tbuckley/cabot-search huggingface dataset:
Relation of Birth Weight to Fasting Insulin, Insulin Resistance, and Body Size in Adolescence
Authors: Maureen A. Murtaugh, David R. Jacobs, Antoinette Moran, Julia Steinberger, Alan R. Sinaiko
Journal: Diabetes Care (2003)

OBJECTIVE—A relationship between birth weight and the insulin resistance syndrome has been reported in adults but has not been defined in adolescents. RESEARCH DESIGN AND METHODS—Data were analyzed in 296 children (132 girls and 164 boys) mean age 15.0 ± 1.2 years who had euglycemic insulin clamp studies (intravenous administration of 1 mU · kg–1 · min–1 of insulin balanced by a variable infusion of 20% glucose to maintain blood glucose at 100 mg/dl). Insulin sensitivity (MLBM) was determined by glucose uptake per kg lean body mass (LBM), and parents reported birth weight. RESULTS—Birth weight ranged from 1,021 to 4,848 g (mean ± SD 3,433 ± 551), with 4.0% &amp;lt;2,500 g. Fat mass and BMI had U-shaped relations with birth weight after adjustment for race, age, sex, and blood pressure. Lean mass index (lean mass/height squared) was stable across birth weight quartiles. Fasting insulin decreased nonsignificantly across birth weight quartiles but became significant after adjustment for adolescent weight (P = 0.008). Although MLBM was highest in the highest birth weight quartile, the pattern was not significant. Triglycerides tended to increase with birth weight, whereas LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) tended to decrease. Blood pressure was unrelated to birth weight. CONCLUSIONS—In this cohort, fat mass was greater in adolescents with low and high birth weight; fasting insulin was lower with higher birth weight after adjustment for adolescent weight. Insulin sensitivity increased nonsignificantly with birth weight.
Dihydroartemisinin Is Cytotoxic to Papillomavirus-Expressing Epithelial Cells <i>In vitro</i> and <i>In vivo</i>
Authors: Gary L. Disbrow, Astrid C. Baege, Katie A. Kierpiec, Hang Yuan, Jose A. Centeno, Clare A. Thibodeaux, Dan Hartmann, Richard Schlegel
Journal: Cancer Research (2005)

Abstract Nearly all cervical cancers are etiologically attributable to human papillomavirus (HPV) infection and pharmaceutical treatments targeting HPV-infected cells would be of great medical benefit. Because many neoplastic cells (including cervical cancer cells) overexpress the transferrin receptor to increase their iron uptake, we hypothesized that iron-dependent, antimalarial drugs such as artemisinin might prove useful in treating HPV-infected or transformed cells. We tested three different artemisinin compounds and found that dihydroartemisinin (DHA) and artesunate displayed strong cytotoxic effects on HPV-immortalized and transformed cervical cells in vitro with little effect on normal cervical epithelial cells. DHA-induced cell death involved activation of the mitochondrial caspase pathway with resultant apoptosis. Apoptosis was p53 independent and was not the consequence of drug-induced reductions in viral oncogene expression. Due to its selective cytotoxicity, hydrophobicity, and known ability to penetrate epithelial surfaces, we postulated that DHA might be useful for the topical treatment of mucosal papillomavirus lesions. To test this hypothesis, we applied DHA to the oral mucosa of dogs that had been challenged with the canine oral papillomavirus. Although applied only intermittently, DHA strongly inhibited viral-induced tumor formation. Interestingly, the DHA-treated, tumor-negative dogs developed antibodies against the viral L1 capsid protein, suggesting that DHA had inhibited tumor growth but not early rounds of papillomavirus replication. These findings indicate that DHA and other artemisinin derivatives may be useful for the topical treatment of epithelial papillomavirus lesions, including those that have progressed to the neoplastic state.
CXCL10 Inhibits Viral Replication Through Recruitment of Natural Killer Cells in Coxsackievirus B3-Induced Myocarditis
Authors: Ji Yuan, Zhen Liu, Travis Lim, Huifang Zhang, Jianqing He, Elizabeth Walker, Courtney Shier, Yinjing Wang, Yue Su, Alhousseynou Sall, Bruce McManus, Decheng Yang
Journal: Circulation Research (2009)

Coxsackievirus (CV)B3 is the primary cause of viral myocarditis. We previously observed CXC chemokine ligand 10 (CXCL10) upregulation in the myocardium early in infection. However, the impact of CXCL10 in CVB3-induced myocarditis is unknown. Using isolated primary mouse cardiomyocytes we demonstrated for the first time that cardiomyocytes can express CXCL10 on interferon-gamma stimulation. To explore the role of CXCL10 in CVB3-induced myocarditis, both CXCL10 transgenic and knockout mice were used. Following CVB3 challenges, the viral titer in the hearts inversely correlated with the levels of CXCL10 at early phase of infection before visible immune infiltration. Furthermore, as compared with the control mice, the decreased virus titers in the CXCL10 transgenic mouse hearts led to less cardiac damage and better cardiac function and vice verse in the knockout mice. This antiviral ability of CXCL10 might be through recruitment of natural killer (NK) cells to the heart and increased interferon-gamma expression early in infection. At day 7 postinfection, with massive influx of mononuclear cells the expression of CXCL10 enhanced the infiltration of CXCR3(+) cells, CD4(+), and CD8(+) T cells, as well as the expression of associated inflammatory cytokines. However, the augmented accumulation of these immune cells and associated cytokines failed to alter the viral clearance and mice survival. These results suggest the protective role of CXCL10 during the early course of CVB3 infection, which is attributed to the recruitment of NK cells. Nonetheless, CXCL10-directed chemoattractant effect is not sufficient for host to clear the virus in the heart.
Is the atypical neutrophilic dermatosis with subcorneal IgA deposits a variant of pemphigus foliaceus?
Authors: Wilhelm Stolz, Thomas Bieber, Michael Meurer
Journal: British Journal of Dermatology (1989)

Journal Article Is the atypical neutrophilic dermatosis with subcorneal IgA deposits a variant of pemphigus foliaceus? Get access Wilhelm Stolz, Wilhelm Stolz Department of Dermatology, University of Munich, Frauenlobstr. 9–11, 8000 München 2, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar Thomas Bieber, Thomas Bieber Department of Dermatology, University of Munich, Frauenlobstr. 9–11, 8000 München 2, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar Michael Meurer Michael Meurer Department of Dermatology, University of Munich, Frauenlobstr. 9–11, 8000 München 2, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue 2, 1 August 1989, Pages 276–279, https://doi.org/10.1111/j.1365-2133.1989.tb01812.x Published: 01 August 1989
Fashions change but tattoos are forever: time to regret
Authors: A. Aslam, C.M. Owen
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Tattoos and body art have been a part of human culture since the earliest beginnings of modern civilization and are becoming increasingly popular and widely acceptable throughout society. The incidence of tattooing among respondents in North America and Europe is approximately 25%.1 We undertook a questionnaire survey to investigate the incidence of satisfaction and regret relating to tattoos and tried to determine what factors influenced this. The study took place over a 6‐month period (August 2010 to February 2011) in the dermatology department of a large district general hospital. Patients aged ≥ 16 years who had a visible tattoo during general skin examination were asked to complete a short confidential questionnaire. All responses were anonymous. Ethical approval was granted. Patients detailed their current age, the age at which they acquired their first tattoo, whether it was performed by an amateur or professional artist, the number of tattoos, whether they still liked their tattoo and if they regretted their tattoo. We also determined the site of the tattoos but not their design or colour.
Nasal challenge with serotonin in asymptomatic hay fever patients
Authors: P. Tønnesen, O. B. Schaffalitzky de Muckadell, N. Mygind
Journal: Allergy (1987)

To study the nasal response to serotonin, 14 asymptomatic hay fever patients received intranasal serotonin in increasing doses. Itching and the number of sneezes were noted, and the amount of secretion was measured and assayed for substance P. Nasal airway resistance was recorded by active posterior rhinomanometry. Serotonin induced a dose‐dependent increase in nasal itching, number of sneezes and secretion. Substance P was found in 41 of 42 secretions. The median concentration was 10.3 pmol/1 (range 0‐28.9), and increased parallel to increasing doses of serotonin ( P &lt; 0.001).
Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes
Authors: Matej Orešič, Satu Simell, Marko Sysi-Aho, Kirsti Näntö-Salonen, Tuulikki Seppänen-Laakso, Vilhelmiina Parikka, Mikko Katajamaa, Anne Hekkala, Ismo Mattila, Päivi Keskinen, Laxman Yetukuri, Arja Reinikainen, Jyrki Lähde, Tapani Suortti, Jari Hakalax, Tuula Simell, Heikki Hyöty, Riitta Veijola, Jorma Ilonen, Riitta Lahesmaa, Mikael Knip, Olli Simell
Journal: The Journal of Experimental Medicine (2008)

The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward β cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies.
Scanning electron microscopic studies on cultured heart cells after the induction of arrhythmias and fibrillation
Authors: S. YONEDA, S. TOYAMA
Journal: Cardiovascular Research (1978)

Scanning electron microscopic observations were made of mouse embryonic heart cells in culture to clarify the interrelationship between morphological damage and cardiac arrhythmias and fibrillation induced by changes of ion concentrations. They were studied with particular reference to the abnormalities in the heart cell and the intercellular connections. The cells exhibited arrhythmias with any alteration in ion concentration (MgSO4, CaCl2, KCl, NaCl) in the culture medium, and they developed fibrillation-like beating under certain conditions of lowered potassium, or sodium, and increased sodium with a reduction in calcium or potassium. The heart cells showing arrhythmias were revealed by scanning electron microscopy to have more or less fine morphological changes in their slender processes, and detached or raised cell edges. Fold-like undulations in the cell body and cell edge were also numerous in cells exhibiting fibrillation-like beating. These cell body changes may, however, be characteristic of cells maintained in cultures with lowered potassium content, since only these cultures showed such changes. Changes of cell edge were also demonstrable in cultures with altered MgSO4, CaCl2 content or increased KCl or NaCl content although the cells in these cultures did not develop fibrillation. It was noted that there was a tendency for the changes of cell body and cell edge to be conspicuous in cells exhibiting fibrillation. The results obtained indicated that fibrillation developed only in the presence of altered concentrations of certain ions, in association with subtle morphological changes in the cells and intercellular connections.
STUDIES ON THE MECHANISM OF ACTION OF RILEY VIRUS
Authors: R. Evans, M. H. Salaman
Journal: The Journal of Experimental Medicine (1965)

A study was made of the replication of Riley virus in various tissue cultures. It was observed that Riley virus replicated in primary mouse embryo cultures for 8 to 12 days. As they aged primary cultures became less susceptible to Riley virus infection, and subcultured cells were not susceptible. Suspensions of virus, in the absence of cells, were inactivated at 36.5 degrees C. Serial passage by transfer of supernatant fluids to fresh embryo cultures was not successful. Replication of the virus was more active in mouse embryo liver cultures than in the cultures of the embryo minus the livers. In cultures of mouse macrophages, the supernatants remained infective throughout the life of the cultures (21 days). The virus was passed 23 times through fresh macrophage cultures over a period of 80 days, during which the original inoculum (10(6.0)ID(50)/ml) was theoretically diluted to 10(-14). The possibility that the cells of the RES are involved in Riley virus replication is discussed.
Frequency Analysis of Ventricular Fibrillation in Swine Ventricles
Authors: Miguel Valderrábano, Junzhong Yang, Chikaya Omichi, John Kil, Scott T. Lamp, Zhilin Qu, Shien-Fong Lin, Hrayr S. Karagueuzian, Alan Garfinkel, Peng-Sheng Chen, James N. Weiss
Journal: Circulation Research (2002)

It has been suggested from frequency analysis that cardiac fibrillation is driven by stable intramural reentry, with wavebreak occurring due to failure of 1:1 propagation. We tested this hypothesis with a combined experimental and theoretical approach. Optical mapping was performed on epicardial, endocardial, and transmural cut surfaces of fibrillating swine ventricles. Wavelets were characterized, the frequency content of optical signals analyzed, and space-time plots (STPs) constructed to detect Wenckebach-like conduction. The findings were compared with simulations in 2D and 3D cardiac tissue using the Luo-Rudy action potential model. The incidence of reentry in the cut transmural surface (11.8% in right ventricle, 14.3% in left ventricle) was similar to that on the endocardial surface (13.1%, P=NS) but greater than on the epicardial surface (7.7%, P<0.01). Frequency spectra of optically recorded membrane voltage were organized into spatial domains with the same dominant frequency, but these domains were nonstationary. In STPs, pseudo-2:1 conduction block was caused by double potentials arising when reentry occurred on the recording site rather than true Wenckebach conduction. The latter was observed in 11 of 166 STPs but did not occur at borders of high-to-low frequency domains. In simulations, similar findings were obtained when action potential duration (APD) restitution slope was steep. Stationary dominant frequency domains with Wenckebach conduction patterns were observed only in the presence of shallow APD restitution slope and marked nonuniform tissue heterogeneity. In conclusion, stable intramural reentry as the engine of fibrillation was not observed. Our findings support the idea that dynamic wavebreak plays a fundamental role in the generation and maintenance of ventricular fibrillation.
Associations of factor VIII<sub>c</sub>, D‐dimer, and plasmin–antiplasmin with incident cardiovascular disease and all‐cause mortality
Authors: Aaron R. Folsom, Joseph A.C. Delaney, Pamela L. Lutsey, Neil A. Zakai, Nancy S. Jenny, Joseph F. Polak, Mary Cushman
Journal: American Journal of Hematology (2009)

To examine the associations of three understudied hemostatic factors--D-dimer, factor VIII(c), and plasmin-antiplasmin (PAP) complex--with incident cardiovascular disease (CVD) and all cause mortality in the Multiethnic Study of Atherosclerosis cohort. Hemostatic factors were measured at baseline in 45-84-year-old patients (n = 6,391) who were free of clinically recognized CVD. Over 4.6 years of follow-up, we identified 307 CVD events, 207 hard coronary heart disease events, and 210 deaths. D-dimer, factor VIII(c), and PAP were not associated with CVD incidence after adjustment for other risk factors. In contrast, each factor was associated positively with total mortality, and D-dimer and factor VIII(c) were associated positively with cancer mortality. When modeled as ordinal variables and adjusted for risk factors, total mortality was greater by 33% (95% CI 15-54) for each quartile increment of D-dimer, 26% (11-44) for factor VIIIc, and 20% (4-38) for PAP. This prospective cohort study did not find D-dimer, factor VIII(c), or PAP to be risk factors for CVD. Instead, elevated levels of these three hemostatic factors were associated independently with increased risk of death. Elevated D-dimer and factor VIII(c) were associated with increased cancer death.
Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf
Authors: Martin O. Bergo, Bryant J. Gavino, Christine Hong, Anne P. Beigneux, Martin McMahon, Patrick J. Casey, Stephen G. Young
Journal: Journal of Clinical Investigation (2004)

Isoprenylcysteine carboxyl methyltransferase (Icmt) methylates the carboxyl-terminal isoprenylcysteine of CAAX proteins (e.g., Ras and Rho proteins). In the case of the Ras proteins, carboxyl methylation is important for targeting of the proteins to the plasma membrane. We hypothesized that a knockout of Icmt would reduce the ability of cells to be transformed by K-Ras. Fibroblasts harboring a floxed Icmt allele and expressing activated K-Ras (K-Ras-Icmtflx/flx) were treated with Cre-adenovirus, producing K-Ras-IcmtΔ/Δ fibroblasts. Inactivation of Icmt inhibited cell growth and K-Ras–induced oncogenic transformation, both in soft agar assays and in a nude mice model. The inactivation of Icmt did not affect growth factor–stimulated phosphorylation of Erk1/2 or Akt1. However, levels of RhoA were greatly reduced as a consequence of accelerated protein turnover. In addition, there was a large Ras/Erk1/2-dependent increase in p21Cip1, which was probably a consequence of the reduced levels of RhoA. Deletion of p21Cip1 restored the ability of K-Ras-IcmtΔ/Δ fibroblasts to grow in soft agar. The effect of inactivating Icmt was not limited to the inhibition of K-Ras–induced transformation: inactivation of Icmt blocked transformation by an oncogenic form of B-Raf (V599E). These studies identify Icmt as a potential target for reducing the growth of K-Ras– and B-Raf–induced malignancies.
Malignant Hypertension: Effect of Therapy on Renin and Aldosterone
Authors: R. G. MCALLISTER, C. W. VAN WAY, K. DAYANI, W. J. ANDERSON, E. TEMPLE, A. M. MICHELAKIS, W. S. COPPAGE, J. A. OATES
Journal: Circulation Research (1971)

Plasma renin activity (PRA) and aldosterone secretion rate (ASR) were measured in 22 patients in balance on a 100 mEq sodium diet during the malignant phase of hypertension and at intervals during long-term follow-up on pharmacological therapy. Three patients had normal PRA and ASR during malignant hypertension. Eighty-six per cent of patients had an increased ASR, but only in 36% was PRA concomitantly increased during malignant hypertension (one patient developed elevated PRA in the postmalignant period). PRA fell to normal in 87% of patients after antihypertensive therapy. ASR fell to normal on drug therapy in six patients, and in all of these there was a period during the postmalignant phase in which ASR was increased while PRA was normal or suppressed. In addition to this group with reversible hyperaldosteronism, all but two of the remaining patients with elevated ASR had periods during which ASR was increased at the same time that PRA was normal or suppressed. These data raise the possibility that either a nonrenin aldosterone-stimulating hormone is secreted in malignant hypertension or that excessive stimulation of the adrenal by angiotensin can lead to persistent hyperfunction of aldosterone-secreting cells with a quantitatively deranged feedback control. One patient had an aldosterone-secreting adenoma and had manifestations of the hyperaldosteronism antedating the development of malignant hypertension.
Are the Ranks Closed? Attitudinal Social Distance and Mental Illness
Authors: GUIDO CROCETTI, HERZL R. SPIRO, IRADJ SIASSI
Journal: American Journal of Psychiatry (1971)

The authors review previous studies on social attitudes toward the mentally ill and present data from their field survey on the opinions and attitudes of a blue-collar population toward mental illness. Almost all the 937 respondents considered mental illness an illness requiring the care of a physician and one that can be cured with proper treatment. Responses to questions about social distance showed significantly greater acceptance than rejection of all those who were formerly mentally ill.
Epigenetic States of Cells of Origin and Tumor Evolution Drive Tumor-Initiating Cell Phenotype and Tumor Heterogeneity
Authors: Kin-Hoe Chow, Dong-Mi Shin, Molly H. Jenkins, Emily E. Miller, David J. Shih, Seungbum Choi, Benjamin E. Low, Vivek Philip, Brad Rybinski, Roderick T. Bronson, Michael D. Taylor, Kyuson Yun
Journal: Cancer Research (2014)

Abstract A central confounding factor in the development of targeted therapies is tumor cell heterogeneity, particularly in tumor-initiating cells (TIC), within clinically identical tumors. Here, we show how activation of the Sonic Hedgehog (SHH) pathway in neural stem and progenitor cells creates a foundation for tumor cell evolution to heterogeneous states that are histologically indistinguishable but molecularly distinct. In spontaneous medulloblastomas that arise in Patched (Ptch)+/− mice, we identified three distinct tumor subtypes. Through cell type–specific activation of the SHH pathway in vivo, we determined that different cells of origin evolved in unique ways to generate these subtypes. Moreover, TICs in each subtype had distinct molecular and cellular phenotypes. At the bulk tumor level, the three tumor subtypes could be distinguished by a 465-gene signature and by differential activation levels of the ERK and AKT pathways. Notably, TICs from different subtypes were differentially sensitive to SHH or AKT pathway inhibitors, highlighting new mechanisms of resistance to targeted therapies. In summary, our results show how evolutionary processes act on distinct cells of origin to contribute to tumoral heterogeneity, at both bulk tumor and TIC levels. Cancer Res; 74(17); 4864–74. ©2014 AACR.