tbuckley/cabot-search huggingface dataset:
The irritancy of anthralin is inhibited by repeat applications of a subirritant concentration
Authors: None Parslew, None Friedmann
Journal: British Journal of Dermatology (1999)

Anthralin is a safe, effective treatment for psoriasis, but its efficacy is hampered by the side-effects of irritation and staining of the uninvolved skin. To avoid burning, it is customary to start at low concentrations and increase every 48-72 h until the therapeutically effective concentration is reached, which takes time and appears to prolong treatment. We felt that if the minimal erythema concentration (MEC) of anthralin could be determined initially in an individual, this ought to be near or at the final achievable therapeutic concentration. Hence, by analogy with ultraviolet therapy, treatment could start just below this concentration and thus avoid delay. A series of concentrations of anthralin in Lassar's paste was applied to the back for 3 h, and erythemal responses assessed at 24 and 48 h. MECs (0.015-0.03%) were far below those usually reached during normal therapy. To test the possibility that the skin was adapting to anthralin, we pretreated areas of skin with a subirritant concentration of anthralin (0.007%) for 3 h on 2 consecutive days prior to application of the full dose series. On the pretreated areas, the MEC increased fourfold from 0. 015% to 0.06% (P < 0.01); the concentration of anthralin required to produce the mid-point on the dose-response curve increased from 0. 06% to 0.25% (P = 0.01), demonstrating a clear adaptive response. One pretreatment produced a 52% reduction in erythema compared with control challenge, and maximal 61% inhibition was seen after three applications. Pretreatment with a subirritant concentration of a control irritant, croton oil, had no effect on the response to anthralin and vice versa. Pretreatment of skin with danthron, the non-irritant oxidation product of anthralin, had no effect, suggesting that the attenuation effect is specific to native anthralin. To see whether the attenuation might be due to modulation of xenobiotic metabolizing enzymes, skin was pretreated with inducers and inhibitors of the cytochrome P450 and NADPH-dependent quinone reductase (NDQR) enzyme systems. However, no effect was seen. In conclusion, we have shown that the irritant response to anthralin is attenuated by repeated applications of a subirritant concentration of anthralin; this is not a non-specific response to all irritants, but a specific property of native anthralin, and the enzymes P450 and NDQR are apparently not responsible for this effect.
Scientists refute claims that pesticides cause ill health
Authors: Adrian O'Dowd
Journal: BMJ (2006)

Scientists have hit back at claims that agricultural pesticides are dangerous enough to warrant a 5 m buffer zone to separate areas where they are to be used from residential areas.

The danger of proximity to the chemicals is not as severe as was claimed by a government commissioned investigation that reported last year, said the Advisory Committee on Pesticides last week.

The committee, an independent scientific group that advises the government on pesticide control, was making its official response to last year's report Crop Spraying and the Health …
In utero cigarette smoke exposure impairs somatic and lung growth in BALB/c mice
Authors: A. N. Larcombe, R. E. Foong, L. J. Berry, G. R. Zosky, P. D. Sly
Journal: European Respiratory Journal (2011)

The aim of this study was to assess whether <i>in utero</i> tobacco smoke exposure alone affects early-life lung growth and development. Pregnant BALB/c mice were exposed to cigarette smoke from six cigarettes per day, or air, from day 8 to 20 of gestation. At 2 weeks of age, pups were weighed and had their lung volumes and lung mechanics measured. Pups born from mothers exposed to cigarette smoke (CS pups; n=17) were significantly lighter (6.76±0.76 <i>versus</i> 7.72±0.68 g) and had lower lung volumes (0.123±0.02 <i>versus</i> 0.149±0.02 mL) than control pups (n=20). Respiratory mechanics were adversely impacted by cigarette smoke exposure. CS pups had higher baseline airway resistance, tissue damping and tissue elastance. These differences were largely due to lower lung volumes. Both tissue damping and elastance were increased excessively in CS pups at high transrespiratory pressures, while other parameters were not affected. There were no histological differences between groups. <i>In utero</i> tobacco smoke exposure significantly affects growth and development in BALB/c mice. These impacts may partially explain the susceptibility of infants born to smoking mothers to early respiratory disease and chronic respiratory disease as adults.
Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation
Authors: C. L. Barney, A. P. Brown, D. R. Grosshans, M. F. McAleer, J. F. de Groot, V. Puduvalli, S. L. Tucker, C. N. Crawford, M. R. Gilbert, P. D. Brown, A. Mahajan
Journal: Neuro-Oncology (2013)

Proton craniospinal irradiation (p-CSI) has been proposed to reduce side effects associated with CSI. We evaluated acute toxicities and preliminary clinical outcomes in a series of adults treated with p-CSI. We reviewed medical records for 50 patients (aged 16–63 y) with malignancies of varying histologies treated consecutively with vertebral body-sparing p-CSI at MD Anderson Cancer Center from 2007 to 2011. Median CSI and total boost doses were 30.6 and 54 Gy. Forty patients received chemotherapy, varying by histology. Median follow-up was 20.1 months (range, 0.3–59). Median doses to the thyroid gland, pituitary gland, hypothalamus, and cochleae were 0.003 Gy–relative biological effectiveness (RBE; range, 0.001–8.5), 36.1 Gy-RBE (22.5–53.0), 37.1 Gy-RBE (22.3–54.4), and 33.9 Gy-RBE (22.2–52.4), respectively. Median percent weight loss during CSI was 1.6% (range, 10% weight loss to 14% weight gain). Mild nausea/vomiting was common (grade 1 = 46%, grade 2 = 20%); however, only 5 patients experienced grade ≥2 anorexia (weight loss >5% baseline weight). Median percent baseline white blood cells, hemoglobin, and platelets at nadir were 52% (range, 13%–100%), 97% (65%–112%), and 61% (10%–270%), respectively. Four patients developed grade ≥3 cytopenias. Overall and progression-free survival rates were 96% and 82%, respectively, at 2 years and 84% and 68% at 5 years. This large series of patients treated with p-CSI confirms low rates of acute toxicity, consistent with dosimetric models. Vertebral body-sparing p-CSI is feasible and should be considered as a way to reduce acute gastrointestinal and hematologic toxicity in adults requiring CSI.
Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial
Authors: William T Abraham, Philip B Adamson, Robert C Bourge, Mark F Aaron, Maria Rosa Costanzo, Lynne W Stevenson, Warren Strickland, Suresh Neelagaru, Nirav Raval, Steven Krueger, Stanislav Weiner, David Shavelle, Bradley Jeffries, Jay S Yadav
Journal: The Lancet (2011)
The Molecular Action and Regulation of the Testis-Determining Factors, SRY (Sex-Determining Region on the Y Chromosome) and SOX9 [SRY-Related High-Mobility Group (HMG) Box 9]
Authors: Vincent R. Harley, Michael J. Clarkson, Anthony Argentaro
Journal: Endocrine Reviews (2003)

Despite 12 yr since the discovery of SRY, little is known at the molecular level about how SRY and the SRY-related protein, SOX9 [SRY-related high-mobility group (HMG) box 9], initiate the program of gene expression required to commit the bipotential embryonic gonad to develop into a testis rather than an ovary. Analysis of SRY and SOX9 clinical mutant proteins and XX mice transgenic for testis-determining genes have provided some insight into their normal functions. SRY and SOX9 contain an HMG domain, a DNA-binding motif. The HMG domain plays a central role, being highly conserved between species and the site of nearly all missense mutations causing XY gonadal dysgenesis. SRY and SOX9 are architectural transcription factors; their HMG domain is capable of directing nuclear import and DNA bending. Whether SRY and SOX9 activate testis-forming genes, repress ovary-forming genes, or both remains speculative until downstream DNA target genes are identified. However, factors that control SRY and SOX9 gene expression have been identified, as have a dozen sex-determining genes, allowing some of the pieces in this molecular genetic puzzle to be connected. Many genes, however, remain unidentified, because in the majority of cases of XY females and in all cases of XX males lacking SRY, the mutated gene is unknown.
Peliosis hepatis in recipients of renal transplants.
Authors: C Degott, B Rueff, H Kreis, A Duboust, F Potet, J P Benhamou
Journal: Gut (1978)

Peliosis hepatis, an uncommon liver lesion characterised by blood-filled cavities bordered by hepatocytic plates, was found in 12 patients three to 17 months after renal transplantation. Hepatomegaly and portal hypertension were present in five of the six patients with major peliosis hepatis, and were absent in the other six with minor hepatic lesions. Alterations of centrilobular vein walls in some of these patients suggest that peliosis hepatis could be the result of a blockade or liver blood outflow at the junctions of sinusoids and centrilobular veins. The cause of these alterations might be azathioprine.
Elevated Serum Levels of Stromal-Derived Factor-1α Are Associated with Increased Osteoclast Activity and Osteolytic Bone Disease in Multiple Myeloma Patients
Authors: Andrew C.W. Zannettino, Amanda N. Farrugia, Angela Kortesidis, Jim Manavis, L. Bik To, Sally K. Martin, Peter Diamond, Hirokazu Tamamura, Tsvee Lapidot, Nobutaka Fujii, Stan Gronthos
Journal: Cancer Research (2005)

Abstract Multiple myeloma (MM) is an incurable plasma cell (PC) malignancy able to mediate massive destruction of the axial and craniofacial skeleton. The aim of this study was to investigate the role of the potent chemokine, stromal-derived factor-1α (SDF-1α) in the recruitment of osteoclast precursors to the bone marrow. Our studies show that MM PC produce significant levels of SDF-1α protein and exhibit elevated plasma levels of SDF-1α when compared with normal, age-matched subjects. The level of SDF-1α positively correlated with the presence of multiple radiological bone lesions in individuals with MM, suggesting a potential role for SDF-1α in osteoclast precursor recruitment and activation. To examine this further, peripheral blood–derived CD14+ osteoclast precursors were cultured in an in vitro osteoclast-potentiating culture system in the presence of recombinant human SDF-1α. Although failing to stimulate an increase in TRAP+, multinucleated osteoclast formation, our studies show that SDF-1α mediated a dramatic increase in both the number and the size of the resorption lacunae formed. The increased osteoclast motility and activation in response to SDF-1α was associated with an increase in the expression of a number of osteoclast activation–related genes, including RANKL, RANK, TRAP, MMP-9, CA-II, and Cathepsin K. Importantly, the small-molecule CXCR4-specific inhibitor, 4F-Benzoyl-TE14011 (T140), effectively blocked osteoclast formation stimulated by the myeloma cell line, RPMI-8226. Based on these findings, we believe that the synthesis of high levels of SDF-1α by MM PC may serve to recruit osteoclast precursors to local sites within the bone marrow and enhance their motility and bone-resorbing activity. Therefore, we propose that inhibition of the CXCR4-SDF-1α axis may provide an effective means of treatment for MM-induced osteolysis.
Cholinergic Neurotransmission Is Essential for Perirhinal Cortical Plasticity and Recognition Memory
Authors: E.Clea Warburton, Timothy Koder, Kwangwook Cho, Peter V Massey, Gail Duguid, Gareth R.I Barker, John P Aggleton, Zafar I Bashir, Malcolm W Brown
Journal: Neuron (2003)
Plumbagin reverses proliferation and resistance to apoptosis in experimental PAH
Authors: Audrey Courboulin, Marjorie Barrier, Tanya Perreault, Pierre Bonnet, Veronique L. Tremblay, Roxane Paulin, Ève Tremblay, Caroline Lambert, Maria H. Jacob, Sandra N. Bonnet, Steeve Provencher, Sébastien Bonnet
Journal: European Respiratory Journal (2012)

Like cancer, pulmonary arterial hypertension (PAH) is characterised by a pro-proliferative and anti-apoptotic phenotype. In PAH, pulmonary artery smooth muscle cell (PASMC) proliferation is enhanced and apoptosis suppressed. The sustainability of this phenotype requires the activation of pro-survival transcription factors, such as signal transducer and activator of transcription (STAT)3 and nuclear factor of activated T-cells (NFAT). There are no drugs currently available that are able to efficiently and safely inhibit this axis. We hypothesised that plumbagin (PLB), a natural organic compound known to block STAT3 in cancer cells, would reverse experimental pulmonary hypertension. Using human PAH-PASMC, we demonstrated in vitro that PLB inhibits the activation of the STAT3/NFAT axis, increasing the voltage-gated K + current bone morphogenetic protein receptor type II (BMPR2), and decreasing intracellular Ca 2+ contentration ([Ca 2+ ] i ), rho-associated coiled-coil containing protein kinase (ROCK)1 and interleukin (IL)-6, contributing to the inhibition of PAH-PASMC proliferation and resistance to apoptosis (proliferating cell nuclear antigen (PCNA), TUNEL, Ki67 and anexine V). In vivo , PLB oral administration decreases distal pulmonary artery remodelling, mean pulmonary artery pressure and right ventricular hypertrophy without affecting systemic circulation in both monocrotaline- and sugen/chronic hypoxia-induced PAH in rats. This study demonstrates that the STAT3/NFAT axis can be therapeutically targeted by PLB in human PAH-PASMC and experimental PAH rat models. Thus, PLB could be considered a specific and attractive future therapeutic strategy for PAH.
Contraindicated Use of Cisapride
Authors: Walter Smalley, Deborah Shatin, Diane K. Wysowski, Jerry Gurwitz, Susan E. Andrade, Michael Goodman, K. Arnold Chan, Richard Platt, Stephanie D. Schech, Wayne A. Ray
Journal: JAMA (2000)

ISAPRIDE IS A GASTROINTESTInal tract promotility agent that was first marketed in the United States in August 1993 with a label indication for nocturnal heartburn. 1Use grew rapidly so that in 1995 there were approximately 5 million outpatient cisapride prescriptions filled in the United States. 2 However, by this time, the Food and Drug Administration (FDA) had received 34 cases of torsade de pointes and 23 of prolonged QT interval in cisapride users, including 4 deaths. 3ince many of these cases were in patients taking drugs that inhibited the cytochrome P450-3A4 enzymes that metabolize cisapride, 1 a "blackbox" warning was added to the cisapride label in 1995 contraindicating use in patients taking drugs that affected cisapride metabolism and the manufacturer sent a "Dear Health Care Professional" letter.In April 1996, more information on the cases was published. 3The second report also suggested that use of cisapride could be hazardous in patients taking medications that prolonged the QT interval or with chronic diseases that predisposed to cardiac arrhythmias.Despite the black-box warning, use of cisapride continued to increase in the United States so that in 1998 there were 7 million prescriptions dispensed. 2Further information accumulated on the potential adverse effects of cisapride.Clinical studies demonstrated that
Type 1 Diabetes and Autism Association Seems to Be Linked to the Incidence of Diabetes
Authors: Dario Iafusco, Maurizio Vanelli, Marco Songini, Giovanni Chiari, Francesca Cardella, Annarita Fifi, Fortunato Lombardo, Annamaria Marinaro, Annafranca Melia, Alberto Marsciani, Anna Vaccà, Franco Prisco
Journal: Diabetes Care (2006)

We read with interest the article of Freeman et al. (1) reporting a higher prevalence of autism spectrum disorder in pediatric patients with type 1 diabetes in Toronto than in the general population (0.9% [95% CI 0.3–1.5 vs. 0.34–0.67]).

The finding was, however, not confirmed by Harijutsalo and Tuomilehto (2), who reported a prevalence of autism spectrum disorders in type 1 diabetic patients similar to that in the population aged <18 years in …
Teleoanticipation in all-out short-duration cycling
Authors: A L Wittekind, D Micklewright, R Beneke
Journal: British Journal of Sports Medicine (2009)

to investigate the effect of all-out cycling test duration on indices of power, anaerobic lactic energy metabolism, perceived exertion and mood.nine physically active men undertook four all-out cycling tests of 5, 15, 30 or 45 s from seated stationary start on an ergometer fit with power cranks. The participants completed a Profile of Mood States questionnaire before each test and indicated perceived exertion immediately post-test (Borg 6-20 scale). Indices of anaerobic lactic metabolism were determined from blood lactate concentrations.pacing strategy was apparent in the 45-s tests with lower peak (p<0.01) and mean power in the initial 10 s compared to the 5- and 15-s tests (p<0.05). The first 15 s of the 30- and 45-s tests revealed lower fatigue indices compared to the 15-s tests (p<0.05) indicating some pacing in the 30-s tests. Perceived exertion increased with duration, with no difference between the 15- and 30-s tests (p>0.05). Extravascal lactate generation (reflecting exercising muscle lactate production) explained 59% of the variance in perceived exertion. There was no effect of knowledge of test duration on mood states or total mood disturbance (p>0.05).an all-out pacing strategy was apparent for at least up to 15 s, with indicators of dampened power in both 30 and 45 s sprints. Reduced power at the start of all-out long-duration sprints support a central control of at least initial pacing strategy.
Psychological Evaluation after Cardiac Transplantation: The Integration of Different Criteria
Authors: Silvana Grandi, Stefania Fabbri, Eliana Tossani, Lara Mangelli, Angelo Branzi, Carlo Magelli
Journal: Psychotherapy and Psychosomatics (2001)

&lt;i&gt;Background:&lt;/i&gt; The psychological evaluation of patients undergoing cardiac transplantation is currently based on DSM-IV criteria. An alternative diagnostic and conceptual framework has been proposed by an international group of psychosomatic investigators. The aim of this study was to compare these new criteria (Diagnostic Criteria for Psychosomatic Research, DCPR) with DSM-IV in a population where a high prevalence of psychological problems is expected (heart-transplanted patients). &lt;i&gt;Method:&lt;/i&gt; 129 consecutive patients who underwent heart transplant surgery were assessed according to DSM-IV and DCPR criteria. &lt;i&gt;Results:&lt;/i&gt; The results showed a higher number of diagnoses made using the DCPR than with the use of the DSM-IV. At least one DCPR diagnosis was found in 85 (66%) patients, whereas at least one DSM diagnosis was present in 23 (18%) patients. The number of DCPR diagnoses was almost the triple of DSM criteria. While patients who were given a DSM diagnosis frequently had additional DCPR diagnoses, many patients with DCPR criteria did not fulfill any DSM criteria. Four DCPR syndromes appeared to be particularly frequent: demoralization, type A behavior, irritable mood and alexithymia. &lt;i&gt;Conclusions:&lt;/i&gt; The joint use of DSM and DCPR criteria was found to improve the identification of psychological factors which could result in a worsening of quality of life in heart-transplanted patients.
Demonstration of antiglobulin activity in the synovial membrane of patients with rheumatoid arthritis and ankylosing spondylitis after pepsin treatment: real or artefact?
Authors: P G Davies, P A Revell, V Mayston
Journal: Annals of the Rheumatic Diseases (1986)

The results of immunofluorescence studies in nine cases of rheumatoid arthritis and nine cases of ankylosing spondylitis are presented. Antiglobulin activity was sought with fluorescein labelled, heat aggregated human IgG and rabbit immunoglobulin (indirect immunofluorescence). A similar degree of increased staining for rheumatoid factor activity was seen after pepsin digestion in all cases of rheumatoid arthritis and three of the ankylosing spondylitic cases. This staining for rheumatoid factor could also be shown in control tissue after pepsin digestion, suggesting that the enhanced staining was an artefact.
Functional status and well being in chronic obstructive pulmonary disease with regard to clinical parameters and smoking: a descriptive and comparative study.
Authors: C. P. Engstrom, L. O. Persson, S. Larsson, A. Ryden, M. Sullivan
Journal: Thorax (1996)

Self-assessment questionnaires which measure the functional and affective consequences of chronic obstructive pulmonary disease (COPD) give valuable information about the effects of the disease and may serve as important tools with which to evaluate treatment.A cross sectional comparative study was performed between patients with COPD (n = 68), stratified according to pulmonary function, and a healthy control group (n = 89). A battery of well established clinical and quality of life measures (the Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression scale (HAD)) was used to examine in which functional and affective aspects the patient group differed from the control group and how these measures related to pulmonary function and smoking habits.Compared with the controls, COPD affected functional status in most areas, not just those requiring physical activity. Forty six patients with forced expiratory volume in one second (FEV1) below 50% predicted showed particularly high levels of dysfunction in ambulation, eating, home management, and recreation/ pastimes (SIP). Despite this, their level of psychosocial functioning and mood status was little different from that of the healthy controls. Among the patients, a subgroup reported substantial psychological distress, but mood status was only weakly, or not at all, related to pulmonary function. Smoking habits did not affect functional status or well being.Quality of life is not significantly affected in patients with mild to moderate loss of pulmonary function, possibly due to coping and/or pulmonary reserve capacity. This suggests that generic self-assessment questionnaires are of limited value for detecting the early consequences of COPD. However, in later stages of the disease they are sensitive enough to discriminate between patients with different levels of pulmonary dysfunction. The low correlations between the indices of pulmonary function and the indices of affective status suggest that well being depends, to a large extent, on factors outside the clinical domain.