tbuckley/cabot-search huggingface dataset:
Folliculotropic mycosis fungoides with CD30+ large-cell transformation in a young woman: beneficial effect of bexarotene
Authors: C. Mitteldorf, R. Stadler, H.P. Bertsch, C. Neumann
Journal: British Journal of Dermatology (2006)

Journal Article Folliculotropic mycosis fungoides with CD30+ large‐cell transformation in a young woman: beneficial effect of bexarotene Get access C. Mitteldorf, C. Mitteldorf Department of Dermatology, Goettingen University, von‐Siebold‐Str. 3, 37073 Goettingen, Germany *Department of Dermatology, Medical Centre Minden, Portastrasse 7–9, 32427 Minden, Germany. E‐mail: derhigoe@med.uni‐goettingen.de Search for other works by this author on: Oxford Academic Google Scholar R. Stadler, R. Stadler Department of Dermatology, Goettingen University, von‐Siebold‐Str. 3, 37073 Goettingen, Germany *Department of Dermatology, Medical Centre Minden, Portastrasse 7–9, 32427 Minden, Germany. E‐mail: derhigoe@med.uni‐goettingen.de Search for other works by this author on: Oxford Academic Google Scholar H.P. Bertsch, H.P. Bertsch Department of Dermatology, Goettingen University, von‐Siebold‐Str. 3, 37073 Goettingen, Germany *Department of Dermatology, Medical Centre Minden, Portastrasse 7–9, 32427 Minden, Germany. E‐mail: derhigoe@med.uni‐goettingen.de Search for other works by this author on: Oxford Academic Google Scholar C. Neumann C. Neumann Department of Dermatology, Goettingen University, von‐Siebold‐Str. 3, 37073 Goettingen, Germany *Department of Dermatology, Medical Centre Minden, Portastrasse 7–9, 32427 Minden, Germany. E‐mail: derhigoe@med.uni‐goettingen.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 3, 1 March 2007, Pages 584–586, https://doi.org/10.1111/j.1365-2133.2006.07672.x Published: 01 March 2007
CTLA-4 polymorphisms in allergy and asthma and the TH1/ TH2 paradigm
Authors: Monica Cheng Munthe-Kaas, Kai Håkon Carlsen, Peter J Helms, Jorrit Gerritsen, Moira Whyte, Marlies Feijen, Beate Skinningsrud, Margaret Main, Georges Ng Man Kwong, Benedicte A Lie, Karin C Lødrup Carlsen, Dag E Undlien
Journal: Journal of Allergy and Clinical Immunology (2004)
Endoneurial Macrophages Induce Perineural Invasion of Pancreatic Cancer Cells by Secretion of GDNF and Activation of RET Tyrosine Kinase Receptor
Authors: Oren Cavel, Olga Shomron, Ayelet Shabtay, Joseph Vital, Leonor Trejo-Leider, Noam Weizman, Yakov Krelin, Yuman Fong, Richard J. Wong, Moran Amit, Ziv Gil
Journal: Cancer Research (2012)

Abstract Perineural invasion of cancer cells (CPNI) is found in most patients with pancreatic adenocarcinomas (PDA), prostate, or head and neck cancers. These patients undergo palliative rather than curative treatment due to dissemination of cancer along nerves, well beyond the extent of any local invasion. Although CPNI is a common source of distant tumor spread and a cause of significant morbidity, its exact mechanism is undefined. Immunohistochemical analysis of specimens excised from patients with PDAs showed a significant increase in the number of endoneurial macrophages (EMΦ) that lie around nerves invaded by cancer compared with normal nerves. Video microscopy and time-lapse analysis revealed that EMΦs are recruited by the tumor cells in response to colony-stimulated factor-1 secreted by invading cancer cells. Conditioned medium (CM) of tumor-activated EMΦs (tEMΦ) induced a 5-fold increase in migration of PDA cells compared with controls. Compared with resting EMΦs, tEMΦs secreted higher levels of glial-derived neurotrophic factor (GDNF), inducing phosphorylation of RET and downstream activation of extracellular signal–regulated kinases (ERK) in PDA cells. Genetic and pharmacologic inhibition of the GDNF receptors GFRA1 and RET abrogated the migratory effect of EMΦ-CM and reduced ERK phosphorylation. In an in vivo CPNI model, CCR2-deficient mice that have reduced macrophage recruitment and activation showed minimal nerve invasion, whereas wild-type mice developed complete sciatic nerve paralysis due to massive CPNI. Taken together, our results identify a paracrine response between EMΦs and PDA cells that orchestrates the formation of cancer nerve invasion. Cancer Res; 72(22); 5733–43. ©2012 AACR.
Role of Galectin-3 in Diabetic Nephropathy
Authors: Carla Iacobini, Lorena Amadio, Giovanna Oddi, Carlo Ricci, Paola Barsotti, Serena Missori, Mariella Sorcini, Umberto Di Mario, Flavia Pricci, Giuseppe Pugliese
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The advanced glycosylation end products (AGE) participate in the pathogenesis of nephropathy and other diabetic complications through several mechanisms, including their binding to cell surface receptors. The AGE receptors include RAGE, the macrophage scavenger receptors, OST-48 (AGE-R1), 80K-H (AGE-R2), and galectin-3 (AGE-R3). Galectin-3 interacts with the β-galactoside residues of cell surface and matrix glycoproteins via the carbohydrate recognition domain and with intracellular proteins via peptide–peptide associations mediated by its N-terminus domain. These structural properties enable galectin-3 to exert multiple functions, including the mRNA splicing activity, the control of cell cycle, the regulation of cell adhesion, the modulation of allergic reactions, and the binding of AGE. The lack of transmembrane anchor sequence or signal peptide suggests that it is associated with other AGE receptors, possibly AGE-R1 and AGE-R2, to form an AGE-receptor complex, rather than playing an independent role. In target tissues of diabetic vascular complications, such as the endothelium and mesangium, galectin-3 is weakly expressed under basal conditions and is markedly upregulated by the diabetic milieu (and to a lesser extent by aging). Galectin-3–deficient mice were found to develop accelerated diabetic glomerulopathy versus the wild-type animals, as evidenced by the more pronounced increase in proteinuria, mesangial expansion, and matrix gene expression. This was associated with a more marked renal/glomerular AGE accumulation, suggesting that it was attributable to the lack of galectin-3 AGE-receptor function. These data indicate that galectin-3 is upregulated under diabetic conditions and is operating in vivo to provide protection toward AGE-induced tissue injury, as opposed to RAGE. E-mail: [email protected]
P168 Factors Associated with Advanced Stage Lung Cancer at Diagnosis – a Retrospective Cohort Study: Abstract P168 Table 1
Authors: E Ghorani, B O’Leary, K Asif, S Hafiz, AK Reinhardt
Journal: Thorax (2012)

<h3>Introduction</h3> Lung cancer is a major cause of mortality in the UK, with survival related to stage of disease at presentation. Better understanding of factors contributing to presentation delay might aid earlier identification and assessment of patients. Here we set out to characterise demographic features of the late presenting population at an East London hospital. <h3>Methods</h3> Local lung cancer diagnoses between June 2005 and November 2011 (n=554) were retrospectively determined from the National Lung Cancer Audit database. Cases for whom staging information at diagnosis was available, were selected for study (n=460) and divided into those with early (stage I-IIIA, n=135) and late (stage IIIB-IV, n=325) disease. Socioeconomic quintiles based on patients’ postcodes were defined using the Income domain of the Index of Multiple Deprivation 2010. Data were analysed by logistic regression in SPSS. <h3>Results</h3> We found increasing age (ORs 0.95, 0.55, 0.58 for age groups &lt;60, 60–69, 70–79 and ≥80 years respectively, p=0.027) to be associated with decreased risk of late presentation. Male gender (OR=1.59, 95% CI 1.06–2.38, p=0.016) and emergency presentation as opposed to community based referral to services (OR=1.92, 95% CI 1.19–3.10, p=0.008) were associated with advanced stage disease at diagnosis. Socioeconomic group was not found to contribute significantly to stage of disease at presentation. <h3>Conclusion</h3> We report that age, gender but not socioeconomic status are risk factors for late stage of lung cancer at diagnosis. These findings are in line with a recent large study of the East of England cancer registry (<i>BJC</i> 2012; 106:1068–1075). We extend that work to show a relationship between mode of presentation and disease stage at diagnosis, in keeping with national data indicating that emergency presentation is associated with poorer survival outcomes (NCIN 2010). In summary, this study adds to the increasing evidence that patient factors are associated with potentially avoidable late stage presentations of lung cancer, reiterating the need for targeted health promotion activities to engage at risk patient groups.
Delicate Balance among Three Types of T Cells in Concurrent Regulation of Tumor Immunity
Authors: Liat Izhak, Elena Ambrosino, Shingo Kato, Stanley T. Parish, Jessica J. O'Konek, Hannah Weber, Zheng Xia, David Venzon, Jay A. Berzofsky, Masaki Terabe
Journal: Cancer Research (2013)

Abstract The nature of the regulatory cell types that dominate in any given tumor is not understood at present. Here, we addressed this question for regulatory T cells (Treg) and type II natural killer T (NKT) cells in syngeneic models of colorectal and renal cancer. In mice with both type I and II NKT cells, or in mice with neither type of NKT cell, Treg depletion was sufficient to protect against tumor outgrowth. Surprisingly, in mice lacking only type I NKT cells, Treg blockade was insufficient for protection. Thus, we hypothesized that type II NKT cells may be neutralized by type I NKT cells, leaving Tregs as the primary suppressor, whereas in mice lacking type I NKT cells, unopposed type II NKT cells could suppress tumor immunity even when Tregs were blocked. We confirmed this hypothesis in 3 ways by reconstituting type I NKT cells as well as selectively blocking or activating type II NKT cells with antibody or the agonist sulfatide, respectively. In this manner, we showed that blockade of both type II NKT cells and Tregs is necessary to abrogate suppression of tumor immunity, but a third cell, the type I NKT cell, determines the balance between these regulatory mechanisms. As patients with cancer often have deficient type I NKT cell function, managing this delicate balance among 3 T-cell subsets may be critical for the success of immunotherapy for human cancer. Cancer Res; 73(5); 1514–23. ©2012 AACR.
Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study
Authors: P. M Matricardi
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. <b>Design:</b> Retrospective case-control study. <b>Participants:</b> 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. <b>Setting:</b> Air force school in Caserta, Italy. <b>Main outcome measures:</b> Serology for <i>Toxoplasma gondii, Helicobacter pylori</i>, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis. <b>Results:</b> Compared with controls there was a lower prevalence of <i>T gondii</i> (26% <i>v</i> 18%, P=0.027), hepatitis A virus (30% <i>v</i> 16%, P=0.004), and <i>H pylori</i> (18%<i>v</i> 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to <i>H pylori</i>, <i>T gondii</i>, and hepatitis A virus (none, odds ratio 1; one, 0.70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (<i>H pylori</i>, <i>T gondii</i>, hepatitis A virus). <b>Conclusion:</b> Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.
Spontaneous Skin Ulceration and Defective T Cell Function in CD18 Null Mice
Authors: Karin Scharffetter-Kochanek, Huifang Lu, Keith Norman, Nicole van Nood, Flor Munoz, Stephan Grabbe, Mark McArthur, Isabel Lorenzo, Sheldon Kaplan, Klaus Ley, C. Wayne Smith, Charles A. Montgomery, Susan Rich, Arthur L. Beaudet
Journal: The Journal of Experimental Medicine (1998)

A null mutation was prepared in the mouse for CD18, the β2 subunit of leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with extensive facial and submandibular erosions. The phenotype includes elevated neutrophil counts, increased immunoglobulin levels, lymphadenopathy, splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney. Very few neutrophils were found in spontaneously occurring skin lesions or with an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell proliferation was found in the CD18 null mice when T cell receptors were stimulated either by staphylococcal enterotoxin A or by major histocompatibility complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T cell responses than previously documented. The null mice are useful for delineating the functions of CD18 in vivo.
British Thoracic Society Winter Meeting 2005
Authors: T M A Wilkinson
Journal: Thorax (2006)

An overview of some of the key topics presented at the BTS Winter Meeting held in London in December 2005

The annual winter British Thoracic Society (BTS) meeting held in London on 7–9 December 2005 combined a fascinating retrospective of past achievements in respiratory medicine while looking forward to the challenges that lie ahead. The meeting provided, as usual, a vital platform for clinicians to share best practice and to keep abreast of the rapidly advancing speciality. A highlight was the celebration of the 20th anniversary of British Lung Foundation, with a review of the major advances in respiratory medical research made in recent years.

The priority given to chronic obstructive pulmonary disease (COPD) at this meeting reflected both the clinical burden of disease and the current interest in terms of clinical and basic research in this field. In a lively “pro-con” debate, some of the more controversial issues in disease management were addressed. Arguments included the new BTS President Professor Peter Calverley’s persuasive case that COPD was indeed a useful diagnostic term, as well as lively debate on the evidence for the use of inhaled corticosteroids. With the radical reforms to the provision of home oxygen imminent, a number of sessions concentrated on the new service and the potential impact on patients and providers alike. A presentation highlighted the increase in service provision required to support home oxygen assessments,1 while posters highlighted the benefits of developing a register of COPD patients suitable for long term oxygen therapy (LTOT)2 and the efficacy of ambulatory oxygen in pulmonary rehabilitation.3

The pathogenesis of airways obstruction and exacerbations were the focus for presentations on the role of infection and inflammation in COPD. Highlighting the recent advances in our understanding of this condition, presentations ranged from the findings of a study …
Pressure-induced hypertrophy of cat right ventricle. An evaluation with the force-interval relationship.
Authors: P A Anderson, A Manring, C E Arentzen, J S Rankin, E A Johnson
Journal: Circulation Research (1977)

We evaluated the force-interval relationship for papillary muscle isolated from two groups of cats, one sham-operated (control group), the other having undergone pulmonary artery constriction (hypertrophy group) 18.6 ± 2.9 weeks prior to sacrifice.The right ventricular free wall muscle mass and the peak systolic right ventricular pressure were significantly greater in the hypertrophy than in the control group.The peak force and maximum rate of rise of force (F max ) per cross-sectional area were not significantly different for the two groups.The qualitative features of the force-interval relationship, in particular postextrasystolic potentiation, were the same for both groups.There were quantitative differences between the groups, however.The amount of potentiation expressed, the ratio of F max of the potentiated to that of the previous regular contraction (i.e., the force-interval ratio), was significantly greater in the hypertrophied than in the control group.In both groups, the force-interval ratio was independent of muscle length, yet was altered by changing the inotropic state of the muscle (e.g., by alterations in calcium concentration).Increasing and decreasing the calcium concentration decreased and increased, respectively, the force-interval ratios in both groups.The application of these results to theories about the mechanisms underlying the alterations in mechanical performance induced by hypertrophy is discussed.CHANGES IN THE mechanical properties of isolated cardiac muscle accompanying pressure-induced hypertrophy have been the subject of a number of investigations, but no unanimous view has yet emerged.Bassett and Gelband, 1 Kaufmann et al., 2 and Cooper et al. 3 reported the peak force per cross-sectional area developed by papillary muscles from hypertrophied hearts to be less than that from control hearts, whereas Pannier, 4 Spann et al., 5 Grimm et al., 6 Fisher and Kavaler, 7 and Bing et al. 8 found no significant differences between the two groups; Kerr et al. 9 found the force per muscle weight to be greater in hypertrophied hearts.Similarly, Spann et al., Bassett and Gelband, and Cooper et al. found the maximum rate of force development per cross-sectional area to be depressed in hypertrophied hearts, whereas Pannier and Fisher and Kavaler found no significant difference.Jouannot and Hatt 10 and Williams and Potter" found that, after banding, peak force and maximum rate of force development declined at first and then returned to the control values.The effect of hypertrophy on the force-velocity relationship is similarly controversial.Some investigators found the force-velocity relationship to be depressed, 2 -5
Cervical muscle strength measurement is dependent on the location of thoracic support
Authors: A Rezasoltani, J Ylinen, A-H Bakhtiary, M Norozi, M Montazeri
Journal: British Journal of Sports Medicine (2007)

In all studies in which the strength of the neck extensor muscles has been measured, the level of thoracic support has been adjusted differently so direct comparison of the results is not possible.To measure and compare the isometric force and isometric torque of neck extensor muscles at different levels of thoracic support.Twenty healthy women volunteered for the study. The maximum isometric force of the neck extensor muscles was measured with the thoracic support located at five different levels. The highest level was set at the level of the spine of the scapula (level I) and the other levels were located 2.5 cm lower than the previous one, with the lowest level set 10 cm below the highest level. The maximum isometric torque for each level was calculated by multiplying the isometric force by the length of the lever arm measured from the upper tip of the thoracic support to the centre point of the cell load at the occiput.The maximum isometric force and maximum isometric torque of the neck extensor muscles were increased step by step from 130.5 N to 138.9 N, 141.9 N, 147.9 N and 155.4 N and from 33.7 Nm to 38.7 Nm, 42.5 Nm, 47.2 Nm and 52.7 Nm, respectively. Except for the isometric force of the cervical extensor muscles measured at levels II and III, the differences between the other levels were significant (p<0.05). There was a significant correlation between isometric force and isometric torque measurements of the neck extensor muscles at different levels (0.81<r<0.96).Maximum isometric force and maximum isometric torque measurements of the neck extensor muscles vary with the length of the lever arm. It is recommended that a specific level of thoracic support should be used in follow-up and intervention studies. Setting the level of thoracic support at a specific level will make it possible to compare the strength of the neck extensor muscles in different studies. Measurements at the level of the spine of the scapula were easier and less time consuming.
Overexpression of RhoA Induces Preneoplastic Transformation of Primary Mammary Epithelial Cells
Authors: Xiangshan Zhao, Lin Lu, Nidhi Pokhriyal, Hui Ma, Lei Duan, Simon Lin, Nadereh Jafari, Hamid Band, Vimla Band
Journal: Cancer Research (2009)

Abstract Rho family small GTPases serve as molecular switches in the regulation of diverse cellular functions, including actin cytoskeleton remodeling, cell migration, gene transcription, and cell proliferation. Importantly, Rho overexpression is frequently seen in many carcinomas. However, published studies have almost invariably used immortal or tumorigenic cell lines to study Rho GTPase functions and there are no studies on the potential of Rho small GTPase to overcome senescence checkpoints and induce preneoplastic transformation of human mammary epithelial cells (hMEC). We show here that ectopic expression of wild-type (WT) RhoA as well as a constitutively active RhoA mutant (G14V) in two independent primary hMEC strains led to their immortalization and preneoplastic transformation. These cells have continued to grow over 300 population doublings (PD) with no signs of senescence, whereas cells expressing the vector or dominant-negative RhoA mutant (T19N) senesced after 20 PDs. Significantly, RhoA-T37A mutant, known to be incapable of interacting with many well-known Rho effectors including Rho kinase, PKN, mDia1, and mDia2, was also capable of immortalizing hMECs. Notably, similar to parental normal cells, Rho-immortalized cells have WT p53 and intact G1 cell cycle arrest on Adriamycin treatment. Rho-immortalized cells were anchorage dependent and were unable to form tumors when implanted in nude mice. Lastly, microarray expression profiling of Rho-immortalized versus parental cells showed altered expression of several genes previously implicated in immortalization and breast cancer progression. Taken together, these results show that RhoA can induce the preneoplastic transformation of hMECs by altering multiple pathways linked to cellular transformation and breast cancer. [Cancer Res 2009;69(2):483–91]