tbuckley/cabot-search huggingface dataset:
Therapy of murine tumors with p53 wild-type and mutant sequence peptide-based vaccines.
Authors: J I Mayordomo, D J Loftus, H Sakamoto, C M De Cesare, P M Appasamy, M T Lotze, W J Storkus, E Appella, A B DeLeo
Journal: The Journal of Experimental Medicine (1996)

The BALB/c Meth A sarcoma carries a p53 missense mutation at codon 234, which occurs in a peptide, termed 234CM, capable of being presented to cytotoxic T lymphocytes (CTL) by H-2Kd molecules (Noguchi, Y., E.C. Richards, Y.-T. Chen, and L.J. Old. 1994. Proc. Natl. Acad. Sci. USA. 91:3171-3175). Immunization of BALB/c mice with bone marrow-derived dendritic cells (DC), generated in the presence of granulocyte macrophage colony-stimulating factor and interleukin 4, and prepulsed with the Meth A p53 mutant peptide, induced CTL that specifically recognized peptide-pulsed P815 cells, as well as Meth A cells naturally expressing this epitope. Immunization with this vaccine also protected naive mice from a subsequent tumor challenge, and it inhibited tumor growth in mice bearing day 7 subcutaneous Meth A tumors. We additionally determined that immunization of BALB/c mice with DC pulsed with the p53 peptide containing the wild-type residue at position 234, 234CW, induced peptide-specific CTL that reacted against several methylcholanthrene-induced BALB/c sarcomas, including CMS4 sarcoma, and rejection of CMS4 sarcoma in vaccination and therapy (day 7) protocols. These results support the efficacy of DC-based, p53-derived peptide vaccines for the immunotherapy of cancer. The translational potential of this strategy is enhanced by previous reports showing that DC can readily be generated from human peripheral blood lymphocytes.
Salutary effects of adiponectin on colon cancer: in vivo and in vitro studies in mice
Authors: Hyun-Seuk Moon, Xiaowen Liu, Jutta M Nagel, John P Chamberland, Kalliope N Diakopoulos, Mary T Brinkoetter, Maria Hatziapostolou, Yan Wu, Simon C Robson, Dimitrios Iliopoulos, Christos S Mantzoros
Journal: Gut (2012)

<h3>Background</h3> Obesity and a high-fat diet are associated with the risk and progression of colon cancer. Low adiponectin levels may play an important role in the development of colon and other obesity-related malignancies. No previous studies have directly investigated the mechanistic effects of adiponectin on colon cancer in the settings of obesity, a high-fat diet and/or adiponectin deficiency. <h3>Objective</h3> To investigate the effects of adiponectin on the growth of colorectal cancer in adiponectin-deficient or wild-type-C57BL/6 mice fed a low-fat or high-fat diet. <h3>Results</h3> Mice fed a high-fat-diet gained more weight and had larger tumours than mice fed a low-fat-diet. Adiponectin administration suppressed implanted tumour growth, causing larger central necrotic areas. Adiponectin treatment also suppressed angiogenesis assessed by CD31 staining and VEGFb and VEGFd mRNA expression in tumours obtained from mice fed a high-fat-diet and from adiponectin-deficient mice. Adiponectin treatment decreased serum insulin levels in mice on a high-fat-diet and increased serum-interleukin (IL)-12 levels in adiponectin-deficient mice. In vitro, it was found that adiponectin directly controls malignant potential (cell proliferation, adhesion, invasion and colony formation) and regulates metabolic (AMPK/S6), inflammatory (STAT3/VEGF) and cell cycle (p21/p27/p53/cyclins) signalling pathways in both mouse MCA38 and human HT29, HCT116 and LoVo colon cancer cell lines in a <i>LKB1</i>-dependent way. <h3>Conclusion</h3> These new mechanistic and pathophysiology studies provide evidence for an important role of adiponectin in colon cancer. The data indicate that adiponectin or analogues might be useful agents in the management or chemoprevention of colon cancer.
Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia
Authors: Iris H. I. M. Hollink, Marry M. van den Heuvel-Eibrink, Martin Zimmermann, Brian V. Balgobind, Susan T. C. J. M. Arentsen-Peters, Marielle Alders, Andre Willasch, Gertjan J. L. Kaspers, Jan Trka, Andre Baruchel, Siebold S. N. de Graaf, Ursula Creutzig, Rob Pieters, Dirk Reinhardt, C. Michel Zwaan
Journal: Blood (2009)
Two New β<sub>2</sub>‐Adrenoceptor Agonists, D‐2343 and QH 25, Studied in Asthmatic Patients
Authors: Claes‐Göran Löfdahl, Bengt Bengtsson, Karin Svedmyr, Nils Svedmyr
Journal: Allergy (1982)

Two new β 2 ‐adrenoceptor agonists, D‐2M3 and QH 35, have been studied in asthmatic patients. Animal experiments indicated less effect on skeletal mucsle than on bronchial muscle. D‐2343 (four i.V. cumulatively increasing doses, 0.21‐6.3 μg kg ‐1 min ‐1 ) and i.v. terbutaline (four cumulative doses 0.07‐2.1 μg kg ‐1 min ‐1 ) were single‐blindly compared in a randomized crossover study in eight asthmatics. It was shown that D‐2343 is an effective β 2 ‐adrenoceptor agonist with 5‐6 limes lower potency than terbutaline. The tremor‐inducing effect of D‐2343 was the same as that of terbutaline, when the same degree of bronchodilation was obtained. The effect of QH 25 (0.25. 0.75 and 2.25 mg cumulatively) administered orally, was single‐blindly compared with the effect of oral salbutamol (2, 6 and 18 mg) in a randomized crossover study in eight asthmatics. QH 25 was shown to be an effective β 2 ‐adrenoceptor stimulant about 12 times more potent than salbutamol. The tremor‐inducing capacity was the same as for salbutamol when equipotent bronchodilating doses were studied.
Immune Cell–Poor Melanomas Benefit from PD-1 Blockade after Targeted Type I IFN Activation
Authors: Tobias Bald, Jennifer Landsberg, Dorys Lopez-Ramos, Marcel Renn, Nicole Glodde, Philipp Jansen, Evelyn Gaffal, Julia Steitz, Rene Tolba, Ulrich Kalinke, Andreas Limmer, Göran Jönsson, Michael Hölzel, Thomas Tüting
Journal: Cancer Discovery (2014)

Infiltration of human melanomas with cytotoxic immune cells correlates with spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade of immune-inhibitory receptors in patients with preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity in immune cell-poor melanomas. Here, we show that primary melanomas in Hgf-Cdk4(R24C) mice, which imitate human immune cell-poor melanomas with a poor outcome, escape IFN-induced immune surveillance and editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic inflammatory response in the tumor microenvironment and significantly impaired tumor growth. This critically required the coordinated induction of type I IFN responses by dendritic, myeloid, natural killer, and T cells. Importantly, antibody-mediated blockade of the IFN-induced immune-inhibitory interaction between PD-L1 and PD-1 receptors further prolonged the survival. These results highlight important interconnections between type I IFNs and immune-inhibitory receptors in melanoma pathogenesis, which serve as targets for combination immunotherapies.Using a genetically engineered mouse melanoma model, we demonstrate that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune-inhibitory receptors is a rational strategy to expose immune cell-poor tumors to cellular immune surveillance.
Limitations of current preoperative liver imaging techniques for intrahepatic metastatic nodules of hepatocellular carcinoma
Authors: Tohru Utsunomiya, Takashi Matsumata, Eisuke Adachi, Hiroshi Honda, Keizo Sugimachi
Journal: Hepatology (1992)

To determine the limitations of the latest techniques in preoperative liver imaging for hepatocellular carcinoma, 20 patients with histologically proven intrahepatic metastatic tumors were studied. In 32 masses, we were able to assess the relationship between these intrahepatic metastatic tumors and the findings of preoperative imaging individually. Six intrahepatic metastatic tumors not exceeding 5 mm in diameter were missed in all the imaging examinations. The detection rate was 60% in 13 intrahepatic metastatic tumors of 5 to 10 mm, 77% in 10 intrahepatic metastatic tumors of 10 to 20 mm and 100% in 3 intrahepatic metastatic tumors exceeding 20 mm. In total, computed tomographic imaging during arterial portography demonstrated the highest rate of detection (40%) of all the studies performed. Magnetic resonance imaging, which was recently introduced, was rather disappointing (31%) in this series. In two patients, intrahepatic metastatic tumors were only histologically confirmed. Our study suggests a low rate of detection of intrahepatic metastatic tumors with current preoperative imaging modalities. For improvement of prognosis after hepatectomy for hepatocellular carcinoma adjuvant therapy and extended hepatectomy seem necessary if the functional capacity of the remaining liver permits.
Sexual behavior in women with nonalcoholic liver disease
Authors: Nancy Bach, Fenton Schaffner, Barbara Kapelman
Journal: Hepatology (1989)

Sexual behavior in women with liver disease was examined in 150 women to determine whether liver disease influenced sexual desire, frequency or performance. The average age of women studied was 53 years (range: 26 to 76 years), and a wide variety of liver diseases were represented. Sexual desire was reduced in 33%. Difficulty in becoming sexually aroused was noted by 18%. Orgasm during intercourse was not experienced by 25%. The frequency of sexual intercourse decreased since onset of disease in 27%. Dyspareunia was a complaint by 21%, most often attributed to decreased vaginal lubrication. Liver disease was considered a significant factor interfering with sexual function in 17%. No statistical difference was found between sexual desire or function in our study and in large studies of sexual behavior in women. Each category was subdivided by presence or absence of cirrhosis, pre- or postmenopausal state, laboratory values and duration of disease. Except for a greater number of postmenopausal women with complaints of painful intercourse, no statistical differences or trends were found. Nonalcoholic liver disease does not affect sexual desire, function or performance. Variables other than liver disease influence sexuality. Women with liver disease can thus be reassured that they can maintain normal sexual relations.
Tetanus Eight Days After Administration of Anti-tetanus Serum
Authors: W. W. Woodward
Journal: BMJ (1960)

BJORnrTetanus Eight Days After Administration of Anti-tetanus SerumThe following case, in which tetanus occurred after the prophylactic subcutaneous injection of 1,500 units of anti-tetanus serum, may be found of interest.CASE REPORT After an injury in 1952 a young married woman received an injection of anti-tetanus serum, but did not subsequently receive active immunization with toxoid.Nearly three years
Marked enzymuria after bone marrow transplantation
Authors: J C Fink, M A Cooper, K M Burkhart, G B McDonald, R A Zager
Journal: Journal of the American Society of Nephrology (1995)

During the first month after bone marrow transplantation, approximately 15% of patients develop acute renal failure (ARF). This usually occurs in the setting of hepatic veno-occlusive disease (VOD). Prior clinical data have suggested that this form of ARF has a hemodynamic basis, analogous to the hepatorenal syndrome (HRS). If so, then proximal tubular injury would not be expected. To directly test this hypothesis, enzymuria (N-acetyl-beta-D-glucosaminidase [NAG]) was quantitated in the following groups of patients within the first 35 days after BMT: (1) VOD+ARF (serum creatinine level > 1.5 mg/dL; N = 10); (2) VOD with relatively normal renal function (serum creatinine level < 1.5 mg/dL; N = 11); and (3) patients without hepatic or renal complications (BMT controls; N = 12). For comparison, NAG was also quantitated in the following groups of non-BMT patients: (1) toxic/ischemic acute tubular necrosis (ATN) (N = 10); (2) jaundice without azotemia (N = 5); and (3) HRS (N = 6). Urine samples from eight healthy subjects established normal NAG concentrations (2.5 +/- 0.5 microU/mg urinary creatinine; mean +/- SE). All non-BMT patients with ATN had markedly elevated NAG levels (61 +/- 12; P < 0.001), validating the test as a marker of tubular damage. NAG concentrations were significantly elevated in all of the control BMT patients (24 +/- 3; P < 0.01), and the presence of VOD was associated with further striking increments (approximately 50 times normal). However, the degree of enzymuria was virtually identical for VOD patients with (125 +/- 27) and without (122 +/- 17) ARF. Jaundice in a non-BMT setting was associated with only mild NAG elevations (11 +/- 2). However, striking enzymuria was noted in all HRS patients (61 +/- 20), equaling the levels seen with ATN. The following conclusions were derived: (1) subclinical tubular injury, as defined by enzymuria, appears to be ubiquitous after BMT; (2) VOD dramatically increases the extent of enzymuria; (3) the degree of enzymuria in VOD patients is not correlated with renal dysfunction, implying that the associated ARF has a large hemodynamic component; and (4) HRS and ATN manifest comparable degrees of enzymuria, suggesting that substantial tubular damage exists in both of these forms of ARF.
Are hemostasis and thrombosis two sides of the same coin?
Authors: Robert W. Colman
Journal: The Journal of Experimental Medicine (2006)

Factor XII (FXII), a clotting enzyme that can initiate coagulation in vitro, has long been considered dispensable for normal blood clotting in vivo because hereditary deficiencies in FXII are not associated with spontaneous or excessive bleeding. However, new studies show that mice lacking FXII are protected against arterial thrombosis (obstructive clot formation) and stroke. Thus, FXII could be a unique drug target that could be blocked to prevent thrombosis without the side effect of increased bleeding.
Screening for abdominal aortic aneurysms: single centre randomised controlled trial
Authors: Jes S Lindholt, Svend Juul, Helge Fasting, Eskild W Henneberg
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine whether screening Danish men aged 65 or more for abdominal aortic aneurysms reduces mortality. <b>Design</b> Single centre randomised controlled trial. <b>Setting</b> All five hospitals in Viborg County, Denmark. <b>Participants</b> All 12 639 men born during 1921-33 and living in Viborg County. In 1994 we included men born 1921-9 (64-73 years). We also included men who became 65 during 1995-8. <b>Interventions</b> Men were randomised to the intervention group (screening by abdominal ultrasonography) or control group. Participants with an abdominal aortic aneurysm &gt; 5 cm were referred for surgical evaluation, and those with smaller aneurysms were offered annual scans. <b>Outcome measures</b> Specific mortality due to abdominal aortic aneurysm, overall mortality, and number of planned and emergency operations for abdominal aortic aneurysms. <b>Results</b> 4860 of 6333 men were screened (attendance rate 76.6%). 191 (4.0% of those screened) had abdominal aortic aneurysms. The mean follow-up time was 52 months. The screened group underwent 75% (95% confidence interval 51% to 91%) fewer emergency operations than the control group. Deaths due to abdominal aortic aneurysms occurred in nine patients in the screened group and 27 in the control group. The number needed to screen to save one life was 352. Specific mortality was significantly reduced by 67% (29% to 84%). Mortality due to non-abdominal aortic aneurysms was non-significantly reduced by 8%. The benefits of screening may increase with time. <b>Conclusion</b> Mass screening for abdominal aortic aneurysms in Danish men aged 65 or more reduces mortality.
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: Overview
Authors: David M. Nathan
Journal: Diabetes Care (2013)

OBJECTIVE The Diabetes Control and Complications Trial (DCCT) was designed to test the glucose hypothesis and determine whether the complications of type 1 diabetes (T1DM) could be prevented or delayed. The Epidemiology of Diabetes Interventions and Complications (EDIC) observational follow-up determined the durability of the DCCT effects on the more-advanced stages of diabetes complications including cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS The DCCT (1982–1993) was a controlled clinical trial in 1,441 subjects with T1DM comparing intensive therapy (INT), aimed at achieving levels of glycemia as close to the nondiabetic range as safely possible, with conventional therapy (CON), which aimed to maintain safe asymptomatic glucose control. INT utilized three or more daily insulin injections or insulin pump therapy guided by self-monitored glucose. EDIC (1994–present) is an observational study of the DCCT cohort. RESULTS The DCCT followed &amp;gt;99% of the cohort for a mean of 6.5 years and demonstrated a 35–76% reduction in the early stages of microvascular disease with INT, with a median HbA1c of 7%, compared with CONV, with a median HbA1c of 9%. The major adverse effect of INT was a threefold increased risk of hypoglycemia, which was not associated with a decline in cognitive function or quality of life. EDIC showed a durable effect of initial assigned therapies despite a loss of the glycemic separation (metabolic memory) and demonstrated that the reduction in early-stage complications during the DCCT translated into substantial reductions in severe complications and CVD. CONCLUSIONS DCCT/EDIC has demonstrated the effectiveness of INT in reducing the long-term complications of T1DM and improving the prospects for a healthy life span.
Evidence for Functional Relevance of an Enhanced Expression of the Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger in Failing Human Myocardium
Authors: Markus Flesch, Robert H.G. Schwinger, Frank Schiffer, Konrad Frank, Michael Su¨dkamp, Ferdinand Kuhn-Regnier, Georg Arnold, Michael Bo¨hm
Journal: Circulation (1996)

Background The present study aimed at investigating the expression of the Na + -Ca 2+ exchanger and its functional role in human failing myocardium. Methods and Results Na + -Ca 2+ exchanger mRNA and protein levels were examined in nonfailing (NF, n=8) and failing human myocardium (New York Heart Association functional class IV) with idiopathic dilated cardiomyopathy (DCM, n=8) or ischemic heart disease (ICM, n=6). The inotropic effect of the Na + channel activator BDF 9148 was determined in electrically driven left ventricular papillary muscle strip preparations (1 Hz, 37°C) from nonfailing (n=8) and failing (n=8) human hearts. Na + -Ca 2+ exchanger mRNA levels were significantly increased, by 79% ( P &lt;.001) in DCM and by 58% ( P &lt;.01) in ICM compared with NF; protein levels increased by 36% ( P &lt;.001) and by 20% ( P &lt;.05), respectively. BDF 9148 increased the force of contraction concentration dependently, with a similar maximal effect in NYHA class IV and NF, but was more potent in NYHA class IV as demonstrated by a significantly smaller ( P &lt;.01) EC 50 value (NYHA class IV, 0.18 [0.16 to 0.22] μmol/L; NF, 1.65 [1.3 to 3.0] μmol/L). In NYHA class IV, BDF 9148 (0.1 μmol/L) restored the positive force-frequency relationship and reduced the frequency-dependent increase in diastolic tension in relation to force of contraction. Conclusions The increased expression of the Na + -Ca 2+ exchanger is a possible explanation for the increased inotropic potency of the Na + channel activator BDF 9148 in failing human myocardium. The increase in exchanger molecules could be of functional relevance for the modulation of cardiac contractility by agents that increase the intracellular Na + concentration. Enhancement of Na + -Ca 2+ exchanger activity might be a powerful mechanism for increasing cardiac contractility in chronic heart failure.
Generalised maculopapular rash and multiple nodular pulmonary lesions in an HIV-infected man
Authors: L Meroni, S Trovati, S Antinori
Journal: Thorax (2009)

Generalised maculopapular rash and multiple nodular pulmonary lesions in an HIV-infected man CLINICAL PRESENTATIONA 41-year-old heterosexual man with a recently diagnosed HIV infection was admitted to our department complaining of a 5month history of malaise, non-productive cough and a weight loss of 8 kg.He was a non-intravenous drug user.On physical examination he had a generalised maculopapular rash which was more prominent on the trunk and arms and included the palms and soles (fig 1).Physical examination of the heart, lungs and abdomen was normal.The CD4 count was 176 cells/ml and the plasma HIV-RNA was 4.3 log copies/ml.The results of blood screening laboratory tests were normal.Chest radiography showed multiple bibasilar pulmonary nodules while a CT scan of the lungs showed a wide area of increased density with irregular margins located in the right inferior pulmonary lobe (fig 2).A tuberculin skin test was negative.Cytological examinations of bronchoalveolar lavage (BAL) fluid did not show malignant cells.Gram, PAS, Ziehel-Neelsen and Warthin-Starry stains of specimens from lung brushing and transbronchial biopsy did not reveal infectious agents.Cultures
Use of Cytotoxic Agents and Cyclosporine in the Treatment of Autoimmune Disease: Part 1: Rheumatologic and Renal Diseases
Authors: Carol A. Langford
Journal: Annals of Internal Medicine (1998)

When cytotoxic agents were initially introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease. During the course of this use, however, it became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward the treatment of non-neoplastic diseases in which autoimmune mechanisms were considered important to pathogenesis. As a result of these investigations, cytotoxic agents and, more recently, cyclosporine have emerged to become an important part of the therapeutic regimen for many autoimmune diseases. Nonetheless, these medications may still cause treatment-induced illness or even death. It is therefore particularly important to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. This two-part Clinical Staff Conference reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in selected autoimmune diseases. Part 1 examines the manner in which these agents have been used to treat rheumatologic and renal diseases.