tbuckley/cabot-search huggingface dataset:
Systemic Administration of an Attenuated, Tumor-Targeting<i>Salmonella typhimurium</i>to Dogs with Spontaneous Neoplasia: Phase I Evaluation
Authors: Douglas H. Thamm, Ilene D. Kurzman, Ivan King, Zujin Li, Mario Sznol, Richard R. Dubielzig, David M. Vail, E. Gregory MacEwen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Genetically modified bacteria are a potentially powerful anticancer therapy due to their tumor targeting capacity, inherent antitumor activity, and ability to serve as efficient vectors for gene delivery. This study sought to characterize the acute and short-term toxicities and tumor colonization rates of a genetically modified Salmonella typhimurium (VNP20009) in dogs with spontaneous tumors, in the context of a phase I dose escalation trial. Experimental Design: Forty-one pet dogs with a variety of malignant tumors received weekly or biweekly i.v. infusions of VNP20009, at doses ranging from 1.5 × 105 to 1 × 108 cfu/kg. Vital signs and clinicopathologic variables were monitored regularly. Incisional biopsies were obtained before and 1 week following the first infusion for histopathology and bacterial culture. Results: The nominal maximum tolerated dose was 3 × 107 cfu/kg, with refractory fever and vomiting being the dose-limiting toxicities. One treatment-related acute death occurred. Bacteria were cultured from tumor tissue in 42% of cases. Thirty-five patients were evaluable for antitumor response. Major antitumor responses were seen in 15% (4 complete response and 2 partial response), and disease stabilization for at least 6 weeks in 10%. Conclusions: Administration of VNP20009 at doses with acceptable toxicity results in detectable bacterial colonization of tumor tissue and significant antitumor activity in tumor-bearing dogs.
Immunology of interstitial lung diseases: cellular events taking place in the lung of sarcoidosis, hypersensitivity pneumonitis and HIV infection
Authors: G Semenzato
Journal: European Respiratory Journal (1991)

This paper summarizes our research and the results obtained on the topic of immunology of interstitial lung disorders. Areas of investigation mainly included sarcoidosis, hypersensitivity pneumonitis (HP), and more recently the pulmonary involvement in acquired immunodeficiency syndrome (AIDS). In sarcoidosis patients two major mechanisms account for the alveolitis, i.e. an in situ cellular proliferation and a cellular redistribution from the peripheral blood to the sites of disease activity, including the lung. These findings involve both lymphocytes (CD4 helper-related cells) and macrophages, and lead to the formation and provide maintenance of sarcoid granuloma. In patients with hypersensitivity pneumonitis the lung infiltrates are characterized by cells bearing suppressor/cytotoxic phenotype. The expansion of cells with these characteristics in the lung of these patients is likely to be related to a local immune response to the antigenic stimulus. In the lung of patients with AIDS we also found a discrete lymphocytic alveolitis bearing the CD8 cytotoxic-related phenotype. The role of cytotoxic events, related to the lymphocytes and macrophages, which are operative in the lung of AIDS patients, is being evaluated. The analysis of cells recovered from the lavage, mainly lymphocytes and macrophages, in terms of surface phenotype, functional in vitro evaluations and molecular analysis, has provided new insights into the pathogenesis of the above quoted interstitial lung disorders.
Growth hormone-releasing peptides and the heart: secretagogues or cardioprotectors?
Authors: P Lucchesi
Journal: Cardiovascular Research (2004)

See article by Iwase et al. [13] in this issue. 

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are multifunctional hormones with potent cardiotropic effects in prenatal and postnatal cardiac development. Evidence from animal and clinical studies has documented the beneficial effects of the GH-IGF-1 axis on cardiac hypertrophy and contractile function under conditions of GH deficiency, cardiomyopathy and ischemia reperfusion injury [1]. In rats with heart failure due to myocardial infarction, GH and IGF-1 increased cardiac output and decreased systemic vascular resistance [2]. More recently, Sussman's laboratory demonstrated that cardiac-specific overexpression attenuated dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice and was associated with normalization of left ventricular (LV) mass, increased myocyte number and improved LV end diastolic pressure, d p /d t and −d p /d t [3]. A preliminary, uncontrolled clinical trial with seven patients indicated that GH improved myocardial mass and cardiac output and ventricular mechanical work [4]. However, a later double-blind, placebo-controlled trial … 

*Tel.: +1-205-934-5742; fax: +1-205-975-9028. lucchesi{at}physiology.uab.edu
Resistance genes to murine leukemia in the I immune response gene region of the H-2 complex.
Authors: P Lonai, N Haran-Ghera
Journal: The Journal of Experimental Medicine (1977)

A resistance locus to leukemogenesis in mice by A-RadLV (a variant of the radiation leukemia virus) is described. This locus, Rrv-1, was mapped to subregions I-A, I-B, and I-J of the H-2 complex. It is suggested that Rrv-1 may be in complementation with a second locus to the right of it, between Rrv-1 and H-2D. This localization and the complementation of the two loci for resistance are characteristics similar to Ir genes, and indicate a possible relationship between the genetic regulation of immune responsiveness and susceptibility to leukemia.
Is duration of stay in hospital affected by influenza season in pneumonia patients
Authors: Emel Tellioglu, Aydan Mertoglu, Zuhre Sarp Taymaz, Gunseli Balci
Journal: European Respiratory Journal (2013)

Seasonal incidence variation of infectious diseases is important for clinicians. We assessed the impact of influenza season on duration of stay (DOS) in hospital among pneumonia patients. In our cohort study, data from 261 patients with community acquired pneumonia (CAP) and 43 with hospital acquired pneumonia (HAP) were retrospectively analyzed. Mean age of patients with CAP was 65.8±16.1, 195 (74.7%) were male. Mean age of patients with HAP was 69.2±11.1, 33 (76.7%) were male. There was no significant difference between patients admitted during influenza season (IS) and non-influenza season (NIS) for those with HAP in respect to age, hemograms and DOS. Mean DOS for CAP patients admitted during IS (12.3±8.2 days) was significantly longer than for those admitted during NIS (10.1±6.1 days)(p  Patients with HAP had a significantly longer DOS (17±14.2 days) than those with CAP (12±7.7 days)(p
Temsirolimus Has Activity in Non–Mantle Cell Non-Hodgkin's Lymphoma Subtypes: The University of Chicago Phase II Consortium
Authors: Sonali M. Smith, Koen van Besien, Theodore Karrison, Janet Dancey, Peter McLaughlin, Anas Younes, Scott Smith, Patrick Stiff, Eric Lester, Sanjiv Modi, L. Austin Doyle, Everett E. Vokes, Barbara Pro
Journal: Journal of Clinical Oncology (2010)

Purpose Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas. Patients and Methods We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas). Results Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis. Conclusions Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases.
Suggestive Linkage to Chromosomal Regions 13q31 and 22q12 in Families With Psychotic Bipolar Disorder
Authors: James B. Potash, Peter P. Zandi, Virginia L. Willour, Tsuo-Hung Lan, Yuqing Huo, Dimitrios Avramopoulos, Yin Y. Shugart, Dean F. MacKinnon, Sylvia G. Simpson, Francis J. McMahon, J. Raymond DePaulo, Melvin G. McInnis
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Linkage studies of bipolar disorder and schizophrenia have found overlapping evidence for susceptibility genes in four chromosomal regions—10p12-14, 13q32, 18p11.2, and 22q12-13. The authors previously demonstrated familial clustering of psychotic symptoms—defined as hallucinations and/or delusions—in some bipolar disorder pedigrees. In this study they used stratified linkage analysis to test the hypothesis that those bipolar disorder pedigrees most enriched for psychotic symptoms would show greater evidence of linkage to the regions of previous bipolar disorder/schizophrenia linkage overlap. METHOD: Nonparametric linkage analyses using GENEHUNTER and ASPEX were performed on 65 bipolar disorder families. Family subsets were defined by the number of family members with psychotic mood disorder. RESULTS: The 10 families in which three or more members had psychotic mood disorder showed suggestive evidence of linkage to 13q31 (nonparametric linkage score=3.56; LOD score=2.52) and 22q12 (nonparametric linkage score=3.32; LOD score=3.06). These results differed significantly from those for the entire study group of 65 families, which showed little or no linkage evidence in the two regions. The 10 families with three or more psychotic members did not show evidence of linkage to 10p12-14 or 18p11.2. The 95% confidence interval on 22q12 spanned 4.3 centimorgans (2.6 megabases) and was congruent with previous findings. CONCLUSIONS: Bipolar disorder families in which psychotic symptoms cluster may carry susceptibility genes on chromosomal regions 13q31 and 22q12. Replication should be attempted in similar families and perhaps in schizophrenia families in which mood symptoms cluster because these overlapping phenotypes may correlate most closely with the putative susceptibility genes. The localization of the 22q12 finding particularly encourages further study of this region.
A Potent Pancreatic Carcinogen in Syrian Hamsters: N-Nitrosobis(2-oxopropyl)amine2
Authors: Parviz Pour, Jürgen Althoff, F. W. Krüger, U. Mohr
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article A Potent Pancreatic Carcinogen in Syrian Hamsters: N-Nitrosobis(2-oxopropyl)amine Get access Parviz Pour, Parviz Pour Search for other works by this author on: Oxford Academic PubMed Google Scholar Jürgen Althoff, Jürgen Althoff Search for other works by this author on: Oxford Academic PubMed Google Scholar F. W. Krüger, F. W. Krüger Search for other works by this author on: Oxford Academic PubMed Google Scholar U. Mohr U. Mohr Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 5, May 1977, Pages 1449–1453, https://doi.org/10.1093/jnci/58.5.1449 Published: 01 May 1977 Article history Received: 09 September 1976 Accepted: 24 November 1976 Published: 01 May 1977
Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope.
Authors: A Bertoletti, A Costanzo, F V Chisari, M Levrero, M Artini, A Sette, A Penna, T Giuberti, F Fiaccadori, C Ferrari
Journal: The Journal of Experimental Medicine (1994)

Mutations that abrogate recognition of a viral epitope by class I-restricted cytotoxic T lymphocyte (CTL) can lead to viral escape if the CTL response against that epitope is crucial for viral clearance. The likelihood of this type of event is low when the CTL response is simultaneously directed against multiple viral epitopes, as has been recently reported for patients with acute self-limited hepatitis B virus (HBV) infection. The CTL response to HBV is usually quite weak, however, during chronic HBV infection, and it is generally acknowledged that this is a major determinant of viral persistence in this disease. If such individuals were to produce a mono- or oligospecific CTL response, however, negative selection of the corresponding mutant viruses might occur. We have recently studied two HLA-A2-positive patients with chronic hepatitis B who, atypically, developed a strong HLA-A2-restricted CTL response against an epitope (FLPSDFFPSV) that contains an HLA-A2-binding motif located between residues 18-27 of the viral nucleocapsid protein, hepatitis B core antigen (HBcAg). These patients failed, however, to respond to any of other HLA-A2-restricted HBV-derived peptides that are generally immunogenic in acutely infected patients who successfully clear the virus. Interestingly, DNA sequence analysis of HBV isolates from these two patients demonstrated alternative residues at position 27 (V --&amp;gt; A and V --&amp;gt; I) and position 21 (S --&amp;gt; N, S --&amp;gt; A, and S --&amp;gt; V) that reduced the HLA and T cell receptor-binding capacities of the variant sequences, respectively. Synthetic peptides containing these alternative sequences were poorly immunogenic compared to the prototype HBc18-27 sequence, and they could not be recognized by CTL clones specific for the prototype peptide. While we do not know if the two patients were originally infected by these variant viruses or if the variants emerged subsequent to infection because of immune selection, the results are most consistent with the latter hypothesis. If this is correct, the data suggest that negative selection of mutant viral genomes might contribute to viral persistence in a subset of patients with chronic HBV infection who express a narrow repertoire of anti-HBV CTL responses.
IFN-γ Mediates Crescent Formation and Cell-Mediated Immune Injury in Murine Glomerulonephritis
Authors: A. RICHARD KITCHING, STEPHEN R. HOLDSWORTH, PETER G. TIPPING
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Features of crescentic glomerulonephritis suggest that it results from a T helper 1 (Th1) nephritogenic immune response. Interferon-γ (IFN-γ), produced by Th1 cells, is involved in T cell-directed macrophage activation in effector Th1 responses. The hypothesis that endogenous IFN-γ contributes to the development of crescentic glomerulonephritis was tested by comparing the development of glomerulonephritis (induced by a planted antigen) and immune responses in normal C57BL/6 mice (IFN-γ +/+) and in mice genetically deficient in IFN-γ (IFN-γ -/-). Ten days after the initiation of glomerulonephritis, IFN-γ -/- mice developed fewer glomerular crescents (5 ± 1% versus 26 ± 3%, P &lt; 0.005), less severe glomerular injury, and less renal impairment. Effectors of delayed-type hypersensitivity (CD4+ T cells, macrophages, and fibrin) in glomeruli were reduced in IFN-γ -/- mice. Skin delayed-type hypersensitivity to sheep globulin was reduced. Total antigen-specific Ig and splenocyte interleukin-2 production were unchanged, but antigen-specific serum IgG2a was reduced. Markers of an antigen-specific Th2 response (serum IgG1, splenocyte interleukin-4) were unchanged. Studies 22 d after the initiation of glomerulonephritis showed that IFN-γ -/- mice still had fewer crescents (11 ± 2% versus 22 ± 3%, P = 0.02) and glomerular CD4+ T cells and macrophages than IFN-γ +/+ mice. These studies demonstrate that endogenous IFN-γ mediates crescentic glomerulonephritis by promoting cell-mediated immune injury. They support the hypothesis that crescentic glomerulonephritis is a manifestation of a Th1 nephritogenic immune response.
Oxidized LDL Suppresses NF-κB and Overcomes Protection from Apoptosis in Activated Endothelial Cells
Authors: KATHRIN HEERMEIER, WOLFGANG LEICHT, ALOIS PALMETSHOFER, MARKUS ULLRICH, CHRISTOPH WANNER, JAN GALLE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Atherosclerosis is a chronic inflammatory disease associated with enhanced apoptotic cell death in vascular cells, partly induced by oxidized low-density lipoprotein (OxLDL). However, proinflammatory stimuli such as lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) activate endothelial cells (EC) and inhibit apoptosis through induction of nuclear factor κB (NF-κB)-dependent genes. This study therefore investigated whether OxLDL or its component, lysophosphatidylcholine (LPC), interacts with the effect of LPS or TNF-α on cell survival. Human EC were incubated with LPS, TNF-α, OxLDL, or LPC alone or in combinations. OxLDL (100 to 200 μg/ml) and LPC (100 to 300 μM) induced apoptosis dose-dependently. LPS and TNF-α had no effect on cell survival in the presence or absence of OxLDL or LPC. LPS and TNF-α both induced the antiapoptotic gene A20, whereas OxLDL and LPC suppressed its induction. Expression of A20 is regulated by NF-κB. OxLDL and LPC dose-dependently suppressed NF-κB activity. For functional analysis, bovine EC were transfected with A20 encoding expression constructs in sense and antisense orientation. Bovine EC that overexpressed A20 were protected against OxLDL-induced apoptosis, whereas expression of antisense A20 rendered cells more sensitive to OxLDL. These results suggest that OxLDL not only induces cell death, as has been shown before, but also compromises antiapoptotic protection of activated EC. OxLDL sensitizes EC to apoptotic triggers by interfering with the induction of A20 during the inflammatory response seen in atherosclerotic lesions. This inhibition is based on repression of NF-κB activation. The effect may be caused by the OxLDL component LPC.
Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk
Authors: Judith S. Brand, Yvonne T. van der Schouw, N. Charlotte Onland-Moret, Stephen J. Sharp, Ken K. Ong, Kay-Tee Khaw, Eva Ardanaz, Pilar Amiano, Heiner Boeing, Maria-Dolores Chirlaque, Françoise Clavel-Chapelon, Francesca L. Crowe, Blandine de Lauzon-Guillain, Eric J. Duell, Guy Fagherazzi, Paul W. Franks, Sara Grioni, Leif C. Groop, Rudolf Kaaks, Timothy J. Key, Peter M. Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J. Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María-José Sánchez, Nadia Slimani, Birgit Teucher, Anne Tjonneland, Rosario Tumino, Daphne L. van der A, Edith J.M. Feskens, Claudia Langenberg, Nita G. Forouhi, Elio Riboli, Nicholas J. Wareham
Journal: Diabetes Care (2012)

OBJECTIVE Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04–1.69), 1.09 (0.90–1.31), 0.97 (0.86–1.10), and 0.85 (0.70–1.03) for women with menopause at ages &amp;lt;40, 40–44, 45–49, and ≥55 years, respectively, relative to those with menopause at age 50–54 years. The HR per SD younger age at menopause was 1.08 (1.02–1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01–1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all &amp;gt; 0.05). CONCLUSIONS Early menopause is associated with a greater risk of type 2 diabetes.
Choice of Topology Estimators in Bayesian Phylogenetic Analysis
Authors: J. Sukumaran, C. W. Linkem
Journal: Molecular Biology and Evolution (2008)

Wheeler WC and Pickett KM (2008. Topology-Bayes versus clade-Bayes in phylogenetic analysis. Mol Biol Evol. 25:447–453.) discuss two ways of summarizing the posterior probability distribution of a Bayesian phylogenetic analysis, which they refer to as “topology-Bayes” and “clade-Bayes.” They claim that the clade-Bayes approach leads to problems such as “exaggerated clade support, inconsistently biased priors, and the impossibility of topology hypothesis testing,” which are not problems for the topology-Bayes approach. However, their argument for topology-Bayes over clade-Bayes is based on errors in the interpretation of summary statistics associated with Bayesian phylogenetic analysis. Although there is a well-documented difference between the maximum posterior probability topology and the majority-rule consensus topology (the established terms for topology-Bayes and clade-Bayes summaries, respectively), both have a place in phylogenetic analysis. Choice of summarization strategy should be driven by choice of parameters that need to be estimated versus those to be marginalized given the evolutionary questions being asked or hypotheses being tested.
A Soluble Form of B Cell Maturation Antigen, a Receptor for the Tumor Necrosis Factor Family Member April, Inhibits Tumor Cell Growth
Authors: Paul Rennert, Pascal Schneider, Teresa G. Cachero, Jeffrey Thompson, Luciana Trabach, Sylvie Hertig, Nils Holler, Fang Qian, Colleen Mullen, Kathy Strauch, Jeffrey L. Browning, Christine Ambrose, Jürg Tschopp
Journal: The Journal of Experimental Medicine (2000)

A proliferation-inducing ligand (APRIL) is a ligand of the tumor necrosis factor (TNF) family that stimulates tumor cell growth in vitro and in vivo. Expression of APRIL is highly upregulated in many tumors including colon and prostate carcinomas. Here we identify B cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI), two predicted members of the TNF receptor family, as receptors for APRIL. APRIL binds BCMA with higher affinity than TACI. A soluble form of BCMA, which inhibits the proliferative activity of APRIL in vitro, decreases tumor cell proliferation in nude mice. Growth of HT29 colon carcinoma cells is blocked when mice are treated once per week with the soluble receptor. These results suggest an important role for APRIL in tumorigenesis and point towards a novel anticancer strategy.