tbuckley/cabot-search huggingface dataset:
Homing of Human B Cells to Lymphoid Organs and B-Cell Lymphoma Engraftment Are Controlled by Cell Adhesion Molecule JAM-C
Authors: Carmen Doñate, Christiane Ody, Thomas McKee, Sylvie Ruault-Jungblut, Nicolas Fischer, Patricia Ropraz, Beat A. Imhof, Thomas Matthes
Journal: Cancer Research (2012)

Abstract Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human but not mouse B lymphocytes. The level of JAM-C expression defines B-cell differentiation stages and allows the classification of marginal zone–derived (JAM-C–positive) and germinal center–derived (JAM-C–negative) B-cell lymphomas. In the present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic nonobese diabetic/severe combined immunodeficient mouse model. Treatment with anti-JAM-C antibodies in short-term experiments reduced migration of normal and malignant JAM-C–expressing B cells to bone marrow, lymph nodes, and spleen. Blocking homing to the spleen is remarkable, as most other antiadhesion antibodies reduce homing of B cells only to bone marrow and lymph nodes. Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymphoma cells in bone marrow, spleen, and lymph nodes of mice. Plasmon resonance studies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels. Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C–expressing B cells to their ligand JAM-B, and immunofluorescence analysis showed the expression of JAM-B on murine and human lymphatic endothelial cells. Targeting JAM-C could thus constitute a new therapeutic strategy to prevent lymphoma cells from reaching supportive microenvironments not only in the bone marrow and lymph nodes but also in the spleen. Cancer Res; 73(2); 640–51. ©2012 AACR.
Elevated serum level of the vascular endothelial growth factor predicts radiographic spinal progression in patients with axial spondyloarthritis
Authors: Denis Poddubnyy, Kristina Conrad, Hildrun Haibel, Uta Syrbe, Heiner Appel, Jürgen Braun, Martin Rudwaleit, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To investigate the role of serum vascular endothelial growth factor (VEGF) as a predictor of radiographic spinal progression in patients with axial spondyloarthritis (axSpA). <h3>Methods</h3> Altogether, 172 patients with definite axSpA (95 with ankylosing spondylitis and 77 with non-radiographic axSpA) were included in this study. Spinal radiographs obtained at baseline and after 2 years of follow-up were scored independently by two trained readers in a concealed and randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) scoring system and for the presence of syndesmophytes. Radiographic spinal progression after 2 years was defined as (1) mSASSS worsening by ≥2 units, and (2) new syndesmophyte formation or formation of a bridging syndesmophyte from two single syndesmophytes. Serum VEGF levels were detected at baseline. <h3>Results</h3> Mean baseline VEGF values were significantly higher in patients with mSASSS worsening by ≥2 units after 2 years (n=22) than in those without progression (562±357 vs 402±309 pg/mL, respectively, p=0.027) and in patients with syndesmophyte formation (n=18) again as compared with those without new bone formation (579±386 vs 404±307 pg/mL, respectively, p=0.041). VEGF as a predictor of radiographic spinal progression performed especially well in patients who were already at high risk for such a progression due to the presence of syndesmophytes at baseline (n=48). In these patients, a VEGF serum level of &gt;600 pg/mL had a sensitivity of 53%, a specificity of 97% and an OR=36.6 (95% CI 3.9 to 341.5) as a predictor of mSASSS worsening by ≥2 units. For syndesmophyte formation, elevated VEGF demonstrated a sensitivity of 47%, a specificity of 94% and an OR=13.6 (95% CI 2.4 to 78.3). <h3>Conclusions</h3> An elevated serum level of VEGF (&gt;600 pg/mL) is highly specific as a predictor of radiographic spinal progression in patients with axSpA, especially in patients who are at high risk for further progression due to the presence of syndesmophytes.
Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats
Authors: David E. Blask, George C. Brainard, Robert T. Dauchy, John P. Hanifin, Leslie K. Davidson, Jean A. Krause, Leonard A. Sauer, Moises A. Rivera-Bermudez, Margarita L. Dubocovich, Samar A. Jasser, Darin T. Lynch, Mark D. Rollag, Frederick Zalatan
Journal: Cancer Research (2005)

Abstract The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 μW/cm2) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 μW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.
Individual psychotherapies for depressed HIV-positive patients
Authors: J C Markowitz, G L Klerman, K F Clougherty, L A Spielman, L B Jacobsberg, B Fishman, A J Frances, J H Kocsis, S W Perry
Journal: American Journal of Psychiatry (1995)

The authors present preliminary data from two treatment modalities of a randomized clinical trial in which they compared 16-week interventions of interpersonal psychotherapy to supportive psychotherapy.HIV-positive patients who were not acutely medically ill and had scores of 15 or higher on the Hamilton Depression Rating Scale were randomly assigned to one of four treatment modalities. They were assessed by the Hamilton scale and Beck Depression Inventory at 8 and 16 weeks. Most subjects who underwent either interpersonal psychotherapy (N = 16) or supportive psychotherapy (N = 16) were male, gay or bisexual, white, and college educated.Results of last-observation-carried-forward and completer analyses showed that scores on the Hamilton scale and Beck Depression Inventory decreased significantly for both treatments. Differential improvement for interpersonal psychotherapy appeared by midtreatment (week 8) and persisted at termination.This is the first controlled study of individual psychotherapies for depressed HIV-positive patients. Results suggest that a specific antidepressant psychotherapy, interpersonal psychotherapy, has advantages over a supportive therapy.
1258 ROLE OF LIPOPOLYSACCHARIDE-INDUCED TUMOR NECROSIS FACTOR-α IN LIVER DAMAGE DURING NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Authors: A. Alisi, N. Panera, A. Masotti, L. Da Sacco, R. Raso, M. Pezzullo, R. De Vito, S. Petrini, G. Bruscalupi, S. Leoni, V. Nobili
Journal: Journal of Hepatology (2011)
Epidemiology of multiple Acinetobacter outbreaks in The Netherlands during the period 1999–2001
Authors: P.J. van den Broek, J. Arends, A.T. Bernards, E. De Brauwer, E.M. Mascini, T.J.K. van der Reijden, L. Spanjaard, E.A.P.M. Thewessen, A. van der Zee, J.H. van Zeijl, L. Dijkshoorn
Journal: Clinical Microbiology and Infection (2006)
Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women
Authors: N. D Freedman, W.-H. Chow, Y.-T. Gao, X.-O. Shu, B.-T. Ji, G. Yang, J. H Lubin, H.-L. Li, N. Rothman, W. Zheng, C. C Abnet
Journal: Gut (2007)

Gastric cancer incidence rates are consistently lower in women than men in both high and low-risk regions worldwide. Sex hormones, such as progesterone and estrogen, may protect women against gastric cancer.To investigate the association of menstrual and reproductive factors and gastric cancer risk.These associations were prospectively investigated in 73 442 Shanghai women. After 419 260 person-years of follow-up, 154 women were diagnosed with gastric cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, body mass index, education, income, and cigarette use.No associations were observed between gastric cancer risk and age of menarche, number of children, breast feeding, or oral contraceptive use. In contrast, associations were observed with age of menopause (HR 0.80 per five-year increase in menopausal age, 95% CI 0.66-0.97), years of fertility (participants with less than 30 years of fertility were at increased risk compared with those with 30-36 years of fertility, HR 1.90, 95% CI 1.25-2.90), years since menopause (HR 1.26 per five years, 95% CI 1.03-1.53), and intrauterine device use (HR for users 1.61, 95% CI 1.08-2.39).These results support the hypothesis that female hormones play a protective role in gastric cancer risk.
Authors’ response: metformin and risk of hepatocellular carcinoma—a study focused on anti-diabetic agents
Authors: Chun-Ying Wu, Hsiao-Ping Chen
Journal: Gut (2013)

We thank Singh et al 1 for their letter commenting on our recent paper.2 The authors briefly summarised current evidence regarding the chemopreventive effects of statins on hepatocellular carcinoma (HCC) and noted the lack of analyses on the role of statins in HCC in our study.

We agree that the use of statins was found to be associated with a reduced risk of HCC according to previous studies.2 However, not only statins but also non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, thiazolidinediones, antiviral agents, etc, were all reported to be associated with a lower …
Pulmonary Hypertension in Chronic Lung Diseases
Authors: Werner Seeger, Yochai Adir, Joan Albert Barberà, Hunter Champion, John Gerard Coghlan, Vincent Cottin, Teresa De Marco, Nazzareno Galiè, Stefano Ghio, Simon Gibbs, Fernando J. Martinez, Marc J. Semigran, Gerald Simonneau, Athol U. Wells, Jean-Luc Vachiéry
Journal: Journal of the American College of Cardiology (2013)
The indolent course and high incidence of t(14;18) in primary duodenal follicular lymphoma
Authors: M. Mori, Y. Kobayashi, A.M. Maeshima, T. Gotoda, I. Oda, Y. Kagami, S. Bennett, J. Nomoto, T. Azuma, H. Yokoyama, D. Maruyama, S.-W. Kim, T. Watanabe, Y. Matsuno, K. Tobinai
Journal: Annals of Oncology (2009)
Regulation of Monocarboxylate Transporter MCT1 Expression by p53 Mediates Inward and Outward Lactate Fluxes in Tumors
Authors: Romain Boidot, Frédérique Végran, Aline Meulle, Aude Le Breton, Chantal Dessy, Pierre Sonveaux, Sarab Lizard-Nacol, Olivier Feron
Journal: Cancer Research (2011)

Abstract The monocarboxylate transporter (MCT) family member MCT1 can transport lactate into and out of tumor cells. Whereas most oxidative cancer cells import lactate through MCT1 to fuel mitochondrial respiration, the role of MCT1 in glycolysis-derived lactate efflux remains less clear. In this study, we identified a direct link between p53 function and MCT1 expression. Under hypoxic conditions, p53 loss promoted MCT1 expression and lactate export produced by elevated glycolytic flux, both in vitro and in vivo. p53 interacted directly with the MCT1 gene promoter and altered MCT1 mRNA stabilization. In hypoxic p53−/− tumor cells, NF-κB further supported expression of MCT1 to elevate its levels. Following glucose deprivation, upregulated MCT1 in p53−/− cells promoted lactate import and favored cell proliferation by fuelling mitochondrial respiration. We also found that MCT1 expression was increased in human breast tumors harboring p53 mutations and coincident features of hypoxia, with higher MCT1 levels associated with poorer clinical outcomes. Together, our findings identify MCT1 as a target for p53 repression and they suggest that MCT1 elevation in p53-deficient tumors allows them to adapt to metabolic needs by facilitating lactate export or import depending on the glucose availability. Cancer Res; 72(4); 939–48. ©2011 AACR.
Low Free Testosterone Levels Are Associated With All-Cause and Cardiovascular Mortality in Postmenopausal Diabetic Women
Authors: Elisabeth Wehr, Stefan Pilz, Bernhard O. Boehm, Tanja B. Grammer, Winfried März, Barbara Obermayer-Pietsch
Journal: Diabetes Care (2011)

Hyperandrogenemia is associated with cardiovascular risk factors in women but evidence about the relationship of testosterone levels with mortality is sparse. We aimed to evaluate whether total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) are associated with all-cause and cardiovascular mortality in a cohort of postmenopausal women.We measured TT and SHBG levels in 875 postmenopausal women who were referred for coronary angiography (during 1997-2000). FT was calculated according to the Vermeulen method. The main outcome measures were Cox proportional hazard ratios (HRs) for mortality from all causes and from cardiovascular causes.After a median follow-up time of 7.7 years, 179 women (20.5%) had died. There were 101 deaths due to cardiovascular disease (56.4% of all deaths). We found no association of FT, TT, and SHBG levels with mortality in all postmenopausal women. In postmenopausal diabetic women, multivariable-adjusted HRs (with 95% CIs) in the fourth compared with the first FT quartile for all-cause and cardiovascular mortality were 0.38 (0.08-0.90), P = 0.025, and 0.28 (0.08-0.90), P = 0.032, respectively. We found no association of TT and SHBG with mortality in diabetic postmenopausal women.In postmenopausal diabetic women referred for coronary angiography, low FT levels are independently associated with increased all-cause and cardiovascular mortality.
Predictive Factors of Postoperative Mortality After Junctional and Gastric Adenocarcinoma Resection
Authors: William B. Robb
Journal: JAMA Surgery (2013)

Postoperative mortality after junctional and gastric adenocarcinoma resection remains a significant issue.To identify factors predictive of mortality within 30 days of junctional and gastric adenocarcinoma resection in a large national multicenter cohort.A retrospective study collecting data from a multicenter database of patients who underwent resection for junctional and gastric adenocarcinoma from January 1, 1997, through January 31, 2010. A stepwise logistic regression model was built to identify, by multivariate analysis, variables independently predictive of 30-day postoperative mortality (POM).Nineteen university teaching hospitals in France.Two thousand six hundred seventy patients with available data.The primary end point was POM. Secondary end points included (1) late mortality (30-90 days after resection) and (2) postoperative morbidity.One thousand eight hundred ninety-six patients (71.01%) had gastric adenocarcinoma and 774 (28.99%) had junctional tumors. Neoadjuvant treatment was given to 655 patients (24.53%), and 114 patients (4.27%) died within 30 days of surgery. Postoperative mortality was higher in patients who experienced grades III and IV toxic effects during neoadjuvant treatment compared with those who did not (8.7% vs 2.9%, respectively; P = .007). Multivariate analysis revealed metastatic disease at diagnosis (odds ratio, 9.13 [95% CI, 3.29-25.35]; P < .001) and poor tolerance of neoadjuvant treatment (3.33 [1.25-8.85]; P = .02) as being independently predictive of POM. Centers performing at least 10 resections per year were found to be protective against POM (odds ratio, 0.29 [95% CI, 0.12-0.72]; P = .008).This large national cohort study confirms that advanced disease heightens the risk of POM; centralization of junctional and gastric adenocarcinoma resection is warranted. The novel finding that grades III to IV toxic effects during neoadjuvant therapy increase POM has significant implications for decision making in this subgroup of patients.clinicaltrials.gov Identifier: NCT01249859.
Gender-specific effects of caloric restriction on the balance of vascular nitric oxide and superoxide radical
Authors: Shih-Hsuan Chou, Yung-Chen Lee, Chiu-Feng Huang, Yu-Ren Wang, Huang-Ping Yu, Ying-Tung Lau
Journal: Cardiovascular Research (2010)

Caloric restriction (CR) and female gender attenuate oxidative damage and improve vascular endothelium-dependent relaxation (EDR). Multiple mechanisms that ameliorate vascular O2•− could enhance the NO•/O2•− balance and thus improve EDR. The aim of this study is to compare the effects of short-term (2 weeks) CR and gender on molecular mechanisms involved in NO•/O2•− balance and EDR. Wistar rats (8 weeks old) of both genders were fed ad libitum (control) or were subjected to CR (60% of food intake of controls) for 2 weeks. Plasma levels of NO•, insulin, and ghrelin, EDR, vascular NO• and O2•− production, as well as endothelial NO• synthase (eNOS) and NADPH oxidase (Nox) expression were examined and analysed. CR improved EDR and vascular NO• levels and ameliorated NADPH-sensitive O2•− production in male rats more than in females. Both CR and female gender reduced mRNA expression of Nox1 and Nox p22phox (p22phox); however, CR reduced Nox4 and p47phox only in males. Protein expression studies showed that CR enhanced eNOS and reduced Nox4 only in males. Short-term CR improved the NO•/O2•− balance by lowering vascular O2•− production through decreased expression of Nox in males, thus enhancing bioactive NO• levels and EDR. In this regard, CR shifted the state of vascular NO•/O2•− balance in males to a state similar to that in females.
A unique B2 B cell subset in the intestine
Authors: Yasuyo Shimomura, Atsuhiro Ogawa, Mayumi Kawada, Ken Sugimoto, Emiko Mizoguchi, Hai-Ning Shi, Shiv Pillai, Atul K. Bhan, Atsushi Mizoguchi
Journal: The Journal of Experimental Medicine (2008)

Over 80% of the body's activated B cells are located in mucosal sites, including the intestine. The intestine contains IgM+ B cells, but these cells have not been characterized phenotypically or in terms of their developmental origins. We describe a previously unidentified and unique subset of immunoglobulin M+ B cells that present with an AA4.1−CD21−CD23− major histocompatibility complex class IIbright surface phenotype and are characterized by a low frequency of somatic hypermutation and the potential ability to produce interleukin-12p70. This B cell subset resides within the normal mucosa of the large intestine and expands in response to inflammation. Some of these intestinal B cells originate from the AA4.1+ immature B2 cell pool in the steady state and are also recruited from the recirculating naive B cell pool in the context of intestinal inflammation. They develop in an antigen-independent and BAFF-dependent manner in the absence of T cell help. Expansion of these cells can be induced in the absence of the spleen and gut-associated lymphoid tissues. These results describe the existence of an alternative pathway of B cell maturation in the periphery that gives rise to a tissue-specific B cell subset.
Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia
Authors: Johanna Raidt, Julia Wallmeier, Rim Hjeij, Jörg Große Onnebrink, Petra Pennekamp, Niki T. Loges, Heike Olbrich, Karsten Häffner, Gerard W. Dougherty, Heymut Omran, Claudius Werner
Journal: European Respiratory Journal (2014)

Primary ciliary dyskinesia (PCD) is a rare genetic disorder leading to recurrent respiratory tract infections. High-speed video-microscopy analysis (HVMA) of ciliary beating, currently the first-line diagnostic tool for PCD in most centres, is challenging because recent studies have expanded the spectrum of HVMA findings in PCD from grossly abnormal to very subtle. The objective of this study was to describe the diversity of HVMA findings in genetically confirmed PCD individuals. HVMA was performed as part of the routine work-up of individuals with suspected PCD. Subsequent molecular analysis identified biallelic mutations in the PCD-related genes of 66 individuals. 1072 videos of these subjects were assessed for correlation with the genotype. Biallelic mutations (19 novel) were found in 17 genes: DNAI1, DNAI2, DNAH5, DNAH11, CCDC103, ARMC4, KTU/DNAAF2, LRRC50/DNAAF1, LRRC6, DYX1C1, ZMYND10, CCDC39, CCDC40, CCDC164, HYDIN, RSPH4A and RSPH1. Ciliary beat pattern variations correlated well with the genetic findings, allowing the classification of typical HVMA findings for different genetic groups. In contrast, analysis of ciliary beat frequency did not result in additional diagnostic impact. In conclusion, this study provides detailed knowledge about the diversity of HVMA findings in PCD and may therefore be seen as a guide to the improvement of PCD diagnostics.
Identification in rat liver and serum of water-soluble class I MHC molecules possibly homologous to the murine Q10 gene product.
Authors: S C Spencer, J W Fabre
Journal: The Journal of Experimental Medicine (1987)

We have identified large quantities of a water-soluble, non-RT1.A class I MHC molecule in the serum of the DA rat strain, with a similar molecule being found in aqueous extracts of DA liver. The non-RT1.A class I molecules have heavy chains of 41 kD, which is smaller than RT1.A class I molecules isolated from liver membranes (45 kD) but larger than water-soluble RT1.A class I molecules previously identified in serum and aqueous extracts of liver and kidney (40 kD). NH3-terminal amino acid sequencing of bulk-purified RT1.A class I molecules and of this novel non-RT1.A class I molecule revealed two substitutions, in the first 25 amino acids, Tyr----His at position 9, and Ala----Ser at position 24. The non-RT1.A class I molecule did not react with any of the well-characterized polymorphic and monomorphic antibodies directed against RT1.Aa class I molecules, but did react with the MRC OX18 antibody. A similar class I molecule could not be identified on liver membranes. The non-RT1.A class I molecule was found in large quantities (approximately 20 micrograms/ml) in the serum of the DA rat strain, and similarly large quantities appeared to be present in the sera of BN, PVG, and LEW.RT1a rats. WAG and LEW.RT1u rats had readily detectable but lower amounts of this molecule in their serum, while LEW and SHR rats had little if any present. This molecule probably represents the rat homologue of the murine Q10 gene product, and is the major class I product in the serum of the DA rat strain.
Musings on genome medicine: is there hope for ethical and safe stem cell therapeutics?
Authors: Mahendra Rao, Maureen L Condic
Journal: Genome Medicine (2009)

Although most stem cell therapy has been non-controversial, therapy based on pluripotent stem cells has raised both ethical and safety concerns. Despite these concerns, the use of cells derived from pluripotent stem cells has recently been approved for clinical trials. We suggest that recent advances in the field have provided avenues to develop pluripotent cells that raise far fewer ethical concerns. Moreover, advances in cell sorting, gene modification and screening have allowed the development of safer therapeutic approaches. Continued advances in this rapidly evolving field are likely to allow therapy to be delivered in a safe and effective manner without socially divisive ethical controversy in the not-so-distant future.