Claude Bernard Hospital, 46 Rue Henri‐Huchard, Paris Cedex 18, France Search for other works by this author on: Oxford Academic Google Scholar S. Fraitag, S. Fraitag Department of Pathology, Necker‐Enfants Malades Hospital, Assistance Publique‐Hôpitaux de Paris, Paris, France Search for other works by this author on: Oxford Academic Google Scholar B. Crickx B. Crickx Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 1, 1 July 2003, Pages 170–173, https://doi.org/10.1046/j.1365-2133.2003.05384.x Published: 01 July 2003 Article history Accepted: 19 December 2002 Published: 01 July 2003
Biological activity of vitamin D analogues in the skin, with special reference to antipsoriatic mechanisms
Authors: P.C.M. KERKHOF
Journal: British Journal of Dermatology (2006)

Active vitamin D3 modulates epidermal growth, keratinization and inflammation, and various vitamin D3 analogues have been shown to be effective in the treatment of psoriasis. These analogues now provide a useful addition to the therapeutic modalities available for the treatment of psoriasis. Epidermal hyperproliferation, abnormal keratinization and inflammation are the well-established hallmarks of the psoriatic plaque. The aim of this review is to provide an update of information on the cell biological effects of vitamin D3, and the influence of vitamin D analogues on the pathomechanisms of psoriasis.
Interactions of Lanatoside C and Potassium on Atrioventricular Conduction in Rabbits
Authors: YOSHIO WATANABE, LEONARD S. DREIFUS
Journal: Circulation Research (1970)

Intra-atrial, intranodal and His-Purkinje conduction times were determined in perfused rabbit hearts. In one series, the concentration of lanatoside C was increased by 0.4 mg/liter every 30 minutes, in the presence of normal (4.5) or high (7.5 mM) K + in the perfusion fluid. At high (K + ) the glycoside produced a greater increase in intra-atrial and His-Purkinje conduction times but caused a smaller increase of intranodal conduction time than at normal (K + ). Second-degree A-V block always occurred intranodally, but the incidence was lower with high (K + ). In another series, (K + ) was increased by 3 mM every 30 minutes, in the absence or presence (0.4, 0.8 or 1.2 mg/liter) of lanatoside C. No difference was seen between hearts treated with lanatoside C and those untreated at the level of (K + ) producing failure of conduction. At all levels of glycoside, conduction delay caused by high (K + ) was greatest within the atria, less in the His-Purkinje system and insignificant within the A-V node. Intra-atrial and His Purkinje block were observed but never an intranodal block. It is concluded that (1) cardiac glycoside and high (K + ) primarily affect different regions of the A-V conducting system, and (2) aggravation of glycoside-induced A-V block by high (K + ) may result from additional intra-atrial and His-Purkinje block rather than from further depression of intranodal conduction. Electrophysiological mechanisms underlying these interactions were also discussed.
A positive feedback sympathetic pressor reflex during stretch of the thoracic aorta in conscious dogs.
Authors: M Pagani, P Pizzinelli, M Bergamaschi, A Malliani
Journal: Circulation Research (1982)

The role of pressor sympathetic reflexes in circulatory control was investigated in conscious dogs. Animals were previously instrumented with a 6- to 8-cm rigid core cannula covered by an inflatable rubber cylinder in the thoracic aorta, a pressure catheter implanted in the aorta above the cannula, and a second catheter inserted into the aorta below the cannula through a femoral artery. Two piezoelectric crystals were positioned at opposing adventitial sites to measure aortic distension with ultrasound techniques. After recovery from surgery, the diameter of the aortic segment surrounding the cannula was increased by 9.6 +/- 0.4% from 16 +/- 1 mm by inflating the rubber cylinder, without obstructing blood flow. Mean aortic pressure rose 31 +/- 3% from 100 +/- 3 mm Hg and heart rate 20 +/- 3% from 91 +/- 3 beats/min (P less than 0.01). The pressor response was abolished by alpha-adrenergic blockade (phentolamine 1 mg/kg, iv). The heart rate response was reduced either by beta-blockade (propranolol 1 mg/kg, iv) or muscarinic blockade (atropine 0.2 mg/kg, iv) and abolished by their combination. During aortic stretch, the sensitivity of the baroreflex was reduced 57 +/- 7% from 18 +/- 2 msec/mm Hg (P less than 0.01). The pressor response was increased by 49 +/- 8% after bilateral carotid sinus nerve section and vagotomy. These excitatory reflex responses were obtained in absence of any pain reaction. Thus, in the conscious dog, aortic distension within physiological ranges induces a potent pressor sympathetic reflex with positive feedback characteristics. Such a pressor reflex not only occurs in the presence of functioning baroreflexes, but is also capable of reducing their sensitivity.
TORC1 Suppression Predicts Responsiveness to RAF and MEK Inhibition in <i>BRAF-</i> Mutant Melanoma
Authors: Ryan B. Corcoran, Stephen Michael Rothenberg, Aaron N. Hata, Anthony C. Faber, Adriano Piris, Rosalynn M. Nazarian, Ronald D. Brown, Jason T. Godfrey, Daniel Winokur, John Walsh, Mari Mino-Kenudson, Shyamala Maheswaran, Jeffrey Settleman, Jennifer A. Wargo, Keith T. Flaherty, Daniel A. Haber, Jeffrey A. Engelman
Journal: Science Translational Medicine (2013)

Suppression of TORC1 activity after treatment with RAF or MEK inhibitors predicts drug sensitivity in BRAF -mutant melanoma and can be monitored in patients.
Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis
Authors: S M van der Kooij, Y P M Goekoop-Ruiterman, J K de Vries-Bouwstra, M Guler-Yuksel, A H Zwinderman, P J S M Kerstens, P A H M van der Lubbe, W M de Beus, B A M Grillet, H K Ronday, T W J Huizinga, F C Breedveld, B A C Dijkmans, C F Allaart
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To compare the occurrence of drug-free remission, functional ability and radiological damage after 4 years of response-driven treatment according to four different treatment strategies for rheumatoid arthritis (RA). <h3>Methods:</h3> Patients with recent-onset, active RA (n = 508) were randomly assigned to four different treatment strategies: (1) sequential monotherapy; (2) step-up combination therapy; (3) initial combination therapy with prednisone and (4) initial combination therapy with infliximab. Treatment was adjusted based on 3-monthly disease activity score (DAS) assessments, aiming at a DAS ⩽2.4. From the third year, patients with a sustained DAS &lt;1.6 discontinued treatment. <h3>Results:</h3> In total, 43% of patients were in remission (DAS &lt;1.6) at 4 years and 13% were in drug-free remission: 14%, 12%, 8% and 18% of patients in groups 1–4, respectively. The absence of anti-cyclic citrullinated peptide antibodies, male gender and short symptom duration were independently associated with drug-free remission. Functional ability and remission were maintained in all four groups with the continuation of DAS-driven treatment, without significant differences between the groups. Significant progression of joint damage was observed in 38% and 31% of patients in groups 3 and 4 versus 51% and 54% of patients in groups 1 and 2 (p&lt;0.05, group 4 versus groups 1 and 2, group 3 versus group 2). <h3>Conclusions:</h3> In patients with recent-onset active RA, drug-free remission was achieved in up to 18% of patients. DAS-driven treatment maintained clinical and functional improvement, independent of the treatment strategy. Joint damage progression remained significantly lower after initial combination therapy compared with initial monotherapy.
Commentary on “Acute patellofemoral pain: aggravating activities, clinical examination, MRI and ultrasound findingsAcute patellofemoral pain: aggravating activities, clinical examination, MRI and ultrasound findings”
Authors: Jan E Näslund
Journal: British Journal of Sports Medicine (2008)

The authors state that acute patellofemoral pain caused by overuse should be recognised as a true subgroup of patellofemoral pain syndrome (PFPS). The argument for this view is the fact that they find most …
Differences in Smad4 Expression in Human Papillomavirus Type 16–Positive and Human Papillomavirus Type 16–Negative Head and Neck Squamous Cell Carcinoma
Authors: Adriana Báez, Alan Cantor, Sharon Fonseca, Maria Marcos-Martinez, Linda A. Mathews, Carlos A. Muro-Cacho, Teresita Muñoz-Antonia
Journal: Clinical Cancer Research (2005)

The SMADs are a group of interrelated proteins that mediate transforming growth factor beta (TGF-beta) signaling. Upon TGF-beta binding the TGF-beta type I receptor phosphorylates Smad2 and Smad3, which then complex with Smad4 and translocate to the nucleus, with subsequent activation of target genes. Disruption of TGF-beta signaling is thought to contribute to the development of head and neck squamous cell carcinomas (HNSCC). Alterations in the function of the DPC4/Smad4 tumor suppressor gene have been found to inactivate TGF-beta signaling in several tumor types. For example, DPC4/Smad4 is lost or mutated in colorectal, pancreatic, and esophageal cancers. In addition, DPC4/Smad4 transcriptional activity and TGF-beta ability to inhibit DNA synthesis is blocked by the E7 protein of the human papillomavirus type 16 (HPV16) in cervical carcinoma cell lines. HPV16 infection is a risk factor for the development of a subset of HNSCC. This study was undertaken to investigate a potential correlation between expression of components of the TGF-beta signaling pathway and HPV16 status in HNSCC tumors. We examined the expression of TGF-beta signaling proteins Smad2, Smad2-P, and Smad4 by immunohistochemistry in 27 HPV16-negative and 16 HPV16-positive HNSCCs. We compared the expression patterns and assessed their relationship to HPV16 status. No significant differences were detected between HPV16-positive and HPV16-negative tumors in the expression of Smad2 and Smad2-P. Smad4 expression, however, was decreased in 56% of the HPV16-positive tumors and in 39% of HPV16-negative tumors. This difference was statistically significant (P = 0.01) suggesting that loss of Smad4 expression may be involved in HPV16-induced carcinogenesis of HNSCC.
Cbl-b and Itch: Key Regulators of Peripheral T-cell Tolerance
Authors: K. Venuprasad
Journal: Cancer Research (2010)

Abstract E3 ligases Cbl-b and Itch have emerged as dominant “tolerogenic” regulators of T cells because their deficiency results in severe autoimmune diseases. Cbl-b and Itch ligase activity regulate T-cell anergy and development of Foxp3+ regulatory T cells (Treg) in the periphery by modulating key components of T-cell receptor (TCR) and transforming growth factor-β (TGF-β) signaling. Manipulation of Cbl-b and Itch activities may provide unique opportunities to develop future therapies for immune disorders such as autoimmunity and cancer. Cancer Res; 70(8); 3009–12. ©2010 AACR.
Effects of Exercise on the Absorption of Insulin Glargine in Patients With Type 1 Diabetes
Authors: Rajesh Peter, Stephen D. Luzio, Gareth Dunseath, Andy Miles, Barry Hare, Karianne Backx, Vassen Pauvaday, David R. Owens
Journal: Diabetes Care (2005)

OBJECTIVE—To study the effects of exercise on the absorption of the basal long-acting insulin analog insulin glargine (Lantus), administered subcutaneously in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 13 patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen were studied. 125I-labeled insulin glargine at the usual basal insulin dose was injected subcutaneously into the thigh on the evening (2100) before the study day on two occasions 1 week apart. Patients were randomly assigned to 30 min intense exercise (65% peak oxygen uptake [Vo2peak]) on one of these visits. The decay of radioactive insulin glargine was compared on the two occasions using a thallium-activated Nal gamma counter. Blood samples were collected at regular intervals on the study days to assess plasma glucose and insulin profiles. RESULTS—No significant difference was found in the 125I-labeled insulin glargine decay rate on the two occasions (exercise vs. no exercise; repeated-measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was observed over the exercise period (area under curve above fasting [ΔAUC] glucose: −0.39 ± 0.11 vs. −1.30 ± 0.16 mmol · l−1 · h−1; nonexercise vs. exercise; P = 0.001), but insulin levels did not differ significantly on the two occasions (ΔAUC insulin: −2.1 ± 3.9 vs. 1.5 ± 6.2 pmol · l−1 · h−1; nonexercise versus exercise; P = 0.507). CONCLUSIONS—An intense 30-min period of exercise does not increase the absorption rate of the subcutaneously injected basal long-acting insulin analog insulin glargine in patients with type 1 diabetes.
Molecular Detection of Tumor Cells in Bronchoalveolar Lavage Fluid From Patients With Early Stage Lung Cancer
Authors: S A Ahrendt, J T Chow, L H Xu, S C Yang, C F Eisenberger, M Esteller, J G Herman, L Wu, P A Decker, J Jen, D Sidransky
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Conventional cytologic analysis of sputum is an insensitive test for the diagnosis of non-small-cell lung cancer (NSCLC). We have recently demonstrated that polymerase chain reaction (PCR)-based molecular methods are more sensitive than cytologic analysis in diagnosing bladder cancer. In this study, we examined whether molecular assays could identify cancer cells in bronchoalveolar lavage (BAL) fluid. METHODS: Tumor-specific oncogene mutations, CpG-island methylation status, and microsatellite alterations in the DNA of cells in BAL fluid from 50 consecutive patients with resectable (stages I through IIIa) NSCLC were assessed by use of four PCR-based techniques. RESULTS: Of 50 tumors, 28 contained a p53 mutation, and the identical mutation was detected with a plaque hybridization assay in the BAL fluid of 39% (11 of 28) of the corresponding patients. Eight of 19 adenocarcinomas contained a K-ras mutation, and the identical mutation was detected with a mutation ligation assay in the BAL fluid of 50% (four of eight) of the corresponding patients. The p16 gene was methylated in 19 of 50 tumors, and methylated p16 alleles were detected in the BAL fluid of 63% (12 of 19) of the corresponding patients. Microsatellite instability in at least one marker was detected with a panel of 15 markers frequently altered in NSCLC in 23 of 50 tumors; the identical alteration was detected in the BAL fluid of 14% (three of 22) of the corresponding patients. When all four techniques were used, mutations or microsatellite instability was detected in the paired BAL fluid of 23 (53%) of the 43 patients with tumors carrying a genetic alteration. CONCLUSION: Although still limited by sensitivity, molecular diagnostic strategies can detect the presence of neoplastic cells in the proximal airway of patients with surgically resectable NSCLC.