tbuckley/cabot-search huggingface dataset:
Controversial Practices in Allergy
Authors: Joseph B. Miller
Journal: JAMA (1982)

To the Editor.—  In regard to an article by Michael H. Grieco, MD, JD, entitled Controversial Practices in Allergy (1982;247:3106), I will confine my remarks to the intradermal provocative-neutralizing  The technique described by Grieco was abandoned almost 20 years ago. The technique used effectively today is described in my book, Food Allergy: Provocative Testing and Injection Therapy (Charles C Thomas Publisher, 1972).  The communication by Grieco indicated that the positive test results of my double-blind study were followed by four controlled studies [that] were unable to support the efficacy of this method. In fact, all of these negative study results preceded my positive results, and none of these findings were concerned with my subject.  The Kailin-Collier study, reported only in a letter published inThe Journal, attempted to determine the validity of symptom neutralization testing. However, the physician was not allowed to see the wheals! His choice of neutralizing
“Tightness” Sensation of Asthma Does Not Arise from the Work of Breathing
Authors: ANDREW P. BINKS, SHAKEEB H. MOOSAVI, ROBERT B. BANZETT, RICHARD M. SCHWARTZSTEIN
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Asthma evokes several uncomfortable sensations including increased "effort to breathe" and chest "tightness." We have tested the hypotheses that "effort" and "tightness" are due to perception of increased work performed by the respiratory muscles. Bronchoconstriction was induced by inhaled methacholine in 15 subjects with mild asthma (FEV1/FVC baseline = 81.9% ± 5.8; bronchoconstriction = 64.0% ± 8.6). To relieve the work of breathing, and thereby minimize activation of respiratory muscle afferents and motor command, subjects were mechanically ventilated. Subjects separately rated effort to breathe and tightness during mechanical ventilation and during spontaneous breathing. Bronchoconstriction produced elevated end-expiratory lung volume (279 ± 62 ml); in a control study, end-expiratory lung volume was increased equally in the absence of bronchoconstriction by increasing end-expiratory pressure. During bronchoconstriction, ratings of effort were greater during spontaneous breathing than during mechanical ventilation (p < 0.05). Ratings of tightness were unchanged by the absence of respiratory muscle activity (p = 0.12). Hyperinflation alone did not produce tightness or effort. We conclude that tightness is not related to the increase in respiratory work during bronchoconstriction.
Rbtis medicamentosa: aspects of pathophysiology and treatment
Authors: Peter Graf
Journal: Allergy (1997)

With modern vasoconstrictors, such as oxy‐ and xylometazoline, the risk of developing rhinitis medicamentosa (RM) has been considered to be small or even nonexistent. However, recent studies have shown that overuse of these drugs may result in rebound congestion, nasal hyperreactivity, tolerance, and histologic changes of the nasal mucosa. Using rhinostereometry, it has also been shown that the long‐term use of the preservative benzalkonium chloride (BKC) in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers. A nasal decongestant spray composed of a combination of vasoactive substances and BKC has a long‐term adverse effect on the nasal mucosa. BKC alone induces mucosal swelling after 30 days use of the nasal spray in healthy subjects, unlike placebo. According to the author, rhinitis medicamentosa can be defined as a condition of nasal hyperreactivity, mucosal swelling, and tolerance that is induced, or aggravated, by the overuse of topical vasoconstrictors with or without a preservative. An adequate treatment of these patients consists of a combination of vasoconstrictor withdrawal and a topical corticosteroid to alleviate the withdrawal process. The underlying nasal disorder must then be treated. Patients with rhinitis medicamentosa who overuse topical decongestants and are able to stop using such drugs should be careful about taking these drugs again, even for a few days. They must be informed about the rapid onset of rebound congestion upon repeated use in order to avoid the return of the vicious circle of nose‐drop abuse.
Interventions in OXCHECK study waste resources
Authors: I U Haq, W W Yeo, P R Jackson, L E Ramsay
Journal: BMJ (1995)

EDITOR,--The OXCHECK study showed significant reductions in total cholesterol concentration (3.1%) and blood pressure (2.5/1.5 mm Hg) with health checks over three years.1 The reductions in cholesterol concentration are in line with responses shown in previous controlled trials.2 The authors seem in some doubt about whether these effects are large enough to justify the cost of the health checks. This may be clearer when the projected …
Heat shock protein 72 and apoptosis indicate cardiac decompensation during early multiple organ failure in sheep
Authors: HideoA. Baba, Jeremias Wohlschlaeger, HenningD. Stubbe, Florian Grabellus, HugoVan Aken, KlausJ. Schmitz, Friedrich Otterbach, KurtW. Schmid, Christian August, Bodo Levkau, Frank Hinder
Journal: Intensive Care Medicine (2004)
731. Hematopoietic Stem Cell Gene Transfer and Integration Site Analysis in Tumor-Prone Mice Uncovers Low Genotoxicity of Lentiviral Vector Integration
Authors: Eugenio Montini, Daniela Cesana, Manfred Schmidt, Francesca Sanvito, Maurilio Ponzoni, Lucia Sergi Sergi, Fabrizio Benedicenti, Cynthia Bartholomae, Clelia Di Serio, Claudio Doglioni, Christof von Kalle, Luigi Naldini
Journal: Molecular Therapy (2006)

Insertional mutagenesis represents a major hurdle to successful gene therapy and mandates for sensitive pre-clinical assays of genotoxicity. Cdkn2a-/- mice are defective for p53 and Rb pathways, and are susceptible to a broad range of cancer-triggering genetic lesions. We exploited the sensitivity of these tumor-prone mice to develop an in-vivo genotoxicity assay, based on transplantation of Cdkn2a-/- hematopoietic stem cells (HSC), treated or not with prototypical retroviral (RV) and lentiviral (LV) vectors. In our rationale if RV or LV treatment is genotoxic, then transplanted mice will show a significantly earlier tumor onset. The sensitivity of the model was shown by the ability to detect a vector dose-dependent acceleration in tumor onset in mice transplanted with RV-treated cells. Such acceleration, as in previous studies, is consequent to genetic lesions, produced by vector integration, that cooperate with the germ-line mutation, and is contingent on LTR activity. We then compared the integration site selection in pre-transplant cells and tumors from the transplanted mice. RV showed a strong bias for genes previously described as common integration sites (CIS) in the Retroviral Tagged Cancer Gene Database, transcription factors and kinases. Moreover, RV insertions at CIS and cell cycle genes were further enriched in early-onset tumors, suggesting cooperation in tumorigenesis. Indeed, retrospective survival analysis of mice stratified according to the presence or absence of tumor integrations targeting each given gene class demonstrated that RV integrations close to CIS or cell cycle genes were associated with a significantly earlier tumor onset. These data showed that the RV integrations which were enriched in the tumors were non-neutral and likely triggered early tumor onset. Remarkably, LV, tested in the same conditions, did not show any tumor acceleration, despite high integration loads and robust transgene expression in all hematopoietic lineages. LV targeted CIS much less frequently than RV in pre-transplant cells and tumors, and did not show selection for integrations at any specific gene class in tumors. We are now studying whether incorporating strong LTR-like promoters in LV results in a similar genotoxicity as the prototypical RV we tested. Similarly, we are comparing Self-INactivating RV and LV carrying cellular promoters. This assay provides a validated strategy to conduct such inquiries. Our results provide the first direct evidence that prototypic LV have low oncogenic potential, and encourage their application to HSC gene therapy.
Book Review Interventions Following Mass Violence and Disasters: Strategies for Mental Health Practice Edited by Elspeth Cameron Ritchie, Patricia J. Watson, and Matthew J. Friedman. 430 pp. New York, Guilford Press, 2006. $48. 978-1-59385-256-6
Authors: Schuyler W. Henderson, Andrés Martin
Journal: New England Journal of Medicine (2007)
Jejunal lysozyme activity and the Paneth cell in coeliac disease.
Authors: M Ward, A Ferguson, M A Eastwood
Journal: Gut (1979)

The jejunal mucosa of patients with coeliac disease contains significantly fewer Paneth cells (PCC) per crypt (p less than 0.001) and tissue lysozyme activity (JLA) P less than 0.001) when compared with a group of subjects with normal jejunal mucosa. Neither PCC nor JLA return to normal with complete clinical recovery and otherwise complete histological recovery on a gluten free diet. There is a significant linear correlation between JLA and PCC suggesting that the Paneth cell is the principal source of jejunal lysozyme.
Effect of Hypercholesterolemia on Myocardial Necrosis and Apoptosis in the Setting of Ischemia-Reperfusion
Authors: Robert M. Osipov, Cesario Bianchi, Jun Feng, Richard T. Clements, Yuhong Liu, Michael P. Robich, Hilary P. Glazer, Neel R. Sodha, Frank W. Sellke
Journal: Circulation (2009)

Background— Hypercholesterolemia is prevalent in patients who experience myocardial ischemia-reperfusion injury (IR). We investigate the impact of dietary-induced hypercholesterolemia on the myocardium in the setting of acute IR. Methods and Results— In normocholesterolemic (NC, n=7) and hypercholesterolemic (HC, n=7) Yucatan male pigs, the left anterior descending coronary artery was occluded for 60 minutes, followed by reperfusion for 120 minutes. Hemodynamic values were recorded, and TTC staining was used to assess necrosis. Oxidative stress was measured. Specific cell death and survival signaling pathways were assessed by Western blot and TUNEL staining. Infarct size was 45% greater in HC versus NC (42% versus 61%, P &lt;0.05), whereas the area at risk (AAR) was similar in both groups ( P =0.61). Whereas global LV function (+dP/dt, P &lt;0.05) was higher during entire period of IR in HC versus NC, regional function deteriorated more following reperfusion in HC ( P &lt;0.05). Ischemia increased indices of myocardial oxidative stress such as protein oxidation ( P &lt;0.05), lipid peroxidation ( P &lt;0.05), and nitrotyrosylation in HC versus NC, as well as the expression of phospho-eNOS ( P &lt;0.05). The expression of myeloperoxidase, p38 MAPK, and phospho-p38 MAPK was higher in HC versus NC (all P &lt;05). Ischemia caused higher expression of the proapoptotic protein PARP ( P &lt;0.05), and lower expression of the prosurvival proteins Bcl2 ( P &lt;0.05), phospho-Akt, ( P &lt;0.05), and phospho-PKCε ( P &lt;0.05) in the HC versus NC. TUNEL-positive cell count was 3.8-fold ( P &lt;0.05) higher in the AAR of HC versus NC. Conclusions— This study demonstrates that experimental hypercholesterolemia is associated with increased myocardial oxidative stress and inflammation, attenuation of cell survival pathways, and induction of apoptosis in the ischemic territory, which together may account for the expansion of myocardial necrosis in the setting of acute IR.
CDK2 is required for LMW-cyclin E mediated murine mammary tumorigenesis.
Authors: S Akli, CS Van Pelt, TN Bui, K Keyomarsi
Journal: Cancer Research (2009)

Abstract Abstract #2007 Cyclin E is a regulatory protein with multiple functions that activates CDK2, controls centrosome duplication, and regulates histone gene transcription. Our previous studies have shown that the presence of Low-molecular-weight (LMW) forms of cyclin E correlates strongly with decreased survival in patients with breast cancer. Transgenic mice overexpressing LMW cyclin E had increased incidence of mammary tumors and distant metastasis when compared to full length cyclin E. The critical role of LMW cyclin E in mammary tumorigenesis may be the result of the ability of LMW cyclin E to bind and activate the cyclin-dependent kinase 2 (CDK2). To specifically test the importance of LMW cyclin E-associated CDK2 kinase activity in mammary tumorigenesis, we generated double and triple transgenic mice LMW cyclin E-T1;CDK2-/-, and LMW cyclin E-T1;p53+/-;CDK2-/-. We found that: (i) The development of the mammary glands proceeds relatively normally in these animals demonstrating that CDK2 kinase activity is largely dispensable for mammary gland development; (ii) These mice were resistant to breast cancers initiated by LMW cyclin E overexpression. Whereas LMW-cyclin E-T1 mice in CDK2+/- or CDK2+/+ background succumb to mammary tumors with mean latencies of 16 and 19.5 months respectively, their LMW cyclin E-T1; CDK2-/- littermates do not form mammary tumors up to 24 months (P=0.05 CDK2+/+ versus CDK2-/-; P=0.0252 CDK2+/- versus CDK2-/-; P=0.1457 CDK2+/+ versus CDK2+/-, Log rank test). Similarly, while MMTV-LMW cyclin E-T1/p53+/- transgenic mice in CDK2+/- or CDK2+/+ background succumb to mammary gland tumors between 7 and 13 months with 100% penetrance, their MMTV-LMW cyclin E-T1;p53+/-; CDK2-/- littermates are resistant to tumor formation (P&amp;lt;0.01 CDK2+/+ versus CDK2-/-; P=0.011 CDK2+/- versus CDK2-/-, P=0.5072 CDK2+/+ versus CDK2+/-, Log rank Test). In fact none of the CDK2-/- mice developed mammary tumors when crossed with cyclin E LMW transgenic mice. However, 2 out of the 12 MMTV-LMW cyclin E; p53+/-; CDK2-/- mice generated salivary gland tumors. Hence, these LMW cyclin E; p53+/-; CDK2-/- are susceptible to LMW cyclin E induced salivary tumors in the absence of CDK2. We concluded that CDK2 is critically required for LMW cyclin E induced mammary tumorigenesis and consequently, the loss of CDK2 renders CDK2-/- mice resistant to breast cancer induced by LMW cyclin E expression. In clear contrast to mammary epithelial cells, we found that in salivary gland cells LMW cyclin E continued to elicit malignant transformation even in the absence of CDK2. Our work suggests that due to the requirement of CDK2 for LMW-cyclin E mediated mammary tumorigeneis, these tumors are prime candidates for anti-CDK2 therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2007.
Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential.
Authors: K J Tracey, S F Lowry, B Beutler, A Cerami, J D Albert, G T Shires
Journal: The Journal of Experimental Medicine (1986)

Lethal infections are associated with cellular dysfunction as evidenced by a decrease in the resting transmembrane potential difference (Em) of skeletal muscle fibers. Endotoxin stimulation of macrophages evokes production of cachectin, a protein that has been implicated as a mediator of the lethal effects of endotoxemia. In the present study, rat skeletal muscle fiber Em decreased when incubated with recombinant human cachectin. The reduction of Em induced by cachectin occurred in a dose-related fashion and was inhibited by mAb against the monokine. Infusion of cachectin induced a decline of skeletal muscle Em in vivo, and suggests that cachectin may acutely mediate alterations of skeletal muscle membrane function after infection.
COSTS OF REMOTE MONITORING VERSUS AMBULATORY FOLLOW-UP OF IMPLANTED CARDIOVERTER DEFIBRILLATORS IN THE RANDOMIZED ECOST STUDY
Authors: Laurence Guédon-Moreau, Dominique Lacroix, Nicolas Sadoul, Jacques Clémenty, Claude Kouakam, Jean Sylvain Hermida, Etienne Aliot, Salem Kacet
Journal: Journal of the American College of Cardiology (2013)
Concanavalin A simultaneously primes liver hematopoietic and epithelial progenitor cells for parallel expansion during liver regeneration after partial hepatectomy in mice
Authors: Toshiki Sakamoto, Tsukasa Ezure, John Lunz, Noriko Murase, Hirokazu Tsuji, John J. Fung, Anthony J. Demetris
Journal: Hepatology (2000)

Liver hematopoietic progenitor cells (LHPC) and liver epithelial progenitor cells (LEPC) share a remarkable number of growth and differentiation-controlling receptor-ligand signaling systems. These likely account for the ability of the liver to support hematopoiesis in fetal life, and possibly for suggestions that LHPC can differentiate into hepatocytes. In these experiments, the kinetics and magnitude of LHPC and LEPC activation and expansion were studied by using a concanavalin A (Con A) liver injury model followed by partial hepatectomy (PH). Studies were performed in interleukin 6-deficient (IL-6(-/-)) mice and wild-type (IL-6(+/+)) controls, which show equal susceptibility to Con A- induced injury, because IL-6/gp130 signaling has been implicated in both LHPC and LEPC expansion. Con A pretreatment primed LHPC and LEPC for a rapid and parallel expansion after PH in IL-6(+/+) mice, which was significantly blunted and delayed in the IL-6(-/-) mice. Exogenous IL-6 given immediately before PH after Con A, augmented both LHPC and LEPC expansion in the IL-6(-/-) mice. Thus, the proinflammatory cytokine IL-6, commonly produced in liver injury and inflammatory disease, is an important growth factor involved in the expansion of LHPC and LEPC. This observation has implications for both hepatic carcinogenesis and transplantation.
Mechanism of Increased Coxsackie and Adenovirus Receptor Gene Expression and Adenovirus Uptake by Phytoestrogen and Histone Deacetylase Inhibitor in Human Bladder Cancer Cells and the Potential Clinical Application
Authors: Rey-Chen Pong, Ryan Roark, Jiun-Yih Ou, Jianhai Fan, Jennifer Stanfield, Eugene Frenkel, Arthur Sagalowsky, Jer-Tsong Hsieh
Journal: Cancer Research (2006)

Abstract Coxsackie and adenovirus receptor (CAR) is known as a principal receptor for adenovirus commonly used as a gene delivery vector. Down-regulation of CAR is often detected in several cancer types. Epigenetic modifiers such as histone deacetylase inhibitor FK228 (depsipeptide) have been shown to increase CAR expression as well as the uptake of adenovirus in bladder cancer in vivo and in vitro, indicating that altered transcriptional regulation of CAR is the key mechanism responsible for the decreased CAR levels in this cancer. In this study, we screened agents that could induce CAR expression in bladder cancer cells. Fifty-eight drugs with various chemical properties were tested. Ipriflavone and plant isoflavones were found to exhibit the ability to induce CAR gene expression in combination with FK228. Genistein, the natural isoflavone found in soybean, when combined with FK228, exerts a synergistic effect on CAR gene and protein expression in bladder cancer cells. Chromatin immunoprecipitation results showed an increased histone acetylation in the CAR promoter gene, which is due to the suppression of histone deacetylase activity by both agents. Also, our data indicated that combination treatment is a potent chemotherapeutic regimen for bladder cancer cells and the subsequent administration of recombinant adenovirus could further eliminate the remaining cells. Taken together, our results provide a strong rationale for combining chemotherapeutic and gene therapeutic agents to enhance the therapeutic efficacy in bladder cancer. (Cancer Res 2006; 66(17): 8822-8)
Sodium Gradient and Renoprival Hypertension in the Rat
Authors: SYDNEY M. FRIEDMAN, CONSTANCE L. FRIEDMAN, MIYOSHI NAKASHIMA
Journal: Circulation Research (1959)

Following nephrectomy in the rat blood pressure rises while the extracellular fluid volume increases, sodium concentration falls and potassium rises. These changes (without the potassium rise) can be mimicked by simple hyperosmotic loading while the reverse can be induced by dehydration. The rise in blood pressure is not due to either expansion of the extracellular space or the fall in sodium concentration alone but probably to the resultant decrease in the Na o /Na 1 gradient.
Prescribing and hospital admissions for asthma in east London
Authors: C. Griffiths, J. Naish, P. Sturdy, F. Pereira
Journal: BMJ (1996)

The incidence of coronary mortality is higher among populations with low dietary intake of flavonoids * The protective effect of flavonoids was associated with a diet high in intake of apples and onions * The effect may be mediated through prevention of oxidation of low density lipoproteins but other mechanisms could be involved * Flavonoids offer an explanation for the suggested beneficial effect of fruits and vegetables in coronary heart disease * Further studies should concentrate on the effects of various flavonoid compounds and on populations with different intakes significantly to intake of the antioxidant vitamins C or E or fi carotene the association observed for flavonoids was probably not due to these antioxidants.With the exception of berries in men, foods repre- senting sources of flavonoids were inversely associated with coronary mortality risk.In contrast with fruits and vegetables some berries also contain considerable amounts of flavonoids (for example, myricetin), which, according to in vitro studies, modify low density lipoprotein to increase its uptake by macrophages, thus possibly having an opposite effect on the risk of coronary heart disease.24This and the low accuracy of our estimates of flavonoid concentration in berries may explain the absence of an association.In summary, the results of the present study suggest that people with very low dietary intakes of flavonoids have increased risks of coronary heart disease.This could not, however, be fully distinguished from the possible effects of other dietary substances or lifestyle.Further longitudinal studies of other populations are needed to confirm the importance of flavonoids in the prevention of coronary heart disease.
HTLV-II and HTLV-I associated myelopathy
Authors: Walid Heneine, RimaF. Khabbaz, JonathanE. Kaplan, Kazuaki Ishibashi, Nobuhito Ohno, Kimiharu Uozumi, Shuichi Hanada, Terukatsu Arima
Journal: The Lancet (1991)
Patients with mild Alzheimer's disease should have access to drugs, says draft NICE guidance
Authors: Z. Kmietowicz
Journal: BMJ (2010)

Patients with mild forms of Alzheimer’s disease should have access to three drugs previously reserved for people with more serious forms of the disease, says the National Institute for Health and Clinical Excellence (NICE).

In draft guidance for England and Wales NICE is proposing that the use of three acetylcholinesterase inhibitors—donepezil (marketed as Aricept), galantamine (Reminyl), and rivastigmine (Exelon)—should be extended to patients with mild Alzheimer’s disease. At the moment the drugs are reserved for those with moderate disease. …
Spontaneous Peripelvic Urinary Extravasation without Kidney Rupture
Authors: Harold A. Serebro, Malcolm Druskin, Martin A. Robbins
Journal: New England Journal of Medicine (1965)

SPONTANEOUS peripelvic urinary extravasation occurring in the absence of rupture of the renal parenchyma or renal pelvis is rare. This may follow acute ureteral obstruction, the urinary extravasation spreading by way of the calyceal fornices, to the pericalyceal connective tissue and then through the hilus into the perirenal fat within Gerota's fascia. Since the differential diagnosis of pain in the flank and lower quadrant of the abdomen is of great clinical importance, and because there have been few reports of spontaneous urinary extravasation proved by excretory urography, the following complex diagnostic problem and case history is presented. An awareness of . . .