tbuckley/cabot-search huggingface dataset:
Abstract 4774: LC-MS/MS detection of the dansyl-modified biologically active CDK inhibitor VMY-1-103 using an in vivo model system
Authors: Paul Sirajuddin, Sudeep Das, Lymor Ringer, Patricia Salinas, Olga Rodriguez, Bahram Moasser, Venkata M. Yenugonda, Christopher Albanese, Milton Brown
Journal: Cancer Research (2012)

Abstract The development of new small molecule kinase inhibitors as cancer therapeutic drugs has placed increased emphasis on determining the mechanism of action of the new compounds preclinically, such as in genetically engineered mice or using human tissue xenografts. The ability to accurately measure the pharmacokinetics and pharmacodynamics of new compounds is often hampered by the lack of suitable platforms to measure serum and tissue distribution with high sensitivity and specificity. We have recently developed a novel dansylated cyclin dependent kinase inhibitor called VMY-1-103 (VMY) that has purvalanol B as its base compound. We established that VMY was significantly more effective in blocking cell cycle progression and inducing apoptosis than purvalanol B. Since dansylation is frequently used to enhance mass spectrometry-based quantitative analyses, we hypothesized that this modality could similarly be used to evaluate the tissue distribution of VMY in mouse models. In the current study, we developed a rapid liquid phase-extraction of VMY and purvalanol B from mouse tissue and validated a sensitive liquid chromatography-tandem mass spectrometry based assay to quantify tissue delivery of these compounds in vivo. Comparisons of the standard curves for VMY versus Purvalanol B revealed a greater than 7.7-fold increase in sensitivity for VMY. Using both the ND-2 SmoA1, a genetically engineered mouse model of medulloblastoma, and normal mice, we quantified tissue delivery by mass spectrometry as well as Area Under the Curve (AUC) analysis by integrating the peak intensity normalized by an internal standard. Our analyses revealed that VMY delivered intraperitoneally at 20mg/kg was found at its highest concentration in serum 4 hours after injection. We further established that VMY was distributed in multiple tissues, including pancreas and prostate at varying levels and, importantly, we establish that VMY was able to traverse an intact blood-brain barrier as it was detected in the brain and cerebellum of normal mice. Purvalanol B delivered in the same manner as VMY was found at significantly lower levels in all tissues examined and unlike VMY, we failed to detect purvalanol B in brain or and cerebellar tissue. The significance of this study illustrates that a biologically active compound can be modified by dansylation and exhibit both increased sensitivity to mass spectrometry and enhanced bioavailability and tissue delivery, including the brain, in vivo. We also define a simple mass spectrometry-based tissue and serum assay. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4774. doi:1538-7445.AM2012-4774
Voriconazole versus Liposomal Amphotericin B in Patients with Neutropenia and Persistent Fever
Authors: John H. Powers, Cheryl A. Dixon, Mark J. Goldberger
Journal: New England Journal of Medicine (2002)

To the Editor: On October 4, 2001, the Antiviral Drugs Advisory Committee of the Food and Drug Administration (FDA) discussed1 the results of the clinical trial reported by Walsh and colleagues in ...
COMPLETE RUPTURE OF THE SUPRASPINATUS TENDON
Authors: PHILIP D. WILSON
Journal: JAMA (1931)

It is a trite remark to say that there is no teacher like experience, but it is unfortunately a truism which, when applied to surgery, carries unpleasant implications for the patient. My excuse in offering this paper is to record a personal experience in relation to injuries of the shoulder and to present the conclusions I have drawn from it in the hope that they may be of benefit to other surgeons. In the last eighteen months I have come to realize that complete rupture of the supraspinatus tendon is a common lesion. During that period I have made this diagnosis in ten patients, of whom seven have submitted to operation, at which time I was able to confirm the diagnosis and repair the tendon. Previous to this, in a surgical experience covering approximately sixteen years, I had made this diagnosis only twice. I am convinced from what I have
Applying Platelet Function Testing in Clinical Practice
Authors: Dominick J. Angiolillo
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
Brain Function: Cortical Excitability and Steady Potentials, Relations of Basic Research to Space Biology
Authors: John F. Simpson
Journal: JAMA (1964)

The co-chairmen of the conference, H. W. Magoun and F. Fremont-Smith, assembled a distinguished group of 29 participants from the United States, Canada, England, Germany, Argentina, Brazil, and Russia, who discussed certain specialized areas of brain function. Beginning with an admirable historical review by Brazier, the volume includes papers on ultrastructure and chemical organization of synapses; spreading depression; steady potential shifts; metabolic and electrical measurements, with isolated cerebral tissues; and the effects of transcortical polarizing currents on learning and on steady potential shifts in learning. The first portion of the volume ends with consideration of unidirectional potential shifts in petit mal. The second portion consists of three papers concerned with space biology. The first deals with certain aspects of brain physiology in the space environment; the second, with studies of brains exposed to cosmic rays and to accelerated alpha particles; and the third, with some relations of basic research to
EVALUATION OF THE " BREATH TEST " IN THE DETECTION OF BACTERIAL COLONISATION OF THE UPPER GASTROINTESTINAL TRACT
Authors: D.M. Parkin, R.R. O'Moore, D.J. Cussons, R.R.G. Warwick, P. Rooney, I.W. Percy-Robb, D.J.C. Shearman
Journal: The Lancet (1972)
Length of gestation.
Authors: W. M. Moore
Journal: BMJ (1970)

unwarranted.I recently had in my care a patient from eastern Europe sent for investigation of a suspected haemoglobin anomaly.3It turned out that this patient was taking huge amounts of phenacetin-containing analgesics, which were never found on him but which he stopped taking-as proved by the above urine test-when threatened with being returned to his country with the diagnosis of a grave psy- chiatric abnormality.Screening large numbers of persons in Switzerland for Nacetyl-p-aminophenol in urine has shown that up to 10%O of a given population is taking phenacetin-containing analgesics.3Intake of salicylate on its own is rare in Switzerland.Only two of five leading brands4 contain 0-125 g. and 0-37 g.In addition, it seems important that patients who have regularly abused anal- gesics containing phenacetin should have their urinary tract searched for tumours at necropsy.Within the last year five of 625 women regularly taking analgesics contain- ing phenacetin died while under close observation, and one developed a carcinoma of the bladder.5This tends to confirm the findings of Bengtsson6 and underlines the appeal by Dr. Koutsaimanis and Professor de Wardener that phenacetin should be sold only on prescription, although the evidence for an increased incidence of tumours of the urinary tract after many years' intake of phenacetin-containing analgesics is so far inclusive.-Iam, etc.,
Budd-Chiari syndrome after oral contraceptives.
Authors: A. W. Clubb, C. Giles
Journal: BMJ (1968)

BDIC^Lvesicles on the body.In the next few days there was further improvement.From thirteen days on, palms and soles desquamated in large flakes.On the sixteenth day the mouth had healed, with residual brown spots on lips.Skin of soles peeled off like sandals, in one piece.The patient was admitted to a general ward and treatment was symptomatic.On discharge the patient was warned that for some time he might spread foot-and-mouth disease among animals, and that therefore he should avoid contact with susceptible animals.Veterinary authorities were notified about this patient and carried out inspections in the district in which the slaughterhouse was situated.Foot-and-mouth disease was found among animals, although previously this district was declared free from disease.In conclusion I would like to emphasize that the health authorities would be well advised to pay close attention to the possibility of the disease in man as a potential factor in the spread of foot-and-mouth disease.-Iam, etc., London W. 13.
Expression of the chemokine receptors CXCR4, CXCR5, and CCR7 in primary central nervous system lymphoma
Authors: Kristoph Jahnke, Sarah E. Coupland, Il-Kang Na, Christoph Loddenkemper, Ulrich Keilholz, Agnieszka Korfel, Harald Stein, Eckhard Thiel, Carmen Scheibenbogen
Journal: Blood (2005)
Expression of the sarco/endoplasmic reticulum calcium ATPase type 2 and 3 isoforms in normal skin and Darier's disease
Authors: S. Tavadia, K.S. Authi, M.B. Hodgins, C.S. Munro
Journal: British Journal of Dermatology (2004)

Darier's disease (DD) is caused by mutations in ATP2A2, which encodes the sarco/endoplasmic reticulum calcium ATPase type 2 (SERCA2), a member of a family of calcium pumps important in intracellular calcium signalling. SERCA2 has two isoforms. SERCA2a occurs mainly in cardiac and skeletal muscle, whereas SERCA2b occurs ubiquitously and is coexpressed with the related SERCA type 3 (SERCA3) in many tissues. It is not known why mutations in the widely expressed SERCA2 manifest as a focal skin disease.To provide insight into the pathogenesis of DD by examining SERCA isoform expression in normal skin and DD skin.Using immunohistochemistry we studied SERCA2a, SERCA2b and SERCA3 expression in nonlesional and lesional skin from seven patients with DD and normal skin from seven control subjects. We quantified SERCA2a and SERCA2b staining intensity by grey scale analysis of fluorescence intensity.In normal and DD epidermis both SERCA2a and SERCA2b staining was seen. SERCA2a staining in epidermis was less intense relative to pilar muscle whereas SERCA2b staining in epidermis was of marginally greater intensity than in pilar muscle. SERCA3 was not expressed in normal or DD epidermis, but was found in eccrine glands and blood vessels. No reduction was detected in SERCA2a or SERCA2b staining intensity in DD nonlesional epidermis compared with control epidermis. In within-patient comparisons, SERCA2a and SERCA2b staining in lesional epidermis was less intense than in nonlesional epidermis.Both SERCA2a and SERCA2b are present in epidermis, although the latter may predominate. The absence of coexpressed SERCA3 in epidermis may explain the localization of DD. Comparable SERCA2 staining intensity in nonlesional DD and control epidermis, even in patients predicted to be haploinsufficient, suggests partial compensation by upregulation of the normal allele. Unknown additional factors may trigger focal lesions by overcoming this compensation. Reduced staining intensity in lesional tissue may be secondary, or may reflect local downregulation of SERCA2 expression predisposing to development of focal lesions.
Woman can challenge hospital over forced caesarean
Authors: C. Dyer
Journal: BMJ (1997)

A woman who was detained in hospital against her will and forced to undergo a caesarean section was given permission last week to challenge her treatment in an important test case.

Three judges at the Court of Appeal gave the 29 year old woman from London leave to seek a judicial review against the social worker who sectioned her for assessment under the Mental Health Act; the NHS trusts responsible for Springfield Hospital, the psychiatric hospital where she was first detained; and St George's Hospital, where …
Factors associated with spread of dengue fever in urban Lahore, Punjab, Pakistan, 2013
Authors: A Altaf
Journal: The Lancet Global Health (2015)

BackgroundIn Pakistan during 2005–06, an unprecedented increase in dengue fever occurred in the country, with a large number of cases reported in Karachi. During this time, more than 3640 patients were admitted to hospital with dengue. In the province of Punjab, disease incidence increased sharply towards August, 2011, especially in Lahore, with 17 256 cases and 279 deaths reported in that year. After Lahore, the next highest numbers of cases were reported in Faisalabad (783 cases), followed by Rawalpindi (410 cases), Pakpattan (233 cases), and Sheikhupura (225 cases). Since 2011 Lahore has been experiencing outbreaks of dengue fever every year. The aim of this study was to identify risk factors for dengue during the 2013 outbreak in Punjab, Pakistan, so as to help prevent future outbreaks.MethodsBetween Oct 4 and Nov 23, 2014, we conducted a descriptive study followed by a case control study to identify the risk factors for spread of dengue fever. A case was defined as any person resident of Data Gunj Bakhsh Town who presented with fever and any three of headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations, leukopenia, or abdominal pain, and also laboratory confirmation through ELISA. Control participants were taken from the same town and included people with dengue symptoms, but negative ELISA results. A standardised questionnaire was developed to collect data. A line listing of cases was developed and data were analysed with EpiInfo version 7·0.FindingsWe identified 147 cases and 300 controls (221 [73%] were men). Mean age was 30·9 years (range 5–70 years) and most cases were men (n=94 [64%]). Overall, the attack rate (AR) during the study period was 15 per 100 000 population. Residents in the 15–49 years age group had more dengue infections (n=114; AR=23·84 per 100 000) than did those aged 50 years and older (n=6; AR=15·3 per 100 000). On bivariate analysis, the presence of indoor stagnant water (OR=3·7 [95% CI=2.5-4.8], p<0·0001), presence of indoor larvae (OR=3·1 [2·3-4·4], p=0·001), and non-use of repellents (OR=2·7 [CI=1·5–3·2], p=0·01) were found to be independent determinants of dengue infection.InterpretationThere is a strong association between dengue transmission and both stagnant water indoors and the non-use of mosquito repellent in Punjab. That more men than women and younger rather than older people presented with dengue is consistent with other findings and may be because these groups are more likely to be outdoors and, therefore, be exposed to mosquitos. In areas at risk of dengue transmission, we undertook health education activities to improve use of repellents and remove sources of indoor stagnant water.FundingNone.
Open Segmental Tibial Fracture
Authors: Otto E. Aufranc
Journal: JAMA (1966)

<h3>Dr. Turner:</h3> A 17-year-old boy was riding his motorcycle and collided with an automobile. His right tibia was crushed between the running board of the automobile and the frame of his motorcycle. He arrived at the Massachusetts General Hospital emergency ward 30 minutes following his injury and was found to have a blood pressure of 80/40 mm Hg with a pulse rate of 140 beats per minute. Intravenous fluids were started, blood was sent for cross matching, and his injuries were then further assessed. There was no evidence of head, spine, chest, or abdominal trauma, and the patient's skeletal injuries were limited to the right leg. There was a 6-inch open wound over the anterolateral aspect of the right leg. There was a second, 1 1/2-inch open wound more distally, over the medial face of the tibia (Fig. 1). A segmented piece of the tibia 5 inches long presented between
Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey
Authors: C. Meier
Journal: BMJ (2003)

Primary hypothyroidism is a graded phenomenon with a wide spectrum of severity between subclinical hypothyroidism and overt hypothyroidism.Patients with biochemically severe hypothyroidism may present with only mild clinical manifestations, whereas some patients with moderate changes in thyroid hormones may present with severe signs of tissue hypothyroidism. 1 The measurement of pituitary thyroid stimulating hormone (TSH) is the most sensitive test for early diagnosis of primary hypothyroidism.The magnitude of elevation of TSH is commonly believed to correspond to the severity of tissue hypothyroidism.We aimed to evaluate the value of measuring serum TSH in assessing the severity of tissue hypothyroidism in patients with overt hypothyroidism.
Sugar sweetened drinks should carry obesity warnings
Authors: S. Capewell
Journal: BMJ (2014)

<h3>Abstract</h3> <h3>Objectives</h3> To use data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) to estimate mortality and disability trends for the population aged ≥70 and evaluate patterns in causes of death, disability, and risk factors. <h3>Design</h3> Systematic analysis. <h3>Setting</h3> Participants were aged ≥70 from 204 countries and territories, 1990-2019. <h3>Main outcomes measures</h3> Years of life lost, years lived with disability, disability adjusted life years, life expectancy at age 70 (LE-70), healthy life expectancy at age 70 (HALE-70), proportion of years in ill health at age 70 (PYIH-70), risk factors, and data coverage index were estimated based on standardised GBD methods. <h3>Results</h3> Globally the population of older adults has increased since 1990 and all cause death rates have decreased for men and women. However, mortality rates due to falls increased between 1990 and 2019. The probability of death among people aged 70-90 decreased, mainly because of reductions in non-communicable diseases. Globally disability burden was largely driven by functional decline, vision and hearing loss, and symptoms of pain. LE-70 and HALE-70 showed continuous increases since 1990 globally, with certain regional disparities. Globally higher LE-70 resulted in higher HALE-70 and slightly increased PYIH-70. Sociodemographic and healthcare access and quality indices were positively correlated with HALE-70 and LE-70. For high exposure risk factors, data coverage was moderate, while limited data were available for various dietary, environmental or occupational, and metabolic risks. <h3>Conclusions</h3> Life expectancy at age 70 has continued to rise globally, mostly because of decreases in chronic diseases. Adults aged ≥70 living in high income countries and regions with better healthcare access and quality were found to experience the highest life expectancy and healthy life expectancy. Disability burden, however, remained constant, suggesting the need to enhance public health and intervention programmes to improve wellbeing among older adults.
GDF-15 Contributes to Proliferation and Immune Escape of Malignant Gliomas
Authors: Patrick Roth, Markus Junker, Isabel Tritschler, Michel Mittelbronn, Yvonne Dombrowski, Samuel N. Breit, Ghazaleh Tabatabai, Wolfgang Wick, Michael Weller, Jörg Wischhusen
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family. GDF-15 is necessary for the maintenance of pregnancy but has also been linked to other physiologic and pathologic conditions. Experimental Design: The expression of GDF-15 in glioma cell lines was assessed by quantitative reverse transcriptase-PCR and immunoblot. GDF-15 levels in situ and in the peripheral blood of glioma patients were examined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The effects of short hairpin RNA-mediated GDF-15 inhibition on proliferation and immunogenicity of SMA-560 glioma cells were investigated by [methyl-3H]thymidine incorporation and immune-mediated target cell lysis. The impact of GDF-15 on glioma growth in vivo was assessed in syngeneic mice. Results: GDF-15 is expressed by gliomas of different WHO grades as assessed by immunohistochemistry. The high expression of GDF-15 in tumor tissue translates into elevated GDF-15 serum levels in glioblastoma patients compared with healthy controls. GDF-15 mRNA and protein are also detectable in human and mouse glioma cells in vitro. Silencing of GDF-15 by RNA interference reduces the proliferation of malignant glioma cells. Immunologically, the depletion of glioma-derived GDF-15 enhances the susceptibility of mouse glioma cells towards syngeneic natural killer cells and splenocytes. This results in a reduced in vivo tumorigenicity and increased T-cell infiltration of GDF-15–deficient glioma cells in syngeneic mice. Conclusions: Although previous studies focusing on ectopic overexpression of GDF-15 have proposed unclear or antitumorigenic effects of GDF-15 in glioma cells, we here show that GDF-15 at endogenous levels contributes to proliferation and immune escape of malignant gliomas in an immunocompetent host. Clin Cancer Res; 16(15); 3851–9. ©2010 AACR.
NEEDED SANITARY LEGISLATION.Read before the Illinois State Board of Health Auxiliary Association at Springfield, 111., Noy. 13, 1894.
Authors: ARTHUR R REYNOLDS
Journal: JAMA (1894)

In offering these remarks as to needed legislation in the interests of the public health, I follow some indications suggested as much by observation in my practice as by experience in my official position. In Chicago, where is concentrated more than one-third of the population of the State of Illinois, many of the defects and inadequacies of existing health laws are more apparent than in smaller communities; evils that are scarcely felt in the rural districts, and only slightly in smaller municipalities, strongly impress themselves upon us. I shall, however, confine myself to a few subjects in regard to which it seems to me some general legislation, applicable to the whole State, is needed or would, at least, be advisable. Even if the necessity therefor seems the greater in such a center of population as Chicago and is hardly felt in many other localities, it does not follow that these