tbuckley/cabot-search huggingface dataset:
Multi-targeted kinase inhibitor PKC412 diminishes osteoclastogenesis and counteracts osteoclast function in vitro
Authors: D. Sykoutri, S. Hayer, J. S. Smolen, K. Redlich
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Rheumatoid arthritis is a chronic inflammatory disease characterised by osteoclast mediated bone erosions. Small molecule multi-kinase inhibitors are being explored as potential therapeutic targets. PKC412 is a small molecule multi-kinase inhibitor targeting class III tyrosine-protein-kinases such as FMS-like tyrosine kinase 3 (FLT-3) and multiple isoforms of serine/threonine protein kinase C. PKC412 has been shown to inhibit macrophage function in vitro. However, the role of PKC412 in modulating the commitment of the monocyte/macrophage lineage to osteoclast precursors and their differentiation into mature osteoclasts has not been fully elucidated. <h3>Objectives</h3> The authors aimed to investigate the effect of PKC412 on osteoclast differentiation and function. <h3>Materials and methods</h3> The authors differentiated mouse bone marrow derived cells in the presence of macrophage colony-stimulating factor and RANKL into tartrate-resistant acid phosphatase positive (TRAP+) mononucleated preosteoclasts and TRAP+ multinucleated mature osteoclasts, and added PKC412 in increasing concentrations (10 nM to 10 μM) to the culture. The authors assessed the role of PKC412 in the bone resorbing capacity of osteoclasts by culturing osteoclasts on dentine slices. To further characterise the effect of PKC412 on cell proliferation the authors performed MTT assays. The authors used quantitative PCR to evaluate expression levels of mRNA encoding for osteoclast specific markers such as nuclear factor of activated T cells cytoplasmic 1 (NFATc1), matrix metalloproteinase 9 (MMP9), Cathepsin K and TRAP. Flow cytometry analysis for annexin V and 7 Aminoactinomycin D (7-AAD) was performed to determine potential apoptotic effects of PKC412. <h3>Results</h3> Increasing concentrations of PKC412 (IC50: 250 nM) dose-dependently reduced osteoclast numbers. Preosteoclasts were also significantly decreased after addition of PKC412, indicating an effect of PKC412 on early stages of osteoclastogenesis. In line with this finding, the authors showed a dose-dependent reduction of preosteoclast proliferation using MTT proliferation assays. Moreover, the authors detected a significant time- and dose-dependent increase in the ratio of apoptotic cells in the PKC412-treated cells by annexin V and 7-AAD staining. In the presence of PKC412 the authors obtained a significant reduction in osteoclast size, nuclei number and resorption pit formation. Consistently, the authors were able to demonstrate a dose dependent downregulation of mRNA coding for osteoclast markers, such as NFATc1, MMP9, Cathepsin K and TRAP in the presence of PKC412. <h3>Conclusion</h3> These results suggest a regulatory role of PKC412 in preosteoclast differentiation und osteoclastogenesis through apoptosis induction.
Effect of Dietary Calcium and Age on Jejunal Calcium Absorption in Humans Studied by Intestinal Perfusion
Authors: Patricia Ireland, John S. Fordtran
Journal: Journal of Clinical Investigation (1973)

Jejunal calcium absorption was measured from test solutions containing 1.0, 2.5, 5, and 10 mM calcium (as calcium gluconate). Absorption rates increased progressively as luminal calcium concentration was increased, although there was a tendency toward saturation of the absorptive process at the higher concentrations. Calcium absorption was higher in normal young adults than in normal subjects over age 60. In both groups a 300 mg calcium diet for 4-8 wk enhanced calcium absorption relative to absorption rates after 4-8 wk on a 2,000 mg calcium diet. This adaptation was more definite and dramatic in the young than in the old subjects. Indirect estimates suggest that adaptation to a low calcium diet and the higher absorption in young than old normal subjects are mediated by an increased V(max) rather than a decreased K(m).
Platelet hypersensitivity induced by cholesterol incorporation.
Authors: S J Shattil, R Anaya-Galindo, J Bennett, R W Colman, R A Cooper
Journal: Journal of Clinical Investigation (1975)

Platelets from individuals with familial hypercholesterolemia show increased sensitivity to the aggregating atents, epinephrine and ADP. Since the mechanism of this abnormal sensitivity is unknown, we examined, in vitro, the influence of the plasma lipid environment on the function of platelets. The composition of plasma lipids was altered by the addition of sonicated cholesterol-dipalmitoyl lecithin liposomes which were "cholesterol normal" (cholesterol-phospholipid mole ratio [C/P] equals 1.0, "cholesterol rich" (C/P eauals 2.2), or "cholesterol poor" (C/P equals 0). Cholesterol-normal liposomes had no influence on platelet lipids or platelet function. In contrast, after incubation for 5 h at 37 degrees C with cholesterol-rich liposomes, normal platelets acquired 39.2% excess cholesterol with no change in phospholipids or protein. The percent increase in platelet membrane cholesterol was three-fold that of the granule fraction. The acquisition of cholesterol by platelets was associated with a 35-fold increase in sensitivity to epinephrine-induced aggregation (P less than 0.001) and 15-fold increase to ADP aggregation (P less than 0.001), as determined both by aggregometry and by [13C]serotonin release. Response to thrombin or collagen was unchanged. Platelets incubated with cholesterol-poor liposomes underwent a selective loss of 21.4% cholesterol and this was associated with an 18-fold reduction in their sensitivity to epinephrine. These studies demonstrate that the cholesterol content of platelets is dependent on the lipid composition of the milier. Cholesterol acquired by platelets may exert its effect on platelet function by a modification of the platelet membrane.
Acute leg ischaemia may present without pain in some cases
Authors: O. M. Jolobe
Journal: BMJ (2013)

The excellent account of acute leg ischaemia would not be complete without mentioning that acute leg ischaemia can have a pain-free presentation.1 2 3 4

A report of 330 unselected cases of peripheral arterial embolism (“embolism of the extremities”) noted that 52 patients had “sudden numbness and coldness …
Intra-articular rheumatoid nodules and triggering of the knee joint.
Authors: Z Diamant, F J Hooning van Duyvenbode, F Eulderink, M Janssen, Z Tak-Diamant
Journal: Annals of the Rheumatic Diseases (1992)

Rheumatoid nodules are a common extra-articular manifestation in rheumatoid arthritis. Intra-articular localisation of these nodules is rare and may produce clinical symptoms. Seven patients with walking problems due to an intra-articular rheumatoid nodule, which became entrapped on the ridge of the tibial plateau of the knee joint resulting in a phenomenon referred to as trigger knee, are described. After excision of the nodules all symptoms completely disappeared.
Reviews and Notes: Cardiology: Pathophysiology of Hypertension in Blacks
Authors: Luther T. Clark
Journal: Annals of Internal Medicine (1994)

Literature of Medicine15 February 1994Reviews and Notes: Cardiology: Pathophysiology of Hypertension in BlacksLuther T. ClarkLuther T. ClarkState University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-4-199402150-00043 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Pathophysiology of Hypertension in BlacksJohn C. S. Fray and Janice G. Douglas; eds. 299 pages. New York: Oxford University Press; 1993. $85.00.Hypertension is more prevalent, severe, complicated, and difficult to manage in black patients than in white. Although considerable evidence suggests that genetic, environmental, sociocultural, and psychosocial factors contribute to the pathogenesis of hypertension in blacks, and many anatomic, physiologic, and pharmacologic differences between hypertension in blacks and whites have been defined, our understanding of this disorder remains limited and the effectiveness of our therapeutic approaches suboptimal. Perhaps, as the editors of this text suggest, key reasons for ... Author, Article, and Disclosure InformationAffiliations: State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDarstellung und Beurteilung von Ausgestaltungsmöglichkeiten des Normensetzungsprozesses im Bereich der Rechnungslegung anhand ausgewählter Länder 15 February 1994Volume 120, Issue 4Page: 351KeywordsBlood pressureGlucoseHyperinsulinemiaHypertensionInsulin resistanceNutritionPathogenesisPsychologySaltsSodium ePublished: 15 August 2000 Issue Published: 15 February 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Multiple signaling pathways induced by hexavalent, monospecific, anti-CD20 and hexavalent, bispecific, anti-CD20/CD22 humanized antibodies correlate with enhanced toxicity to B-cell lymphomas and leukemias
Authors: Pankaj Gupta, David M. Goldenberg, Edmund A. Rossi, Chien-Hsing Chang
Journal: Blood (2010)
Quality of life in adults with brain tumors: Current knowledge and future directions
Authors: Raymond Liu, Margaretta Page, Karla Solheim, Sherry Fox, Susan M. Chang
Journal: Neuro-Oncology (2008)

Quality of life is an important area of clinical neurooncology that is increasingly relevant as survivorship increases and as patients experience potential morbidities associated with new therapies. This review of quality-of-life studies in the brain tumor population aims to summarize what is currently known about quality of life in patients with both low-grade and high-grade tumors and suggest how we may use this knowledge to direct future research. To date, reports on quality of life have been primarily qualitative and focused on specific symptoms such as fatigue, sleep disorders, and cognitive dysfunction, as well as some symptom clusters. However, the increasing interest in exploring quality of life as a primary end point for cancer therapy has established a need for prospective, controlled studies to assess baseline and serial quality-of-life parameters in brain tumor patients in order to plan and evaluate appropriate and timely interventions for their symptoms.
Eric William Hardman
Authors: A. HARDMAN
Journal: BMJ (2003)

Former general practitioner Chepstow, Gwent (b Salford 1907; q Manchester 1930; MRCGP), d 20 August 2003.

After qualification he had hoped for a career in general surgery but finances did not allow this. He began general practice in Leeds but soon decided to buy into a practice in semi-rural Chepstow. In the late 1960s the practice published a paper in the BMJ following a local outbreak of hepatitis caused by liver fluke in watercress. He retired in 1972 and for many years continued to enjoy golf and, increasingly, vegetable gardening. He leaves a wife, four children, and seven grandchildren.
Recovery from Rabies
Authors: MICHAEL A. W. HATTWICK
Journal: Annals of Internal Medicine (1972)

A 6-year-old boy developed clinical rabies 20 days after he was bitten on the left thumb by a bat and 2 days after he completed a 14-day course of duck embryo rabies vaccine. The diagnosis of rabies was supported by epidemiologic, clinical, and laboratory investigations. Rabies virus was isolated from the bat but not from the child. Serum, cerebrospinal fluid, and brain tissue antibodies against rabies rose to levels compatible with clinical rabies rather than vaccination. Rabies serum neutralization titers peaked at 1:63 000, 3 months after onset. Recovery from the clinical illness was complete 6 months after onset, with no demonstrable residua. Aggressive treatment to prevent hypoxia, intracranial hypertension, cardiac arrhythmias, seizures, and superinfection may have contributed to the patients' recovery.
Megakaryocyte growth and development factor. Analyses of in vitro effects on human megakaryopoiesis and endogenous serum levels during chemotherapy-induced thrombocytopenia.
Authors: J L Nichol, M M Hokom, A Hornkohl, W P Sheridan, H Ohashi, T Kato, Y S Li, T D Bartley, E Choi, J Bogenberger
Journal: Journal of Clinical Investigation (1995)

The present study shows that recombinant human megakaryocyte growth and development factor (r-HuMGDF) behaves both as a megakaryocyte colony stimulating factor and as a differentiation factor in human progenitor cell cultures. Megakaryocyte colony formation induced with r-HuMGDF is synergistically affected by stem cell factor but not by interleukin 3. Megakaryocytes stimulated with r-HuMGDF demonstrate progressive cytoplasmic and nuclear maturation. Measurable levels of megakaryocyte growth and development factor in serum from patients undergoing myeloablative therapy and transplantation are shown to be elaborated in response to thrombocytopenic stress. These data support the concept that megakaryocyte growth and development factor is a physiologically regulated cytokine that is capable of supporting several aspects of megakaryopoiesis.
Complications of the Arrested Primary Histoplasmic Complex
Authors: Jan Schwarz
Journal: JAMA (1976)

THE GAMUT of clinically active and symptomatic histoplasmosis has become well known, especially in endemic areas. Manifestations such as disseminated forms, active histoplasmoma in the young adult, and cavitary pulmonary disease in elderly men are well-recognized syndromes. Less attention has been focused on mechanically induced (noninfectious) complications related to healing or arrested primary infection. Such complications presented here include simple and complicated broncholithiasis, bronchial compression with resulting atelectasis or bronchiectasis, fistula formation from mediastinal lymph nodes, superior vena cava syndrome, and giant mediastinal cyst. <h3>Diagnosis</h3> The presence of<i>Histoplasma capsulatum</i>was established (primarily by microscopy) in the following cases from surgical or autopsy specimens, except in patients 1 and 2 in whom roentgenographic and serologic evidence strongly indicated the diagnosis. <h3>Giant Cyst of the Mediastinum.—</h3> Caseous lymphadenitis during primary infection with<i>H capsulatum</i>is common in the lymph nodes that drain the primary lung lesion. The extent of involvement and
SHO training: Protected time essential
Authors: B. Ramsay, A. Lloyd
Journal: BMJ (1993)

We hope that this extension ofour assessment of the senior house officers in our department proves to be both useful and acceptable to them.The main drawback to this form of assessment is that it is labour intensive, requiring the synchronous participation of both the junior and senior doctors of the department.This programme of assessment is being extended to include other hospitals in our region.Towards the end of this year we hope to report our experiences after assessing the training of further groups of senior house officers working in our department.
Comment on: Zhu et al. Fasting Plasma Glucose at 24–28 Weeks to Screen for Gestational Diabetes Mellitus: New Evidence From China. Diabetes Care 2013;36:2038–2040
Authors: Charles Savona-Ventura, Josanne Vassallo, Michel Marre, Basil G. Karamanos
Journal: Diabetes Care (2013)

The article by Zhu et al. (1) published in Diabetes Care concludes that a fasting plasma glucose (FPG) at 24–28 weeks’ gestation can be used in low-resource regions as a screening test to identify gestational diabetes mellitus (GDM) in Chinese patients. However, in their experience, a screening protocol using FPG cutoff points of ≥4.4 and ≤5.0 mmol/L would fail to identify about 12% of the GDM cases and require a formal oral glucose tolerance test (OGTT) to be performed in about half of the pregnant population (1). These observations contrast with our findings in a circum-Mediterranean population (2). In our …
The prevalence of primary open-angle glaucoma in Japanese
Authors: Aiko Iwase, Yasuyuki Suzuki, Makoto Araie, Tetsuya Yamamoto, Haruki Abe, Shiroaki Shirato, Yasuaki Kuwayama, Hiromu K. Mishima, Hiroyuki Shimizu, Goji Tomita, Yoichi Inoue, Yoshiaki Kitazawa
Journal: Ophthalmology (2004)
Human Sleep and Its Disorders
Authors: Anthony Kales
Journal: JAMA (1978)

This book is intended for the student as well as the professional researcher. It aims to discuss the current knowledge on the mechanisms of sleep and relate this information to a variety of disorders, including insomnia and narcolepsy as well as schizophrenia, depressive illness, and alcoholism. The authors discuss in detail pharmacologic and endocrinologic data relating to the regulation of sleep. The primary difficulty with this book is that the various topics and chapters are treated in an uneven and inconsistent manner. The most striking examples are the two chapters on narcolepsy and disorders of excessive sleep and on clinical studies of insomnia. These topics are treated in a superficial and incomplete manner, and the book would have been much better had these chapters not been included in this form. Also, there is absolutely no mention in the book about common sleep disorders such as enuresis, somnambulism, and night terrors.
The imaging core lab perspective on glioblastoma imaging and response assessment in clinical trials
Authors: G. V. Goldmacher, D. Raunig
Journal: Neuro-Oncology (2014)

Multicenter clinical trials that include medical images as a key component of response assessment often involve an imaging service provider (a core laboratory or contract research organization) to collect images and often to provide independent assessments of treatment response. The brief discussion and recommendations provided here are not intended as a rigorous academic analysis but reflect the practical experience accumulated at one such institution, which has conducted the image collection and review for numerous glioblastoma trials, in every phase of drug development, encompassing over 4000 patients scanned at over 900 sites.
Pediatric Atopic Dermatitis and Associated Morbidities
Authors: Dawn Davis
Journal: JAMA Dermatology (2014)

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 Dermatology 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 Dermatology journal
Histologic Diagnosis of Inflammatory Skin Diseases: A Method by Pattern Analysis
Authors: Ernest B. Howard
Journal: JAMA (1979)

This book has numerous photomicrographs and illustrations with six full-color plates and is printed on heavy white paper with large margins. The author explains the genesis of the book thus: "There is need for a textbook that weds the gross and microscopic features of skin diseases and simultaneously provides a logical systematic and reproducible method of histologic diagnosis." The book is aimed at "all students of skin disease be they dermatologists, pathologists, surgeons, residents, or medical students." This approach, however, "presumes a rudimentary knowledge of general pathology and hardly any of dermatology." The dilemma posed by writing for such a readership is that trained pathologists and dermatologists will find much of the content elementary, while those without such knowledge will find large sections difficult to comprehend.
Abstract 2346: Lung cancer progression by efficient cre-mediated deletion of Pten and Smad4
Authors: Bindu Akkanti, Sung-Nam Cho, Nili Jin, Martin Matzuk, Ignacio Wistuba, Francesco DeMayo
Journal: Cancer Research (2012)

Abstract Introduction: Lung cancer is the leading cause of cancer death in the world and the incidence of pulmonary adenocarcinoma, the most common type of lung cancer in the United States has been increasing in recent years. Mouse models have played a crucial role in understanding the tumor biology and progression of disease. The need for more clinically relevant preclinical mouse models for lung cancer is clear. Most mouse models for lung cancer use adenoviral delivery or cre recombinase models that result in development of cancers of the distal air ways. The tumors resulting from these mouse models are usually a mixed phenotype with mice developing adenocarcinoma, squamous cell carcinoma and benign adenomas depending on the combination of genetic alterations. We wanted to study lung cancer in the setting of more efficient cre that is present in the proximal as well as the distal lung epithelium. Utilizing this cre-system, we created a double knockout murine model with conditional ablation of pten and smad4 genes and wanted to compare tumor development and progression in these mice when compared to wildtype or smad 4 d/d or pten d/d mice. Methods: All mice were maintained at our core facility under approved protocols. The efficient cre system was accomplished by inserting the iCre recombinase into the Clara Cell Secretory protein locus. Tissues were collected at the time of sacrifice and compared to wild-type mice. Methods include Microarray analysis, RT-PCR, Immunohistochemistry and CHIP-Seq. Results: When compared with wildtype mice, smad 4 d/d or pten d/d alone mice, we have recognized that this particular mouse model has reproducibly developed proximal lung cancers that stain negative for SPC, a marker for distal airways. Additionally, this mouse model has developed metastatic disease, with metastasis to stomach. The immunohistochemistry results confirmed that the metastasis site was positive for TTF-1. Immunohistochemistry for EMT makers show that there is gradual loss of E-Cadherin. Conclusions: We have successfully created a mouse model with CCSPicre/Pten/Smad4 that results in proximal lung tumor development that advances to metastatic disease. Previous studies showed that tissue specific knockout of Smad 4 results in malignancy including gastric polyposis, pancreatic cancer, mammary gland epithelial hyperproliferation and SCC of the skin. Our results add to the previous findings in that loss of Smad4 in conjunction Pten may provide a novel platform to study lung cancer especially as it relates to proximal lung cancers that metastasize. 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 2346. doi:1538-7445.AM2012-2346