tbuckley/cabot-search huggingface dataset:
Role of the kidneys in the metabolism of plasma mevalonate. Studies in humans and in rhesus monkeys.
Authors: D J McNamara, E H Ahrens, T S Parker, K Morrissey
Journal: Journal of Clinical Investigation (1985)

Studies were carried out in humans and in rhesus monkeys to determine the role of the kidneys in the metabolism of circulating mevalonic acid (MVA). Following intravenous infusion of [14C]MVA and [3H]cholesterol, there was a rapid appearance of [14C]squalene in the kidneys that exhibited a significantly longer half-life than plasma or hepatic squalene. In man and in rhesus monkeys there was a rapid equilibration between newly synthesized cholesterol from MVA and exogenously administered cholesterol in all tissues except the kidneys, where the specific activity ratio of newly synthesized to exogenous cholesterol was significantly higher. Estimates of the quantitative metabolism of intravenously infused radiolabeled MVA in the monkey demonstrated that 23% was excreted in the urine, 67% metabolized to cholesterol (58% in nonrenal tissues and 9% in the kidneys), and 10% catabolized to CO2 and nonsteroid products. Measurements of MVA metabolism in anephric and uninephric patients demonstrate that, in the absence of renal uptake of MVA, exogenous and newly synthesized cholesterol achieve almost instantaneous equilibrium in the plasma; whereas in control subjects with normal renal function, this equilibration required at least 21 d for the two cholesterol decay curves to become parallel. These results suggest that the kidneys are solely responsible for the observed disequilibrium between newly synthesized and exogenous cholesterol; we suggest that this was due to the delayed release of newly synthesized cholesterol from the kidneys into the plasma compartment following intravenous infusion with radiolabeled MVA. The data document the importance of the kidneys in the metabolism of circulating MVA. However, calculation of the quantitative significance of this pathway in relation to whole body MVA metabolism indicates that renal metabolism of MVA accounts for approximately 0.1% of daily MVA turnover, and that alterations in this pathway due to any form of renal pathology would not result in significant changes in hepatic or whole body sterol synthesis rates. We urge caution in the use of radiolabeled MVA in long-term kinetic studies of sterol metabolism because our data show that the plasma compartment of MVA is not necessarily in isotopic equilibrium with tissue MVA.
The Inflammatory Bowel Disease Yearbook 2004
Authors: S Ghosh
Journal: Gut (2005)

Edited by C N Bernstein. London: Remedica Publishing Ltd, 2003, £25.00, pp 200. ISBN 1901346579

This is the second edition of an annual update on inflammatory bowel disease (IBD). Yearbooks are useful resources for quickly catching up with a field, “Readers Digest” style. Being concise as well as giving coverage of the advances of the entire field in a year are therefore requisites for success. This yearbook is …
Multiple and large simple renal cysts are associated with prehypertension and hypertension
Authors: Chih-Ting Lee, Yi-Ching Yang, Jin-Shang Wu, Ying-Fang Chang, Ying-Hsiang Huang, Feng-Hwa Lu, Chih-Jen Chang
Journal: Kidney International (2013)

Although simple renal cysts are thought to be related to hypertension, no reports have examined the relationship between simple renal cysts and prehypertension. Here, we evaluated the effects of simple renal cysts on prehypertension and hypertension and the role of serum renin levels in the cyst-related prehypertension/hypertension in adults. A total of 14,995 patients were enrolled and divided into normotension, prehypertension, and hypertension groups. Simple renal cysts were classified into different categories based on number (1 vs. ≥ 2 cm) and size (<2 vs. ≥ 2 cm). In multivariate analysis, simple renal cysts were independently related to prehypertension/hypertension. Two or more simple renal cysts or cyst of ≥ 2 cm were independently associated with prehypertension/hypertension. However, the association between cyst of ≥ 2 cm and prehypertension/hypertension disappeared after further adjusting for serum renin level in an exposure-matched subgroup analysis. Thus, the presence of two or more simple renal cysts and cyst of ≥ 2 cm were the important determinants of prehypertension and hypertension in adults. One possible mechanism of cyst-related prehypertension/hypertension may be related to an increased serum renin level. We recommend close monitoring of blood pressure routinely among patients with two or more simple renal cysts.
Structural diversity of mast cell granules in black and white skin
Authors: H. Sueki, D. Whitaker-Menezes, A.M. Kligman
Journal: British Journal of Dermatology (2001)

Journal Article Structural diversity of mast cell granules in black and white skin Get access H. Sueki, H. Sueki Department of Dermatology, University of Pennsylvania School of Medicine and Hirohiko Sueki, MD, Department of Dermatology, Showa University School of Medicine, 1‐5‐8, Hatanodai, Shinagawa‐ku, Tokyo 142‐8666, Japan. E‐mail: hirsueki@med.showa‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar D. Whitaker‐Menezes, D. Whitaker‐Menezes Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar A.M. Kligman A.M. Kligman Department of Dermatology, University of Pennsylvania School of Medicine and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 1, 1 January 2001, Pages 85–93, https://doi.org/10.1046/j.1365-2133.2001.03957.x Published: 01 January 2001
Stakeholder Priorities for Comparative Effectiveness Research in Chronic Obstructive Pulmonary Disease
Authors: Jerry A. Krishnan, Peter K. Lindenauer, David H. Au, Shannon S. Carson, Todd A. Lee, Mary Ann McBurnie, Edward T. Naureckas, William M. Vollmer, Richard A. Mularski
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Comparative effectiveness research (CER) is intended to address the expressed needs of patients, clinicians, and other stakeholders. Representatives of 54 stakeholder groups with an interest in chronic obstructive pulmonary disease (COPD) participated in workshops convened by the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation (CONCERT) over a 2-year period. Year 1 focused on chronic care and care coordination. Year 2 focused on acute care and transitions in care between healthcare settings. Discussions and provisional voting were conducted via teleconferences and e-mail exchanges before the workshop. Final prioritization votes occurred after in-person discussions at the workshop. We used a modified Delphi approach to facilitate discussions and consensus building. To more easily quantify preferences and to evaluate the internal consistency of rankings, the Analytic Hierarchy Process was incorporated in Year 2. Results of preworkshop and final workshop voting often differed, suggesting that prioritization efforts relying solely on requests for topics from stakeholder groups without in-person discussion may provide different research priorities. Research priorities varied across stakeholder groups, but generally focused on studies to evaluate different approaches to healthcare delivery (e.g., spirometry for diagnosis and treatment, integrated healthcare strategies during transitions in care) rather than head-to-head comparisons of medications. This research agenda may help to inform groups intending to respond to CER funding opportunities in COPD. The methodologies used, detailed in the online supplement, may also help to inform prioritization efforts for CER in other health conditions.
The development of applied action levels for soil contact: a scenario for the exposure of humans to soil in a residential setting.
Authors: R M Sedman
Journal: Environmental Health Perspectives (1989)

The California Site Mitigation Decision Tree Manual, 1985, was developed by the California Department of Health Services to provide a detailed technical basis for managing uncontrolled hazardous waste sites. The Decision Tree describes a process that relies on criteria, Applied Action Levels (AALs) to evaluate and, if necessary, mitigate the impact of uncontrolled hazardous waste sites on the public health and the environment. AALs are developed for individual substances, species, and media of exposure. AALs have been routinely developed for the media of air and water; however, an approach for developing AALs for soil contact was lacking. Given that the air pathway for soil contact is addressed in AALs for air, two routes of exposure, ingestion and dermal contact, are addressed in developing AALs for soil contact. The approach assumes a lifetime of exposure to soil in a residential setting. Age-related changes in exposure are included in the scenario. Exposure to soil due to ingestion and dermal contact are quantitated independently and then integrated in the final exposure scenario. A mass balance approach using four elements is employed to quantitate soil ingestion for a young child. Changes in soil ingestion with age are based on age-related changes in blood lead concentration and mouthing behavior. Dermal exposure to soil was determined from studies that reported skin soil load and from estimates of exposed skin surface area. Age-related changes in the dermal exposure to soil are also based on changes with age of blood lead concentration and mouthing behavior. The estimates of exposure to soil due to ingestion and dermal contact are integrated, and an approach for developing AALs is advanced. AALs are derived by allocating the Maximum Exposure Level as described in the Decision Tree to the average daily exposure to soil. Toxicokinetic considerations for the two routes of exposure must be included in deriving AALs for the soil medium of exposure.
Catheter Balloon Valvuloplasty of the Mitral Valve in Adults Using a Double-Balloon Technique
Authors: Charles R. McKay
Journal: JAMA (1987)

Catheter balloon valvuloplasty (CBV) using the double-balloon technique was performed on 12 symptomatic patients (mean age, 43 years) with rheumatic mitral valve stenosis. Two dilatation balloons were used in which the diameters approximately equaled the mitral valve anulus diameter as determined. After CBV, the mean mitral valve gradient decreased in all patients (mean +/- SD, 16 +/- 6 to 5 +/- 2 mm Hg), the mean left atrial pressure decreased (29 +/- 7 to 16 +/- 4 mm Hg), and the cardiac output increased (4.4 +/- 1.2 to 5.5 +/- 1.4 L/min). The mitral valve area increased from 1.0 +/- 0.3 to 2.4 +/- 0.8 cm2. Oximetry demonstrated small left to right shunts of pulmonary to systemic flow ratios of 1.4:1 and 1.3:1 in two patients. Mitral regurgitation did not increase. Gradual decreases in mean pulmonary artery pressures and pulmonary vascular resistance were recorded over the subsequent 24 hours. Our patients left the hospital two days after CBV. The New York Heart Association Functional Class improved in 11 of 12 patients. We conclude that CBV using the double-balloon technique effectively relieves mitral valve obstruction, reduces elevated pulmonary pressures, and reduces symptoms in selected adult patients with symptomatic mitral stenosis.
The 2-pyridone antibacterial agents: bacterial topoisomerase inhibitors
Authors: Qun Li, Lester A. Mitscher, Linus L. Shen
Journal: Medicinal Research Reviews (2000)

Many attempts have been made to prepare analogs of 4-quinolone antibacterial agents bearing novel ring systems, which might retain the favorable properties of these widely used antibacterial agents and at the same time increase activity against multidrug-resistant bacteria, streptococci, and anaerobic microorganisms. One such attempt involved bioisosteric exchange of the 1-N atom and 4a-C atom of naphthyridones, quinolones, and benzoxazines to produce a family of highly active pyridopyrimidines, quinolizines, and ofloxacin bioisosteres. These new antibacterial agents have been named collectively as the 2-pyridones. Many hundreds of 2-pyridones have been synthesized and evaluated in vitro and in vivo, and selected members are advancing toward human clinical trials. Preparation of these bioisosteres required the development of enabling chemistry, as previous methods were unsuccessful in producing the needed core structures. This review compares the structure-activity relationships of these agents with known trends among 4-quinolones, from which it is seen that there are many parallels, but also some significant departures as well. Generally, 2-pyridones are more highly active in vitro and in vivo and more water soluble than comparable 4-quinolones. These properties are posited to arise from electronic and conformational alternations in these new substances. Selected members show excellent pharmacodynamic properties, justifying the view that this is a very promising new class of totally synthetic antibacterial agents. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 4, 231–293, 2000
Leukemic Stem Cell Gene Expression Signature and Clinical Outcomes in Acute Myeloid Leukemia
Authors: Shigeo Masuda
Journal: JAMA (2011)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect of some anti-inflammatory drugs on fibroblast-leucocyte interaction in vitro.
Authors: M Yaron, I Yaron, D Allalouf
Journal: Annals of the Rheumatic Diseases (1971)

<h3>Abstract</h3> It is tempting to mine the abundance of DNA data that is now available from direct-to-consumer genetic tests, but this approach has its pitfalls A recent study put forth a list of 50 single nucleotide polymorphisms (SNPs) that predispose to Chronic Fatigue Syndrome (CFS), a potentially major advance in understanding this still mysterious disease. However, only the patient cohort data came from a commercial company (23andMe) while the control was a genetic database. The extent to which 23andMe data agree with genetic reference databases is unknown. We reanalyzed the 50 purported CFS SNPs by comparing to control data from 23andMe which are available through public platform OpenSNP. In addition, large high-quality database ALFA was used as an additional control. The analysis lead to dramatic change with the top of the leaderboard for CFS risk reduced and reversed from an astronomical 129,000 times to 0.8. Errors were found both within 23andMe data and the original study-reported Kaviar database control. Only 3 of 50 SNPs survived initial study criterion of at least twice as prevalent in patients, EFCAB4B involving calcium ion channel, LINC01171, and MORN2 genes. We conclude the reported top-50 deleterious polymorphisms for Chronic Fatigue Syndrome were more likely the top-50 errors in the 23andMe and Kaviar databases. In general, however, correlation of 23andMe control with ALFA was a respectable 0.93, suggesting an overall usefulness of 23andMe results for research purposes but only if caution is taken with chips and SNPs.
Hazard of Influenza Vaccine In Neurologic Patients
Authors: Jack Rabin
Journal: JAMA (1973)

To the Editor.—  For many years the use of vaccines and immunization in certain neurologic cases, especially of demyelinating disease, has been controversial. The consensus of neurologists is that immunization procedures can be hazardous in cases that might involve altered immune mechanisms such as multiple sclerosis.  Apparently, many public health authorities and pharmaceutical companies mislead practicing physicians into thinking that immunization procedures are generally safe and proper for patients with chronic debilitating neurological disease. Actually, the contrary would appear to be the case.  I recently reviewed a patient who had recovered from a single attack of retrobulbar neuritis in 1961, had functioned as an executive secretary for a major insurance company without physical disability until 1968 when she received an injection of influenza vaccine, and shortly thereafter became blind and quadriplegic. She has since made a partial recovery but has been left paraplegic with bladder incontinence and only partial use
Plastic Balloon Catheter
Authors: S. Power
Journal: BMJ (1965)

BRiTisH 879 but when assessing symptoms that are by definition subjective the patients' opinions are of importance.'Whether or not symptomatic improvement correlates with objective measurements is another matter.It would appear to be particularly important to consider patients' opinions in fluctua- ting conditions such as bronchospasm, where they may well be able to give an overall im- pression of their clinical condition during a period of time, while isolated objective tests only give information on a few minutes separated by many weeks.Another example occurred in the same issue of the B.M.7. in a review of inhaled steroids for asthma (" Any Questions ?" 18 September, p. 691).Admittedly the trials quoted differed in many ways, but the studies relying mainly on subjective assessments2-5 found that inhalations of hydrocortisone acetate were significantly better than placebo while trials utilizing isolated lung function tests'7 were unable to demonstrate a difference between the two regimens.In the trial of breathing exercises it is possible that cough and sputum were worse in the treated group owing to the higher incidence of colds (58% as opposed to 40%), and that the patients took this into considera- tion when they declared an overall improve- ment in the symptom of dyspnoea after breathing exercises.It was, of course, impossible to conduct a double-blind trial on breathing exercises, and Stewart and Anderson8 are probably quite correct in stating that such exercises produce little or no benefit and that apparent im- provement was due to gratitude for extra attention.Nevertheless, it is worth mentioning that in trials of this sort where assessments of subjective symptoms are made over a prolonged period due weight should be given to patients' opinions, as isolated objective tests have considerable limitations.-Iam, etc.,
INFLUENCE OF VARIATIONS OF MEDIA ON ACID PRODUCTION BY STREPTOCOCCI
Authors: F. S. Jones
Journal: The Journal of Experimental Medicine (1920)

The results of variations in acid production in 1 per cent dextrose fermented and unfermented veal broth modified by the addition of 4 per cent of horse serum or 2 per cent of peptone have been recorded. Human streptococci and a group of low acid-producing streptococci from milk produce less acid in the simpler broths (fermented and unfermented). 2 per cent peptone fails to increase the amount of acid produced by these two groups. The bovine streptococci act much the same as those of human origin. The equine streptococci apparently do not require serum in addition to carbohydrate since they tend to produce less acid in serum media. The following figures indicate the average minimum and maximum acid production of the various streptococci under the conditions set forth in the experiment. Human: pH 4.97 to 5.66; titratable acidity 4.51 to 3.66 Bovine: pH 4.56 to 4.77; titratable acidity 7.0 to 5.74 Equine: pH 4.86 to 5.42; titratable acidity 5.38 to 4.24 Low acid-producing streptococci from milk: pH 6.28 to 5.14; titratable acidity 2.56 to 4.28
CD86 (B7–2) antigen on B cells from atopic patients shows selective, antigen‐specific upregulation
Authors: M. Nakada, K. Nishizaki, T. Yoshino, M. Okano, Y. Masuda, N. Ohta, T. Akagi
Journal: Allergy (1998)

To determine whether B7 signals are associated with atopic responses in man, we assayed CD80 and CD86 expression on B cells and monocytes from atopic patients and controls. Peripheral blood mononuclear cells from 10 patients with perennial allergic rhinitis and from 10 normal subjects were cultured in the presence or absence of house‐dust‐mite antigen, and B cells and monocytes were assayed for expression of CD80 and CD86 by flow cytometry. CD86 on B cells was significantly and selectively upregulated in all atopic subjects, but not in normal subjects, whereas CD80 expression was not altered in B cells from the atopic subjects or controls. In contrast, both CD80 and CD86 were upregulated in monocytes from the atopic subjects as well as the controls. However, CD86 upregulation was significantly higher in the atopic subjects than in controls. Our results seem to suggest that selective upregulation of CD86 on B cells by a challenging antigen may play a critical role in the development of Th2 cells in patients with atopic disease.
Abstract 4396: Conjugation site modulates the stability and biological activity of antibody drug conjugates
Authors: Ben-Quan Shen, Keyang Xu, Luna Liu, Kathryn Parsons, Sunil Bhakta, Helga Raab, Kelly Flagella, Susan D. Spencer, Surinder Kaur, Richard H. Scheller, Mark X. Sliwkowski, Paul Polakis, Jagath Reddy Junutula
Journal: Cancer Research (2010)

Abstract Antibody drug conjugates (ADCs) are attractive targeted chemo-therapeutic molecules as they combine ideal properties of both antibodies and cytotoxic drugs by targeting potent cytotoxic drugs to the antigen-expressing tumor cells, thereby enhancing their anti-tumor activity. The successful ADC development for a given target antigen depends on optimization of antibody selection, linker stability, cytotoxic drug potency and mode of linker-drug conjugation to the antibody. Recently, we have developed antibodies with cysteine substitutions (THIOMABs) at sites where the engineered cysteines are available for conjugation but do not perturb immunoglobulin folding and assembly or alter antigen binding and effector functions (Junutula, et al., Nature Biotech., 26, 925-932, 2008). These THIOMABs can then be derivatized through the engineered cysteine thiol group to obtain ADCs with uniform stoichiometry (∼2 drugs per antibody). Studies with multiple antibodies against different antigens have shown that THIOMAB drug conjugates (TDCs) are as efficacious as conventional conjugates in xenograft models and are tolerated at higher doses in relevant preclinical models. To further understand improved therapeutic activity and in vivo metabolism of TDCs, we have engineered TDCs with drug attachment at different parts of the antibody (light chain-Fab, heavy chain-Fab and heavy chain-Fc). TDCs produced by THIOMAB technology provided an unique advantage over conventional ADCs to answer several unresolved questions in ADC therapeutics due to their homogeneity and site-specific conjugation to cytotoxic drugs. We will discuss novel findings that were observed with these TDC varaints and the influence of conjugation site in modulating stability and biological activity of antibody drug conjugates. 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 4396.