tbuckley/cabot-search huggingface dataset:
Gender difference in skin prick sensitivity to allergens in 10-15 year cases with respiratory symptoms vs controls in Sicily and Malta
Authors: Martin Balzan, Christopher Zammit, David Bilocca, Fabio Cibella, Silvia Ruggieri, Gaspare Drago, Remo Minardi, Stephen Montefort, Giovanni Viegi
Journal: European Respiratory Journal (2014)

The RESPIRA study (EU-funded Italia-Malta) was performed in the District of Gela (Southern Sicily) and Malta in 2012/3 in 10-15 years children (n=2,047) by questionnaires and clinical exam of cases and controls. Aims: To assess sensitivity to common allergens in these southern Mediterranean islands. Cases (n=137, M=84) reported wheeze and/or use of asthma medications in the last 12 months, while controls (n=159, M=70) answered negatively to both and rhinitis in the last 12 months. A positive SPT (>=3mm) for at least one allergen tested was found in 80/137 cases and 51/159 controls (p=0.0001). House Dust Mite (cases 62/137, controls 28/159, p=0.001), Parietaria (22/137, 10/159, p=0.008), Alternaria (19/137, 9/159, p=0.018), and Blattella (12/137, 5/159, p=0.046) were more frequently positive in cases than in controls. Olive (25/137, 19/159, p=0.142), cat (17/137, 11/159, P=0.116), and dog (9/137, 5/159, p=0.182) did not show a significant difference . Grass pollen sensitization was slightly higher in controls (10/137, 13/159). There was a significant difference by gender in a 2x4 chi 2  comparing positive subjects amongst cases and controls. HDM: Males (cases 41/84 Controls 15/70), females (cases 21/53, controls 13/89) p=0.011; Olive: in Males (cases 19/84, controls 10/70) Females (cases 6/53, controls 9/89) p=0.007; Cat: Males (cases.12/84, controls 6/70) Females (cases.5/53 and 5/89) p=0.019; Dog: Males (cases 7/84 and 2/70) and Females (Cases 2 /53 and 4/89) p=0.017. SPT sensitivity to common Mediterranean aero-allergens in asthma patients vs controls was significantly higher in 10-15 year old Males when compared to females.
Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate
Authors: Amanda L. Woerman, David Mendelowitz
Journal: Cardiovascular Research (2013)

Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO₂ exposure.
Constitutive relations and finite deformations of passive cardiac tissue II: stress analysis in the left ventricle.
Authors: J D Humphrey, F C Yin
Journal: Circulation Research (1989)

We present a new approach for estimation of transmural distributions of stress and strain in the equatorial region of a passive left ventricle. We employ a thick-walled cylindrical geometry, assume that myocardium is incompressible, and use a three-dimensional constitutive relation that yields a material symmetry consistent with observed transmural variations in muscle fiber orientations. Moreover, we consider finite deformations including inflation, extension, twist, and transmural shearing and suggest a new method for determination of the requisite deformation parameters directly from experimental strain data. We show representative transmural distributions of stress and strain, and perform a parametric study to illustrate differing predictions of stress induced by varying boundary conditions, muscle fiber orientations, or modes of deformation. Our analysis can be used to guide and check future predictions of cardiac stresses, and to guide experimentalists by suggesting the accuracy of measurements essential for stress analysis in the heart.
Glycosylated neuropeptides: A new vista for neuropsychopharmacology?
Authors: Robin Polt, Muthu Dhanasekaran, Charles M. Keyari
Journal: Medicinal Research Reviews (2005)

Abstract The application of endogenous neuropeptides (e.g., enkephalins) as analgesics has been retarded by their poor stability in vivo and by their inability to effectively penetrate the blood–brain barrier (BBB). Effective BBB transport of glycosylated enkephalins has been demonstrated in several labs now. Analgesia (antinociception) levels greater than morphine, and with reduced side effects have been observed for several glycopeptides related to enkephalin. Somewhat paradoxically, enhanced BBB transport across this lipophilic barrier is achieved by attaching water‐soluble carbohydrate groups to the peptide moieties to produce biousian glycopeptides that can be either water‐soluble or membrane bound. Transport is believed to rely on an endocytotic mechanism (transcytosis), and allows for systemic delivery and transport of the water‐soluble glycopeptides. Much larger endorphin/dynorphin glycopeptide analogs bearing amphipathic helix address regions also have been shown to penetrate the BBB in mice. This holds forth the possibility of transporting much larger neuropeptides across the BBB, which may encompass a wide variety of receptors beyond the opioid receptors. © 2005 Wiley Periodicals, Inc.
Inhaling and lung cancer: an anomaly explained.
Authors: N J Wald, M Idle, J Boreham, A Bailey
Journal: BMJ (1983)

An objective index of inhaling cigarette smoke based on carboxyhaemoglobin concentrations and the carbon monoxide yields of cigarettes was used to investigate possible systematic differences in the extent of inhaling among light and heavy smokers when classified according to their self described inhaling habits.A total of 2108 men who smoked cigarettes were studied.Heavy smokers (20 or more cigarettes a day) had a higher average inhaling index than light smokers (fewer than 20 cigarettes a day) both among those who said that they inhaled and among those who said that they did not.This observation, together with indirect evidence that heavy smokers who inhale deeply may to some extent avoid depositing smoke condensate on their main bronchial epithelium, explains a hitherto unresolved anomaly-namely, that the risk of lung cancer is less among heavy cigarette smokers who say that they inhale than it is among those who say that they do not inhale.
Tolloid-like Proteinases Orchestrate Extracellular Matrix Formation
Authors: Hirokazu Okada
Journal: Journal of the American Society of Nephrology (2011)

Purification of osteogenic activity initially isolated bone morphogenic proteins (BMPs) 1 through 7 from bone extracts.[1][1] BMPs 2 through 7 are members of the TGF-β superfamily, and on the basis of sequence homology, more than 30 TGF-β-like BMPs have been identified.[1][1] In contrast, despite
Thrombin-Cleaved COOH-Terminal Osteopontin Peptide Binds with Cyclophilin C to CD147 in Murine Breast Cancer Cells
Authors: Zhiyong Mi, Tim Oliver, Hongtao Guo, Chengjiang Gao, Paul C. Kuo
Journal: Cancer Research (2007)

Abstract Osteopontin is a glycoprotein that has been linked to metastatic function in breast, lung, and prostate cancers. However, the mechanism by which osteopontin acts to induce metastatic properties is largely unknown. One intriguing feature of osteopontin is the presence of a conserved thrombin cleavage site that is COOH-terminal from a well-characterized RGD domain. Although the COOH-terminal fragment may bind to cell surface CD44 receptors, little is known about the COOH-terminal osteopontin fragment. In the current study, we use the murine mammary epithelial tumor cell lines 4T1 and 4T07; these cells are thioguanine-resistant sublines derived from the parental population of 410.4 cells from Balb/cfC3H mice. Using flow cytometry and Forster resonance energy transfer, we show that the COOH-terminal fragment of osteopontin binds with another marker of metastatic function (cyclophilin C or rotamase) to the CD147 cell surface glycoprotein (also known as extracellular matrix metalloproteinase inducer), to activate Akt1/2 and matrix metalloproteinase-2. In in vitro assays, thrombin cleavage of osteopontin to generate short COOH-terminal osteopontin in the presence of cyclophilin C increases migration and invasion of both 4T07 and 4T1 cells. This interaction between osteopontin peptide and cyclophilin C has not been previously described but assigns a heretofore unknown function for the thrombin-cleaved osteopontin COOH-terminal fragment. [Cancer Res 2007;67(9):4088–97]
Grade A Eggs as a Source of Salmonella enteritidis Infections
Authors: R. Dean Thomas
Journal: JAMA (1989)

<h3>To the Editor. —</h3> This letter concerns an article that appeared in<i>JAMA</i>on April 8, 1988, entitled "The Emergence of Grade A Eggs as a Major Source of<i>Salmonella enteritidis</i>Infections."<sup>1</sup> When I observed the title of this aritcle, my immediate reaction was one of concern. It appeared that a severe epidemic had started in the northeastern United States and was threatening to sweep the country. The summary raised the possibility of hens with infected ovaries spreading a dangerous pathogen in one of our most important food supplies. After analyzing the article, however, it became evident that the authors prepared the article after completing only a small research project that had little substance and was poorly designed. All they did was take 50 samples of bulk eggs from the Northeast region and 25 samples of bulk eggs from each of the other three US regions and test them
Suppression of Constitutive but Not IL-1β-Inducible Expression of Monocyte Chemoattractant Protein-1 in Mesangial Cells by Retinoic Acids
Authors: JAVIER LUCIO-CAZANA, KENJI NAKAYAMA, QIHE XU, TSUNEO KONTA, VICTORIA MORENO-MANZANO, AKIRA FURUSU, MASANORI KITAMURA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Retinoic acid regulates a wide range of biologic processes, including inflammation. This study investigated the effect of all-trans-retinoic acid (t-RA) on the constitutive and cytokine-inducible expression of monocyte chemoattractant protein 1 (MCP-1) in rat mesangial cells. Serum-deprived mesangial cells exhibited substantial levels of MCP-1 mRNA, and the expression was markedly upregulated by interleukin-1β (IL-1β). Pretreatment with t-RA abrogated the constitutive mRNA expression but did not inhibit the IL-1β-inducible expression. The similar effects were observed by 9-cis-RA. The suppressive effect of t-RA required retinoic acid receptors. t-RA did not affect the stability of MCP-1 mRNA, indicating that its suppressive effect was at the transcriptional level. Experiments that used pharmacologic and genetic inhibitors showed that the IL-1β-inducible MCP-1 expression was dependent on nuclear factor-κB (NF-κB) and independent of activator protein 1 (AP-1). In contrast, the constitutive expression of MCP-1 was dependent on both NF-κB and AP-1. t-RA substantially inhibited the constitutive activity of AP-1 but did not inhibit NF-κB activity in mesangial cells. These data suggested that ( 1 ) constitutive and IL-1β-inducible expression of MCP-1 was differently regulated by AP-1 and NF-κB and ( 2 ) t-RA inhibited selectively the constitutive expression of MCP-1 via intervention in the AP-1 pathway.
A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma
Authors: Paul G. Richardson, Bart Barlogie, James Berenson, Seema Singhal, Sundar Jagannath, David Irwin, S. Vincent Rajkumar, Gordan Srkalovic, Melissa Alsina, Raymond Alexanian, David Siegel, Robert Z. Orlowski, David Kuter, Steven A. Limentani, Stephanie Lee, Teru Hideshima, Dixie-Lee Esseltine, Michael Kauffman, Julian Adams, David P. Schenkein, Kenneth C. Anderson
Journal: New England Journal of Medicine (2003)

Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity.In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee.Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients.Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.
Insulin Induces Renal Vasodilation, Increases Plasma Renin Activity, and Sensitizes the Renal Vasculature to Angiotensin Receptor Blockade in Healthy Subjects
Authors: Todd S. Perlstein, Marie Gerhard-Herman, Norman K. Hollenberg, Gordon H. Williams, Abraham Thomas
Journal: Journal of the American Society of Nephrology (2007)

Insulin stimulates the renin-angiotensin system and induces renal vasodilation. The relationship between these opposing influences of insulin on renal vascular tone has not been explored. A hyperinsulinemic euglycemic clamp and sham insulin clamp each of 270 min duration were performed in 15 healthy individuals during high sodium balance. An angiotensin receptor blocker was administered at time 180 min. Renal plasma flow and plasma renin activity were measured serially. The response to insulin or sham insulin infusion was defined as the change from time 0 to 180 min; the response to angiotensin receptor blockade (ARB) was defined as the change from time 180 to 270 min. Insulin infusion increased plasma renin activity (P < 0.01) and renal plasma flow (P < 0.01); the latter effect plateaued by time 150 min. ARB caused a greater vasodilator response during insulin infusion compared with during sham insulin infusion (P = 0.02). Increasing renin response to insulin predicted blunting of the renal vasodilator response to insulin infusion (R(2) = 0.36, P = 0.02) and sensitizing of the renal vasodilator response to ARB during insulin infusion (R(2) = 0.59, P < 0.01). Insulin-induced activation of the renin-angiotensin system modulates insulin-induced renal vasodilation in healthy individuals. Further studies are warranted to address this balance in states of insulin resistance and the possible implications for the association of insulin resistance with risk for chronic kidney disease.
The p47phox mouse knock-out model of chronic granulomatous disease.
Authors: S H Jackson, J I Gallin, S M Holland
Journal: The Journal of Experimental Medicine (1995)

Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47phox-/- mice produced no superoxide and killed staphylococci ineffectively. p47phox-/- mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. This model mirrors human CGD and confirms a critical role for the phagocyte NADPH oxidase in mammalian host defense.
PEAK: A Randomized, Multicenter Phase II Study of Panitumumab Plus Modified Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or Bevacizumab Plus mFOLFOX6 in Patients With Previously Untreated, Unresectable, Wild-Type <i>KRAS</i> Exon 2 Metastatic Colorectal Cancer
Authors: Lee S. Schwartzberg, Fernando Rivera, Meinolf Karthaus, Gianpiero Fasola, Jean-Luc Canon, J. Randolph Hecht, Hua Yu, Kelly S. Oliner, William Y. Go
Journal: Journal of Clinical Oncology (2014)

To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS.Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and safety.Of 285 randomly assigned patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group, PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P = .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab arms, respectively. Treatment discontinuation rates because of adverse events were similar between arms.PFS was similar and OS was improved with panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more clinical benefit with anti-epidermal growth factor receptor therapy.
Occupational asthma caused by palladium
Authors: M. Daenen, PH. Rogiers, C Van de Walle, F. Rochette, M. Demedts, B. Nemery
Journal: European Respiratory Journal (1999)

Occupational exposure to complex platinum salts is a well-known cause of occupational asthma. Although there is evidence that platinum refinery workers may also be sensitized to other precious metals, such as palladium or rhodium, no instances of occupational asthma due to an isolated sensitization to palladium have been reported. A case is reported of occupational rhinoconjunctivitis and asthma in a previously healthy worker exposed to the fumes of an electroplating bath containing palladium. There was no exposure to platinum. Sensitization to palladium was documented by skin-prick tests. The skin-prick test was positive with Pd(NH3)4Cl2, but not with (NH4)2PdCl4. Corresponding salts of platinum were all negative. A bronchial provocation test with Pd(NH3)4Cl2 (0.0001% for a total of 315 s, followed by 0.001% for a total of 210 s) led to an early decrease in forced expiratory volume in one second (-35%). A similar exposure (0.001% for a total of 16 min) in an unrelated asthmatic gave no reaction. This case shows that an isolated sensitization to palladium can occur and that respiratory exposure to palladium is a novel cause of metal-induced occupational asthma.
Mast cell–derived particles deliver peripheral signals to remote lymph nodes
Authors: Christian A. Kunder, Ashley L. St. John, Guojie Li, Kam W. Leong, Brent Berwin, Herman F. Staats, Soman N. Abraham
Journal: The Journal of Experimental Medicine (2009)

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.
Who Should Get the HPV Vaccine? Usage Expands Amid Debate
Authors: Judy Peres
Journal: JNCI Journal of the National Cancer Institute (2010)

Both the U.S. Food and Drug Administration and the CDC’s Advisory Committee on Immunization Practices are looking at data from Merck on Gardasil’s ability to prevent anal cancer in 16- to 26-year-old men who have sex with men, a population at elevated risk for the disease. Both Merck and GlaxoSmithKline are also testing their vaccines for the prevention of cervical cancer and other HPVrelated diseases in women beyond their mid-20s. A spokesman for Merck said that the company expects the FDA to decide by the end of this year whether to grant the company’s application to expand the indications for Gardasil.
Acute Hypertensive Response in Patients With Stroke
Authors: Adnan I. Qureshi
Journal: Circulation (2008)

A cute hypertensive response is the elevation of blood pressure (BP) above normal and premorbid values that initially occurs within the first 24 hours of symptom onset in patients with stroke.This phenomenon was reported in Ͼ60% of patients presenting with stroke in a nationally representative study from the United States. 1 With Ϸ980 000 patients 2 admitted with stroke each year in the United States, the estimated annual prevalence of acute hypertensive response is more than half a million patients.With Ϸ15 million patients experiencing stroke worldwide each year, 3 the acute hypertensive response may be expected in Ϸ10 million patients per year.The acute hypertensive response in stroke patients is managed by a diverse group of physicians, including emergency physicians, intensivists, internists, primary care physicians, neurologists, neurosurgeons, and cardiologists.Previous audits suggest that antihypertensive agents and management strategies vary considerably and are not always consistent with recommended guidelines. 4Data from 1181 acute ischemic stroke patients enrolled in the Project for Improvement of Stroke Care Management suggested that administration of antihypertensive medication within 24 hours in 56% of the patients was inconsistent with guidelines provided by the American Stroke Association (ASA). 5The present review article summarizes the current concepts pertaining to treatment of the acute hypertensive response derived from recent guidelines provided by professional organizations and "best available" evidence derived from experimental and clinical studies and discusses incorporation of these concepts into clinical practice.Randomized trials, nonrandomized controlled studies, and selected observational studies were identified with multiple searches on Medline from 1980 to 2007 by cross-referencing the key words of stroke, acute hypertension, antihypertensive agents, acute stroke, and hypertension.Pertinent articles identified from bibliographies of selected articles were also reviewed.Treatment targets and strategies were identified by review of existing guidelines from professional organizations.