tbuckley/cabot-search huggingface dataset:
Effects of lead exposure before pregnancy and dietary calcium during pregnancy on fetal development and lead accumulation.
Authors: S Han, D H Pfizenmaier, E Garcia, M L Eguez, M Ling, F W Kemp, J D Bogden
Journal: Environmental Health Perspectives (2000)

Millions of women of child-bearing age have substantial bone lead stores due to lead exposure as children. Dietary calcium ingested simultaneously with lead exposure can reduce lead absorption and accumulation. However, the effects of dietary calcium on previously accumulated maternal lead stores and transfer to the fetus have not been investigated. We studied the effects of lead exposure of female rats at an early age on fetal development during a subsequent pregnancy. We gave 5-week-old female Sprague-Dawley rats lead as the acetate in their drinking water for 5 weeks; controls received equimolar sodium acetate. This was followed by a 1-month period without lead exposure before mating. We randomly assigned pregnant rats (n = 39) to diets with a deficient (0.1%) or normal (0.5%) calcium content during pregnancy. A total of 345 pups were delivered alive. Lead-exposed dams and their pups had significantly higher blood lead concentrations than controls, but the concentrations were in the range of those found in many pregnant women. Pups born to dams fed the calcium-deficient diet during pregnancy had higher blood and organ lead concentrations than pups born to dams fed the 0. 5% calcium diet. Pups born to lead-exposed dams had significantly (p<0.0001) lower mean birth weights and birth lengths than controls. There were significant inverse univariate associations between dam or pup organ lead concentrations and birth weight or length. The 0.5% calcium diet did not increase in utero growth. Stepwise regression analysis demonstrated that greater litter size and female sex were significantly associated with reduced pup birth weight and length. However, lead exposure that ended well before pregnancy was significantly (p<0.0001) associated with reduced birth weight and length, even after litter size, pup sex, and dam weight gain during pregnancy were included in the regression analysis. The data demonstrate that an increase in dietary calcium during pregnancy can reduce fetal lead accumulation but cannot prevent lead-induced decreases in birth weight and length. The results provide evidence that dietary nutrients can influence the transfer of toxins to the fetus during pregnancy. If these results are applicable to women, an increase in diet calcium during pregnancy could reduce the transfer of lead from prepregnancy maternal exposures to the fetus.
2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up
Authors: J. Vansteenkiste, L. Crinò, C. Dooms, J.Y. Douillard, C. Faivre-Finn, E. Lim, G. Rocco, S. Senan, P. Van Schil, G. Veronesi, R. Stahel, S. Peters, E. Felip, Rolf Stahel, Enriqueta Felip, Solange Peters, Keith Kerr, Benjamin Besse, Johan Vansteenkiste, Wilfried Eberhardt, Martin Edelman, Tony Mok, Ken O'Byrne, Silvia Novello, Lukas Bubendorf, Antonio Marchetti, Paul Baas, Martin Reck, Konstantinos Syrigos, Luis Paz-Ares, Egbert F. Smit, Peter Meldgaard, Alex Adjei, Marianne Nicolson, Lucio Crinò, Paul Van Schil, Suresh Senan, Corinne Faivre-Finn, Gaetano Rocco, Giulia Veronesi, Jean-Yves Douillard, Eric Lim, Christophe Dooms, Walter Weder, Dirk De Ruysscher, Cecile Le Pechoux, Paul De Leyn, Virginie Westeel
Journal: Annals of Oncology (2014)
On the role of transforming growth factor-β in the growth inhibitory effects of retinoic acid in human pancreatic cancer cells
Authors: Brahmchetna Singh, Richard F Murphy, Xian-Zhong Ding, Alexandra B Roginsky, Richard H Bell, Thomas E Adrian
Journal: Molecular Cancer (2007)

Abstract Background Retinoids are potent growth inhibitory and differentiating agents in a variety of cancer cell types. We have shown that retinoids induce growth arrest in all pancreatic cancer cell lines studied, regardless of their p53 and differentiation status. However, the mechanism of growth inhibition is not known. Since TGF-β2 is markedly induced by retinoids in other cancers and mediates MUC4 expression in pancreatic cancer cells, we investigated the role of TGF-β in retinoic acid-mediated growth inhibition in pancreatic cancer cells. Results Retinoic acid markedly inhibited proliferation of two cell lines (Capan-2 and Hs766T) in a concentration and time-dependent manner. Retinoic acid increased TGF-β2 mRNA content and secretion of the active and latent forms of TGF-β2 (measured by ELISA and bioassay). The concentrations of active and TGF-β2 secreted in response to 0.1 – 10 μM retinoic acid were between 1–5 pM. TGF-β2 concentrations within this range also inhibited proliferation. A TGF-β neutralizing antibody blocked the growth inhibitory effects of retinoic acid in Capan-2 cells and partially inhibitory the effects in Hs766T cells. Conclusion These findings indicate that TGF-β can cause growth inhibition of pancreatic cancer cells, in a p53-independent manner. Furthermore, it demonstrates the fundamental role of TGF-β in growth inhibition in response to retinoic acid treatment is preserved in vitro .
Role of Donor-Derived Monocyte Chemoattractant Protein-1 in Murine Islet Transplantation
Authors: Bernd Schro[Combining Diaeresis]ppel, Nan Zhang, Peng Chen, Dongmei Chen, Jonathan S. Bromberg, Barbara Murphy
Journal: Journal of the American Society of Nephrology (2004)

Monocyte chemoattractant protein-1 (CCL2/MCP-1) is a proinflammatory chemokine produced by several cell types, including pancreatic islets. High levels of donor-derived CCL2 have been associated with poor islet allograft outcome in patients with type 1 diabetes; however, the causal relationship is unknown. The constitutive and inducible expression of chemokines and their receptors by pancreatic islets in vitro were investigated, specifically the role of donor-derived CCL2 in marginal mass murine islet transplantation. The results showed that inflammatory cytokine stimulation of islets induced de novo expression of CCL2, CCL5/RANTES, CXCL9/MIG, and CXCL10/IP-10 and increased expression of CXCL2/macrophage-inflammatory protein-2. CCL2 mRNA and protein were highly expressed within 2 d in cultures. Transplantation of islets with high levels of CCL2 into syngeneic recipients led to a significantly greater influx of CCR2(+) cells and higher expression of monocyte/macrophage-associated inflammatory cytokines compared with low CCL2-donor islets. The level of pretransplantation CCL2 inversely correlated (P < 0.0001) with isograft function. In contrast, in CCR2-/- recipients, this correlation was not present. A direct toxic effect of CCL2 on islets was excluded by assessing cell viability and insulin release in vitro. In conclusion, CCL2 secreted by islets plays an important role in the immediate islet graft function. Strategies to decrease islet-derived CCL2 release may increase the success of islet transplantation.
Species-Specific <i>In vivo</i> Engraftment of the Human BL Melanoma Cell Line Results in an Invasive Dedifferentiated Phenotype Not Present in Xenografts
Authors: Jessica Cedervall, Seema Jamil, Lina Prasmickaite, YenFu Cheng, Malihe Eskandarpour, Johan Hansson, Gunhild M. Mælandsmo, Ulrik Ringborg, Miklos Gulyas, He Suo Zhen, Lena Kanter, Lars Ährlund-Richter
Journal: Cancer Research (2009)

For clinically relevant studies on melanoma progression and invasiveness, in vivo experimental systems with a human cellular microenvironment would be advantageous. We have compared tumor formation from a human cutaneous malignant melanoma cell line (BL), after injection as conventional xenografts in the mouse, or when injected into a predominantly species-specific environment of human embryonic stem cell-derived teratoma induced in the mouse (the hEST model). The resulting melanoma histology was generally analogous, both systems showing delimited densely packed areas with pleomorphic cells of malignant appearance. A specificity of the integration process into the human embryonic teratoma tissues was indicated by the melanoma exclusively being found in areas compatible with condensed mesenchyme, similar to neural crest development. Here, also enhanced neovascularization was seen within the human mesenchymal tissues facing the BL melanoma growth. Furthermore, in the hEST model an additional melanoma cell phenotype occurred, located at the border of, or infiltrating into, the surrounding human loose mesenchymal fibrous stroma. This BL population had a desmoplastic spindle-like appearance, with markers indicative of dedifferentiation and migration. The appearance of this apparently more aggressive phenotype, as well as the induction of human angiogenesis, shows specific interactions with the human embryonic microenvironment in the hEST model. In conclusion, these data provide exciting options for using the hEST model in molecular in vivo studies on differentiation, invasiveness, and malignancy of human melanoma, while analyzing species-specific reactions in vivo.
Metabolism of Proinsulin, Insulin, and C-Peptide in the Rat
Authors: Adrian I. Katz, Arthur H. Rubenstein
Journal: Journal of Clinical Investigation (1973)

The renal extraction and excretion of bovine proinsulin, insulin, and C-peptide and the contribution of the kidney to their total metabolic clearance rate (MCR) were studied in the rat. Metabolic clearance rates were measured by the constant infusion technique and plasma and urine concentrations of each polypeptide were determined by radioimmunoassay.
Manual of Panic Focused Psychodynamic Psychotherapy: eXtended Rangeby BuschFredric N., MilrodBarbara L., SingerMeriamne B., and AronsonAndrew C.. London, Routledge, 2011, 230 pp., $34.95.
Authors: J. Stuart Ablon, Raymond A. Levy
Journal: American Journal of Psychiatry (2012)
<i>Plasmodium berghei</i> infection ameliorates atopic dermatitis‐like skin lesions in <scp>NC</scp>/Nga mice
Authors: C. Kishi, H. Amano, K. Suzue, O. Ishikawa
Journal: Allergy (2014)

Atopic diseases are more prevalent in industrialized countries than in developing countries. In addition, significant differences in the prevalence of allergic diseases are observed between rural and urban areas within the same country. This difference in prevalence has been attributed to what is called the 'hygiene hypothesis'. Although parasitic infections are known to protect against allergic reactions, the mechanism is still unknown. The aim of this study was to investigate whether or not malarial infections can inhibit atopic dermatitis (AD)-like skin lesions in a mouse model of AD.We used NC/Nga mice which are a model for AD. The NC/Nga mice were intraperitoneally infected with 1 × 10(5) Plasmoduim berghei (Pb) XAT-infected erythrocytes.Malarial infections ameliorated AD-like skin lesions in the NC/Nga mice. This improvement was blocked by the administration of anti-asialo GM1 antibodies, which are anti-natural killer (NK) cells. Additionally, adoptive transfer of NK cells markedly improved AD-like skin lesions in conventional NC/Nga mice; these suggest that the novel protective mechanism associated with malaria parasitic infections is at least, in part, dependent on NK cells.We have experimentally demonstrated for the first time that malarial infections ameliorated AD-like skin lesions in a mouse model of AD. Our study could explain in part the mechanism of the 'hygiene hypothesis', which states that parasitic infections can inhibit the development of allergic diseases.
Prostaglandin H Synthase 2 Expression in Airway Cells from Patients with Asthma and Chronic Obstructive Pulmonary Disease
Authors: RAME TAHA, RON OLIVENSTEIN, TOMOKI UTSUMI, PIERRE ERNST, PETER J. BARNES, IAN W. RODGER, ADEL GIAID
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Products of the prostaglandin H synthase (PGHS) metabolic pathway are thought to play a role in the pathogenesis of asthma. We determined the level of expression of the constitutive (PGHS-1) and inducible (PGHS-2) isoforms of the enzyme in induced sputum and bronchial biopsies of patients with asthma, patients with chronic obstructive pulmonary disease (COPD), and unaffected control subjects by immunocyto- and immunohistochemistry. Immunoreactivity for PGHS-2 was significantly greater in the induced sputum of patients with asthma and patients with COPD compared with unaffected control subjects. The level of PGHS-2 was greater in asthma than in COPD. Immunoreactivity for PGHS-1 increased in cells in the induced sputum of patients with asthma and patients with COPD compared with that of unaffected control subjects. Immunostained cells included macrophages, eosinophils, and neutrophils. Greater PGHS-2 immunoreactivity was seen in the submucosal inflammatory infiltrate and in the airway epithelium of patients with asthma compared with unaffected control subjects. In summary, we demonstrate an induction of PGHS-2 in asthma, suggesting increased formation of prostanoids, which may contribute to the inflammatory process. Taha R, Olivenstein R, Utsumi T, Ernst P, Barnes PJ, Rodger IW, Giaid A. Prostaglandin H synthase 2 expression in airway cells from patients with asthma and chronic obstructive pulmonary disease.
What love has to do with it: An attachment perspective on pair bonding and sexual behavior
Authors: Vivian Zayas, Daphna Ram
Journal: Behavioral and Brain Sciences (2009)

Abstract Del Giudice proposes that short-term mating strategies are adaptive for attachment-avoidant men. We argue that this model (1) does not apply to the majority of avoidant men (fearful-avoidants); (2) is based on limited evidence that the remaining subset of avoidant men (dismissing-avoidants) engage in short-term mating strategies; and (3) disregards the importance of pair bonding even for dismissing-avoidants.
281. Modulating the Immune Response to Oncolytic Measles Viruses
Authors: Mikael Rinne, David Caldwell, Ying He, Mark R. Kelley
Journal: Molecular Therapy (2004)

Top of pageAbstract
In an effort to improve the efficacy of cancer chemotherapy by intervening into the cellular responses to chemotherapeutic change, we have used adenoviral overexpression of N-methylpurine DNA glycosylase (MPG, ANPG or AAG) in breast cancer cells, to study its ability to imbalance base excision repair (BER) and sensitize cancer cells to alkylating agents. Our results demonstrate that MPG overexpressing cells are significantly more sensitive to the alkylating agents methyl methanesulfonate (MMS), N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), methyl nitrosourea (MNU), dimethyl sulfate (DMS) and the clinical chemotherapeutic temozolomide (TMZ). Sensitivity is further increased through co-administration of the BER inhibitor methoxyamine (MX), which covalently binds abasic (AP) sites and makes them refractory to subsequent repair. MX reduction of cell survival is significantly greater in cells overexpressing MPG than in control cells, suggesting a heightened production of AP sites that if made persistent, results in increased cellular toxicity. We further explored the mechanism of MPG-induced sensitivity, and found that sensitivity was associated with a significant increase in the number of AP sites and/or single strand breaks in overexpressing cells, confirming an MPG-driven accumulation of toxic BER intermediates. This data establishes transient MPG overexpression as a potential therapeutic approach for increasing cellular sensitivity to alkylating agent chemotherapy.
Molecular Footprints of Local Adaptation in Two Mediterranean Conifers
Authors: D. Grivet, F. Sebastiani, R. Alia, T. Bataillon, S. Torre, M. Zabal-Aguirre, G. G. Vendramin, S. C. Gonzalez-Martinez
Journal: Molecular Biology and Evolution (2010)

This study combines neutrality tests and environmental correlations to identify nonneutral patterns of evolution in candidate genes related to drought stress in two closely related Mediterranean conifers, Pinus pinaster Ait. and P. halepensis Mill. Based on previous studies, we selected twelve amplicons covering six candidate genes that were sequenced in a large sample spanning the full range of these two species. Neutrality tests relatively robust to demography (DHEW compound test and maximum likelihood multilocus Hudson–Kreitman–Aguadé test) were used to detect selection events at different temporal scales. Environmental associations between variation at candidate genes and climatic variables were also examined. These combined approaches detected distinct genes that may be targeted by selection, most of them specific to only one of the two conifers, despite their recent divergence (<10 Ma). An exception was 4-coumarate: CoA ligase, a gene involved in the production of various important secondary products that appeared to play a role in local adaptation processes of both pines. Another remarkable result was that all significant environmental correlations involved temperature indices, highlighting the importance of this climatic factor as a selective driver on Mediterranean pines. The ability to detect natural selection at the DNA sequence level depends on the nature and the strength of the selection events, on the timescale at which they occurred, and on the sensitivity of the methods to other evolutionary forces that can mimic selection (e.g., demography and population structure). Using complementary approaches can help to capture different aspects of the evolutionary processes that govern molecular variation at both intra- and interspecific levels.
False aneurysm of the common femoral vein in a footballer: Figure 1
Authors: M Karahan, S Isbir, F Baltacýoglu, M M Caglar
Journal: British Journal of Sports Medicine (2005)

Traumatic false aneurysm of the femoral vein has never been reported in the English literature. The case is here reported of a footballer with a traumatic false aneurysm of the common femoral vein which was initially misdiagnosed as an arterial pseudoaneurysm. This is a very rare clinical condition, but this diagnosis should be among those considered for post-traumatic unexplained thigh pain after trauma.
Loose lipid rafts lead to trigger-happy mast cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Mast cells that accumulate cholesterol precursors in their membranes tend to overreact, according to Kovarova and colleagues on page 1161. This mast cell hyperresponsiveness might help explain why patients with a genetic disease known as Smith-Lemli-Opitz syndrome (SLOS) are prone to food allergies.






Figure 1

Degranulation is enhanced in mast cells lacking the enzyme that reduces 7-dehydrocholesterol (DHCR KO).




Patients with SLOS have abnormally low levels of circulating cholesterol—and a corresponding abundance of the cholesterol precursor 7-dehydrocholesterol (DHC)—due to defects in the gene that encodes the DHC-reducing enzyme (DHCR7). This cholesterol deficiency causes a bevy of developmental defects, consistent with the known requirement for cholesterol during embryonic development.

But the allergic manifestations of SLOS are poorly understood. Kovarova and colleagues suspected that mast cells—the principle allergy-triggering cell type—might be involved, as mast cells rely on the proper distribution of cholesterol-rich lipid rafts in their membranes for appropriate activation and deactivation.

Their hunch was right. Mast cells from Dhcr7-deficient mice were hyperactive compared with wild-type cells, as measured by increased degranulation and proinflammatory cytokine production upon activation. But to their surprise, the deficient cells had normal numbers of lipid rafts—although the abundance of DHC and paucity of cholesterol made the rafts less stable than normal.

The destabilized rafts contained fewer molecules of the kinase Lyn, leading to a decrease in the Lyn-dependent activation of Csk-binding protein, a negative regulator of the degranulation-stimulating kinase Fyn. Depleting wild-type cells of cholesterol had the same activation-enhancing effect, which was reversed when cholesterol was added back. But adding cholesterol to the Dhcr7-deficient cells had minimal effect, suggesting that the activation defect was caused by the accumulation of DHC, rather than the depletion of cholesterol.

These results suggest that patients with other diseases involving defects in cholesterol biosynthesis might be more prone to allergies—a possibility that remains to be tested.
Treatment with corticosteroids reduces arterial stiffness in patients with polymyalgia rheumatica as measured with pulse wave analysis: Table 1
Authors: H Pieringer, U Stuby, S Hargassner, G Biesenbach
Journal: Annals of the Rheumatic Diseases (2008)

In recent years there has been increasing interest in the influence of inflammatory rheumatic diseases on the cardiovascular system.1 There is growing evidence that inflammation plays a major part in the initiation and progression of atherosclerosis.2

Polymyalgia rheumatica (PMR) affects primarily the elderly and exhibits evidence of a systemic inflammatory response.3 Because PMR is known to respond well clinically to corticosteroids, we wanted to examine whether this treatment might also have an effect on arterial stiffness in these patients. The aim of this study, therefore, was to investigate the influence of therapy with steroids on the augmentation index (AIx), a marker of arterial stiffness, as measured with …
Implementation of a Sensitive Troponin I Assay and Risk of Recurrent Myocardial Infarction and Death in Patients With Suspected Acute Coronary Syndrome
Authors: Nicholas L. Mills
Journal: JAMA (2011)

Although troponin assays have become increasingly more sensitive, it is unclear whether further reductions in the threshold of detection for plasma troponin concentrations will improve clinical outcomes in patients with suspected acute coronary syndrome (ACS).To determine whether lowering the diagnostic threshold for myocardial infarction (MI) with a sensitive troponin assay could improve clinical outcomes.All consecutive patients admitted with suspected ACS to the Royal Infirmary of Edinburgh, Edinburgh, Scotland, before (n = 1038; February 1-July 31, 2008, during the validation phase) and after (n = 1054; February 1-July 31, 2009, during the implementation phase) lowering the threshold of detection for myocardial necrosis from 0.20 to 0.05 ng/mL with a sensitive troponin I assay were stratified into 3 groups (<0.05 ng/mL, 0.05-0.19 ng/mL, and ≥0.20 ng/mL). During the validation phase, only concentrations above the original diagnostic threshold of 0.20 ng/mL were reported to clinicians.Event-free survival (recurrent MI and death) at 1 year in patients grouped by plasma troponin concentrations.Plasma troponin concentrations were less than 0.05 ng/mL in 1340 patients (64%), 0.05 to 0.19 ng/mL in 170 patients (8%), and 0.20 ng/mL or more in 582 patients (28%). During the validation phase, 39% of patients with plasma troponin concentrations of 0.05 to 0.19 ng/mL were dead or had recurrent MI at 1 year compared with 7% and 24% of those patients with troponin concentrations of less than 0.05 ng/mL (P < .001) or 0.20 ng/mL or more (P = .007), respectively. During the implementation phase, lowering the diagnostic threshold to 0.05 ng/mL was associated with a lower risk of death and recurrent MI (from 39% to 21%) in patients with troponin concentrations of 0.05 to 0.19 ng/mL (odds ratio, 0.42; 95% confidence interval, 0.24-0.84; P = .01).In patients with suspected ACS, implementation of a sensitive troponin assay increased the diagnosis of MI and identified patients at high risk of recurrent MI and death. Lowering the diagnostic threshold of plasma troponin was associated with major reductions in morbidity and mortality.