tbuckley/cabot-search huggingface dataset:
Biotransformation of BDE-47 to Potentially Toxic Metabolites Is Predominantly Mediated by Human CYP2B6
Authors: Maria Luisa Feo, Michael S. Gross, Barbara P. McGarrigle, Ethel Eljarrat, Damià Barceló, Diana S. Aga, James R. Olson
Journal: Environmental Health Perspectives (2012)

Background: Previous studies have indicated that cytochrome P450s (CYPs) are involved in the metabolism of polybrominated diphenyl ether (PBDE) flame retardants in humans, resulting in the formation of hydroxylated PBDEs (OH-PBDEs) that are potentially more toxic than the parent PBDEs. However, the specific enzymes responsible for the formation of OH-PBDEs are unknown.Objectives: The purposes of this study were to characterize the in vitro metabolism of 2,2´,4,4´-tetrabromodiphenyl ether (BDE-47) by human liver microsomes (HLM) and recombinant human CYPs, and to identify the CYP(s) that are active in the oxidative metabolism of BDE-47.Methods: Recombinant human CYPs (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) were incubated with BDE-47 (20 µM), and the metabolites were measured and characterized using gas chromatography with tandem mass spectrometry (GC-MS/MS). For kinetic studies, CYP2B6 and pooled human liver microsomes (HLMs) were incubated with BDE-47 (0–60 µM).Results: CYP2B6 was the predominant CYP capable of forming six OH-BDEs, including 3-OH-BDE-47, 5-OH-BDE-47, 6-OH-BDE-47, 4-OH-BDE-42, 4´-OH-BDE-49, and a metabolite tentatively identified as 2´-OH-BDE-66. On the basis of full-scan GC-MS analysis, we hypothesized the formation of two other metabolites: di-OH-tetra-BDE and di-OH-tetrabrominated dioxin. In kinetic studies of BDE-47 metabolism by CYP2B6 and pooled HLMs, we found Km values ranging from 3.8 to 6.4 µM and 7.0 to 11.4 µM, respectively, indicating the high affinity toward the formation of OH-BDEs.Conclusion: Our findings support a predominant role of CYP2B6 in the metabolism of BDE-47 to potentially toxic metabolites, including a hypothesized di-OH-tetrabrominated dioxin metabolite. These results will assist future epidemiological studies investigating the potential of PBDEs and their metabolites to produce neurobehavioral/neurodevelopmental disorders.
Excision of the Patella
Authors: G. O. Tippett
Journal: BMJ (1938)

<h3>Abstract</h3> Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative DNA/RNA helicase, as the strongest predictor of sensitivity to DNA-damaging agents. However, its role as a prognostic biomarker is undefined, partially due to the lack of validated methods to score SLFN11 in human tissues. Here, we implemented a pipeline to quantify SLFN11 in human cancer samples. By analyzing a cohort of high-grade serous ovarian carcinoma specimens prior platinum-based chemotherapy treatment, we demonstrate that SLFN11 is expressed by infiltrating innate and adaptive immune cells. We show, for the first time, that SLFN11 density in both the neoplastic and microenvironmental components was independently associated with favorable outcome. Transcriptomic analyses suggested the presence of a hitherto modulation of the cancer-immunity cycle orchestrated by SLFN11. We propose SLFN11 as a dual biomarker capturing simultaneously interconnected immunological and cancercell-intrinsic functional dispositions associated with sensitivity to DNA damaging agents.
VENESECTION AND BLOOD TRANSFUSION IN CARBON MONOXIDE POISONING
Authors: C. Gordon-Watson
Journal: BMJ (1925)

_~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~LMDCLJuNl the size of a chestnut, was found in the posterior mediastinum, with the thoracic duct running through it (Fig. 1).Exploration of the abdomen revealed the presence of a mass the size of a clenched fist in the ri-ht lumbar region, with the inferior vena cava running through it (Fig. 2).The kidney was ,healthy, and the mass in the lumbar region did not involve the adrenal body, so it was thought that it must be due to glands ,secondary to a primary growth elsewhere.Palpation of the testis revealed no gross abnormality, but there was a small prominence about the size of a pea on the lower part of the body of the testis, near the globus minor of the epididymis.The testis was removed, and, on cutting it across, the small tumour, slhown in Fig. 3, was seen.All the specimens were sent to the Bland-Sutton Institute of Pathology -at the Middlesex Hospital, where they were examined by Professor Browning.He found that the primary tumour in the testis was a small embryoma, with the usual characteristics of these tumours.Its microscopic appearances are well shown in Figs. 4 and 5.
Peripheral Vascular Disease in Diabetics—An Angiographic Study.
Authors: William Jennings
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Peripheral Vascular Disease in Diabetics—An Angiographic Study.William Jennings, M.D., Fred W. Whitehouse, M.D., F.A.C.P., Roger F. Smith, M.D.William Jennings, M.D.Search for more papers by this author, Fred W. Whitehouse, M.D., F.A.C.P.Search for more papers by this author, Roger F. Smith, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-858_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAre diabetics who are prone to diffuse atherosclerotic disease candidates for peripheral angioplasty? The records of 102 diabetics who had translumbar aortograms during the 1965 to 1968 period because of symptomatic peripheral vascular disease (intermittent claudication, ischemic rest pain, or pedal ulceration or gangrene, or both, were reviewed. Of 56 diabetics who had potentially operable vascular lesions, 37 underwent angioplastic surgery (aortoiliofemoral bypass, 17; femoropopliteal bypass, 17; other, three) and 19 others either refused surgery or were followed medically. An endangered foot was saved in nine patients, and a total of 28 operations were deemed successful (relief of the major... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: William Jennings, M.D.; Fred W. Whitehouse, M.D., F.A.C.P.; Roger F. Smith, M.D.Affiliations: Detroit, Mich. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 858-859KeywordsAngioplastyLesionsPeripheral vascular diseaseUlcersVascular surgery ePublished: 1 December 2008 Issue Published: 1 May 1972 PDF downloadLoading ...
Recurrent aphthae: treatment with vitamin B12, folic acid, and iron.
Authors: D Wray, M M Ferguson, D K Mason, A W Hutcheon, J H Dagg
Journal: BMJ (1975)

A series of 130 consecutive outpatients with recurrent aphthous stomatitis were screened at the oral medicine department, Glasgow Dental Hospital, for deficienciesin vitamin b12, folic acid, and iron. In 23 patients (17.7%) such deficiencies werefound; five were deficient in vitamin B12, seven in folic acid, and 15 in iron. Four had more than one deficiency. Out of 130 controls matched for age and sex 11 (8.5%) were found to have deficiencies. The 23 deficient patients with recurrent aphthaewere treated with specific replacement therapy, and all 130 patients were followed up for at least one year. Of the 23 patients on replacement therapy 15 showed complete remission of ulceration and eight definite improvement. Of the 107 patientswith no deficiency receiving local symptomatic treatment only 33 had a remission or wereimproved. This difference was significant (P less than 0.001). Most patients withproved vitamin B12 or folic acid deficiency improved rapidly on replacement therapy;those with iron deficiency showed a less dramatic response. The 23 deficient patientswere further investigated to determine the cause of their deficiencies and detect the presence of any associated conditions. Four were found to have Addisonian perniciousanaemia. Seven had a malabsorption syndrome, which in five proved to be a gluten-induced enteropathy. In addition, there were single patients with idiopathic proctocolitis, diverticular disease of the colon, regional enterocolitis, and adenocarcinoma of thecaecum. We suggest that the high incidence of deficiencies found in this series andthe good response to replacement therapy shows the need for haematological screening of such patients.
Optimizing Diagnosis and Management of Nocardia Keratitis, Scleritis, and Endophthalmitis: 11-Year Microbial and Clinical Overview
Authors: Francis Char DeCroos, Prashant Garg, Ashok K. Reddy, Ashish Sharma, Sannapaneni Krishnaiah, Meeta Mungale, Prithvi Mruthyunjaya
Journal: Ophthalmology (2011)
A NEW BIOPSY KNIFE
Authors: Eugene A. Dupin
Journal: JAMA (1926)

In doing a biopsy of a new growth, it is our object to remove that portion of the growth in which the cells are young and actively proliferating. This area is at the periphery of the mass. We should accomplish our object with as little discomfort as possible to the patient. If we excise a wedge-shape portion of a growth by means of an ordinary scalpel it is necessary to make three or more separate incisions, and to use thumb forceps, etc. When the lesion is small I have found the use of the ordinary scalpel cumbersome. To obviate some of the difficulties of doing a simple biopsy and to accomplish our object more effectively, I would suggest the use of the knife here described. This instrument is a scalpel with a blade curved on the flat and with a cutting edge on each side and at its tip. The
Janus kinase 3 inhibitor WHI-P131/JANEX-1 prevents graft-versus-host disease but spares the graft-versus-leukemia function of the bone marrow allografts in a murine bone marrow transplantation model
Authors: Fatih M. Uckun, Bertram A. Roers, Barbara Waurzyniak, Xing-Ping Liu, Marina Cetkovic-Cvrlje
Journal: Blood (2002)
Abstract 5485: Modular nanotransporters: a chimeric multi-functional platform for drug delivery <i>in vivo</i>
Authors: Alexander S. Sobolev, Tatiana A. Slastnikova, Andrey A. Rosenkranz, Raymond M. Schiffelers, Michael R. Zalutsky
Journal: Cancer Research (2010)

Abstract A major challenge in the development of specific and effective targeted treatments is the paradoxical situation: one needs to exploit surface molecular targets for achieving tumor selectivity and nevertheless needs to deliver the therapeutic inside the target cell, e.g. to the cell nucleus because subcellular targeting is generally required for maximizing the therapeutic effect. We created modular nanotransporters (MNT) unifying these 2 contradictory features into one chimeric macromolecule consisting of:- (i) an internalizable ligand module, (ii) a module with nuclear localization sequence, (iii) an endosomolytic module, and (iv) a carrier module. The modules retained their functions within the MNT: they showed high-affinity interactions with target receptors and alpha/beta-importin dimers, and form holes in lipid bilayers at endosomal pH. Anti-cancer therapeutics (photosensitizers, alpha-particle emitting radionuclides) carried by MNT acquired 20-3000 times greater cytotoxicity and cell specificity if compared with free therapeutics. Herein, we have demonstrated in vivo that MNT possess a unique combination of properties compared with other scaffolds for drug delivery such as antibodies, nanoparticles, and liposomes. The MNT can be freeze-dried and reconstituted without loss of activity. Different modules can be inserted into the MNT in order to impart them with a specific set of capabilities; the modules are interchangeable, so they can be adapted for different cell types and/or different subcellular targets. The MNT can be used for the delivery of many types of therapeutics; they demonstrate low toxicity and low induction of delayed type hypersensitivity in mice. The MNT accumulated in murine tumors with high tumor: non-tumor ratios and displayed preferential accumulation in the subcellular compartment of choice, e.g. the cell nucleus. And finally, anti-cancer therapeutics carried by MNT acquired significantly greater cytotoxicity and cell specificity compared with free therapeutics. We think that the MNT represent a new platform for targeted drug delivery that could be applied to the treatment of aberrant cell populations characterized by up regulation of a receptor for which there is a known ligand. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5485.
GPs can shape services by bidding for provider contracts
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

GPs need to get to grips with the ins and outs of alternative provider medical services (APMS)—a new type of contract for providing primary care services—if they are to compete with private enterprise and shape the future of community health services, says the BMA.

The new contractual arrangement was first outlined in the NHS Improvement Plan in June 2004. It allows primary care trusts to commission medical services from the independent sector, voluntary sector, not for profit organisations, NHS trusts, other primary care trusts, and foundation trusts. They can also commission services from doctors who are on the …
Gastrointestinal Angiodysplasia in Chronic Renal Failure
Authors: MICHAEL MCKINNEY
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 December 1985Gastrointestinal Angiodysplasia in Chronic Renal FailureMICHAEL MCKINNEY, M.D.MICHAEL MCKINNEY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-6-960_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Zuckerman and coworkers (1) have reported a high incidence of angiodysplasia as the cause of upper gastrointestinal tract bleeding in patients with chronic renal failure. They report finding a "vascular appearing lesion" in 23% of these patients at endoscopy. I find it interesting that the diagnosis was made by visual inspection alone, with no histologic confirmation, because the differentiation between angiodysplasia and submucosal hemorrhage can be difficult macroscopically, at least in our experience.We are frequently asked to evaluate upper gastrointestinal tract bleeding in patients with chronic renal failure. Recently, we have found many small, irregular, red,...References1. ZUCKERMANCORNETTECLOUSEHERSCHEL GGRR. Upper gastrointestinal bleeding in patients with chronic renal failure. Ann Intern Med. 1985;102:588-92. LinkGoogle Scholar2. WILLIAMS C. The use of hot biopsies. Endoscopy Rev. 1985;2:12-7. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The University of Texas Medical Branch at Galveston Galveston, TX 77550 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1985Volume 103, Issue 6_Part_1Page: 960-961KeywordsEndoscopyGastrointestinal tractHemorrhageLesionsRenal failure Issue Published: 1 December 1985 PDF DownloadLoading ...
901–48 Antibody Conjugation of Acoustically Reflective Liposomes for Tissue Targeting
Authors: Vallerie V. Valentini, Sasha E. Murer, Bonnie J. Kane, Michael J. Vonesh, Hayat Alkan Onyuksel, Melvin E. Klegerman, David D. McPherson
Journal: Journal of the American College of Cardiology (1995)
Outcomes of Women Who Were Premenopausal at Diagnosis of Early Stage Breast Cancer in the NCIC CTG MA17 Trial.
Authors: P. Goss, J. Ingle, S. Martino, N. Robert, H. Muss, L. Shepherd, K. Pritchard, R. Livingston, N. Davidson, E. Perez, D. Cameron, T. Whelan, M. Palmer, D. Tu
Journal: Cancer Research (2009)

Abstract Background: MA17 showed that adjuvant letrozole after 5 years of tamoxifen markedly reduced the risk of recurrence in women with ER+ early stage breast cancer and improved overall survival in women presenting with node +ve disease. Most trials of early adjuvant aromatase inhibitor therapy required women to be postmenopausal at diagnosis to be eligible. We report here on a subset of women in the MA17 trial who were premenopausal at initial diagnosis and in whom subsequent menopause, prior to randomization, may have influenced their outcome on extended adjuvant letrozole.Methods: Women randomized to MA17 were divided into 2 groups: 1) pre-menopausal (&amp;lt; 50 years of age but underwent bilateral oophorectomy at time when tamoxifen treatment started or &amp;lt; 50 years of age at the start of tamoxifen treatment but became amenorrheic during adjuvant chemotherapy or tamoxifen treatment) and 2) post-menopausal. Disease-free survival (DFS) from time of randomization for women in these two groups were summarized by Kaplan-Meier curves and compared based on log-rank test and Cox model.Results: 889 women were identified as premenopausal and 4,277 as postmenopausal. Treatment, age, race, duration of tamoxifen, prior adjuvant chemotherapy, and mastectomy were independently associated with menopausal status on multivariate analysis. The interaction between treatment and menopausal status was statistically significant for DFS (p=0.02), indicating that women diagnosed with pre-menopausal breast cancer had significantly greater benefit (Hazard ratio=0.25, 95% CI: 0.12-0.51) with letrozole treatment in terms of DFS than those with post-menopausal status (hazard ratio=0.69 with 95% CI from 0.52 to 0.91). In comparison with women treated with placebo, pre-menopausal women on letrozole had a significantly higher incidence of arthralgia (24 vs. 16%; p=0.004) but a lower incidence of vaginal bleeding (10 vs. 16%; p=0.01). Compared with placebo post-menopausal women receiving letrozole had a higher incidence of hot flashes/flashes (55 vs. 50%; p=0.001), arthralgia (25 vs. 21%; p=0.002), myalgia (15 vs. 12%; p=0.007) and alopecia (5 vs. 3%; p=0.003).Conclusions: Letrozole after tamoxifen was more effective in improving DFS in women who were premenopausal at primary diagnosis than those who were postmenopausal. Letrozole was well tolerated in premenopausal women. These data indicate that women who are premenopausal at the time of diagnosis but become postmenopausal anytime before, or during, adjuvant tamoxifen should be considered for extended adjuvant therapy with letrozole. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 13.
BMJ briefing: meet the new masters of public health
Authors: R. Vize
Journal: BMJ (2013)

Public health felt the brunt of English health reorganisations last year as key parts moved from the NHS into local government—an area more used to housing and road problems than a mass measles outbreak. <b>Richard Vize</b> maps what’s happened to the old NHS run services and asks doctors how the new masters of public health are coping
Bone lead as a new biologic marker of lead dose: recent findings and implications for public health.
Authors: H Hu
Journal: Environmental Health Perspectives (1998)

Measurements of lead in bone have recently become the focus of research because a) bone lead levels serve as a cumulative dosimeter of lead exposure over many years (because of lead's long residence time in bone), and cumulative exposure may be more predictive of chronic toxicity than recent exposure, which is what blood lead levels mostly reflect; b) there is suspicion that heightened bone turnover (e.g. during pregnancy, lactation, and aging) may liberate enough stored lead to pose a significant threat of delayed toxicity; and c) although lead exposure has largely declined in the United States over the past 10 to 15 years, decades of heavy environmental pollution have resulted in significant accumulation of lead in bone among most members of the general U.S. population. Epidemiologic research on the impact of lead stored in bone is now possible with the development of 109Cd K-X-ray fluorescence (KXRF) instruments for the in vivo measurement of lead in bone. In this paper, the KXRF method will be briefly reviewed, followed by a summary of several Superfund-supported studies (and others) of blood lead and KXRF-measured bone lead in which these measures are compared as biologic markers of lead dose. Measurement of bone lead in epidemiologic studies has proved useful in exposure assessment studies, i.e., in identifying factors that contribute most to retained body lead burden, and in investigating cumulative lead exposure as a risk factor for poor health outcomes such as hypertension, kidney impairment, cognitive impairment, behavioral disturbances, and adverse reproductive outcomes.
Sudden Painless Nail Shedding
Authors: Romano Silvio Kasper, Stephan Nobbe, Martin Theiler, Lisa Weibel
Journal: JAMA Pediatrics (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Intensive chemotherapy regimen (LMB86) for St Jude stage IV AIDS-related Burkitt lymphoma/leukemia: a prospective study
Authors: Lionel Galicier, Claire Fieschi, Raphael Borie, Véronique Meignin, Marie-Thérèse Daniel, Laurence Gérard, Eric Oksenhendler
Journal: Blood (2007)
Upper Airway Epithelial Structural Changes in Obstructive Sleep-disordered Breathing
Authors: Friedrich P. Paulsen, Philipp Steven, Michael Tsokos, Karl Jungmann, Andreas Müller, Thomas Verse, Wolfgang Pirsig
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The etiology of upper airway collapsibility in patients with snoring and obstructive sleep apnea (OSA) remains unclear. Structural mucosal changes could be contributory factors. The objective of this study was to determine whether pathologic changes in the epithelium or the epithelial-connective tissue interface are present in patients with snoring and/or OSA by means of scanning electron microscopy and immunohistochemistry. Uvulae were obtained by uvulopalatopharyngoplasty from three patients with habitual snoring and nine patients with mild to severe OSA, as well as by dissection from 43 nonsnoring body donors. Scanning electron microscopy revealed structural changes in the epithelial-connective tissue boundary that significantly differed from age-related changes in the control subjects. The immunohistochemical staining with antibodies against epithelial cytokeratins showed differences in the expression pattern of cytokeratin 13 between patients and control subjects. No differences were found in the distribution pattern of laminin. Analysis of defense cells revealed a significant diffuse infiltration of leukocytes, mainly T cells, inside the lamina propria of the patient group, which was not observed in the control group. In conclusion, these results support the hypothesis that progressive structural changes in the mucosa caused by the trauma of snoring are a possible contributory factor to upper airway collapsibility.