tbuckley/cabot-search huggingface dataset:
Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants
Authors: Y. Miyake, S. Sasaki, K. Tanaka, Y. Hirota
Journal: European Respiratory Journal (2009)

The present prospective study examined the association between maternal consumption of dairy products, calcium, and vitamin D during pregnancy and the risk of wheeze and eczema in the infants aged 16–24 months. Subjects were 763 Japanese mother–child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood. Higher maternal intake of total dairy products, milk, cheese and calcium during pregnancy was significantly related to a decreased risk of infantile wheeze, but not eczema (adjusted ORs (95% CI) between extreme quartiles were 0.45 (0.25−0.79), 0.50 (0.28−0.87), 0.51 (0.31−0.85), and 0.57 (0.32−0.99), respectively). When maternal vitamin D consumption during pregnancy was categorised into two groups using a cut-off point at the 25th percentile, children whose mothers had consumed ≥4.309 μg·day<sup>−1</sup> had a significantly reduced risk of wheeze and eczema (adjusted ORs (95% CI) were 0.64 (0.43−0.97) and 0.63 (0.41−0.98), respectively). Higher consumption of calcium and dairy foods other than yoghurt during pregnancy may reduce the risk of infantile wheeze. Higher vitamin D intake during pregnancy may be protective against childhood wheeze and eczema.
RADIOIRON ABSORPTION IN ANEMIC DOGS
Authors: Wellington B. Stewart, Charles L. Yuile, Herbert A. Claiborne, Richard T. Snowman, George H. Whipple
Journal: The Journal of Experimental Medicine (1950)

The control of iron absorption appears to reside in the mucosa of the gastrointestinal tract. The normal dog absorbs very little iron, but the anemic iron-depleted dog may absorb 10 to 20 times as much. This "mucosal block" of the normal dog probably is due largely to iron stores in the mucosa. "Mucosal block" can be effected in the anemic iron-depleted dog by feeding of iron salts, but the degree of "mucosal block" under these conditions never reaches the high degree of "mucosal block" in the normal dog. Rapid movement of iron through the mucosa may explain the short duration of "mucosal block" due to iron feeding in the anemic iron-depleted dogs (18 to 20 hours, Fig. 1). The colon absorbs very little iron under the conditions described. The stomach and duodenum seem to be most active in its absorption. This suggests the existence of a gradient in the capacity of the gastrointestinal tract to absorb iron.
Comprehensive Geriatric Assessment Adds Information to Eastern Cooperative Oncology Group Performance Status in Elderly Cancer Patients: An Italian Group for Geriatric Oncology Study
Authors: Lazzaro Repetto, Lucia Fratino, Riccardo A. Audisio, Antonella Venturino, Walter Gianni, Marina Vercelli, Stefano Parodi, Denise Dal Lago, Flora Gioia, Silvio Monfardini, Matti S. Aapro, Diego Serraino, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (≥ 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS: We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satariano’s index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS: These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL-independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two-fold higher probability of having an elevated Satariano’s index than independent patients. A strong association emerged between PS and CGA, with a nearly five-fold increased probability of having a poor PS (ie, ≥ 2) recorded in patients dependent for ADL or IADL. CONCLUSION: The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients.
Lack of Functional Immunoregulatory Cells in a Patient With Mycosis Fungoides and Circulating Sézary Cells: Brief Communication 2
Authors: Vali Kermani-Arab, Janet L. Roberts, Jon M. Hanifin, Gerrie A. Leslie
Journal: JNCI Journal of the National Cancer Institute (1978)

Peripheral blood lymphocytes obtained at various intervals from normal individuals and from a patient with mycosis fungoides (MF) were cultured with phytohemagglutinin (PHA) for 3 days to activate suppressor cells. After being cultured, the PHA-treated cells were irradiated, washed, and then transferred to fresh medium with PHA. The PHA responsiveness of the cells from normal individuals was suppressed approximately 90% by autologous or normal allogeneic Iymphocytes activated for 3 days with PHA, whereas the cells activated for 3 days with PHA from the patient with MF lacked the capacity to Inhibit the mitogenic response of autologous or allogeneic lymphocytes. These data suggest that this patient lacked suppressor T-cells that have a specificity for helper T-cells.
Changes in Skin Cancer Morbidity Between 1971–72 and 1977–78
Authors: T R Fears, J Scotto
Journal: JNCI Journal of the National Cancer Institute (1982)

Skin cancer incidence rates for two geographic areas of the United States were analyzed for detection of significant changes in risk over a 6-year period (1971–72 to 1977–78). Changes in rates were examined by cell type, anatomic site, sex, and age. In general risk has increased, but the size of the increase varied by cell type, sex, and anatomic site. Statistically significant increases were limited to tumors of the basal type. The risk of basal cell skin cancer appears to have increased about 18% or almost 3% per year. Increases did not depend on age group. Among males the increases were most notable for sites other than face, head, and neck, whereas among females the increases were not associated with site.
The <i>c-myc</i> Gene Is a Direct Target of Mammalian SWI/SNF–Related Complexes during Differentiation-Associated Cell Cycle Arrest
Authors: Norman G. Nagl, Daniel R. Zweitzig, Bayar Thimmapaya, George R. Beck, Elizabeth Moran
Journal: Cancer Research (2006)

Abstract The activity of mammalian SWI/SNF–related chromatin remodeling complexes is crucial for differentiation, development, and tumor suppression. Cell cycle–regulating activities dependent on the complexes include induction of the p21WAF1/CIP1 kinase inhibitor and repression of E2F-responsive promoters. These responses are linked through effects on pRb phosphorylation, but the direct role of the SWI/SNF–related complexes in their regulation is not fully understood. Results presented here reveal that the complexes are required for regulation of a distinct pathway of proliferation control involving repression of c-myc expression in differentiating cells. This involves direct promoter targeting of the c-myc gene by the complexes. Induction of p21WAF1/CIP1 is specifically dependent on prior repression of c-myc, but repression of E2F-responsive genes is dissociable from the regulation of c-myc and p21WAF1/CIP1. (Cancer Res 2006; 66(3): 1289-93)
Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes
Authors: Katja Christodoulou, Anthony E Wiskin, Jane Gibson, William Tapper, Claire Willis, Nadeem A Afzal, Rosanna Upstill-Goddard, John W Holloway, Michael A Simpson, R Mark Beattie, Andrew Collins, Sarah Ennis
Journal: Gut (2012)

<h3>Background</h3> Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. <h3>Objective</h3> To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. <h3>Design</h3> DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. <h3>Results</h3> Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and <i>HLA</i>-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of &lt;5%, of which 17 were novel. Only two patients with early onset Crohn9s disease exhibited rare deleterious variations within <i>NOD2</i>: the previously described R702W variant was the sole <i>NOD2</i> variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the <i>GSDMB</i>, <i>ERAP2</i> and <i>SEC16A</i> genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the <i>BACH2</i> and <i>IL10</i> genes not seen in other patients. <h3>Conclusion</h3> For each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this complex disease.
The Perlecan Fragment LG3 Is a Novel Regulator of Obliterative Remodeling Associated With Allograft Vascular Rejection
Authors: Mathilde Soulez, Eve-Annie Pilon, Mélanie Dieudé, Héloïse Cardinal, Nathalie Brassard, Shijie Qi, Shyh-Jong Wu, Yves Durocher, François Madore, Claude Perreault, Marie-Josée Hébert
Journal: Circulation Research (2011)

Rationale: Endothelial apoptosis is increased in association with acute and chronic vascular rejection (VR) of solid allografts. Apoptotic endothelial cells (EC) release LG3, a C-terminal fragment of perlecan of potential importance in vascular remodeling and neointima formation. Objective: Our 2 goals were to determine whether circulating levels of LG3 are increased in association with acute VR of renal allografts and to evaluate the impact of LG3 on vascular remodeling. Methods and Results: We conducted a case-control study to compare serum LG3 levels in human renal transplant patients with acute VR, tubulo-interstitial rejection (ATIR) and normal graft function. Aorta transplantation between fully MHC-mismatched mice in association with intravenous LG3 injection was used to characterize the impact of LG3 on vascular remodeling. Scratch assays evaluated the promigratory activity of LG3 on vascular smooth muscle cells (VSMC) in vitro. Serum LG3 levels were significantly elevated in human renal transplant patients with acute VR ( n =16) compared to ATIR ( n =16) and normal graft function ( n =32, P =0.004). In patients with acute VR, graft loss was associated with elevated LG3 levels. Increasing LG3 serum levels in aortic allograft recipients significantly increased neointima formation. LG3 injection fostered accumulation of α-smooth muscle actin–positive cells and decreased the number of CD31 positive EC. LG3 increased the migration of VSMC through extracellular signal-regulated kinases 1/2-dependent pathways. Conclusion: These results indicate that LG3 is a novel regulator of obliterative vascular remodeling during rejection.
CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease
Authors: Deepika Mahajan, Yiping Wang, Xiahong Qin, Ying Wang, Guoping Zheng, Yuan Min Wang, Stephen I. Alexander, David C.H. Harris
Journal: Journal of the American Society of Nephrology (2006)

Studies of mechanisms of disease regulation by CD4+CD25+ regulatory T cells (Treg) have been focused on their interaction with effector T cells; however, the possibility that regulation might involve noncognate cells has not been explored in detail. This study investigated the effect of CD4+CD25+ Treg on macrophage proinflammatory properties and phenotype in vitro and found that they modulate macrophages by inhibiting their activation, leading to reduced proinflammatory cytokine production and a downregulated effector phenotype. For testing the in vivo significance of this effect, CD4+CD25+ T cells that expressed high levels of Foxp3 were reconstituted into SCID mice after induction of Adriamycin nephropathy, a noncognate model of chronic renal disease. CD4+CD25+ T cells significantly reduced glomerular and interstitial injury. In addition, there was a significant fall in the number of macrophages in both the glomeruli and interstitium of SCID mice that were reconstituted with Treg as compared with the Adriamycin alone group. Blockade of TGF-beta using neutralizing antibodies significantly impaired the protective effect of Treg. These findings delineate a TGF-beta-dependent Treg-macrophage inhibitory interaction that can explain cognate-independent protection by Treg.
<i>MLH1</i> Founder Mutations with Moderate Penetrance in Spanish Lynch Syndrome Families
Authors: Ester Borràs, Marta Pineda, Ignacio Blanco, Ethan M. Jewett, Fei Wang, Àlex Teulé, Trinidad Caldés, Miguel Urioste, Cristina Martínez-Bouzas, Joan Brunet, Judith Balmaña, Asunción Torres, Teresa Ramón y Cajal, Judit Sanz, Lucía Pérez-Cabornero, Sergi Castellví-Bel, Ángel Alonso, Ángel Lanas, Sara González, Víctor Moreno, Stephen B. Gruber, Noah A. Rosenberg, Bhramar Mukherjee, Conxi Lázaro, Gabriel Capellá
Journal: Cancer Research (2010)

The variants c.306+5G>A and c.1865T>A (p.Leu622His) of the DNA repair gene MLH1 occur frequently in Spanish Lynch syndrome families. To understand their ancestral history and clinical effect, we performed functional assays and a penetrance analysis and studied their genetic and geographic origins. Detailed family histories were taken from 29 carrier families. Functional analysis included in silico and in vitro assays at the RNA and protein levels. Penetrance was calculated using a modified segregation analysis adjusted for ascertainment. Founder effects were evaluated by haplotype analysis. The identified MLH1 c.306+5G>A and c.1865T>A (p.Leu622His) variants are absent in control populations and segregate with the disease. Tumors from carriers of both variants show microsatellite instability and loss of expression of the MLH1 protein. The c.306+5G>A variant is a pathogenic mutation affecting mRNA processing. The c.1865T>A (p.Leu622His) variant causes defects in MLH1 expression and stability. For both mutations, the estimated penetrance is moderate (age-cumulative colorectal cancer risk by age 70 of 20.1% and 14.1% for c.306+5G>A and of 6.8% and 7.3% for c.1865T>A in men and women carriers, respectively) in the lower range of variability estimated for other pathogenic Spanish MLH1 mutations. A common haplotype was associated with each of the identified mutations, confirming their founder origin. The ages of c.306+5G>A and c.1865T>A mutations were estimated to be 53 to 122 and 12 to 22 generations, respectively. Our results confirm the pathogenicity, moderate penetrance, and founder origin of the MLH1 c.306+5G>A and c.1865T>A mutations. These findings have important implications for genetic counseling and molecular diagnosis of Lynch syndrome.
Anti-Vascular Endothelial Growth Factor Receptor-1 Antagonist Antibody as a Therapeutic Agent for Cancer
Authors: Yan Wu, Zhaojing Zhong, James Huber, Rajiv Bassi, Bridget Finnerty, Erik Corcoran, Huiling Li, Elizabeth Navarro, Paul Balderes, Xenia Jimenez, Henry Koo, Venkata R.M. Mangalampalli, Dale L. Ludwig, James R. Tonra, Daniel J. Hicklin
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Vascular endothelial growth factor receptor-1 (VEGFR-1) plays important roles in promotion of tumor growth by mediating cellular functions in tumor vascular endothelium and cancer cells. Blockade of VEGFR-1 activation has been shown to inhibit pathologic angiogenesis and tumor growth, implicating VEGFR-1 as a potential therapeutic target for the treatment of cancer. We have thus developed a VEGFR-1 antagonist human monoclonal antibody designated as IMC-18F1 and evaluated its antitumor activity in preclinical experimental models to show the therapeutic potential of the antibody for cancer treatment in clinic. Experimental Design: Human IgG transgenic mice were used for generation of anti-VEGFR-1 antibodies. Anti-VEGFR-1-specific blocking antibodies were identified using solid-phase binding and blocking assays. Inhibitory antitumor cell activity of IMC-18F1 was assessed in cell-based kinase and growth assays. Pharmacokinetic/pharmacodynamic studies were done to determine the association of antibody blood level with antitumor efficacy of the antibody in vivo. Antitumor efficacy of the anti-VEGFR-1 antibodies as monotherapy and in combination with cytotoxic agents was evaluated in human breast cancer xenograft models. Results: A fully human neutralizing antibody, IMC-18F1, was shown to be a high-affinity (KD = 54 pmol) inhibitor of VEGFR-1 ligand binding (VEGF-A, VEGF-B, and placental growth factor). IMC-18F1 inhibited ligand-induced intracellular activation of VEGFR-1 and mitogen-activated protein kinase signaling and prevented ligand-stimulated in vitro growth of breast cancer cells. In vivo, IMC-18F1 suppressed the growth of human breast tumor xenografts in association with reduced mitogen-activated protein kinase and Akt activation, reduced tumor cell proliferation, and increased tumor cell apoptosis. Pharmacokinetic/pharmacodynamic studies established a plasma elimination half-life of 5 days for IMC-18F1 and a steady-state trough plasma therapeutic threshold of 88 μg/mL. Importantly, inhibition of mouse and human VEGFR-1 with MF1 and IMC-18F1, respectively, enhanced the antitumor efficacy of cytotoxic agents commonly used to treat breast cancer. Conclusions: Based on preclinical validation studies, IMC-18F1 anti-VEGFR-1 has potential to provide clinical benefit to cancer patients.
Development of a Diabetes Diet-Related Quality-of-Life Scale
Authors: Eiko Sato, Yoshimi Suzukamo, Mitsunori Miyashita, Keiko Kazuma
Journal: Diabetes Care (2004)

OBJECTIVE—The purpose of this study was to assess the reliability and validity of the Diabetes Diet-Related Quality-of-Life (DDRQOL) scale, which is a measure of the influence of diet therapy on patients’ quality of life (QOL). RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes (n = 236) who were being treated on an outpatient basis were asked to complete the self-administered DDRQOL instrument. The factor validity, convergent and discriminant validity, internal consistency, and reproducibility of the DDRQOL scale were then assessed. Spearman’s rank correlation coefficients among the DDRQOL scale and each of the SF-36 subscale scores were calculated to evaluate its convergent and discriminant validity. RESULTS—Based on the results of the factor analysis, the following seven subscales were adopted for the DDRQOL: “satisfaction with diet,” “burden of diet therapy,” “perceived merits of diet therapy,” “general perception of diet,” “restriction of social functions,” “vitality,” and “mental health.” As hypothesized, the DDRQOL scale was associated with each of the SF-36 subscales, with convergent and discriminant validity being generally exhibited. Cronbach’s α-coefficient was between 0.71 and 0.84, suggesting strong internal consistency. The intraclass correlation coefficient of the subscales, with the results of a test-retest conducted 2 weeks later, was between 0.46 and 0.75, suggesting some degree of reproducibility. CONCLUSIONS—These findings indicate that the DDRQOL scale has a reasonable degree of reliability and validity, and its application for the assessment of the needs of a patient’s diet and the evaluation of diet education with regard to QOL is awaited.
Impaired Angiogenesis, Delayed Wound Healing and Retarded Tumor Growth in Perlecan Heparan Sulfate-Deficient Mice
Authors: Zhongjun Zhou, Jianming Wang, Renhai Cao, Hiroyuki Morita, Raija Soininen, Kui Ming Chan, Baohua Liu, Yihai Cao, Karl Tryggvason
Journal: Cancer Research (2004)

Abstract Perlecan, a modular proteoglycan carrying primary heparan sulfate (HS) side chains, is a major component of blood vessel basement membranes. It sequesters growth factors such as fibroblast growth factor 2 (FGF-2) and regulates the ligand-receptor interactions on the cell surface, and thus it has been implicated in the control of angiogenesis. Both stimulatory and inhibitory effects of perlecan on FGF-2 signaling have been reported. To understand the in vivo function of HS carried by perlecan, the perlecan gene heparan sulfate proteoglycan 2 (Hspg2) was mutated in mouse by gene targeting. The HS at the NH2 terminus of perlecan was removed while the core protein remained intact. Perlecan HS-deficient (Hspg2Δ3/Δ3) mice survived embryonic development and were apparently healthy as adults. However, mutant mice exhibited significantly delayed wound healing, retarded FGF-2-induced tumor growth, and defective angiogenesis. In the mouse corneal angiogenesis model, FGF-2-induced neovascularization was significantly impaired in Hspg2Δ3/Δ3 mutant mice. Our results suggest that HS in perlecan positively regulates the angiogenesis in vivo.
PGS:Gelatin nanofibrous scaffolds with tunable mechanical and structural properties for engineering cardiac tissues
Authors: Mahshid Kharaziha, Mehdi Nikkhah, Su-Ryon Shin, Nasim Annabi, Nafiseh Masoumi, Akhilesh K. Gaharwar, Gulden Camci-Unal, Ali Khademhosseini
Journal: Biomaterials (2013)
ASSOCIATIONS OF VISCERAL AND SUBCUTANEOUS ADIPOSE TISSUE MASS WITH MARKERS OF CARDIOMETABOLIC RISK IN OBESE ADULTS: OBSERVATIONS FROM THE DALLAS HEART STUDY
Authors: Ian Neeland, Colby R. Ayers, Anand Rohatgi, Jarett Berry, Sandeep Das, Gloria L. Vega, Amit Khera, Darren McGuire, Scott Grundy, James de Lemos
Journal: Journal of the American College of Cardiology (2012)