tbuckley/cabot-search huggingface dataset:
Abstract 3893: Overexpression of FOXQ1 is important factor in tumorigenicity and tumor growth
Authors: Hiroyasu Kaneda, Tokuzo Arao, Kaoru Tanaka, Daisuke Tamura, Keiichi Aomatsu, Kanae Kudo, Kazuko Sakai, Marco Antonio De Velasco, Kazuko Matsumoto, Fujita Yoshihiko, Yasuhide Yamada, Junji Tsurutani, Isamu Okamoto, Kazuhiko Nakagawa, Kazuto Nishio, Tomoyuki Nagai, Kazuyuki Furuta
Journal: Cancer Research (2010)

Abstract Forkhead Box Q1 (FOXQ1) is a member of the forkhead transcription factor family, and it has recently been proposed to participate in gastric acid secretion and mucin gene expression in mice. However, the role of FOXQ1 in humans and especially in cancer cells remains unknown. We found that FOXQ1 mRNA is overexpressed in clinical specimens of colorectal cancer (28-fold / colonic mucosa). A microarray analysis revealed that the knockdown of FOXQ1 using siRNA resulted in a decrease in p21CIP1/WAF1 expression, and a reporter assay and ChIP assay showed that p21CIP1/WAF1 was one of target genes of FOXQ1. Stable FOXQ1-overexpressing cells (H1299/FOXQ1) exhibited elevated levels of p21CIP1/WAF1 expression and inhibition of apoptosis induced by doxorubicin or camptothecin. Although cellular proliferation was decreased in H1299/FOXQ1 cells in vitro, H1299/FOXQ1 cells significantly increased tumorigenicity (EGFP: 2/15, FOXQ1: 7/15) and enhanced tumor growth (437 ± 301 vs. 1735 ± 769 mm3, p&amp;lt;0.001) in vivo. Meanwhile, stable p21CIP1/WAF1 knockdown of H1299/FOXQ1 cells increased tumor growth, suggesting that FOXQ1 promotes tumor growth independent of p21CIP1/WAF1. Microarray analysis of H1299/EGFP and H1299/FOXQ1 revealed that FOXQ1-overexpression upregulated several genes that have positive roles for tumor growth including VEGFA, WNT3A, RSPO2 and BCL11A. CD31 and TUNEL staining of the tumor specimens showed that FOXQ1-overexpression mediated the angiogenic and anti-apoptotic effect in vivo. In conclusion, FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth presumably through its angiogenic and anti-apoptotic effects. Our findings demonstrate that FOXQ1 is a new member of the cancer-related FOX family. 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 3893.
Malignant Lymphoproliferative Diseases: Interactions Between Immunological Abnormalities and Oncogenic Viruses
Authors: R S Schwartz, J Andre-Schwartz
Journal: Annual Review of Medicine (1968)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Anamnestic and psychological features in diagnosis and prognosis of functional abdominal complaints: a prospective study.
Authors: G Bleijenberg, J F Fennis
Journal: Gut (1989)

Psychological and anamnestic data from 308 patients were collected to investigate whether patients with abdominal complaints from organic causes could be distinguished psychologically or by their case histories from patients with functional abdominal complaints. Two years later the same patients took part in a follow up study. Only 9% of the patients with functional abdominal complaints became symptom free. Most variables showed no significant difference between the organic and the functional group. The most important variables with predictive value were psychological factors, factors associated with the severity and factors associated with the duration of the complaints.
Hepatocyte transplantation for metabolic liver disease: UK experience
Authors: R. D Hughes
Journal: Journal of the Royal Society of Medicine (2005)

For end-stage liver disease and liver-based metabolic conditions the accepted treatment is liver transplantation. With developments in surgical techniques and immunosuppressive drug therapy the survival of patients and grafts is now good. In the conventional procedure the patient's whole liver is replaced with a liver obtained from a braindead or living donor. When the donor liver is too big it can be reduced to a compatible size; and, recently, split-liver procedures have been performed whereby the right lobe is transplanted into an adult and the smaller left lobe into a child,1 thus increasing the effective donor pool.

Another important advance in surgical technique is the use of auxiliary liver transplantation for patients with acute liver failure and certain liver-based metabolic defects such as Crigler–Najjar syndrome type I, urea cycle defects, and familial hypercholesterolaemia. In this procedure, part of the patient's liver, often the left lobe, is replaced with part of a donor liver. In a patient with acute liver failure this leaves open the possibility of regeneration of the native liver, in which case immunosuppression can be stopped and the graft allowed to atrophy; and in a patient with a metabolic disorder the native liver will be available for future gene therapy. The results of auxiliary liver transplantation in man2 have supported observations in animals that small amounts of liver tissue can provide sufficient function to correct an underlying metabolic defect. This finding was a spur to work on hepatocyte transplantation for such disorders. The aim is to repopulate the liver with donor hepatocytes, injected either directly into the liver or into the spleen, from which they migrate to the liver.

If the technique proves successful, hepatocyte transplantation offers several potential advantages. In terms of supply, there is the possibility of using cells from livers that are unsuitable for conventional transplantation because of steatosis or trauma. The patient does not have to undergo major surgery; moreover, in metabolic conditions the native liver provides a safety net in case of failure. One of the most important advantages is the availability of the liver as a target organ for gene therapy when this becomes a clinical reality. Experience of hepatocyte transplantation has been gained in patients with acute liver failure3,4 and metabolic liver diseases such as Crigler–Najjar syndrome type I,5 glycogen storage disease type 1a,6 and urea cycle defects.7 The background to this work has been described elsewhere.8–11 The current paper discusses the sources of hepatocytes, the isolation process, preclinical studies and clinical experience in the UK, especially in the treatment of liver-based inborn errors of metabolism.
An unsuitable and degraded diet? Part one: public health lessons from the mid-Victorian working class diet
Authors: Paul Clayton, Judith Rowbotham
Journal: Journal of the Royal Society of Medicine (2008)

Principal findings
The research resulting in this series of three papers (further papers to be published in succeeding issues of JRSM), drawing on a range of historical datasets viewed through the lens of current scientific understanding, indicates that cultural and other biases have distorted the historical record, leading to conclusions which test many current health policy assumptions about a steady improvement in British nutrition since the nineteenth century. As these papers show, the urban mid-Victorians, including the working classes, ate a notably good diet, including significant amounts of vegetables and fruit, which enabled a life expectancy matching that of today. We follow the example of George Rosen (a public health practitioner, and in his time editor of the American Journal of Public Health and Journal of the History of Medicine, among others), in believing that a historical dimension is essential to a sound perspective in public health today.1
Bortezomib Improves Adoptive T-cell Therapy by Sensitizing Cancer Cells to FasL Cytotoxicity
Authors: Anil Shanker, Samuel T. Pellom, Duafalia F. Dudimah, Menaka C. Thounaojam, Rachel L. de Kluyver, Alan D. Brooks, Hideo Yagita, Daniel W. McVicar, William J. Murphy, Dan L. Longo, Thomas J. Sayers
Journal: Cancer Research (2015)

Cancer immunotherapy shows great promise but many patients fail to show objective responses, including in cancers that can respond well, such as melanoma and renal adenocarcinoma. The proteasome inhibitor bortezomib sensitizes solid tumors to apoptosis in response to TNF-family death ligands. Because T cells provide multiple death ligands at the tumor site, we investigated the effects of bortezomib on T-cell responses in immunotherapy models involving low-avidity antigens. Bortezomib did not affect lymphocyte or tissue-resident CD11c(+)CD8(+) dendritic cell counts in tumor-bearing mice, did not inhibit dendritic cell expression of costimulatory molecules, and did not decrease MHC class I/II-associated antigen presentation to cognate T cells. Rather, bortezomib activated NF-κB p65 in CD8(+) T cells, stabilizing expression of T-cell receptor CD3ζ and IL2 receptor-α, while maintaining IFNγ secretion to improve FasL-mediated tumor lysis. Notably, bortezomib increased tumor cell surface expression of Fas in mice as well as human melanoma tissue from a responsive patient. In renal tumor-bearing immunodeficient Rag2(-/-) mice, bortezomib treatment after adoptive T-cell immunotherapy reduced lung metastases and enhanced host survival. Our findings highlight the potential of proteasome inhibitors to enhance antitumor T-cell function in the context of cancer immunotherapy.
Testosterone Replacement and Resistance Exercise in HIV-Infected Men With Weight Loss and Low Testosterone Levels
Authors: Shalender Bhasin
Journal: JAMA (2000)

2][3][4] Of the various therapies being considered for the treatment of HIV-associated weight loss, testosterone and exercise are attractive because they are relatively inexpensive and safe.][6][7][8][9][10][11] Serum testosterone levels are lower in those with weight loss 9 and correlate with deficits in muscle mass, 11 low Karnofsky scores, 12 and disease progression. 10,135][16] These data have led to the hypothesis that testosterone replacement might also increase muscle mass and strength in HIV-infected men with low testosterone levels.Some of the studies [17][18][19][20][21][22][23][24][25][26][27][28][29] that have examined the effects of
Evidence of autoantibodies to cell membrane associated DNA (cultured lymphocytes): a new specific marker for rapid identification of systemic lupus erythematosus
Authors: G. Servais, M.-P. Guillaume, N. Dumarey, J. Duchateau
Journal: Annals of the Rheumatic Diseases (1998)

Autoantibodies to cell membrane associated DNA are described in systemic lupus erythematosus (SLE). The specificity of these antibodies differ from antibodies to nuclear DNA.Using indirect immunofluorescence, a specific IgG was detected giving a characteristic pattern of continuous peripheral membrane fluorescence on cultured B-lymphocytes.This pattern was observed in 53 of 80 serum samples of SLE patients but absent in the serum samples of the control populations: 15 rheumatoid arthritis, 38 ankylosing spondylarthritis, 17 non-inflammatory osteopenic patients, and 224 blood donors. In 34 Sjögren syndrome's patients one only showed a positive test. The cmDNA specificity of these antibodies was confirmed by pattern extinction with DNAse but not RNase or protease pre-treatment of the cells. IgG to cmDNA, separated by absorption/elution from purified cmDNA immobilised on DEAE-nitrocellulose reproduced the immunofluorescence pattern pictures. Extensive serum depletion of anti-double strand or single strand DNA antibodies by absorption to cellulose bound ds- or ss-DNA affected marginally the pericellular fluorescence revealing some minor cross reactivity with nuclear DNA. Moreover, in SLE patients without detectable antibody to ds-DNA, pericellular fluorescence could be visible.This novel rapid immunofluorescence method may serve as an identification test of SLE patients. Given its positive (97.1%) and negative (92.9%) predictive value, sensitivity (66%) and specificity (99.5%), it improves on other diagnostic tests such as the detection of antibodies to Sm.
Local nasal immunotherapy in allergic rhinitis to <i>Parietaria</i>
Authors: L. Andri, G. E. Senna, C. Betteli, S. Givanni, G. Andri, P. Falagiani, G. Lugo
Journal: Allergy (1992)

Preseasonal local nasal immunotherapy (LNIT) by means of an extract in macronized powder form has been studied in allergic rhinitis to parielaria . Twenty‐four Parietari‐sensitive patients have been studied for 18 weeks in a double‐blind controlled trial. Subjects were selected on the basis of a positive skin test, RAST and intranasal challenge to Parietaria antigen. Three eight‐patient groups were randomly planned: the first group was given native Parietaria product, the second modified Parietaria product, and the third placebo. During the pollen season no difference was observed in mean weekly symptom score between the three groups, while the mean weekly medication score was significantly lower in the treated groups than the control group. Only the treated groups showed a significant increase in specific nasal threshold to Parietaria after treatment. Adverse reactions to LNIT, limited to the upper respiratory tract, occurred rarely and did not interfere with the dose schedule. This study indicates that L nit in powder form may be a suitable alternative to the traditional subcutaneous immunotherapy in terms of clinical efficacy and safety.
The Relevance of Research on Red Cell Membranes to the Understanding of Complex Human Disease: A Personal Perspective
Authors: Vincent T. Marchesi
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Molecular analysis in the service of research on human disease has finally come of age, as the chapters within this volume testify. Many technical advances, among them the development of recombinant DNA and its many applications, opened the way to study cells and processes that were unapproachable in the 1960s, when I first began my research career. The state of molecular biological studies at that time limited studies of human cell membrane proteins to experimental material most available and accessible, making the human erythrocyte membrane the favored target. I describe here how studies of red blood cell membrane proteins evolved and how results from those studies still inform present-day research.
Impact of tuberculosis exposure at home on mortality in children under 5 years of age in Guinea-Bissau
Authors: V. F. Gomes, A. Andersen, C. Wejse, I. Oliveira, F. J. Vieira, L. C. Joaquim, C. S. Vieira, P. Aaby, P. Gustafson
Journal: Thorax (2010)

To assess mortality related to exposure to tuberculosis (TB) at home among children in urban areas of Guinea-Bissau.In four suburban areas included in the demographic surveillance system of the Bandim Health Project in Bissau, the mortality of children aged <5 years living with an adult with TB was compared with the mortality of children in the general population.Children <5 years of age exposed to an adult with intrathoracic TB had 66% higher mortality than unexposed children (HR 1.66, 95% CI 1.2 to 2.3). The risk was higher for children living in the same family as a TB case (HR 2.15, 95% CI 1.3 to 3.7) than for children living in the same house but not belonging to the same family as the TB case (HR 1.51, 95% CI 1.0 to 2.2). For children whose mother had TB, mortality was increased eightfold (HR 7.82, 95% CI 2.1 to 30). The risk of death was particularly increased from 6 months following exposure (HR 2.16, 95% CI 1.5 to 3.2) and the highest rate of excess mortality was found in children aged 3–4 years. Excess mortality was highest among children with close contact with an adult with sputum-positive pulmonary TB (HR 1.90, 95% CI 1.1 to 3.2), but contact with a sputum-negative case was also associated with increased mortality (HR 1.55, 95% CI 1.0 to 2.3). Adjusting for potential confounding factors did not change these results. The mortality among children living in the same houses 3 years earlier was not increased (HR 0.90, 95% CI 0.6 to 1.3).Intimate family contact with a TB case represents a significant risk factor for child mortality in a low-income country.
Patterns of Nucleotide Substitution Among Simultaneously Duplicated Gene Pairs in Arabidopsis thaliana
Authors: Liqing Zhang, Todd J Vision, Brandon S Gaut
Journal: Molecular Biology and Evolution (2002)

We characterized rates and patterns of synonymous and nonsynonymous substitution in 242 duplicated gene pairs on chromosomes 2 and 4 of Arabidopsis thaliana. Based on their collinear order along the two chromosomes, the gene pairs were likely duplicated contemporaneously, and therefore comparison of genetic distances among gene pairs provides insights into the distribution of nucleotide substitution rates among plant nuclear genes. Rates of synonymous substitution varied 13.8-fold among the duplicated gene pairs, but 90% of gene pairs differed by less than 2.6-fold. Average nonsynonymous rates were approximately fivefold lower than average synonymous rates; this rate difference is lower than that of previously studied nonplant lineages. The coefficient of variation of rates among genes was 0.65 for nonsynonymous rates and 0.44 for synonymous rates, indicating that synonymous and nonsynonymous rates vary among genes to roughly the same extent. The causes underlying rate variation were explored. Our analyses tentatively suggest an effect of physical location on synonymous substitution rates but no similar effect on nonsynonymous rates. Nonsynonymous substitution rates were negatively correlated with GC content at synonymous third codon positions, and synonymous substitution rates were negatively correlated with codon bias, as observed in other systems. Finally, the 242 gene pairs permitted investigation of the processes underlying divergence between paralogs. We found no evidence of positive selection, little evidence that paralogs evolve at different rates, and no evidence of differential codon usage or third position GC content.
Complement breakdown products in plasma from patients with systemic lupus erythematosus and patients with membranoproliferative or other glomerulonephritis.
Authors: L H Perrin, P H Lambert, P A Miescher
Journal: Journal of Clinical Investigation (1975)

A dynamic estimation of the involvement of the complement system in various diseases was obtained by the direct quantitation of breakdown products of C3 and of properdin factor B. The methods used were based, first on the separation of native and fragmented molecules according to their molecular size through a precipitation with polyethylene glycol and, secondly, on an immunochemical quantitation, using specific antisera for the major antigens of C3 and factor B. The sensitivity and the specificity of these methods were demonstrated by activation of complement in vitro with generation of C3 and factor B fragments. A clinical investigation was carried out in 41 patients with systemic lupus erythematosus (SLE), 31 with membranoproliferative glomerulonephritis (MPGN), 26 with other types of glomerulonephritis, and 6 with severe alcoholic cirrhosis of the liver. The following observations were made: (a) an elevated plasma level of C3d fragment of C3 was found in 68% of SLE patients, in 87% of MPGN patients, in 62% of patients with other hypocomplementemic nephritis, and in 15% of those with normocomplementemic nephritis, but in only 33% of patients with liver cirrhosis and very low levels of C3; (b) a significant difference was observed between the levels of C3 obtained with either anti-"native" C3 or anti-C3c sera for immunochemical quantitation, in patients with SLE or MPGN, indicating the presence of "altered" or fragmented C3 in plasma; (c) an elevated plasma level of Ba fragment of properdin factor B was found in 46% of SLE patients, in 67% of MPGN patients, in 50% of patients with other hypocomplementemic nephritis, and in 9% of patients with normocomplementemic nephritis, while the level of properdin factor B was only slightly decreased in these diseases; (d) in SLE and MPGN there was an inverse correlation between the levels of C3d and Ba and the level of C3 in plasma. The level of these fragments was directly correlated with the clinical manifestations of SLE; (e) some patients with a normal C3 level exhibited an elevated plasma concentration of C3 and factor B fragments, suggesting the coexistence of an increased synthesis with a hypercatabolism of complement components. Therefore, the quantitation of complement breakdown products by simple immunochemical methods provides additional information concerning the involvement of complement in disease and new features for the evaluation of the intensity of immune reactions during immune complex diseases.
Rapid Antimanic Effect of Risperidone Monotherapy: A 3-Week Multicenter, Double-Blind, Placebo-Controlled Trial
Authors: Robert M A Hirschfeld, Paul E Keck, Michelle Kramer, Keith Karcher, Carla Canuso, Marielle Eerdekens, Fred Grossman
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania. METHOD: Patients with DSM-IV bipolar I disorder experiencing an acute manic episode (baseline Young Mania Rating Scale score ≥20) were randomly assigned to 3 weeks of treatment with risperidone (flexible dose: 1–6 mg/day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale. Secondary efficacy measures included the Clinical Global Impression (CGI) severity rating and scores on the Montgomery-Åsberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Global Assessment Scale (GAS). Safety assessments consisted of monitoring adverse events, vital signs, electrocardiogram and laboratory results, and scores on the Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259) received treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose of risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total score (adjusted for covariates) was significantly greater in the risperidone than in the placebo group at endpoint (mean change=–10.6 [SD=9.5] versus –4.8 [SD=9.5], respectively), with significant between-group differences seen as early as 3 days after start of treatment (change with risperidone: mean=–6.8 [SD=5.8]; change with placebo: mean=–4.0 [SD=5.8]) and continuing throughout all time points. Improvements in CGI severity ratings and scores on the Montgomery-Åsberg Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater among patients receiving risperidone than those given placebo. The most common adverse event reported among risperidone patients was somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone, mean total and subscale scores were low. CONCLUSIONS: Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action. Risperidone was well tolerated by patients in this study.