tbuckley/cabot-search huggingface dataset:
Reduced Susceptibility to Two-Stage Skin Carcinogenesis in Mice with Low Circulating Insulin-Like Growth Factor I Levels
Authors: Tricia Moore, Steve Carbajal, Linda Beltran, Susan N. Perkins, Shoshana Yakar, Derek LeRoith, Stephen D. Hursting, John DiGiovanni
Journal: Cancer Research (2008)

Abstract Calorie restriction has been shown to inhibit epithelial carcinogenesis and this method of dietary restriction reduces many circulating proteins, including insulin-like growth factor I (IGF-I). Previously, we identified a relationship between elevated tissue IGF-I levels and enhanced susceptibility to chemically induced skin tumorigenesis. In this study, liver IGF-I–deficient (LID) mice, which have a 75% reduction in serum IGF-I, were subjected to the standard two-stage skin carcinogenesis protocol using 7,12-dimethylbenz(a)anthracene as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. We observed a significant reduction in epidermal thickness and labeling index in LID mice treated with either vehicle or TPA. A significant decrease in both tumor incidence and tumor multiplicity was observed in LID mice undergoing two-stage skin carcinogenesis relative to wild-type littermates. Western blot analyses of epidermal extracts revealed reduced activation of both the epidermal growth factor and IGF-I receptors in response to TPA treatment in LID mice. In addition, reduced activation of both Akt and the mammalian target of rapamycin (mTOR) was observed in LID mice following TPA treatment relative to wild-type controls. Signaling downstream of mTOR was also reduced. These data suggest a possible mechanism whereby reduced circulating IGF-I leads to attenuated activation of the Akt and mTOR signaling pathways, and thus, diminished epidermal response to tumor promotion, and ultimately, two-stage skin carcinogenesis. The current data also suggest that reduced circulating IGF-I levels which occur as a result of calorie restriction may lead to the inhibition of skin tumorigenesis, at least in part, by a similar mechanism. [Cancer Res 2008;68(10):3680–8]
THE CUTANEOUS TUBERCULIN REACTION OF VON PIRQUET
Authors: A. J. B. Leckie
Journal: BMJ (1914)

VON PIRQUJET S CUTANEOUJS TUBERCULIN REACTION.[MAY I6, I914 six strychnine inijectionis.Gainied 1 lb., anid sputum and cough nearly disappeare(l.7. Scottish apprenitice, aged 19.After admission for trivial injury of wvrist (leveloped symptoms of acute general tuber- culosis.Pyrexia, rhles at left apex, obstinate constipationi, abdoninlal pain and retraction and vomiting; dry cough and night swveats.Von Pirquet's reaction strongly positive, but v-ery slow in (leveloping.Had one tuberculini and ten strych- niine inijectionis.Wlheni he left felt well, but there was dullness over left apex.8. Englislh A.B., aged 31.Cavity left apex.T1bercle bacilli 0to eft apx T erl bail in sputum' 1O5 -Von Pirquet's reaction feebl]y positive.Ill some mionths.In thiirty-two days lhad tlhree tuberculin and twenity-four strychnine inijections.Sahli's inoculationis over site of trouble seenmed to ease couiglh anid sputum.Patient left practically free from coughl with scant sputumii.No night sweats, anid witlh a good appetite.9. Greelk stoker, aged 34.. Ill six nlonths.Both apices affected.Excavationi.Anorexia and night sweats.Severe pain over right apex.reliev'ed by Sahli's inoculationis.Tlhree tuberculin and( twenity-five stryjchnine inijections in thirty-one (lays.Gained 2 lb., lost cou-gi anld night sweats.Regained apl)etite.10. Swe(dislh carpenter, aged 37. Ill fifteen months(?).Evident fibrosis.Tlhree attacks of pleurisy with effusioni.Rapidly losinig fleslh lately.Initenlse loathin)g for food.Severe pleuritic pains (wvliicli were relieved by iInoculatiOnS).Von Pirquet's reaction positive.Fingers aid nose congested and clubbed.In tflirty-one days lha(l three tuberculin' and fifteen strychnine injections, andl left witlh a good appetite, feeling fit, but still occasionally sweated at night.Plhvsical signs statt qulo.11.Irislh A.B., a'ged 36.Acute 'dry tuberculous pleurisy and lunig fibrosis.Great anorexia; made what seemed to be a good recovery iii forty-six days.'Had five tuberculin and thirty-four strychlnille injections.Sahli's inoculations relieved chest and shoul(lei painis.Eacl-h scarificitioln developed aln erythema bump larger than a five-shilling piece.There was a history of pl'imbismn.-12.Australiani seamlani, aged 32.Ill over eighteen months.Elxpelled from workmani's homle oni accounLt of cough keeping the inmates awakel at niiglht.BIoth apices excavated.Five tuberculiin, thirty-four strychninie inijections, and three inocu- lationis iii thirty-eigbt days.Gain'ed 4 lb., and practically lost couLghi.Ttiberele bacilli fewer in sputtum.
Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings
Authors: UD McCann, Z Szabo, U Scheffel, RF Dannals, GA Ricaurte
Journal: The Lancet (1998)

Background (±)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular recreational drug that selectively damages brain serotonin (5-HT) neurons in animals at doses that closely approach those used by humans. We investigated the status of brain 5-HT neurons in MDMA users. Methods We enrolled 14 previous users of MDMA who were currently abstaining from use and 15 controls who had never used MDMA. We used positron emission tomography (PET) with the radioligand carbon-11-labelled McN-5652, which selectively labels the 5-HT transporter. We analysed whether there were differences in 5-HT transporter binding between abstinent MDMA users and participants in the control group. Blood and urine samples were taken and tested to check for abstinence. Findings MDMA users showed decreased global and regional brain 5-HT transporter binding compared with controls. Decreases in 5-HT transporter binding positively correlated with the extent of previous MDMA use. Interpretation Quantitative PET studies with a ligand selective for 5-HT transporters can be used to assess the status of 5-HT neurons in the living human brain. We show direct evidence of a decrease in a structural component of brain 5-HT neurons in human MDMA users.
The current knowledge on radiosensitivity of ovarian follicle development stages
Authors: I. Adriaens, J. Smitz, P. Jacquet
Journal: Human Reproduction Update (2009)

The aim of this paper is to review the available information on ovarian radiation sensitivity and the genetic hazard of ionizing radiation in female mammals including humans. The literature present in the author's laboratories (international papers from the 1970s) was complemented by a Medline literature search using the keywords 'ionizing radiation genetic effects', 'oocyte radiosensitivity' and 'oocyte DNA repair' (1990–2008). Further articles were acquired from citations in the research papers and reports. Animal data show that oocyte radiosensitivity varies widely according to the follicle/oocyte stage and the species. Oocytes near ovulation show the highest susceptibility to radiation induction of mutational events. Congenital anomalies have been observed after exposure to high doses (1–5 Gy), but extrapolation of these data to humans requires caution. In humans, the dose required to induce permanent ovarian failure would vary from 20.3 Gy at birth to 14.3 Gy at 30 years. Most epidemiological studies found little evidence of genetic diseases at the doses at which medical, occupational or accidental exposure occurred. The fact that genetic effects were observed in irradiated animals suggests that these could also occur in humans. The probability of such events remains low compared with the 'spontaneous' risks of genetic effects.
Statin Use and Prognosis in Patients With Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in the Rituximab Era
Authors: Grzegorz S. Nowakowski, Matthew J. Maurer, Thomas M. Habermann, Stephen M. Ansell, William R. Macon, Kay M. Ristow, Cristine Allmer, Susan L. Slager, Thomas E. Witzig, James R. Cerhan
Journal: Journal of Clinical Oncology (2009)

Statins have antilymphoma properties but have also been shown to inhibit the binding of rituximab to the CD20 antigen, resulting in reduced antitumor activity of rituximab in vitro. The clinical impact of statin use on the outcome of lymphoma patients treated with a rituximab-containing regimen is unknown.Consecutive patients with newly diagnosed, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were enrolled onto a registry and observed prospectively. The impact of statin use on patients' outcomes was analyzed.Two hundred twenty-eight patients with DLBCL and 293 patients with FL were enrolled from September 2002 through June 2007; 21% of patients with DLBCL and 19% of patients with FL were on statins at diagnosis, and 20% and 17% remained on statins during lymphoma treatment, respectively. All patients with DLBCL and 39% of patients with FL received initial therapy containing rituximab. The median follow-up time was 47 months (range, 13 to 80 months). Statin use had no impact on the overall response rate (P = .67), overall survival (P = .76), or event-free survival (EFS) in patients with DLBCL (hazard ratio [HR] = 0.85; 95% CI, 0.43 to 1.68). Statin use at diagnosis was associated with improved EFS in patients with FL (HR = 0.45; 95% CI, 0.26 to 0.77), including subgroups treated with rituximab or a rituximab-containing regimen (HR = 0.38; 95% CI, 0.14 to 1.07) and patients who were observed only (HR = 0.38; 95% CI, 0.17 to 0.84).The concurrent use of statins during the treatment of patients with DLBCL and FL in the rituximab era did not adversely affect outcome. The apparent benefit of statin therapy on FL outcome requires further studies.
Impaired ventilatory function and elevated insulin levels in nondiabetic males: the Normative Aging Study
Authors: R Lazarus, D Sparrow, ST Weiss
Journal: European Respiratory Journal (1998)

Lower levels of baseline ventilatory function have consistently been associated with increased risk of cardiovascular mortality in prospective studies, but the underlying mechanisms are not known. Increased risk of coronary heart disease is associated with higher serum insulin levels. This report examines the relationship between ventilatory function and indirect measures of insulin resistance. Cross-sectional data from 922 nondiabetic participants in the Normative Aging Study were analysed using multiple linear regression models with adjustment for potential confounders. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined in relation to indicators of insulin resistance, i.e. fasting insulin and the fasting insulin resistance index (FIRI). Diabetics were excluded because impaired insulin secretion interferes with the validity of these as measures of insulin resistance. Fasting insulin and FIRI were negatively correlated with FVC and FEV1 (all p&lt; 0.001). These associations persisted after adjusting for potential confounders including age, height, body mass index, waist to hip circumference ratio, physical activity, alcohol intake and smoking in separate multiple linear regression models, for both insulin (all p&lt; or =0.0008) and FIRI (all p&lt; or =0.0001). Negative cross-sectional associations between ventilatory function and indirect measures of insulin resistance were found in nondiabetic males. Insulin resistance may contribute to the previously unexplained association between ventilatory function impairment and cardiovascular mortality. Mechanisms underlying the relationship between insulin resistance and decreased ventilatory function remain to be elucidated.
Abstract 4882: Loss of p300 reduces miR-let-7c and enhances ER-positive breast cancer cell tumorigenicity
Authors: Huijun Yuan, Sukanya Sil, Salil Sharma, Nanette Bishopric
Journal: Cancer Research (2010)

Abstract Histone deacetylase (HDAC) inhibitors have been extensively studied as potential anticancer treatments and several are currently in clinical trials. p300 is a nuclear histone acetyltransferase that is an important coordinator of multiple transcription-dependent cellular processes. HDAC inhibitors may directly and indirectly increase the activity of p300. The role of p300 is dependent on cell context but most or all of its biological activity stems from its ability to acetylate histones or non-histone nucleoproteins including p53, HSP) which regulate cell proliferation, differentiation and apoptosis. Whether p300 acts as a tumor suppressor or promoter is controversial, and its role in estrogen positive breast cancer remains to be defined, however, structural studies indicate that it has significant potential as a target for small molecule therapy. To address this issue, we have used a lentiviral approach to achieve 60-70% stable knockdown (KD) of p300 levels in estrogen receptor-positive breast cancer lines MCF-7 and BT 474 respectively. Growth curve and FACS analysis showed that loss of p300 shortened doubling times and increased G2 phase cells in both lines. Xenograft tumors formed from p300 KD cells were on average about three times larger at six weeks post implantation than control tumors (p&amp;lt;0.05). H&amp;E and CD31 staining showed that p300 KD xenograft tumors have a more aggressive phenotype with increased vascularity. In searching for targets of p300 that might regulate its anti-tumor effect, we observed that the microRNA miR-let-7c was downregulated in p300-depleted MCF-7 and BT474 cells. Consistent with this, the miR-let-7c target N-Ras was up-regulated in both p300 KD cell lines and in p300 KD xenograft tumors, and adenovirus-mediated over-expression of p300 caused downregulation of N-RAS. Finally, gene expression analysis showed that loss of p300 resulted in upregulation of E-cadherin, laminin, collagen, IL-6, IFN, TGF-β and components of the Wnt signaling pathway, indicating a shift from epithelial to mesenchymal phenotype. Our data show that p300 loss or inactivation results in altered transcription patterns and suppression of anti-tumor microRNAs, including let-7, and may induce a more invasive and potentially metastatic phenotype. We conclude that p300 likely acts as a tumor suppressor in breast cancer and that activation of p300 may contribute to the anti-tumor effects of TSA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4882.
A Vicious Circle of Alveolar Macrophages and Fibroblasts Perpetuates Pulmonary Fibrosis via CCL18
Authors: Antje Prasse, Dmitri V. Pechkovsky, Galen B. Toews, Wolfgang Jungraithmayr, Florian Kollert, Torsten Goldmann, Ekkehard Vollmer, Joachim Müller-Quernheim, Gernot Zissel
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Recently, models of macrophage activation have been revised. Macrophages stimulated with Th2 cytokines have been classified as alternatively activated.This article examines the expression and regulation of CC chemokine ligand 18 (CCL18), a marker of alternative activation, by human alveolar macrophages (AMs).AM were obtained from bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis, sarcoidosis, or hypersensitivity pneumonitis (n = 69) and healthy volunteers (n = 22). Expression of CCL18 was determined by quantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, flow cytometry, and immunohistochemistry, respectively.Spontaneous CCL18 production by BAL-derived cells was markedly increased in patients with pulmonary fibrosis and correlated negatively with pulmonary function test parameters. CCL18 gene expression and protein production were up-regulated in normal AMs after Th2 cytokine stimulation and/or coculture with human lung fibroblasts. Native collagen significantly up-regulated CCL18 expression in normal AMs activated with Th2 cytokines via a mechanism mediated by beta2-integrin/ scavenger receptor(s). Culture supernatants of AMs from patients with idiopathic pulmonary fibrosis increased collagen production by normal lung fibroblasts partly mediated via CCL18.Our findings suggest that AMs from patients with pulmonary fibrosis disclose a phenotype of alternative activation and might be a part of a positive feedback loop with lung fibroblasts perpetuating fibrotic processes.
The Veterans Administration and Health Manpower
Authors: H. Martin Engle
Journal: JAMA (1968)

For the past two decades the Veterans Administration has provided training in its hospitals in a wide range of health service disciplines. This accomplishment, while considerable in terms of numbers trained annually, has not been commensurate with the potentialities of the VA system for helping to meet the national health manpower crisis. Fortified by recent legislation encouraging the agency to conduct education and training of health manpower, the VA is planning a marked expansion of existent training and the development of new programs adapted to the rapidly changing demands of American medicine.
Targeted Disruption of the <i>Plasmodium berghei</i> Ctrp Gene Reveals Its Essential Role in Malaria Infection of the Vector Mosquito
Authors: Masao Yuda, Hiroshi Sakaida, Yasuo Chinzei
Journal: The Journal of Experimental Medicine (1999)

CTRP (circumsporozoite protein and thrombospondin-related adhesive protein [TRAP]-related protein) of the rodent malaria parasite Plasmodium berghei (PbCTRP) makes up a protein family together with other apicomplexan proteins that are specifically expressed in the host-invasive stage 1. PbCTRP is produced in the mosquito-invasive, or ookinete, stage and is a protein candidate for a role in ookinete adhesion and invasion of the mosquito midgut epithelium. To demonstrate involvement of PbCTRP in the infection of the vector, we performed targeting disruption experiments with this gene. PbCTRP disruptants showed normal exflagellation rates and development into ookinetes. However, no oocyst formation was observed in the midgut after ingestion of these parasites, suggesting complete loss of their invasion ability. On the other hand, when ingested together with wild-type parasites, disruptants were able to infect mosquitoes, indicating that the PbCTRP gene of the wild-type parasite rescued infectivity of disruptants when they heterologously mated in the mosquito midgut lumen. Our results show that PbCTRP plays a crucial role in malaria infection of the mosquito midgut and suggest that similar molecular mechanisms are used by malaria parasites to invade cells in the insect vector and the mammalian host.
STUDIES ON MALARIAL PARASITES
Authors: Ralph W. McKee, Richard A. Ormsbee, Christian B. Anfinsen, Quentin M. Geiman, Eric G. Ball
Journal: The Journal of Experimental Medicine (1946)

1. Normal monkey, Macaca mulatta, plasma and red cells are similar in their inorganic composition to those of human beings. Inorganic phosphate values of plasma and red cells from parasitized monkey blood are lower than normal. Plasma potassium values are higher than normal particularly during segmentation. Other inorganic components of parasitized blood show little variation from normal. 2. Monkey red blood cells parasitized with P. knowlesi consume oxygen in the presence of glucose, lactate, glycerol, and amino acids as substrates. Their respiration is inhibited by cyanide, carbon monoxide, and high oxygen tensions. Normal monkey red blood cells consume oxygen at an appreciable rate only in the presence of methylene blue. 3. Parasitized erythrocytes convert glucose to lactate at a rate 25 to 75 times that of the normal monkey erythrocyte. Unlike the normal red cell, the parasitized cell utilizes lactate if oxygen is present. Lactate is utilized, however, at a rate that is only one-sixth that of its production from glucose. 4. The significance of these findings in relation to the problem of cultivation of malarial parasites is discussed.
Obstructions to Understanding Malignant Bowel Obstruction
Authors: Robert S. Krouse
Journal: JAMA Surgery (2013)

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Defective Trafficking of Nephrin Missense Mutants Rescued by a Chemical Chaperone
Authors: Xiao Li Liu, Stefania Cotta Doné, Kunimasa Yan, Pekka Kilpeläinen, Timo Pikkarainen, Karl Tryggvason
Journal: Journal of the American Society of Nephrology (2004)

The nephrin gene (NPHS1) is mutated in congenital nephrotic syndrome of the Finnish type. Most mutations found in non-Finnish patients are missense mutations. The most common consequence of missense mutations in congenital nephrotic syndrome is a defect in intracellular transport and retention of the mutant proteins in the endoplasmic reticulum (ER), possibly as a result of misfolding and unfavored conformation. Because sodium 4-phenylbutyrate has been shown to function as a chemical chaperone and to correct the cellular trafficking of several mislocalized or misfolded mutant plasma membrane proteins, the effects of this compound on the missense mutants identified in patients with congenital nephrotic syndrome of the Finnish type were investigated. This study was performed using human embryonic kidney 293 cells stably expressing wild-type or missense nephrin mutants trapped in the ER. Immunofluorescence microscopy and cell surface biotinylation showed that treatment with sodium 4-phenylbutyrate rescued several of the missense mutants from the ER to the cell surface. All of the rescued mutants were found to be able to interact with Neph1. Furthermore, their tyrosine phosphorylation was rapidly induced by clustering with anti-nephrin antibodies, suggesting that the rescued mutants may be functionally intact.
Parental Diagnoses in Youth With Narrow Phenotype Bipolar Disorder or Severe Mood Dysregulation
Authors: Melissa A Brotman, Layla Kassem, Michelle M Reising, Amanda E Guyer, Daniel P Dickstein, Brendan A Rich, Kenneth E Towbin, Daniel S Pine, Francis J McMahon, Ellen Leibenluft
Journal: American Journal of Psychiatry (2007)

Objective: Controversy exists regarding whether nonepisodic irritability and hyperarousal (severe mood dysregulation) is a phenotype of pediatric bipolar disorder. The authors compared axis I diagnoses in parents of children with narrow phenotype bipolar disorder and parents of youth with severe mood dysregulation. Method: Parents of youth with narrow phenotype bipolar disorder (proband N=33, parent N=42) and youth with severe mood dysregulation (proband N=30, parent N=37) were interviewed by clinicians who were blind to the child’s diagnostic status using the Diagnostic Interview for Genetic Studies. Results: Compared to parents of youth with severe mood dysregulation, parents of youth with narrow phenotype bipolar disorder were significantly more likely to be diagnosed with bipolar disorder. There were no other diagnostic differences between the two groups. Conclusions: These data suggest that narrow phenotype bipolar disorder may be distinct from severe mood dysregulation in terms of familial aggregation. Additionally, the familiality of narrow phenotype bipolar disorder and adult DSM-IV bipolar disorder is high.