tbuckley/cabot-search huggingface dataset:
Abstract 15863: Macrophage Foxp1 is a Regulator of Pathologic Cardiac Hypertrophy
Authors: Shuichi Yoneda, Saptarsi M Haldar, Jessica Jenkins, Yunmei Wang, Teruo Inoue, Mukesh K Jain, Can Shi, Daniel I Simon
Journal: Circulation (2014)

Introduction: Pathologic cardiac hypertrophy is a maladaptive response to neurohormonal and hemodynamic stress that is a hallmark of human heart failure. While inflammation has been implicated in pathologic hypertrophy, the molecular mechanisms underlying innate immune dysregulation in this disease process are incompletely defined. We have previously demonstrated that the forkhead transcription factor Foxp1 controls monocyte differentiation and suppresses inflammatory activation of macrophages. In this study, we hypothesized that monocyte/macrophage Foxp1 regulates pathologic cardiac hypertrophy. Methods: Macrophage-specific Foxp1 over-expressing (macFoxp1tg=anti-inflammatory) vs. non-tg controls, as well as macrophage-specific Foxp1 knockdown (macFoxp1ko=pro-inflammatory) vs. Cre-control male mice were subject to chronic angiotensin II (AII) infusion (1.8 mcg/kg/min via subcutaneous osmotic mini-pump) for 4 weeks. Results: AII-mediated cardiac hypertrophy (heart mass and cardiomyocyte cross-sectional area), left ventricular (LV) systolic dysfunction, LV dilation, interstitial fibrosis and macrophage (Mac-3+ cells) accumulation were significantly attenuated in macFoxp1tg mice compared to non-tg controls. In contrast, AII-mediated cardiac hypertrophy, LV systolic dysfunction and cavity dilation were significantly exacerbated in macFoxp1ko mice compared to Cre controls. There were no differences in systemic blood pressure between these groups, corroborating a load-independent role for macrophage Foxp1 in cardiac hypertrophy. Conclusion: These studies identify macrophage Foxp1 as a novel negative regulator of pathologic cardiac hypertrophy in vivo. Modulation of Foxp1 signaling may provide a novel strategy for prevention and treatment of heart failure.
A granular variant of CD63 is a regulator of repeated human mast cell degranulation
Authors: T. Schäfer, P. Starkl, C. Allard, R. M. Wolf, T. Schweighoffer
Journal: Allergy (2010)

Mast cells are secretory immune cells whose degranulation can provoke acute allergic reactions. It is presently unclear, however, whether an individual mast cell can repeatedly degranulate or turns dysfunctional after a single antigen stimulus. This work thus aims to better define the mast cell life cycle, with particular focus on new target structures for therapeutic or diagnostic approaches in allergy.Monoclonal antibodies were raised against degranulated cord blood-derived human mast cells. A subset of these antibodies that exclusively recognized degranulated mast cells, but did not cross-react with quiescent mast cells or other hematopoietic cell types, became key reagents in subsequent experiments.We identified a granular variant of tetraspanin CD63 as an exclusive molecular marker of degranulated human mast cells. Mutant analyses indicate that a cysteine cluster around residue C170 and protein glycosylation at residue N172 account for the antibody specificity. Here, we show that mast cells, which underwent an initial FcεRI-mediated degranulation, can be degranulated for at least another cycle in vitro. Repeated degranulation, however, requires an IgE/antigen stimulus that differs from the preceding one. Furthermore, the new variant-specific anti-CD63 antibodies effectively impair repeated cycles of mast cell degranulation.Our findings indicate that mast cells are stable, multiple-use cells, which are capable of surviving and delivering several consecutive hits. Surface expression of the novel CD63 variant is a distinguishing feature of such primed cells. Reagents directed against this molecular hallmark may thus become valuable diagnostic and therapeutic agents.
A novel frameshift mutation in keratin 16 underlies pachyonychia congenita with focal palmoplantar keratoderma
Authors: L-H. Cao, Y. Luo, W. Wen, W-L. Liu, L. Jiang, C. Chen, C-Y. Ji, X. Zhang
Journal: British Journal of Dermatology (2011)

Funding sources: This work was supported by the National 863 Program of China (2007AA02Z440) and the National Natural Science Foundation of China (81000253 and 30971164). Conflicts of interest: none declared. Madam, Pachyonychia congenita (PC) comprises a group of autosomal dominant genetic disorders that involve ectodermal dysplasia. Historically, two main clinical subtypes of PC have been described, PC‐1 (MIM 167200) and PC‐2 (MIM 167210).1 2–3 PC has been linked to mutations in four keratin genes that are expressed in the epithelia, KRT6A, KRT6B, KRT16 and KRT17.4, 5 Recently, more specific molecular genetic nomenclature has been adopted by the International Pachyonychia Congenita Consortium. In this system, PC‐6a, PC‐6b, PC‐16 and PC‐17 refer to cases with mutation identified in the genes KRT6A, KRT6B, KRT16 and KRT17, respectively. PC‐U designates cases of suspected PC, where either a mutation has not been found or has not been investigated.6, 7 We report a large Chinese pedigree of PC with focal palmoplantar keratoderma. Two‐point linkage analysis and haplotype analysis were carried out to map the disease locus; DNA sequencing and restriction endonuclease analysis were then used to identify the pathogenic mutation.
Prediabetes Screening Urged
Authors: Brian Vastag
Journal: JAMA (2002)

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
526. A New Mouse Reporter Strain with Nuclear-Localized lacZ Expression Allows Reliable Detection of Transplanted and Donor-Derived Cells
Authors: Pei-Rong Wang, Daniel G. Miller, George Vassilopoulos, David W. Russell
Journal: Molecular Therapy (2004)

Experiments involving transplantation of cells necessitates sensitive and specific identification of donor cells in recipient tissues. Proof of cell origin can be difficult due to a variety of confounding factors. The original gene trap mouse strain (ROSA26) has been a useful tool in this regard. However X-gal staining of chimeric tissues resulting from transplants with this model can be difficult to interpret because of diffuse b-galactosidase expression that can be derived from donor or recipient cells. Therefore we developed a mouse containing a lacZ gene with a nuclear localization signal, bacterial ori, and ampicillin resistance gene targeted to the ROSA26 locus. This locus can be easily rescued in bacteria for molecular analysis or quantification of percentages of tissue chimerism. We confirmed that lacZ expression was present and localized to the nucleus in all major organs. The utility of this mouse was demonstrated by testing our ability to detect donor cells in a mouse model of hereditary tyrosinemia type I that received bone marrow transplants. These mice have mutations in the fumaryl acetoacetate hydrolase gene (fah) and develop liver disease that can be corrected by transplantation of bone marrow cells from normal donors. Correction of the disease occurs by fusion of donor cells with recipient hepatocytes which results in complementation of the genetic defect. Bone marrow cells from C57/Bl6 donors that express nuclear localized b-galactosidase were injected into lethally irradiated fah(-/-) recipients. We observed nodules consisting of normal appearing hepatocytes surrounded by general liver cirrhosis when NTBC was removed from the water source of the fah(-/-) mice. Liver tissue sections containing these nodules were stained with X-gal reagent and the observation of nuclear localized b-galactosidase activity in hepatocytes forming the nodule confirms that these cells were in part donor derived. These results demonstrate one application of this mouse model for studying the origin of cells after transplantation. The advantage over other lacZ reporter strains is that nuclear localized b-galactosidase differentiates expression of the bacterial enzyme from background staining of endogenous enzyme activity, and additional bacterial sequences allow efficient quantification and rescue in bacteria. This mouse strain should prove useful for preclinical studies of cell and gene therapy, and determining the developmental potential of stem cells.
Dementia and Testosterone Levels in Men
Authors: Harry W Daniell
Journal: JAMA (2005)

To the Editor: The study by Ms Rosario and colleagues reports a relationship between low postmortem brain testosterone levels and preceding dementia in men. To be able to interpret these data it would have been valuable to know the potential impact on their results of body mass index, the intensity of care over the interval immediately preceding death, and recent opioid use. Obesity is associated with diminished serum testosterone and elevated serum estradiol. Expectant care, with no therapeutic interventions for several days immediately preceding death, may have modified tissue hormone levels in comparison with the levels of patients dying while undergoing active therapy. Opioid-induced androgen deficiency usually develops within a few hours of administration of relatively small doses of opioid medications, with plasma testosterone levels occasionally reaching near-castrate range within 24 hours. These low levels are maintained during continued opioid administration. Although tissue concentrations of sex hormones have not been measured during opioid use, the frequent use of these medications during end-of-life patient managementsuggests that theiradministrationshouldbeconsidered in interpreting postmortem tissue sex hormone levels. In contrast to levelsof testosterone,opioid-induced loweringofserum estradiol develops much more slowly, a difference that could have contributed to the observations reported.
XANTHOMATOUS BILIARY CIRRHOSIS: LIPID LEVELS WHILE RECEIVING INOSITOL
Authors: M C GEPHARDT
Journal: Annals of Internal Medicine (1947)

Case Reports1 May 1947XANTHOMATOUS BILIARY CIRRHOSIS: LIPID LEVELS WHILE RECEIVING INOSITOLMAURICE C. GEPHARDT, M.D.MAURICE C. GEPHARDT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-26-5-764 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptVarious studies of the lipotropic action of inositol in experimental animals have been reported. The present case was studied to observe the results of inositol on an extreme hyperlipemia in the human being.CASE REPORTA 37 year old, unmarried, Jewish woman was admitted to the Illinois Research and Educational Hospital on August 9, 1944. In 1942 she had first noted itching of the palms which was followed by the appearance of pale yellow lesions of the skin along the palmar folds. Yellow, non-inflammatory nodules later appeared over the knuckles, over the olecranon processes, along the creases over the cubital...Bibliography1. THANNHAUSER SJ: Lipidoses: diseases of the cellular lipid metabolism, 1940, Oxford University Press, p. 107. Google Scholar2. PAGEKIRKLEWISTHOMPSONVAN SLYKE IHEWHWRDD: Plasma lipids of normal men, Jr. Biol. Chem., 1935, cxi, 613-639. CrossrefGoogle Scholar3. VAN SLYKEFOLCH DDJ: Total carbon determination from Bloor's alcoholether extract, Jr. Biol. Chem., 1940, cxxxvi, 509-541. CrossrefGoogle Scholar4. TRUNER MD: A simplification of the Okey method for the determination of cholesterol by oxidation of the digitonide, Jr. Biol. Chem., 1931, xcii, 495. CrossrefGoogle Scholar5. SCHOENHEIMERSPERRY RWM: A micro method for the determination of free and combined cholesterol, Jr. Biol. Chem., 1934, cvi, 745. CrossrefGoogle Scholar6. STOESSER AV: Influence of sulfadiazine on plasma lipids in pneumonia, Proc. Soc. Exper. Biol. and Med., 1944, lv, 278-280. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Received for publication September 17, 1945.From the Department of Medicine, College of Medicine, University of Illinois. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPrimary Biliary CirrhosisXanthomatous Biliary Cirrhosis in the MaleGeneralized Xanthomatosis with Corneal Involvement 1 May 1947Volume 26, Issue 5Page: 764-769KeywordsCirrhosisHyperlipidemiaLesionsLipidsPruritus Issue Published: 1 May 1947 PDF downloadLoading ...
Abstract 3692: Tight Diabetic Glycemic Control Reduces the Risk of Cardiovascular Disease Only in Individuals with the Hp 2–2 Genotype
Authors: Shany Blum, Uzi Milman, Chen Shapira, Rachel Miller-Lotan, Yefim Anbinder, Junia Alshiek, Lawrence Bennett, Maria Kostenko, Michele Landau, Shlomo Keidar, Yishai Levy, Alexander Khemlin, Arman Radan, Andrew P Levy
Journal: Circulation (2007)

Background. The Haptoglobin (Hp) gene is polymorphic in man with two classes of alleles denoted 1 and 2. Several cross sectional and retrospective analysis have suggested that the Hp genotype may be a major determinant of susceptibility to diabetic CVD. We sought to examine this relationship in a prospective population based study. Methods. We recruited over 3000 individuals 55 years of age or older with DM from 47 primary health care clinics of the Clalit Health Plan in Northern Israel and obtained a Hp genotype on all of these individuals. The prevalence of CVD at baseline was 25%. Patients were followed for two years, for the primary composite outcome of the study which was incident non-fatal myocardial infarction, stroke and CV death. Results. We found that the Hp 2–2 genotype was associated with a highly significant increase in the incidence of myocardial infarction, stroke and CV death. Moreover, after stratification of patients by baseline HbA1c to those above and below 7.0, representing inadequate or adequate glycemic control as currently recommended by the AHA and ADA, only in Hp 2–2 individuals was poor glycemic control found to be associated with an increased risk of major cardiovascular events. Conclusions. Optimal utilization of health care resources for risk factor modification should be focused on DM individuals with the Hp 2–2 genotype. Benefit from tight glycemic control only in a subset of the DM cohort defined by the Hp 2–2 genotype may explain the inability to show a benefit from tight glycemic control on reducing cardiovascular events in the entire DM cohort in multiple prior clinical studies.
Novel Risk Factors for Atherosclerosis
Authors: Arnold von Eckardstein
Journal: JAMA (2004)

To the Editor: In their review article, Drs Hackam and Anand1 discussed the 4 novel risk factors of C-reactive protein, lipoprotein(a) [Lp(a)], fibrinogen, and homocysteine to predict atherosclerosis. The authors concluded that their optimal use remains to be determined.
Optimal Recall Rates Following Mammography
Authors: William H Goodson
Journal: JAMA (2004)

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
Abstract 11747: The TMAO Generating Enzyme Flavin Monooxygenase 3 (FMO3) is a Novel Regulator of Cholesterol Balance
Authors: Manya Warrier, Stephanie Marshall, Allison McDaniel, Zeneng Wang, Amanda L Brown, Anthony D Gromovsky, Jessica Sacks, Jeff Chou, Pavlina T Ivanova, David S Myers, H. Alex Brown, Richard G Lee, Rosanne M Crooke, Mark J Graham, Diana M Shih, Aldon J Lusis, Paolo Parini, Stanley L Hazen, Ryan E Temel, J M Brown
Journal: Circulation (2014)

Circulating trimethylamine-N-oxide (TMAO) levels have recently been linked to cardiovascular disease (CVD) risk, but the mechanism underlying this association is unclear. Here we performed unbiased transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT), and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 inhibition stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic ER stress and inflammation by altering the LXR-Lpcat3-driven phospholipid remodeling pathway. FMO3 is thus identified as a novel integrator of hepatic lipid metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMAO pathway may promote CVD pathogenesis in part by reciprocally regulating lipid metabolism and inflammation.
Tumour necrosis factor-α induces Langerhans cell migration in humans
Authors: None Cumberbatch, None Griffiths, None Tucker, None Dearman, None Kimber
Journal: British Journal of Dermatology (1999)

The role of tumour necrosis factor (TNF)-alpha in the mobilization and migration of human epidermal Langerhans cells (LC) has been investigated. Intradermal injection of normal human volunteers with homologous recombinant TNF-alpha was found to cause a dose-dependent reduction in the frequency of LC within epidermal sheets 2 h later. Equivalent results were obtained when epidermal LC were identified on the basis of either CD1a or HLA-DR expression. At the dose of TNF-alpha used routinely (500 U), treatment resulted in an average reduction in LC density of approximately 24%. Treatment with TNF-alpha was associated with a perivascular polymorphonuclear infiltration at 2 h, but the epidermis appeared normal with neither fibrinoid necrosis nor vasculitis, and LC morphology was not affected significantly. These results demonstrate that TNF-alpha provides an important signal for LC migration in humans and is likely therefore to play a crucial part in the induction of cutaneous immune responses.
Pigmented basal cell epithelioma
Authors: STANLEY S. BLEEHEN
Journal: British Journal of Dermatology (1975)

SUMMARY Light and electron microscopic studies have been carried out on three pigmented basal cell epitheliomas and on cell cultures of two of these tumours, to determine the formation and transfer of pigment and the fine structure of the constituent cells. Scattered in the epithelial tumour buds were many functional melanocytes that contained melanosomes in various stages of development and whose morphology was essentially normal. Many melanophages were present in the dermal stroma, but few transferred melanosomes were to be found in the epithelial tumour cells. Tissue culture studies revealed that melanocytes were present among the proliferating islands of epithelial cells and these contained many melanosomes. However, few melanosomes were found in the epithelial cells. This study indicated a block in the transfer of pigment from the melanocyte to the basal epithelioma cells. Several of the cultured epithelial cells were found to contain dense bundles of filaments resembling amyloid. It is likely that they are abnormal tonofilaments resulting from the differentiation and keratinization of basal cells in vitro.
Abstract 19106: Diabetes Induced Actin S-glutathiolation Increases Vein Graft Accelerated Atherosclerosis Through Delayed Endothelial Regeneration
Authors: Wei Qi, Prakash Krishnan, Arthur Tarricone, Ahsan Waqas, Adrian Zalewski, Tiffany Sia, Gopal Singh, Jose Wiley, Roxana Mehran, Isaac George, Ayyaz A Ali, Martin B Leon, Ziad A Ali
Journal: Circulation (2014)

Endothelial cell (EC) loss and regeneration are important aspects of the response to vascular injury leading to atherosclerosis in vein grafts (VG). EC regeneration is known to be impaired in diabetes mellitus (DM) leading to an accelerated atherosclerosis, however the mechanism remains unclear. Given the increased oxidative stress in DM, we hypothesized that protein s-glutathiolation, the reversible covalent addition of glutathione to cysteine on target proteins was a candidate mechanism. Overall s-glutathiolation of proteins measured by immunoblot was significantly increased in human DM atherosclerotic plaque compared to non-DM (4-fold, P&lt;0.01; n =10) with the increase in protein intensity at ≈ 40kDa. Mass spectrometry peptide fingerprint screening identified actin (42Kda) and the actin regulatory protein annexin A2 (39Kda) as the s-glutathiolated proteins. In cultured ECs in which s-glutathiolation was induced, proliferation (22%, P&lt;0.05) and motility (37%, P&lt;0.05) were significantly decreased compared to control. Assessment of actin conformational state identified a significant decrease in the ratio of filamentous to globular actin (P&lt;0.05) supporting our findings of decreased motility. As an in vivo model of acute vascular injury we constructed VGs in apolipoprotein-E knockout (ApoE-KO) mice with expression of an EC reporter gene (LacZ) in which DM was induced by streptoztocin (n=6-10/group). In VGs harvested 28 days post-operatively, DM increased VG total vessel wall area by 51% (P=0.001) and reduced endothelialization by 44% (P=0.001). S-glutathiolation levels were increased 10-fold in primary cultured ECs from these mice. Although there was no differences in baseline EC content or number of isolated cells, following 3 days of culture, total EC number, colony size and colony number from ApoE-KO/LacZ DM mice were decreased (4-fold P=0.05; 3-fold P=0.02; 3-fold P=0.04 respectively, n=6) as were putative EC progenitor levels from bone-marrow derived mononuclear cells by culture (20%,P=0.03) and FACS (22%, P=0.02). These observations indicate an important role for actin s-glutathiolation in EC regeneration following vascular injury and identify a mechanism by which accelerated atherosclerosis develops in patients with DM.