tbuckley/cabot-search huggingface dataset:
Genetic Variation in the Renin-Angiotensin System and Progression of Diabetic Nephropathy
Authors: Peter Jacobsen, Lise Tarnow, Bendix Carstensen, Peter Hovind, Odette Poirier, Hans-Henrik Parving
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The impact of polymorphisms in the genes coding for angiotensinogen ( M235T ), ACE ( ID ), and angiotensin II type 1 receptor ( A 1166 → C ) on decline in GFR and doubling of s-creatinine or development of ESRD in patients with type 1 diabetes and diabetic nephropathy (DN) was tested. From 1985, all patients ( n = 169) who had established diabetic nephropathy and were treated with angiotensin-converting enzyme inhibition (ACE-I) were identified consecutively at Steno Diabetes Center. Patients were followed for a median of 6 yr (range, 3 to 15 yr), with nine (range, three to 29) measurements of GFR ( 51 Cr-EDTA). In a Cox proportional hazards model corrected for other risk factors, the D allele ( ACE/ID ) was associated with time to doubling of s-creatinine/ESRD (rate ratio, 1.81 per allele; 95% confidence interval, 1.09 to 3.03; P = 0.02). A new interaction hypothesis was generated demonstrating that the following variables were associated with accelerated decline in GFR: albuminuria (estimate, 2.12 ml/min per yr per 10-fold increase in albuminuria; P &lt; 0.001), mean BP (estimate, 0.88 ml/min per yr per 10 mmHg; P = 0.02), hemoglobin A 1c (estimate, 0.54 min/min per yr per 1%; P = 0.02), and number of M ( M235T )/ D ( ID )/ A ( A 1166 → C ) alleles (estimate, 0.45 ml/min per yr per allele; P = 0.049). Number of M/D/A alleles also influenced time to doubling of s-creatinine or ESRD. In this study of patients with type 1 diabetes, the D allele of the ACE/ID polymorphism in addition to nongenetic risk factors independently accelerated progression of DN during ACE-I. Interaction between polymorphisms in the renin-angiotensin system also influenced the loss of kidney function. This new genetic interaction model needs to be confirmed in future studies. E-mail: pkjacobsen@dadlnet.dk
Monoclonal antibodies against viral determinants are not restricted to the K/D end of the major histocompatibility complex.
Authors: B Pestalozzi, L Stitz, R M Zinkernagel
Journal: The Journal of Experimental Medicine (1987)

Monoclonal antibodies against lymphocytic choriomeningitis virus (LCMV), a natural, high-replicating, noncytolytic pathogen in mice, were obtained from fusions between myeloma cells and lymphoid cells of mice of different H-2 haplotypes at various times (4-24 d) after infection. Supernatants from growing hybridomas were tested in a RIA, and approximately 15% of all supernatants were positive when tested for specificity on infected vs. uninfected cells of different haplotypes. Upon retesting for specific fluorescence, only some RIA+ supernatants exhibited specific surface staining of acetone-fixed infected cells or unfixed infected cells. In all these experiments and using various detection methods we could not find antibodies with any preference of recognition of viral antigen in conjunction with the H-2 haplotype of the responder mouse. The absence of H-2 restricted antibodies after a primary virus infection in vivo, whether assayed by RIA or surface immunofluorescence, suggests that antibodies obtained in other experiments using infected tumor cells for induction and in the RIA may not represent the general case.
Fas Ligand Expression in Metastatic Renal Cell Carcinoma During Interleukin-2 Based Immunotherapy
Authors: Frede Donskov, Hans von der Maase, Niels Marcussen, Stephen Hamilton-Dutoit, Hans Henrik Torp Madsen, Jens Jorgen Jensen, Marianne Hokland
Journal: Clinical Cancer Research (2004)

It has been hypothesized that tumor cells expressing Fas ligand (FasL) might be able to counterattack and neutralize tumor-infiltrating lymphocytes. We assessed the effect of FasL tumor counterattack on the clinical outcome of interleukin-2 (IL-2)-based immunotherapy in metastatic renal cell carcinoma.Tumor core needle biopsies were obtained before IL-2-based immunotherapy in 86 patients and repeated within the first cycle in 57 patients. Tumor cells expressing FasL and intratumoral lymphocyte subsets expressing CD4, CD8, CD56, and CD57 were analyzed by immunohistochemistry.At baseline, negative FasL staining in tumor cells was seen in 10 of 86 (12%) biopsies, whereas intense FasL staining was seen (a) in fewer than 10% of tumor cells in 26 (30%) biopsies; (b) in 11 to 50% of tumor cells in 25 (29%) biopsies; (c) in 51 to 90% of tumor cells in 18 (21%) biopsies; and (d) in >90% of tumor cells in 7 (8%) biopsies. On treatment, tumor FasL expression did not change from baseline levels. Moreover, tumor FasL expression was not correlated with objective response or survival whereas the absolute number of CD4(+), CD8(+), CD56(+), and CD57(+) cells per mm(2) tumor tissue at baseline was significantly higher in responding patients compared with nonresponding patients (P = 0.01, P = 0.008, P = 0.015, and P < 0.001, respectively). During the first course of immunotherapy, the absolute number of CD4(+), CD8(+), and CD57(+) cells per mm(2) tumor tissue was significantly higher in responding patients compared with nonresponding patients (P = 0.034, P < 0.001, and P < 0.001, respectively). However, no correlation was observed between the number of intratumoral lymphocytes and tumor FasL expression level.These observations do not support the hypothesis that FasL tumor "counterattack" has an effect on the clinical outcome in metastatic renal cell carcinoma during IL-2-based immunotherapy.
Oxidized Low-Density Lipoprotein Is Associated With Apoptosis of Vascular Smooth Muscle Cells in Human Atherosclerotic Plaques
Authors: Yoshifumi Okura, Marijke Brink, Hiroyuki Itabe, Kathrin J. Scheidegger, Afksendiyos Kalangos, Patrice Delafontaine
Journal: Circulation (2000)

Cytotoxic oxidized LDL (oxLDL) has been shown to promote apoptosis in cultured vascular smooth muscle cells (VSMCs). We investigated the localization of oxLDL and its association with apoptosis and the expression of apoptosis-related proteins in early and advanced atherosclerotic lesions.Atherosclerotic plaques (n=23) from patients undergoing aortic, carotid, or femoral arterial surgery were studied. In early lesions, oxLDL was located predominantly in the superficial intima and in the media just beneath the internal elastic lamina. Medial VSMCs staining positive for oxLDL showed expression of BAX, a proapoptotic protein of the BCL-2 family. Apoptosis, as detected by DNA in situ terminal deoxynucleotidyl transferase end-labeling (TUNEL), was not present in these early lesions. In advanced plaques, areas of the intima positive for oxLDL showed lower alpha-smooth muscle actin immunoreactivity (P<0.01) and higher BAX immunoreactivity (P<0.05). Furthermore, these areas showed an increased number of apoptotic VSMCs (P<0.01). Western blot analysis revealed that oxLDL increases BAX expression in cultured human coronary VSMCs.We conclude that in early atherosclerotic lesions, oxLDL-positive VSMCs express BAX, which increases the susceptibility of these cells to undergo apoptosis. This could be important in our understanding of the transition of early lesions into advanced atherosclerotic plaques, which are characterized by regions of cell death. In advanced plaques, oxLDL-positive areas of the intima show higher BAX immunoreactivity and TUNEL-positive VSMCs, and this may contribute to plaque instability and rupture.
A 75-year-old woman with multifocal jejunal strictures
Authors: Hui Yann Lee, Gina Howarth, Robert Willert
Journal: Gut (2014)

A previously fit and well 75-year-old Caucasian woman presented with a 2-month history of postprandial abdominal pain, vomiting and 10 kg weight loss without diarrhoea.

Blood investigations showed marked hypoalbuminaemia of 18 g/L and elevated C reactive protein (CRP) of 185 mg/L. Tissue transglutaminase IgA level was within normal limits without evidence of IgA deficiency. Faecal calprotectin was elevated at 205 µg/g.

Abdominal CT revealed subacute small bowel obstruction characterised by multiple long, thick walled, dilated loops of jejunum (figure 1) associated with lymphadenopathy. Histological findings from laparoscopic mesenteric lymph node resection showed reactive features only.



Figure 1 
Coronal CT view of …
Mortality and Treatment Patterns Among Patients Hospitalized With Acute Cardiovascular Conditions During Dates of National Cardiology Meetings
Authors: Anupam B. Jena, Vinay Prasad, Dana P. Goldman, John Romley
Journal: JAMA Internal Medicine (2014)

Thousands of physicians attend scientific meetings annually. Although hospital physician staffing and composition may be affected by meetings, patient outcomes and treatment patterns during meeting dates are unknown.To analyze mortality and treatment differences among patients admitted with acute cardiovascular conditions during dates of national cardiology meetings compared with nonmeeting dates.Retrospective analysis of 30-day mortality among Medicare beneficiaries hospitalized with acute myocardial infarction (AMI), heart failure, or cardiac arrest from 2002 through 2011 during dates of 2 national cardiology meetings compared with identical nonmeeting days in the 3 weeks before and after conferences (AMI, 8570 hospitalizations during 82 meeting days and 57,471 during 492 nonmeeting days; heart failure, 19,282 during meeting days and 11,4591 during nonmeeting days; cardiac arrest, 1564 during meeting days and 9580 during nonmeeting days). Multivariable analyses were conducted separately for major teaching hospitals and nonteaching hospitals and for low- and high-risk patients. Differences in treatment utilization were assessed.Hospitalization during cardiology meeting dates.Thirty-day mortality, procedure rates, charges, length of stay.Patient characteristics were similar between meeting and nonmeeting dates. In teaching hospitals, adjusted 30-day mortality was lower among high-risk patients with heart failure or cardiac arrest admitted during meeting vs nonmeeting dates (heart failure, 17.5% [95% CI, 13.7%-21.2%] vs 24.8% [95% CI, 22.9%-26.6%]; P < .001; cardiac arrest, 59.1% [95% CI, 51.4%-66.8%] vs 69.4% [95% CI, 66.2%-72.6%]; P = .01). Adjusted mortality for high-risk AMI in teaching hospitals was similar between meeting and nonmeeting dates (39.2% [95% CI, 31.8%-46.6%] vs 38.5% [95% CI, 35.0%-42.0%]; P = .86), although adjusted percutaneous coronary intervention (PCI) rates were lower during meetings (20.8% vs 28.2%; P = .02). No mortality or utilization differences existed for low-risk patients in teaching hospitals or high- or low-risk patients in nonteaching hospitals. In sensitivity analyses, cardiac mortality was not affected by hospitalization during oncology, gastroenterology, and orthopedics meetings, nor was gastrointestinal hemorrhage or hip fracture mortality affected by hospitalization during cardiology meetings.High-risk patients with heart failure and cardiac arrest hospitalized in teaching hospitals had lower 30-day mortality when admitted during dates of national cardiology meetings. High-risk patients with AMI admitted to teaching hospitals during meetings were less likely to receive PCI, without any mortality effect.
Clinically Relevant Modeling of Tumor Growth and Treatment Response
Authors: Thomas E. Yankeelov, Nkiruka Atuegwu, David Hormuth, Jared A. Weis, Stephanie L. Barnes, Michael I. Miga, Erin C. Rericha, Vito Quaranta
Journal: Science Translational Medicine (2013)

Current mathematical models of tumor growth are limited in their clinical application because they require input data that are nearly impossible to obtain with sufficient spatial resolution in patients even at a single time point--for example, extent of vascularization, immune infiltrate, ratio of tumor-to-normal cells, or extracellular matrix status. Here we propose the use of emerging, quantitative tumor imaging methods to initialize a new generation of predictive models. In the near future, these models could be able to forecast clinical outputs, such as overall response to treatment and time to progression, which will provide opportunities for guided intervention and improved patient care.
Early Investigations of Haematemesis
Authors: G. N. Chandler, A. D. Cameron, A. H. Nunn, D. F. Street
Journal: Gut (1960)

Most series of haematemesis or melaena present data about the clinical problems in relation to the final diagnosis. When a patient is admitted there is the problem of management which depends to a considerable extent on the diagnosis. This paper demonstrates that it is possible to achieve an accurate diagnosis in 80% during the first 24 hours.
Potentiation of Tumor Eradication by Adoptive Immunotherapy with T-cell Receptor Gene-Transduced T-Helper Type 1 Cells
Authors: Kenji Chamoto, Takemasa Tsuji, Hiromi Funamoto, Akemi Kosaka, Junko Matsuzaki, Takeshi Sato, Hiroyuki Abe, Keishi Fujio, Kazuhiko Yamamoto, Toshio Kitamura, Tsuguhide Takeshima, Yuji Togashi, Takashi Nishimura
Journal: Cancer Research (2004)

Abstract Adoptive immunotherapy using antigen-specific T-helper type 1 (Th1) cells has been considered as a potential strategy for tumor immunotherapy. However, its application to tumor immunotherapy has been hampered by difficulties in expanding tumor-specific Th1 cells from tumor-bearing hosts. Here, we have developed an efficient protocol for preparing mouse antigen-specific Th1 cells from nonspecifically activated Th cells after retroviral transfer of T-cell receptor (TCR)-α and TCR-β genes. We demonstrate that Th1 cells transduced with the TCR-α and -β genes from the I-Ad-restricted ovalbumin (OVA)323–339-specific T-cell clone DO11.10 produce IFN-γ but not interleukin-4 in response to stimulation with OVA323–339 peptides or A20 B lymphoma (A20-OVA) cells expressing OVA as a model tumor antigen. TCR-transduced Th1 cells also exhibited cytotoxicity against tumor cells in an antigen-specific manner. Moreover, adoptive transfer of TCR-transduced Th1 cells, but not mock-transduced Th1 cells, exhibited potent antitumor activity in vivo and, when combined with cyclophosphamide treatment, completely eradicated established tumor masses. Thus, TCR-transduced Th1 cells are a promising alternative for the development of effective adoptive immunotherapies.
Fish consumption and respiratory symptoms among young adults in a Norwegian community
Authors: O Fluge, E Omenaas, GE Eide, A Gulsvik
Journal: European Respiratory Journal (1998)

The aim of this study was to investigate the relationship between dietary fish consumption and self-reported respiratory symptoms among young adults. A random sample of 4,300 subjects, aged 20-44 yrs, living in Bergen, Norway, received a postal questionnaire on respiratory symptoms, of whom 80% responded. Mean fish consumption was assessed in a food-frequency questionnaire by asking how often the subject consumed units of fish (150 g) during the last year. Average fish consumption was 1.8 units x week(-1). Fish intake of &lt;1 unit x week(-1) was reported by 24%, 41% reported consumption of 1 unit x week(-1) and 35% intake of &gt;1 unit x week(-1). A high fish intake was significantly associated with increasing age after adjusting for smoking. Adjusted for smoking habits, the prevalence of "cough at night" and "chest tightness" showed a decreasing trend with increasing fish consumption (p&lt;0.05), while such a trend for "wheeze" was demonstrated only in smokers (p=0.008 for interaction). In logistic regression models (adjusting for age, sex, body mass, smoking habits and occupational exposure) fish consumption (three categories) was not significantly associated with "wheeze", "chest tightness", "breathless at night" or "asthma attack", although the odds ratios (OR) were consistently less than 1 (except for "asthma attack"). Fish consumption was of borderline significance as a protective factor of "cough at night", OR = 0.86 (95% confidence interval: 0.76-0.97) but in stratified analyses only in smokers. Subjects reporting very high levels of fish consumption (&gt;14 units x week(-1)) did not have lower prevalences of respiratory symptoms. In conclusion, among young Norwegian adults, with a relatively low prevalence of asthma and an overall high fish intake, fish consumption was not a significant predictor of four out of five respiratory symptoms.
Cell Contact–Dependent Immunosuppression by Cd4+Cd25+Regulatory T Cells Is Mediated by Cell Surface–Bound Transforming Growth Factor β
Authors: Kazuhiko Nakamura, Atsushi Kitani, Warren Strober
Journal: The Journal of Experimental Medicine (2001)

CD4+CD25+ T cells have been identified as a population of immunoregulatory T cells, which mediate suppression of CD4+CD25− T cells by cell–cell contact and not secretion of suppressor cytokines. In this study, we demonstrated that CD4+CD25+ T cells do produce high levels of transforming growth factor (TGF)-β1 and interleukin (IL)-10 compared with CD4+CD25− T cells when stimulated by plate-bound anti-CD3 and soluble anti-CD28 and/or IL-2, and secretion of TGF-β1 (but not other cytokines), is further enhanced by costimulation via cytotoxic T lymphocyte–associated antigen (CTLA)-4. As in prior studies, we found that CD4+CD25+ T cells suppress proliferation of CD4+CD25− T cells; however, we observed here that such suppression is abolished by the presence of anti–TGF-β. In addition, we found that CD4+CD25+ T cells suppress B cell immunoglobulin production and that anti–TGF-β again abolishes such suppression. Finally, we found that stimulated CD4+CD25+ T cells but not CD4+CD25− T cells express high and persistent levels of TGF-β1 on the cell surface. This, plus the fact that we could find no evidence that a soluble factor mediates suppression, strongly suggests that CD4+CD25+ T cells exert immunosuppression by a cell–cell interaction involving cell surface TGF-β1.
PREVALENCE OF HUMAN T-LYMPHOTROPIC RETROVIRUSES TYPE III (HIV) AND TYPE IV IN IVORY COAST
Authors: François Denis, Guy Gershy-Damet, Michel Lhuillier, Guy Leonard, Alain Goudeau, Max Essex, Francis Barin, Jean-Loup Rey, Marcelle Mounier, Affoue Sangare, Souleymane M'Boup, Phyllis Kanki
Journal: The Lancet (1987)
Sleep-related breathing disorders. 6. Obstructive sleep apnoea syndrome in infants and children: established facts and unsettled issues.
Authors: C Gaultier
Journal: Thorax (1995)

The presence of increased upper airway resistive loads during sleep can now be diagnosed by paediatricians. However, diagnostic criteria need to be further clarified to allow accurate identification of episodes of partial airway obstruction. New technological advances can be expected to help to determine the clinical usefulness of ambulatory testing during sleep and thus to establish the indications for polysomnographic investigations in the laboratory. A thorough investigation of the anatomical abnormalities that contribute to airways obstruction is essential for selecting the most appropriate therapy. However, the order in which these investigations should be performed remains unclear. The diagnostic tools, including questionnaires and sleep testing, and methods aimed at investigating pathophysiological mechanisms should be standardised for multicentre studies. Familial factors should be taken into account. The best strategy for preventing the complications of the OSA syndrome is to identify the disorder as early as possible. This requires close cooperation between adult physicians and paediatricians called upon to evaluate sleep-related disorders.
Proteomic Analysis of Urine in Kidney Transplant Patients with BK Virus Nephropathy
Authors: Timo Jahnukainen, David Malehorn, Mai Sun, James Lyons-Weiler, William Bigbee, Gaurav Gupta, Ron Shapiro, Parmjeet Singh Randhawa, Richard Pelikan, Milos Hauskrecht, Abhay Vats
Journal: Journal of the American Society of Nephrology (2006)

The differentiation of BK virus-associated renal allograft nephropathy (BKVAN) from acute allograft rejection (AR) in renal transplant recipients is an important clinical problem because the treatment can be diametrically opposite for the two conditions. The aim of this discovery-phase biomarker development study was to examine feasibility of developing a noninvasive method to differentiate BKVAN from AR. Surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry analysis was used to compare proteomic profiles of urine samples of 21 patients with BKVAN, 28 patients with AR (Banff Ia to IIb), and 29 patients with stable graft function. SELDI analysis showed proteomic profiles that were significantly different in the BKVAN group versus the AR and stable transplant groups. Peaks that corresponded to m/z values of 5.872, 11.311, 11.929, 12.727, and 13.349 kD were significantly higher in patients with BKVAN. Bioinformatics analyses allowed distinction of profiles of patients with BKVAN from patients with AR and stable patients. SELDI profiles also showed a high degree of reproducibility. Proteomic analysis of urine may offer a noninvasive way to differentiate BKVAN from AR in clinical practice. The identification of individual proteomic peaks can improve further the clinical utility of this screening method.
CD73-Deficient Mice Are Resistant to Carcinogenesis
Authors: John Stagg, Paul A. Beavis, Upulie Divisekera, Mira C.P. Liu, Andreas Möller, Phillip K. Darcy, Mark J. Smyth
Journal: Cancer Research (2012)

Abstract CD73 is a cell surface 5′-nucleotidase that converts AMP to adenosine, an immune suppressive molecule. CD73 may promote immune escape in cancer by contributing to the degradation of extracellular ATP released by dying cancer cells in hypoxic tumors or following chemotherapy. However, whether CD73 exerts a critical oncogenic function during tumorigenesis is unknown. In this study, we used genetically deficient mice to investigate its contribution to autochthonous tumor formation. CD73 deficiency suppressed the development of 3-methylcholanthrene (MCA)-induced fibrosarcomas through a mechanism relying upon IFN-γ, natural killer (NK) cells, and CD8+ T cells. Similarly, CD73 deficiency also suppressed prostate tumorigenesis in TRAMP transgenic mice. Importantly, treatment with an anti-CD73 monoclonal antibody effectively suppressed growth of established MCA-induced tumors or TRAMP-C1 prostate tumors and inhibited the development of TRAMP-C1 lung metastases. The therapeutic activity of anti-CD73 monoclonal antibody against primary tumors was dependent on CD8+ T cells, whereas its antimetastatic activity was dependent on host CD73 expression independent of T cells or NK cells. Taken together, our findings indicate that CD73 is a critical factor in tumorigenesis and that anti-CD73 antibodies may offer a novel generalized strategy to blunt immune escape and treat cancer. Cancer Res; 72(9); 2190–6. ©2012 AACR.
Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial
Authors: A. Fléchon, D. Pouessel, C. Ferlay, D. Perol, P. Beuzeboc, G. Gravis, F. Joly, S. Oudard, G. Deplanque, S. Zanetta, P. Fargeot, F. Priou, J.P. Droz, S. Culine
Journal: Annals of Oncology (2011)
β Blocker response may have gene link
Authors: Scott Gottlieb
Journal: BMJ (2001)

Patients with congestive heart failure and who have a mutation in the angiotensin converting enzyme (ACE) gene are likely to respond especially well to b blockers, a new study has suggested ( Circulation 2001;103: 1644-8).

The current findings relate to people with the mutation known as the ACE deletion (so called because it lacks a small piece of DNA found in the normal ACE gene). Activation of the renin-angiotensin system is known to adversely affect progression of heart failure. Although the ACE …