tbuckley/cabot-search huggingface dataset:
Genetic association and functional consequences of a common SNP in the CD40 region with systemic lupus erythematosus and rheumatoid arthritis in a homogeneous Greek population
Authors: Vassilios Vazgiourakis, Maria Zervou, Christianna Choulaki, George Bertsias, Darren Plant, Leendert A Trouw, Rene E Toes, Eleni Kabouraki, Jane Worthington, Prodromos Sidiropoulos, Dimitrios T Boumpas, G N Goulielmos
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> There is increasing evidence that different autoimmune diseases may share some common pathogenetic pathways. The <i>CD40</i> locus has recently been identified by a genome-wide study as a genetic risk factor for rheumatoid arthritis (RA). <i>CD40</i> is a member of the tumour necrosis factor receptor superfamily which is constitutively or inducible expressed on the surface of a variety of immune and non-immune cell types, indicating that this locus might be involved in several autoimmune diseases. <h3>Aim</h3> To investigate whether the rs4810485 single-nucleotide polymorphism (SNP) of <i>CD40</i> gene is associated with the development of RA and systemic lupus erythematosus (SLE) in the genetic homogeneous population of the island of Crete. The functional significance of this gene polymorphism will also be analysed. <h3>Materials and methods</h3> The SLE and RA sample sets consisted of 351 and 272 patients, respectively, while the control group consisted of 670 samples. Genotyping of the rs4810485 SNP was performed by PCR-restriction fragment length polymorphism or using the Sequenom MassArray technology. Genotyping of rs4810485 was performed by PCR-restriction fragment length polymorphism and by the Sequenom MassArray technology. The expression of <i>CD40</i> in SLE patients with different genotypes was assessed in peripheral blood mononuclear cells (PBMCs) by flow cytometry. Quantification of <i>CD40</i> mRNA was performed by quantitative real time PCR in freshly isolated PBMCs from patients with different genotype. <h3>Results</h3> The risk allele G of the <i>CD40</i> rs4810485 SNP was more frequent in individuals with SLE and RA than in healthy controls (p&lt;0.0001, OR 1.5, 95% CI 1.3 to 1.9 and p&lt;0.0001, OR 1.6, 95% CI 1.3 to 1.9 respectively). SLE patients with the rs4810485 G/G genotype had significantly higher CD40 mRNA and protein expression in freshly isolated peripheral blood B cells and monocytes, compared to patients with the G/T or T/T genotype. <h3>Conclusions</h3> The CD40 rs4810485 SNP is associated with increased susceptibility to both SLE and RA in a homogeneous Greek population. Identification of shared genetic susceptibility loci may provide insight to their understanding of the pathophysiology of autoimmune diseases. The risk allele G seems to confer susceptibility to clinically distinct disorders through similar or differential effects on disease-specific cell types. Quantitative analysis of the allelic expression of CD40 in SLE patients demonstrated that the risk allele was accompanied by higher expression of CD40 both at mRNA and protein level especially in B lymphocytes and CD14 monocytes.
ISOFLAVONES IN SOY INFANT FORMULA: A Review of Evidence for Endocrine and Other Activity in Infants
Authors: Aimin Chen, Walter J. Rogan
Journal: Annual Review of Nutrition (2004)

▪ Abstract Soy infant formulas are widely used, but few studies have evaluated long-term safety or examined specific forms of toxicity, such as to the endocrine or immune systems. This review focuses on newer experimental studies of the effects on estrogen activity, immune function, and thyroid economy of genistein and daidzein, two isoflavones in soy infant formula, and existing human studies of soy formula use. In order to judge the likelihood that an endpoint seen in laboratory studies might occur in soy-fed infants, we examined the doses and the resulting serum or plasma concentrations from the laboratory studies and compared them with doses and concentrations seen in soy-fed infants. We also summarized the estimates of the potency of the isoflavone compounds relative to estradiol. Given the scarcity and inconsistency of existing human data and the substantial laboratory evidence of hormonal and other activity at doses relevant to the soy-fed infant, we conclude that more clinical and epidemiological study is warranted.
Haeme oxygenase promotes progenitor cell mobilization, neovascularization, and functional recovery after critical hindlimb ischaemia in mice
Authors: J. Tongers, J.-M. Knapp, M. Korf, T. Kempf, A. Limbourg, F. P. Limbourg, Z. Li, D. Fraccarollo, J. Bauersachs, X. Han, H. Drexler, B. Fiedler, K. C. Wollert
Journal: Cardiovascular Research (2007)

Neovascularization is an important element of long-term functional recovery during chronic ischaemia. We postulated that haeme oxygenase (HO) is required for progenitor cell recruitment, neovascularization, and blood flow recovery after critical hindlimb ischaemia (HLI).The femoral artery was ligated in FVB/N mice proximal to its superficial and deep branches. Blood flow in the ischaemic hindlimb was determined by laser Doppler perfusion imaging. Capillary density was measured by isolectin staining, and mobilization of Sca-1(+)/Kdr(+) progenitor cells by FACS analysis. Progenitor cell recruitment to the ischaemic hindlimb was assessed after Tie2-lacZ transgenic bone marrow transplantation. Blood flow recovery after femoral artery ligation was significantly blunted in mice treated with the HO inhibitor tin protoporphyrin-IX (25 mg/kg i.p., every other day). HO-inhibited mice developed more pronounced limb necrosis, associated with impaired hindlimb motor function. Capillary density in the ischaemic hindlimb and mobilization of Sca-1(+)/Kdr(+) progenitor cells were significantly reduced after HO inhibition. After transplantation of Tie2-lacZ transgenic bone marrow cells into lethally irradiated wild-type mice, fewer LacZ(+) cells were detected in the ischaemic hindlimb muscle of HO-inhibited mice. Mechanistically, HO inhibition prevented the establishment of a stromal cell-derived factor-1 gradient for progenitor cell mobilization between the ischaemic hindlimb and bone marrow.HOs are required for progenitor cell recruitment, neovascularization, and functional recovery after HLI.
Crohn's-like enterocolitis associated with mycophenolic acid treatment
Authors: D Dost, M E van Leerdam, H van Dekken, W Weimar, E J Kuipers, A H Bijl, T van Gelder
Journal: Gut (2008)

In the European Crohn's and Colitis Organisation (ECCO) paper of 2006 ( Gut 2006; 55 (Suppl 1):i1–15), consensus on the diagnosis of Crohn’s disease was described. However, we were surprised that nothing was mentioned about the association between the use of mycophenolate mofetil (MMF, Cellcept) and the occurrence of Crohn’s-like enterocolitis.

MMF is widely used to prevent rejection after solid organ transplantation. The active compound, mycophenolic acid (MPA), is a reversible, non-competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo purine biosynthesis in T and B lymphocytes. The most common adverse drug reactions of MMF are gastro-intestinal complaints.1–3 In 2003, a prospective cohort study including 26 renal transplant recipients with persistent diarrhoea showed for the first time that in patients using MMF, Crohn’s-like enterocolitis could …
&lt;emph type="ital"&gt;Ginkgo biloba&lt;/emph&gt; for Preventing Cognitive Decline in Older Adults&lt;subtitle&gt;A Randomized Trial&lt;/subtitle&gt;
Authors: Beth E. Snitz
Journal: JAMA (2009)

INKGO BILOBA IS MARKETEDwidely and used with the hope of improving, preventing, or delaying cognitive impairment associated with aging and neurodegenerative disorders such as Alzheimer disease.The primary outcome analysis from the Ginkgo Evaluation of Memory (GEM) study, the largest completed randomized, doubleblind, placebo-controlled dementia prevention trial to date, 1 found that G biloba, 120 mg twice daily, was not effective in reducing the incidence of Alzheimer dementia or dementia overall.Beyond consideration of a clinical dementia outcome, however, it is possible that G biloba may have had more subtle, therapeutic effects on the rate of cognitive change.Specifically, G biloba may have prevented or delayed agerelated changes in individuals with nor-
Influence of C4 null alleles on C4 activation in systemic lupus erythematosus.
Authors: D C Briggs, G Senaldi, D A Isenberg, K I Welsh, D Vergani
Journal: Annals of the Rheumatic Diseases (1991)

<h3>Abstract</h3> Disentangling human brain connectivity requires an accurate description of neuronal trajectories. However, a detailed mapping of axonal orientations is challenging because axons can cross one another on a micrometer scale. Diffusion magnetic resonance imaging (dMRI) can be used to infer neuronal connectivity because it is sensitive to axonal alignment, but it has limited resolution and specificity. Scattered Light Imaging (SLI) and small-angle X-ray scattering (SAXS) reveal neuronal orientations with microscopic resolution and high specificity, respectively. Here, we combine both techniques to achieve a cross-validated framework for imaging neuronal orientations, with comparison to dMRI. We evaluate brain regions that include unidirectional and crossing fiber tracts in human and vervet monkey brains. We find that SLI, SAXS, and dMRI all agree regarding major fiber pathways. SLI and SAXS further quantitatively agree regarding fiber crossings, while dMRI overestimates the amount of crossing fibers. In SLI, we find a reduction of peak distance with increasing out-of-plane fiber angles, confirming theoretical predictions, validated against both SAXS and dMRI. The combination of scattered light and X-ray imaging can provide quantitative micrometer 3D fiber orientations with high resolution and specificity, enabling detailed investigations of complex tract architecture in the animal and human brain.
Genetics and pulmonary medicine bullet 7: Somatic mutations in the development of lung cancer
Authors: M Roland, R M Rudd
Journal: Thorax (1998)

Lung cancers exhibit complex heterogeneous karyotypes and to date sequencing the serial somatic mutations which give rise to malignant change has proved difficult. Cigarette smoke causes a field change in the respiratory mucosa with mutations demonstrable even in histologically normal areas. After smoking cessation many of these mutations seem to persist indefinitely so that the risk of an ex-smoker developing lung cancer never reverts to that of a life-long non-smoker. Demonstration of specific somatic mutations in biopsy or sputum samples may eventually provide a useful method of screening for lung cancer. Somatic mutations give useful information about prognosis in non-small cell lung cancer and they are the key to exciting future retroviral and monoclonal antibody mediated therapies.
Bone Morphogenetic Proteins 2 and 5 Are Down-regulated in Adrenocortical Carcinoma and Modulate Adrenal Cell Proliferation and Steroidogenesis
Authors: Inga K. Johnsen, Roland Kappler, Christoph J. Auernhammer, Felix Beuschlein
Journal: Cancer Research (2009)

Bone morphogenetic proteins (BMP) have been shown to affect tumorigenesis in a variety of tumors. Quantitative PCR analysis revealed down-regulation of BMP2 and BMP5 in tissue samples from adrenocortical carcinoma and adrenocortical tumor cell lines compared with normal adrenal glands. Integrity of BMP-dependent pathways in these cell lines could be shown by activation of the Smad1/5/8 pathway with subsequent increase of ID protein expression upon incubation with BMP2 or BMP5. On a functional level, BMP treatment resulted in inhibition of cell proliferation and viability in a dose- and time-dependent manner. This growth inhibitory effect was associated with BMP-dependent reduction of AKT phosphorylation under baseline conditions and under insulin-like growth factor costimulation. Furthermore, steroidogenic function, including melanocortin-2 receptor and steroidogenic enzyme expressions, was profoundly reduced. In vitro demethylation treatment and overexpression of GATA6 resulted in reactivation of BMP-dependent pathways with concomitant modulation of steroidogenesis. Taken together, we show that loss of expression of members of the BMP family of ligands is a common finding in adrenocortical tumors and we provide evidence that BMP-dependent pathways are likely to be involved in the modulation of the malignant and functional phenotype of adrenocortical cancer cells.
Immune Therapy for Cancer
Authors: Michael Dougan, Glenn Dranoff
Journal: Annual Review of Immunology (2008)

Over the past decade, immune therapy has become a standard treatment for a variety of cancers. Monoclonal antibodies, immune adjuvants, and vaccines against oncogenic viruses are now well-established cancer therapies. Immune modulation is a principal element of supportive care for many high-dose chemotherapy regimens. In addition, immune activation is now appreciated as central to the therapeutic mechanism of bone marrow transplantation for hematologic malignancies. Advances in our understanding of the molecular interactions between tumors and the immune system have led to many novel investigational therapies and continue to inform efforts for devising more potent therapeutics. Novel approaches to immune-based cancer treatment strive to augment antitumor immune responses by expanding tumor-reactive T cells, providing exogenous immune-activating stimuli, and antagonizing regulatory pathways that induce immune tolerance. The future of immune therapy for cancer is likely to combine many of these approaches to generate more effective treatments.
The neural underpinnings of self and other and layer 2 of the shared circuits model
Authors: Linda Furey, Julian Paul Keenan
Journal: Behavioral and Brain Sciences (2008)

Abstract Differentiating self from other has been investigated at the neural level, and its incorporation into the model proposed Hurley is necessary for the model to be complete. With an emphasis on the feed-forward model in layer 2, we examine the role that self and other disruptions, including auditory verbal hallucinations (AVHs), may have in expanding the model proposed by Hurley.
Regulation of neuronal input transformations by tunable dendritic inhibition
Authors: Matthew Lovett-Barron, Gergely F Turi, Patrick Kaifosh, Peter H Lee, Frédéric Bolze, Xiao-Hua Sun, Jean-François Nicoud, Boris V Zemelman, Scott M Sternson, Attila Losonczy
Journal: Nature Neuroscience (2012)
High Expression of Methionine Aminopeptidase 2 in Human Colorectal Adenocarcinomas
Authors: Ponniah Selvakumar, Ashakumary Lakshmikuttyamma, Rani Kanthan, Selliah Chandra Kanthan, Jonathan R. Dimmock, Rajendra K. Sharma
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Several viral and eukaryotic proteins required for signal transduction and regulatory functions undergo lipophilic modification by the enzyme N-myristoyltransferase. Previously we reported that N-myristoyltransferase activity is higher in colon and gallbladder carcinoma than in the corresponding normal tissues. Methionine aminopeptidase 2 (MetAP2) is a bifunctional protein that plays a critical role in the regulation of post-translational processing and protein synthesis. To investigate whether MetAP2 contributes to the pathogenesis of colon carcinoma, we investigated the expression of MetAP2 in both normal and invasive tumor components of human samples. Experimental Design: We evaluated 50 cases of colon carcinoma for this study. In this report we analyzed 15 cases for MetAP2 activity and 13 cases for the expression of MetAP2 by Western blot in both the normal and in invasive tumor components of human samples. In addition, immunohistochemistry analysis was also carried out on samples from all patients. Results: MetAP activity was elevated in all cancerous tissues compared with normal tissues. Western blot analysis also showed the higher expression of MetAP2 in all cases of cancerous tissues. In addition, immunohistochemistry analysis revealed that all cases of colorectal adenocarcinoma showed moderate to strong cytoplasmic positivity for MetAP2 with increased intensity in the invasive component. Conclusions: Elevated MetAP protein expression is associated with metastatic tumor progression and appears to be a strong molecular marker for clinical prognosis. MetAP2 inhibition may represent a potential target for therapeutic intervention in colorectal carcinoma.
Chronic lymphocytic leukemia with a t(8;14)(q24;q32): <scp>FISH</scp>ing catches a (sheepish) red herring
Authors: Bryan Rea, T. Danielle Samulski, Honore Strauser, Vania Aikawa, Selina Luger, Adam Bagg
Journal: American Journal of Hematology (2015)

Although translocations involving 14q32 (IGH) are recurrent in a variety of B-cell neoplasms, they are relatively rare in CLL with the most common being t(14;18)(q32;21) and t(14;19)(q32;q13), involving BCL2 and BCL3, respectively 2. Similarly, translocations involving MYC are extremely infrequent in CLL. In a series of 3,405 CLL cases, only 8 had a MYC translocation, 5 of which were t(8;14). These cases were associated with increased numbers of prolymphocytes, histological progression, and an aggressive clinical course 3. The detection of a t(8;14) in this patient, in conjunction with the clinical and morphologic features at the time of the current presentation, was understandably concerning for disease metamorphosis. However, not only did the translocation involve neither IGH nor MYC, it emerged that this seemingly sinister genetic aberration was present ab initio, having been detected at the time of initial diagnosis more than a decade previously. Only with a review of the clinical records, and a bit of FISHing, were we able to ascertain that this was a genetic sheep in wolf's clothing! It remains unclear as to which genes are involved in this well-behaved t(8;14). A number of oncogenes have been mapped to these loci including ZHX2 on 8q24 and TCL1 on 14q32. Importantly, this case highlights the complementary use of FISH to not only confirm (or refute) the involvement of suspected genes, but also its ability to unearth unexpected findings and to keep in mind that things are not always as aggressive as they seem.
Topical PTH (1-34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial
Authors: M.F. Holick, F.N. Chimeh, S. Ray
Journal: British Journal of Dermatology (2003)

Journal Article Topical PTH (1–34) is a novel, safe and effective treatment for psoriasis: a randomized self‐controlled trial and an open trial Get access M.F. Holick, M.F. Holick Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Diabetes, and Nutrition, Departments of Medicine, Dermatology, and Biophysics and Physiology, Boston University Medical Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, U.S.A Michael F.Holick. E‐mail: mfholick@bu.edu Search for other works by this author on: Oxford Academic Google Scholar F.N. Chimeh, F.N. Chimeh Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Diabetes, and Nutrition, Departments of Medicine, Dermatology, and Biophysics and Physiology, Boston University Medical Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, U.S.A Search for other works by this author on: Oxford Academic Google Scholar S. Ray S. Ray Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Diabetes, and Nutrition, Departments of Medicine, Dermatology, and Biophysics and Physiology, Boston University Medical Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 2, 1 August 2003, Pages 370–376, https://doi.org/10.1046/j.1365-2133.2003.05437.x Published: 01 August 2003 Article history Accepted: 27 January 2003 Published: 01 August 2003
Future directions in the use of DNA adducts as internal dosimeters for monitoring human exposure to environmental mutagens and carcinogens.
Authors: C C Harris
Journal: Environmental Health Perspectives (1985)

Scientific opportunities generally arise when two or more research areas converge and/or advances in methodology occur. This occurred at the turn of the 19th century in the field of infectious bacterial and fungal diseases. As we draw near to the 21st century, research in the laboratory is providing us with both critical information on mechanisms of carcinogenesis and new technological advancements, including those in immunology, biochemistry, and molecular biology. Investigations in the field of epidemiology have clearly demonstrated the importance of environmental exposure to carcinogens and have identified populations at high cancer risk. It is now practical to integrate laboratory determinations into classic epidemiological approaches. Several markers, e.g., carcinogen-DNA adducts, related to tumor initiation and perhaps to tumor conversion, are currently being evaluated. We also need to develop indicators of tumor promotion and progression. The potential of biochemical and molecular epidemiology to predict cancer risk in an individual prior to the onset of clinically evident cancer provides an exciting new opportunity in cancer research and prevention.
The Negative Inotropic Effect of Adrenergic Beta-receptor Blocking Drugs on Human Heart Muscle
Authors: W. G. Nayler, D. Chipperfield, T. E. Lowe
Journal: Cardiovascular Research (1969)

Dose-response curves obtained for the negative inotropic effect of three β-adrenergic receptor blocking compounds on human heart muscle closely resemble those obtained when dog heart muscle is used; the negative inotropic effect of Ciba 39,089-Ba on human heart muscle is significantly less than that of propranolol. The depressant effect of propranolol was not abolished by reserpine-pretreatment.
Sensitivity of the relative-rate test to taxonomic sampling
Authors: M. Robinson, M. Gouy, C. Gautier, D. Mouchiroud
Journal: Molecular Biology and Evolution (1998)

Relative-rate tests may be used to compare substitution rates between more than two sequences, which yields two main questions: What influence does the number of sequences have on relative-rate tests and what is the influence of the sampling strategy as characterized by the phylogenetic relationships between sequences? Using both simulations and analysis of real data from murids (APRT and LCAT nuclear genes), we show that comparing large numbers of species significantly improves the power of the test. This effect is stronger if species are more distantly related. On the other hand, it appears to be less rewarding to increase outgroup sampling than to use the single nearest outgroup sequence. Rates may be compared between paraphyletic ingroups and using paraphyletic outgroups, but unbalanced taxonomic sampling can bias the test. We present a simple phylogenetic weighting scheme which takes taxonomic sampling into account and significantly improves the relative-rate test in cases of unbalanced sampling. The answers are thus: (1) large taxonomic sampling of compared groups improves relative-rate tests, (2) sampling many outgroups does not bring significant improvement, (3) the only constraint on sampling strategy is that the outgroup be valid, and (4) results are more accurate when phylogenetic relationships between the investigated sequences are taken into account. Given current limitations of the maximum-likelihood and nonparametric approaches, the relative-rate test generalized to any number of species with phylogenetic weighting appears to be the most general test available to compare rates between lineages.