tbuckley/cabot-search huggingface dataset:
Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function
Authors: F. D Gilliland
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. <h3>METHODS</h3> A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. <h3>RESULTS</h3> In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (–3.0%, 95% CI –4.4 to –1.4), mean mid expiratory flow (MMEF) (–4.6%, 95% CI –7.0 to –2.3), and forced expiratory flow (FEF<sub>75</sub>) (–6.2%, 95% CI –9.1 to –3.1), but not forced expiratory volume in one second (FEV<sub>1</sub>). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (–4.1%, 95% CI –7.6 to –0.4) and FEF<sub>75</sub> (–4.4%, 95% CI –9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF<sub>75</sub> associated with all measurements of ETS were substantially reduced and were not statistically significant. <h3>CONCLUSIONS</h3> In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.
In Defense of Cloning
Authors: John C. Wood
Journal: Annals of Internal Medicine (2000)

Ad Libitum15 February 2000In Defense of CloningJohn C. Wood, MDJohn C. Wood, MDYardley, PA 19067 (Wood)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-4-200002150-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Will mother holding son to breast bend low to say,“Sweet boy you are God's special gift”?Will father holding child on kneeDiscard his manly coat to whisper,“Ah, fair girl, you only, only you will do for me”?Will special tie of twins that binds so close be fractured,Broken by contempt of commonplace?Will lovers be bereft of mystery; Lose or never find their love unique,And love solely by the numbers?Will all forms of nexusBe programmed in advance,So each response be equal on the scale,And barren in the pay,No agony or ecstasy of sports?In outreached hands to ... Author, Article, and Disclosure InformationAffiliations: Yardley, PA 19067 (Wood)Corresponding Author: John C. Wood, MD, 535 River Road, Yardley, PA 19067. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 February 2000Volume 132, Issue 4Page: 324KeywordsCloningDNAForecastingKneesRiversSportsTouchTwins ePublished: 15 August 2000 Issue Published: 15 February 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Structural requirements for parathyroid hormone action in mature bone. Effects on release of cyclic adenosine monophosphate and bone gamma-carboxyglutamic acid-containing protein from perfused rat hindquarters.
Authors: M S Calvo, M J Fryer, K J Laakso, R A Nissenson, P A Price, T M Murray, H Heath
Journal: Journal of Clinical Investigation (1985)

To determine the structural requirements for parathyroid hormone (PTH) activity in mature bone, we perfused the surgically isolated hindquarters of adult male rats with either native bovine PTH-(1-84) [bPTH-(1-84)] or the synthetic amino-terminal fragment, bovine PTH-(1-34) [bPTH-(1-34)]. Changes in the release of cyclic AMP (cAMP) and bone Gla protein (BGP) were monitored as evidence of bone-specific response to PTH; tissue specificity of the cAMP response was confirmed through in vitro examination on nonskeletal tissue response to PTH. Biologically active, monoiodinated 125I-bPTH-(1-84) was administered to determine if mature murine bone cleaves native hormone. We found that perfused rat bone continuously releases BGP, and that both bPTH-(1-84) and bPTH-(1-34) acutely suppress this release. In addition, both hormones stimulate cAMP release from perfused rat hindquarters. When examined on a molar basis, the magnitude of the cAMP response was dose-dependent and similar for both hormones, with doses yielding half-maximal cAMP responses. The response for bPTH-(1-34) was 0.5 nmol and for bPTH-(1-84) was 0.7 nmol. Moreover, biologically active 125I-bPTH-(1-84) was not metabolized in our hindquarter perfusion system. These findings indicate that PTH-(1-84) does not require extraskeletal or skeletal cleavage to an amino-terminal fragment in order to stimulate cAMP generation in, or suppress BGP release from, mature rat bone.
CHANGES IN BLOOD VESSELS (CAPILLARY FRAGILITY) WITH INFLAMMATION
Authors: Ernst Zander
Journal: The Journal of Experimental Medicine (1937)

Suction with a partial vacuum of -70 mm. Hg applied to normal skin of rabbits causes intracutaneous hemorrhage after an average time of 8 minutes. Inflammation produced by various agents, including turpentine, killed streptococci, staphylococci, pneumococci or meningococci, and filtrates from cultures of meningococci or typhoid bacilli, produces a series of changes that are almost uniform. Immediately after injection of the irritant there is greatly increased resistance to the production of hemorrhage by suction so that the time required may be from (1/2) hour to almost 2 hours. This increased resistance to suction applied to the surface of the skin is doubtless caused by contraction of blood vessels following injection of the irritant. The period of increased resistance is soon followed by diminished resistance of the vascular walls so that hemorrhage after 12 to 24 hours following injection occurs within from 1 to 4 minutes of suction. The subsequent course of events varies; resistance of the vascular wall to suction, designated for convenience capillary fragility, may return to normal after from 2 to 9 days (observed with turpentine, streptococcus), or for several days may considerably exceed this level (observed with staphylococcus, pneumococcus), or may remain at a low level for a week or more (observed with tuberculin). With inflammation in a sensitized animal (allergic inflammation) the preliminary period of resistance may be diminished and the appearance of capillary fragility hastened, so that hemorrhage occurs after 2 minutes of suction applied 6 hours after injection, and later it may fall to an even lower level (observed with hemolytic streptococci in sensitized animals). The preparatory injection of toxic substances, such as meningococcus or typhoid filtrate, used in the production of the Shwartzman phenomenon, causes inflammation with injury of small blood vessels indicated by susceptibility to hemorrhage with suction. It is probable that subsequent intravenous injection causes hemorrhage by further injury to these injured blood vessels.
Problems Associated with the Introduction of a Psychiatric Unit Into a Rural General Hospital
Authors: SANFORD BLOOMBERG
Journal: American Journal of Psychiatry (1973)

The author describes the establishment of a psychiatric unit in a rural general hospital in Massachusetts and some of the problems that arose in the first two years; particular attention is paid to the interaction between the psychiatric unit and the hospital's medical staff Emphasizing psychiatry as a medical specialty and attempting to relate psychiatry to traditional medical values were vital in coping effectively with the problems.
Panitumumab in Metastatic Colorectal Cancer: The Importance of Tumour RAS Status
Authors: Marc Peeters, Meinolf Karthaus, Fernando Rivera, Jan-Henrik Terwey, Jean-Yves Douillard
Journal: Drugs (2015)

Tumour biomarker status is being used more and more frequently to guide treatment decisions in patients with metastatic colorectal cancer (mCRC). Continued cycles of hypothesis generation and biomarker testing in retrospective, prospective–retrospective and prospective analyses from studies of the epidermal growth factor (EGFR)-targeted monoclonal antibodies (mAbs), panitumumab and cetuximab, have resulted in improved patient selection in mCRC. Initial data suggested EGFR-targeted mAb treatment should be limited to patients with KRAS exon 2 wild-type (WT) tumours, but the availability of tumour samples from large phase III studies permitted evaluation of additional potential biomarkers of activity for these agents. Subsequent analyses further refined the target population to those patients whose tumours were WT for KRAS and NRAS exons 2, 3 and 4 (i.e., those with RAS WT status). Here, we review key clinical data for panitumumab in mCRC across the lines of treatment, assessing in detail the impact of more comprehensive RAS selection on patient outcomes. Panitumumab data across first- to third-line therapy consistently demonstrate that by testing tumour RAS status, it is possible to select patients more likely to benefit from treatment.
Neoadjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer: primary efficacy analysis of the NOAH trial.
Authors: L Gianni, W Eiermann, V Semiglazov, G Manikhas, A Lluch, S Tjulandin, A Feyereislova, P Valagussa, J Baselga
Journal: Cancer Research (2009)

Abstract Abstract #31 Background: Trastuzumab (Herceptin®; H) improves survival in HER2-positive early and metastatic breast cancer. The Phase III NOAH trial is the largest neoadjuvant study that evaluated the addition of H to an anthracyclines- and taxanes-based chemotherapy (CT) for patients (pts) with HER2-positive locally advanced breast cancer (LABC).&amp;#x2028; Methods: In this multicentre, randomised, open-label trial, women aged ≥18 years with HER2-positive (IHC 3+ or FISH+) LABC (T3N1 or T4; any T + N2 or N3 or + ipsilateral supraclavicular node involvement) were randomised to receive 3 cycles of doxorubicin (60 mg/m²) and paclitaxel (150 mg/m²) q3w, 4 cycles of paclitaxel (175 mg/m² q3w) and 3 cycles of CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², 5-fluorouracil 600 mg/m² q4w) on Days 1 and 8, with or without concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. In parallel, LABC pts screened as HER2-negative (IHC 0/1+) received the same CT regimen. The primary end point was event-free survival (EFS), defined as the time between randomisation and disease recurrence or progression, or death from any cause. Secondary end points were pathological complete response (pCR), overall response rate (ORR), overall survival (OS) and safety. We report for the first time here the study's primary endpoint.&amp;#x2028; Results: 327 pts were enrolled. Baseline characteristics were balanced for randomised pts. Inflammatory breast cancer was present in 27% of HER2-positive vs 14% of HER2-negative tumours, while 35% vs 64%, respectively, were hormone-receptor positive. EFS was analyzed after 88 events in the HER2-positive group (n=228). EFS rate at 3 years was significantly better in the H + CT arm compared with CT alone: 70.1% vs 53.3%, respectively (HR 0.56; p=0.007). EFS rate in the HER2-negative arm was 67.4%. OS data were immature at this stage. Trastuzumab treatment was the only variable significantly associated with EFS outcome in multivariate analysis which included disease stage and hormonal receptor status. Both ORR and pCR were significantly higher in the H + CT arm compared to CT alone: 89% vs 77% for ORR, respectively (p=0.02); 39% vs 20% for pCR, respectively (p=0.002). Similar results for ORR and pCR were observed between the HER2-positive CT-alone arm and the HER2-negative arm. The addition of H to CT in the neoadjuvant setting was well tolerated with acceptable cardiac safety.&amp;#x2028; Conclusion: Neoadjuvant H significantly increased EFS in pts with HER2-positive LABC. This analysis of the NOAH study establishes neoadjuvant H with CT as a standard treatment option in women with HER2-positive LABC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 31.
Insecticides and blood dyscrasias. Chlordane exposure and self-limited refractory megaloblastic anemia
Authors: B. Furie
Journal: JAMA (1976)

INCREASING awareness of the potential harmful effects of household and industrial chemical exposure on healthy individuals has provided impetus to attempts to identify dangerous agents and minimize unprotected exposure of persons who come in contact with these agents. For these reasons, we report our case. The patient was a man in prior good health with well-documented exposure to a commonly used insecticide, chlordane, and with subsequent development of a severe refractory megaloblastic anemia. Protected from further exposure to chlordane, the patient had a spontaneous remission. <h3>Report of a Case</h3> A 56-year-old dentist was in excellent health until August 1973. During the interval March to May 1973, he exterminated termites that had infested the foundation of his office. Exposure to the insecticide chlordane was extensive and is documented in his own words: "The use of Chlorane 74 by Vigoro [active ingredients: technical chlordane 74%, petroleum hydrocarbons 21%; inert ingredients 5%—Swift Agricultural
Abstract 3030: An exosome isolation system for serum-based cancer biomarker discovery
Authors: Fangting Wu, Travis J. Antes
Journal: Cancer Research (2010)

Abstract Exosomes are 40-100 nm membrane vesicles secreted by most cell types, including all cancer cells. While the exact biological functions of exosomes remain unclear, exosomes can mediate communication between cells, facilitating processes such as antigen presentation and in trans signaling to neighboring cells. The abundance of exosomes present in the circulation of cancer patients increases with tumor grade. Studies identifying protein and microRNA biomarkers in these circulating exosomes can reveal the tumor type and origin. These recent studies highlight the growing use and need of standardized exosome enrichment. What is missing in this research area is a method for simple, rapid and reproducible exosome purification to facilitate research into the role of exosome in both physiological and pathological process, as well as possible diagnostic and therapeutic potentials. In this study, SBI utilizes proprietary polymer mixture (ExoQuick) to precipitate exosome from human serum samples. Using ExoQuick, we successfully observe small RNAs in the exosome pellets and detect microRNAs by qPCR. Exosome precipitation from serum samples was verified using Western blot analysis on the ExoQuick supernatant and pellet fractions and probed with antibodies against two commonly found exosome biomarker proteins, CD63 and CD9. Robust signals for CD63 and for CD9 were observed only in the exosome pellet fractions but not in the serum supernatant. These preliminary data provide proof-of-concept for our approach in using polymer-based, one-step exosome purification method from human serum samples. The technologies developed in this study will advance the exosome research field by providing a simple and standardized exosome isolation method that will allow high-throughput exosome analysis to enable major strides forward in serum-based microRNA biomarker discoveries for cancer diagnostics and prognostics tools. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3030.
Polymorphisms in the multidrug resistance gene MDR1 (ABCB1) predict for molecular resistance in patients with newly diagnosed chronic myeloid leukemia receiving high-dose imatinib
Authors: Wendy Deenik, Bronno van der Holt, Jeroen J. W. M. Janssen, Isabel W. T. Chu, Peter J. M. Valk, Gert J. Ossenkoppele, Ilse P. van der Heiden, Pieter Sonneveld, Ron H. N. van Schaik, Jan J. Cornelissen
Journal: Blood (2010)
Emergency referral letters from deputising doctors need to be improved
Authors: J. Wright, N. Prasad, G. Dalrymple
Journal: BMJ (1996)

EDITOR,—Clearly, the service provided out of hours by general practitioners must be restructured if it is to remain of high quality. Various options are being considered, including cooperatives and overnight medical centres. In their survey Val Lattimer and colleagues found that general practitioners were keen to try these options.1 The new agreement gives doctors the opportunity to transfer their out of hours responsibility to a deputising service.2 This service will still be needed, no matter which options become established. …
Small proximal vessels are not always small: an intravascular ultrasound study
Authors: Yoshio Kobayashi, Issam Moussa, Makoto Hirose, Farzana Arif, Octavia Balan, Arlene Reyes, Mohamed Mohamed, Milena Adamian, Roxana Mehran, George Dangas, Alexandra J. Lansky, Gregg W. Stone, Martin B. Leon, Jeffrey W. Moses, Gary S. Mintz
Journal: Journal of the American College of Cardiology (2002)
Expression of corneodesmosin in the granular layer and stratum corneum of normal and diseased epidermis
Authors: M. HAFTEK, M. SIMON, J. KANITAKIS, S. MARECHAL, A. CLAUDY, G. SERRE, D. SCHMITT
Journal: British Journal of Dermatology (1997)

The stratum corneum (SC) has long been considered as a sort of inert membrane destined to be shed at the surface of the epidermis. During the last two decades, however, several lines of evidence have been reported, suggesting that active physical and chemical changes take place in the horny layer despite the absence of intracytoplasmic organelles. In particular, processing of filaggrin, replacement of the plasma membrane by a ceramide envelope and constant, progressive modification of extracellular lipid multilayers have been put forward. Recently, attention has focused on the intercellular junctions, which may be involved in the regulation of SC desquamation. Corneodesmosin, a newly discovered protein of s.c. desmosomes (corneodesmosomes), is synthesized at the latest stages of keratinocyte differentiation and persists between the horny cells until desquamation occurs. In the present study, we performed immunohistochemical and immuno-ultrastructural investigations on corneodesmosin expression in various skin lesions characterized by abnormal production and/or retention of the horny layer. Our results suggest that corneodesmosin expression is independent from profilaggrin synthesis. We found corneodesmosin in almost all morphologically recognizable corneodesmosomal structures and specifically those which persisted up to the SC surface. Hyperkeratotic lesions which are characterized by an increased number of junctions showed intense immunoreactivity with anticorneodesmosin antibody. A complete absence of corneodesmosin was not observed in any disease. This finding, together with our previous biochemical studies, suggests that corneodesmosin may exert a protective function against proteolytic degradation of corneodesmosomes both in normal skin and in the pathological horny layer.
Carbohydrate‐based particles reduce allergic inflammation in a mouse model for cat allergy
Authors: T. Neimert‐Andersson, S. Thunberg, L. Swedin, U. Wiedermann, G. Jacobsson‐Ekman, S.‐E. Dahlén, A. Scheynius, H. Grönlund, M. van Hage, G. Gafvelin
Journal: Allergy (2008)

Background: Allergen‐specific immunotherapy (ASIT) is the only treatment of allergic disease that gives long‐lasting relief of symptoms. However, concerns for safety and efficiency have highlighted the need for improvement of the therapy. We have previously suggested carbohydrate‐based particles (CBPs) as a novel adjuvant and allergen carrier for ASIT. Our aim of this study was to evaluate the therapeutic potential of CBPs in ASIT, employing a mouse model for cat allergy. Methods: BALB/c mice were subcutaneously immunized with the recombinant (r) cat allergen Fel d 1 followed by intranasal challenge with cat dander extract (CDE). The sensitized mice were therapeutically treated with rFel d 1 covalently coupled to CBPs (CBP‐rFel d 1). Airway hyper‐reactivity (AHR), infiltration of leucocytes in bronchoalveolar lavage (BAL) fluid, allergen‐specific serum immunoglobulin levels and in vitro splenocyte responses were evaluated. Results: Mice treated with CBP‐rFel d 1 showed reduced features of allergic inflammation. They responded with (i) significantly decreased AHR and infiltration of eosinophils in BAL fluid after CDE challenge, (ii) the serum level of rFel d 1‐specific IgE was reduced and the level of IgG 2 a was more pronounced after CBP‐rFel d 1 treatment, and (iii) there was also a tendency of decreased allergen‐specific cellular response. Conclusions: Carbohydrate‐based particles are effective tools as adjuvant and allergen carriers for use in ASIT and constitutes a promising strategy to improve allergy treatment.
Changes in normal glycosylation mechanisms in autoimmune rheumatic disease.
Authors: J S Axford, N Sumar, A Alavi, D A Isenberg, A Young, K B Bodman, I M Roitt
Journal: Journal of Clinical Investigation (1992)

To investigate potential mechanisms controlling protein glycosylation we have studied the interrelationship between lymphocytic galactosyltransferase (GTase) activity and serum agalactosylated immunoglobulin G levels (G(0)) in healthy individuals and patients with rheumatoid arthritis and non-autoimmune arthritis. In RA there was reduced GTase activity and increased G(0). A positive linear correlation between B and T cell GTase was found in all individuals. The relationship between GTase and G(0) was found to be positive and linear in the control population and negative and linear in the RA population. Sulphasalazine therapy maintained normal levels of GTase and caused a reduction in G(0) in the RA population. IgG anti-GTase antibodies (abs) were significantly increased in the RA population, whereas IgM anti-GTase abs were significantly decreased in both the RA and the non-autoimmune arthritis groups. These data describe a defect in RA lymphocytic GTase, with associated abnormal G(0) changes, which is corrected by sulphasalazine. A possible regulatory mechanism controlling galactosylation in normal cells is suggested, in which there is parallel control of B and T cell GTase. IgM anti-GTase abs may be integrated into this normal regulatory process. This is disrupted in RA, where the positive feedback between GTase and G(0) is lost and there is an associated increase in IgG anti-GTase abs, which may result from isotype switching as IgM anti-GTase abs are reduced. We suggest that these mechanisms are of relevance to the pathogenesis of RA, and that their manipulation may form part of a novel therapeutic approach.