tbuckley/cabot-search huggingface dataset:
IMPACT OF AGE ON MYOCARDIAL UPTAKE OF I123-MIBG IN SUBJECTS WITHOUT HEART DISEASE: OBSERVATIONS FROM THE ADMIRE-HF TRIAL
Authors: Ji Chen, Liudmila Verdes, Russell D. Folks, Daya N. Manatunga, Arnold F. Jacobson, Ernest V. Garcia
Journal: Journal of the American College of Cardiology (2010)
Effect of prolonged hypothermic ischaemia on myocardial sarcoplasmic reticular calcium transport
Authors: K. Fukumoto, H. Takenaka, Y. Koga, M. Hamada
Journal: Cardiovascular Research (1990)

The aim of the study was to assess the effects of hypothermia on sarcoplasmic reticulum in myocardium subjected to prolonged ischaemia.Calcium regulatory activity of myocardial sarcoplasmic reticulum was measured in hearts subjected to various periods of hypothermic ischaemia in comparison with hearts subjected to normothermic ischaemia.Hearts (n = 5-9 per experiment) were obtained from male New Zealand white rabbits, 2.0-2.8 kg weight.Calcium uptake and calcium dependent ATPase activity were measured in isolated sarcoplasmic reticulum vesicles after hypothermic ischaemia was produced by immersing hearts in saline at 4 degrees C for 3, 6, or 12 h. Normothermic hearts were immersed for 3 h at 37 degrees C. Calcium uptake and calcium dependent ATPase (Ca-ATPase) activity were markedly inhibited by normothermic ischaemia. In hypothermic ischaemia, calcium uptake was only slightly depressed after 3 h, though longer periods of ischaemia resulted in significant depression of uptake. Ca-ATPase activity was unaffected after 6 h of hypothermic ischaemia. The ratio of calcium uptake to Ca-ATPase activity decreased after 3 h of hypothermic ischaemia. The phosphoenzyme concentration in sarcoplasmic reticulum was unaffected up to 6 h. The ratio of Ca-ATPase activity to phosphoenzyme concentration was not significantly altered until 12 h. Protein composition, examined by SDS-polyacrylamide gel electrophoresis, showed a decrease in 100,000 dalton polypeptide in normothermic ischaemia and after 12 h of hypothermic ischaemia.These results suggest that the depression of calcium uptake activity after 6 h of hypothermic ischaemia is likely to be due to uncoupling of calcium transport from ATP hydrolysis. Depressed Ca-ATPase activity at 12 h can be attributed to a reduction in the number of active calcium pump units. Hypothermia preserves function of myocardial sarcoplasmic reticulum during ischaemia for up to 3 h.
Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes.
Authors: M C Nussenzweig, R M Steinman, B Gutchinov, Z A Cohn
Journal: The Journal of Experimental Medicine (1980)

This study establishes that dendritic cells (DC) are the critical accessory cells for the development of anti-trinitrophenol (TNP) cytotoxic T lymphocytes (CTL) in vitro. We developed a model in which nylon wool-nonadherent spleen cells were used both as the responding and stimulating cells, the latter having been TNP-modified and x-irradiated. Thy-1-bearing CTL developed in C57BL/6, B6D2F1, and CBA mice only when small numbers of DC were added. Maximal responses in 5-d cultures were achieved with 0.5-1 DC/100 responding T cells. The DC did not have to be TNP modified directly. Anti-Ia and complement inactivated accessory cells, whereas similar treatment of the responders had no effect. DC exposed to ultraviolet radiation were ineffective, but x-irradiated DC were fully active. Culture media from DC, or from DC-nylon wool-passed spleen T cell cocultures that contained abundant CTL, would not substitute for viable DC. Enriched preparations of macrophages (M phi) were obtained from blood, peritoneal cavity, and spleens of BCG-immune and unprimed mice. M phi added at doses of 0.2-4% were weak or inactive as accessory cells. The level of Ia antigens on test M phi populations was quantitated and visualized by binding of a radioiodinated monoclonal anti-I-Ab,d antibody, clone B-21. M phi that bore substantial amounts of Ia from all organs were weak accessory cells. Addition of M phi to DC-T cell cocultures produced inhibitory effects, usually at a dose of 2% M phi. In contrast, 0.5% Ia-bearing M phi from BCG-immune boosted mice inhibited &amp;gt; 80% of the DC-mediated CTL response. Addition of indomethacin reversed M phi inhibition, and 10(-9) M prostaglandin E2 in turn blocked the indomethacin effect. Indomethacin also restored a low level of accessory cell function in immune-boosted adherent peritoneal cells, but not in preparations of monocytes and spleen M phi. Small numbers of DC were identified in preparations of immune-boosted peritoneal cells and may have accounted for the observed accessory activity. We conclude that the development of anti-TNP CTL is an immune response in which (a) DC are the critical accessory cells; (b) Ia-bearing M phi are weak or inactive; and (c) M phi can inhibit DC-mediated response by an indomethacin-sensitive mechanism.
The Incidence of Giant Cell Arteritis in Olmsted County, Minnesota: Apparent Fluctuations in a Cyclic Pattern
Authors: C Salvarani, S E Gabriel, W M O'Fallon, G G Hunder
Journal: Annals of Internal Medicine (1995)

Objective: To investigate trends in the incidence of giant cell arteritis over a 42-year period in Olmsted County, Minnesota. Design: Population-based incidence study. Setting: Olmsted County, Minnesota. Methods: All incidence cases of giant cell arteritis first diagnosed between 1950 and 1991 were identified using the unified record system at Mayo Clinic. Age- and sex-specific incidence rates were calculated using the number of incidence cases as the numerator and population estimates as the denominator. Overall rates were age-and sex-adjusted to the 1980 United States white population. The annual incidence rates were graphically illustrated using a 3-year centered moving average. Results: Between 1950 and 1991, 125 Olmsted County residents (103 women and 22 men) were diagnosed with giant cell arteritis. The age- and sex-adjusted incidence per 100 000 persons 50 years of age or older was 17.8 (95% CI, 14.7 to 21.0); incidence was significantly higher in women (24.2 [CI, 19.5 to 28.9]) than in men (8.2 [CI, 4.8 to 11.6]). Age-specific incidence rates increased with age (P < 0.0001). The annual incidence rates increased significantly over the study period (P = 0.002) and appear to have clustered in five peak periods, which occurred about every 7 years. A significant calendar-time effect was identified; it predicted an increase in incidence of 2.6% (CI, 0.9% to 4.3%) every 5 years. Conclusions: Our observation of a regular cyclic pattern in incidence rates over time supports the hypothesis of an infectious cause for giant cell arteritis. Similar studies in other populations are needed to confirm our findings.
Adenosine-Induced Atrial Arrhythmia: A Prospective Analysis
Authors: S A Strickberger, K C Man, E G Daoud, R Goyal, K Brinkman, B P Knight, R Weiss, M Bahu, F Morady
Journal: Annals of Internal Medicine (1997)

Background: Adenosine is considered safe and effective for paroxysmal supraventricular tachycardia (PSVT), but anecdotal experience suggests that adenosine can precipitate atrial arrhythmias. Objectives: To determine the frequency and mechanisms of adenosine-induced atrial arrhythmias. Setting: Clinical electrophysiology laboratory at a university medical center. Design: Prospective observational study. Patients: 200 consecutive patients with PSVT undergoing an electrophysiology procedure. Intervention: During PSVT, 12 mg of adenosine was administered centrally through the femoral vein. Measurements: Frequency of adenosine-induced atrial fibrillation. Results: Paroxysmal supraventricular tachycardia terminated after adenosine administration in 198 patients (99% [95% CI, 96% to 100%]). Adenosine led to atrial fibrillation (n = 22) or atrial fibrillation and atrial flutter (n = 2) in 24 patients (12% [CI, 7.5% to 16.5%]). An atrial premature complex occurred in all 24 patients who developed atrial fibrillation, atrial flutter, or both and in 102 of the 176 patients (58%) who did not (P < 0.001). The mean (±SD) time from the preceding atrial complex to the atrial premature complex was shorter when an atrial arrhythmia occurred, and the mean ratio of this interval to the preceding atrial cycle length was also lower when atrial fibrillation developed (0.37 ± 0.16 compared with 0.49 ± 0.16; P = 0.002). Conclusions: The incidence of atrial fibrillation induced by 12 mg of adenosine administered through the femoral vein was 12%. Fibrillation seems to be associated with a “long-short” atrial sequence. If the mechanism of PSVT is unknown and the Wolff-Parkinson-White syndrome is possible, administration of adenosine should be limited to medical facilities that have emergency resuscitation equipment.
CIRCULATING LEVELS OF PRO-INFLAMMATORY MEDIATORS PREDICT THE POSTOPERATIVE development of acute heart failure in patients undergoing elective coronary artery bypass grafting operation
Authors: Alexios S. Antonopoulos, Charalambos Antoniades, Dimitris Tousoulis, Michalis Demosthenous, Antigoni Miliou, Nikolaos Koumallos, Costas Triantafyllou, Constantinos Bakogiannis, Constantinos Psarros, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2013)
Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats.
Authors: D Koya, M R Jirousek, Y W Lin, H Ishii, K Kuboki, G L King
Journal: Journal of Clinical Investigation (1997)

Induction of protein kinase C (PKC) pathway in the vascular tissues by hyperglycemia has been associated with many of the cellular changes observed in the complications of diabetes. Recently, we have reported that the use of a novel, orally effective specific inhibitor of PKC beta isoform (LY333531) normalized many of the early retinal and renal hemodynamics in rat models of diabetes. In the present study, we have characterized a spectrum of biochemical and molecular abnormalities associated with chronic changes induced by glucose or diabetes in the cultured mesangial cells and renal glomeruli that can be prevented by LY333531. Hyperglycemia increased diacylglycerol (DAG) level in cultured mesangial cells exposed to high concentrations of glucose and activated PKC alpha and beta1 isoforms in the renal glomeruli of diabetic rats. The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta1 isoform without decreasing PKC alpha isoform activation. Glucose-induced increases in arachidonic acid release, prostaglandin E2 production, and inhibition of Na+-K+ ATPase activities in the cultured mesangial cells were completely prevented by the addition of LY333531. Oral feeding of LY333531 prevented the increased mRNA expression of TGF-beta1 and extracellular matrix components such as fibronectin and alpha1(IV) collagen in the glomeruli of diabetic rats in parallel with inhibition of glomerular PKC activity. These results suggest that the activation of PKC, predominately the beta isoform by hyperglycemia in the mesangial cells and glomeruli can partly contribute to early renal dysfunctions by alteration of prostaglandin production and Na+-K+ ATPase activity as well as the chronic pathological changes by the overexpression of TGF-beta1 and extracellular matrix components genes.
Hemolysis as a possible indicator of neurotoxicity induced by organic solvents.
Authors: R J Anderson, C E Glasgow, C B Dunham
Journal: Environmental Health Perspectives (1984)

The expense, length of time and number of animals required for routine toxicity testing have provided the incentive for finding alternative techniques which are faster, less expensive and equally valid. The purpose of this work was to examine the value of a simple in vitro test (hemolysis) as a correlate of the neurotoxicity produced by commonly used industrial organic solvents. Incubation of rat erythrocytes with organic alcohols produced hemolysis which correlates with the potency of the same alcohols to suppress membrane excitability, measured as reduction in the evoked action potential of the rat sciatic nerve. The hemolytic activity also reflects changes in water solubility among the compounds and thus can be used as an index of in vivo neurotoxicity, the extent of which partly depends on absorption of the agent and delivery to nerve tissue. Hemolysis therefore may be of value as a preliminary test for assessing the neurotoxicity of organic solvents.
All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)
Authors: Harry J. Iland, Ken Bradstock, Shane G. Supple, Alberto Catalano, Marnie Collins, Mark Hertzberg, Peter Browett, Andrew Grigg, Frank Firkin, Amanda Hugman, John Reynolds, Juliana Di Iulio, Campbell Tiley, Kerry Taylor, Robin Filshie, Michael Seldon, John Taper, Jeff Szer, John Moore, John Bashford, John F. Seymour
Journal: Blood (2012)
Counterregulatory Hormone Responses After Long-Term Continuous Subcutaneous Insulin Infusion With Lispro Insulin
Authors: Elaine Y L Tsui, Jean-Louis Chiasson, Hugh Tildesley, Annette Barnie, Sari Simkins, Thomas Strack, Bernard Zinman
Journal: Diabetes Care (1998)

To determine whether the long-term use of insulin lispro (LP) affects the counterregulatory hormone response to hypoglycemia.Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9 +/- 0.48; mean HbA1c 7.84 +/- 0.25%) with IDDM, treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a double-blind, crossover design. Patients were randomized to LP or human regular insulin (HR) for 3 months and then crossed over to the other insulin for an additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch, and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were evaluated at the end of each treatment period.HbA1c was significantly lower with LP versus HR (7.47 +/- 0.28% vs. 7.9 +/- 0.26%, P = 0.04). The incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l and/or symptoms) during the last month of the study was significantly lower with LP versus HR (8.7 +/- 2.9 vs. 11.8 +/- 2.9, P = 0.03). The total daily insulin dosage was not different in the two treatment periods. There was no episode of severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol, glucagon, and epinephrine responses during the same period of hypoglycemia were not different for each treatment period.The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia.
Abstract 1154: MicroRNA-221, -222 and -181 regulates tamoxifen resistance in breast cancer by downregulating TIMP3 and facilitating growth factor signaling
Authors: Yuanzhi Lu, Satavisha Roy, Tyler Miller, Kalpana Ghoshal, Bhuvaneswari Ramaswamy, Charlie Shapiro, Samson T Jacob, Sarmila Majumder
Journal: Cancer Research (2011)

Abstract We have shown earlier that microRNA (miR)-221 and -222 are upregulated in tamoxifen (TAM) resistant breast cancer cell line MCF-7 (OHTR), and in Her2 positive primary human breast tumors compared to the Her2 negative tumors1. In addition, expression of miR-181b was 3.5-fold higher in OHTR cells compared to the MCF-7 cells and endocrine resistant primary tumors. To determine the underlying mechanism of miR-mediated regulation of TAM resistance, we focused on identification of target genes regulated by these miRs. Bioinformatics search revealed presence of seed sequences for all three miRs on 3’-UTR of TIMP3, a tissue metalloprotease inhibitor. Luciferase assay confirmed TIMP3 to be a direct target of these miRs and was found to be regulated at both RNA and protein levels. In situ hybridization and immunohistochemical analysis demonstrated reciprocal relationship between TIMP3 and miR 221/222 expression in primary human tumors, where invasive ductal carcinomas expressed high level of the miRs and normal or non-invasive cancers expressed TIMP3, but not the miRs. Cell proliferation and wound healing assay demonstrated increased sensitization of the TAM resistant cells to the drug upon ectopic expression of TIMP3. In addition, mouse mammary tumors induced with TIMP3 overexpressing cells were found to be more sensitive to TAM compared to the tumors initiated with control cells. Conversely, knocking down TIMP3 by siRNA reduced sensitivity to TAM, both in cell cultures and in mouse mammary tumors. As TIMP3 is an inhibitor of matrix metalloproteases involved in positive regulation of growth factor signaling, we speculated that reduction in TIMP3 due to high miR-221/222/181 expression could facilitate growth factor signaling in OHTR cells. Indeed, EGF-induced MAPK phosphorylation was significantly higher in OHTR cells compared to MCF-7 cells and miR-221/222 overexpressing MCF-7 cells mimicked this phenomenon. On the contrary, phosphMAPK level was reduced when TIMP3 was overexpressed in OHTR cells and increased upon knocking down of TIMP3 in MCF-7 cells. Similar differences in MAPK phosphorylation was also observed in cells treated with low level estrogen or TAM, agonists for TAM resistant cells. Based on this data we conclude that overexpression of miR-221/222 and -181b facilitates growth factor signaling in TAM resistant cells by downregulating TIMP3. 1. Miller et. al. J. Biol. Chem 2008; 283 (44): 29897 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1154. doi:10.1158/1538-7445.AM2011-1154
Alexithymia, Risk Factor or Consequence of Work-Related Stress?
Authors: W. de Vente, J.H. Kamphuis, P.M.G. Emmelkamp
Journal: Psychotherapy and Psychosomatics (2006)

&lt;i&gt;Background:&lt;/i&gt; Primary alexithymia has been proposed as a trait-like risk factor for various psychiatric disorders. Alternatively, secondary alexithymia has been conceptualized as an inadequate coping reaction to a stressful situation. This study investigated the level and the type of alexithymia associated with occupational stress. &lt;i&gt;Method:&lt;/i&gt; On 2 occasions, 69 patients with work-related stress and 62 healthy participants completed self-report instruments to measure alexithymia (20-item Toronto Alexithymia Scale), burnout complaints (Maslach Burnout Inventory) and general distress complaints (Depression Anxiety Stress Scales, Checklist Individual Strength). Group differences in alexithymia were analyzed using ANOVAs. The type of alexithymia was investigated by (a) determining absolute and relative stability, (b) exploring state dependence by adjusting alexithymia for burnout and distress complaints and (c) associating recovery of complaints with change in alexithymia. &lt;i&gt;Results:&lt;/i&gt; Alexithymia was significantly elevated among patients. In the patient group, absolute stability of two alexithymia dimensions (identifying feelings, describing feelings) and relative stability of one alexithymia dimension (identifying feelings) was lower than in the healthy group. Cross-sectional group differences became small and nonsignificant after adjustment for distress complaints. Among patients, change in alexithymia was moderately associated with symptom recovery. &lt;i&gt;Conclusion:&lt;/i&gt; Elevated alexithymia among patients with occupational stress is highly state dependent, which indicates the presence of secondary alexithymia.
L-Noradrenaline in Treatment of Acute Cor Pulmonale
Authors: J. de Swiet
Journal: BMJ (1955)

Referring to cases of massive pulmonary embolism, Wood (1950) states: "The great majority . . .survive the initial insult; but about one-third die subsequently from circulatory obstruction. . .On the other hand, about two-thirds recover-within hours, days, or weeks.Throughout this anxious period there is a 25% risk of another, and perhaps fatal, embolus."While the immediate and intensive administration of anticoagulants is a valuable contribution towards the prophylaxis and treatment of the thrombo-embolic state, there is an equally urgent demand for measures to combat the profoundly hypotensive condition result- ing from massive pulmonary embolism.The use of L-noradrenaline in the treatment of the shock and hypotensive state of acute myocardial infarction *(Shirley Smith and Guz, 1953) would logically call for
p53MVA Therapy in Patients with Refractory Gastrointestinal Malignancies Elevates p53-Specific CD8+ T-cell Responses
Authors: Nicola R. Hardwick, Mary Carroll, Teodora Kaltcheva, Dajun Qian, Dean Lim, Lucille Leong, Peiguo Chu, Joseph Kim, Joseph Chao, Marwan Fakih, Yun Yen, Jonathan Espenschied, Joshua D. I. Ellenhorn, Don J. Diamond, Vincent Chung
Journal: Clinical Cancer Research (2014)

To conduct a phase I trial of a modified vaccinia Ankara (MVA) vaccine delivering wild-type human p53 (p53MVA) in patients with refractory gastrointestinal cancers.Three patients were vaccinated with 1.0×10(8) plaque-forming unit (pfu) p53MVA followed by nine patients at 5.6×10(8) pfu. Toxicity was classified using the NCI Common Toxicity Criteria and clinical responses were assessed by CT scan. Peripheral blood samples were collected pre- and post-immunization for immunophenotyping, monitoring of p53MVA-induced immune response, and examination of PD1 checkpoint inhibition in vitro.p53MVA immunization was well tolerated at both doses, with no adverse events above grade 2. CD4+ and CD8+ T cells showing enhanced recognition of a p53 overlapping peptide library were detectable after the first immunization, particularly in the CD8+ T-cell compartment (P=0.03). However, in most patients, this did not expand further with the second and third immunization. The frequency of PD1+ T cells detectable in patients' peripheral blood mononuclear cells (PBMC) was significantly higher than in healthy controls. Furthermore, the frequency of PD1+ CD8+ T cells showed an inverse correlation with the peak CD8+ p53 response (P=0.02) and antibody blockade of PD1 in vitro increased the p53 immune responses detected after the second or third immunizations. Induction of strong T-cell and antibody responses to the MVA backbone were also apparent.p53MVA was well tolerated and induced robust CD8+ T-cell responses. Combination of p53MVA with immune checkpoint inhibition could help sustain immune responses and lead to enhanced clinical benefit.