tbuckley/cabot-search huggingface dataset:
Calcified Rheumatic Valve Neoangiogenesis Is Associated With Vascular Endothelial Growth Factor Expression and Osteoblast-Like Bone Formation
Authors: Nalini M. Rajamannan, Thomas B. Nealis, Malayannan Subramaniam, Sanjay Pandya, Stuart R. Stock, Constatine I. Ignatiev, Thomas J. Sebo, Todd K. Rosengart, William D. Edwards, Patrick M. McCarthy, Robert O. Bonow, Thomas C. Spelsberg
Journal: Circulation (2005)

Rheumatic heart disease is the most common cause of valvular disease in developing countries. Despite the high prevalence of this disease, the cellular mechanisms are not well known. We hypothesized that rheumatic valve calcification is associated with an osteoblast bone formation and neoangiogenesis.To test this hypothesis, we examined human rheumatic valves replaced at surgery (n=23), normal human valves (n=20) removed at cardiac transplantation, and degenerative mitral valve leaflets removed during surgical valve repair (n=15). Microcomputed tomography was used to assess mineralization fronts to reconstruct the extents of mineralization. Immunohistochemistry was used to localize osteopontin protein, alpha-actin, osteocalcin, vascular endothelial growth factor, von Willebrand factor, and CD68 (human macrophage). Microcomputed tomography demonstrated complex calcification developing within the heavily calcified rheumatic valves, not in the degenerative mitral valves and control valves. Immunohistochemistry localized osteopontin and osteocalcin to areas of smooth muscle cells within microvessels and proliferating myofibroblasts. Vascular endothelial growth factor was present in areas of inflammation and colocalized with the CD68 stain primarily in the calcified rheumatic valves. Alizarin red, osteopontin, and osteocalcin protein expression was upregulated in the calcified rheumatic valves and was present at low levels in the degenerative mitral valves.These findings support the concept that rheumatic valve calcification is not a random passive process but a regulated, inflammatory cellular process associated with the expression of osteoblast markers and neoangiogenesis.
Role of human-milk lactadherin in protectoin against symptomatic rotavirus infection
Authors: David S Newburg, Jerry A Peterson, Guillermo M Ruiz-Palacios, David O Matson, Ardythe L Morrow, Justine Shults, Maria de Lourdes Guerrero, Prasoon Chaturvedi, Seth O Newburg, Ciaran D Scallan, Michael R Taylor, Robert L Ceriani, Larry K Pickering
Journal: The Lancet (1998)
Dark Chocolate Improves Coronary Vasomotion and Reduces Platelet Reactivity
Authors: Andreas J. Flammer, Frank Hermann, Isabella Sudano, Lukas Spieker, Matthias Hermann, Karen A. Cooper, Mauro Serafini, Thomas F. Lüscher, Frank Ruschitzka, Georg Noll, Roberto Corti
Journal: Circulation (2007)

Background— Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. Methods and Results— We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36±0.51 to 2.51±0.59 mm, P &lt;0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5±11.4% versus −4.3±11.7% in the placebo group, P =0.01). Platelet adhesion decreased from 4.9±1.1% to 3.8±0.8% ( P =0.04) in the dark chocolate group but remained unchanged in the control group. Conclusions— Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.
The Cancer and Leukemia Group B Cancer in the Elderly Committee: Addressing a Major Cancer Need
Authors: Harvey Jay Cohen, Hyman B. Muss
Journal: Clinical Cancer Research (2006)

Abstract Cancer is a disease of aging, and the majority of cancers occur in persons over 65 years of age. In spite of this, few elders have been represented in clinical trials, and the need for information regarding the treatment of elders with cancer remains great. Recognizing these needs, the Cancer and Leukemia Group B (CALGB) formed an elderly Working Group in 1995, and after initial success in developing clinical studies focused on elders, a Cancer in the Elderly Committee. The Committee's objective is to focus attention on issues specifically relevant to the treatment of cancer in the older patient. Two strategies were developed to achieve this objective: (a) to initiate projects and protocols within the Committee and (b) to foster the initiation of studies by other CALGB committees. The research themes of the Committee and the main thrust of committee's research activities are (a) understanding and overcoming barriers to clinical trials participation; (b) treatment efficacy and pharmacokinetic/pharmacologic issues related to chemotherapy and hormone therapy in the older cancer patient; and (c) improving the quality of life for older cancer patients. The Cancer in the Elderly Committee has been successful in developing, implementing, and completing trials in all these areas and serves as a major resource for clinical trials development for the CALGB.
Induction chemotherapy, concurrent chemoradiation and surgery for Pancoast tumour
Authors: A. Marra, W. Eberhardt, C. Pottgen, D. Theegarten, S. Korfee, T. Gauler, M. Stuschke, G. Stamatis
Journal: European Respiratory Journal (2006)

The traditional treatment of Pancoast tumour with local approaches (surgery, radiotherapy or a combination of both) leads to a poor outcome due to the high rate of incomplete resection and the lack of systemic control. The aim of the present prospective feasibility study was to determine whether a trimodality approach improves local control and survival. Patients with stage IIB−IIIB Pancoast tumour received induction chemotherapy (three courses of split-dose cisplatin and etoposide or paclitaxel) followed by concurrent chemoradiotherapy (a course of cisplatin/etoposide combined with 45 Gy hyperfractionated accelerated radiotherapy). After restaging, eligible patients underwent surgery 4−6 weeks post-radiation. A total of 31 consecutive patients with T3 (81%) or T4 (19%) Pancoast tumour were enrolled in the study. Induction chemoradiotherapy was completed in all patients without treatment-related deaths. Grade 3−4 toxicity was observed in 32% of cases. In total, 29 (94%) patients were eligible for surgery. Complete resection was achieved in 94% of patients. The post-operative mortality rate was 6.4% and major complications arose in 20.6% of the patients. The median survival was 54 months with 2- and 5-yr survival rates of 74 and 46%, respectively. In conclusion, this intensive multimodality treatment of Pancoast tumour is feasible and improves local resectability rates and long-term survival as compared with historical series.
The value of biomarkers in the rheumatoid arthritis related interstitial pneumonia
Authors: Young Seok Lee, Ho Cheol Kim, Chang Keun Lee, Mi-Young Kim, Seungbong Han, Feghali-Bostwick Carol, Dong Soon Kim
Journal: European Respiratory Journal (2013)

Background: Because of the highly variable clinical course, it is important to predict the prognosis of rheumatoid arthritis related interstitial pneumonia (RA-IP) at the time of diagnosis. The aim of the study was to find out the blood biomarker that can predict the disease progression and/or survival in the patients with RA-IP at the time of diagnosis.

Method: The plasma levels of biomarkers (KL-6, MMP-7, IL-6, IL-22, and IL-32) were retrospectively compared with the clinical course of 79 patients with RA-IP (biopsy-proven: 33).

Results: The mean age of the patients was 63 years and 45.6% was male. The median follow-up period was 42 months. Among the 5 biomarkers, only KL-6 has clinical significance. KL-6 level was significantly higher in the patient with acute exacerbation (≥1447.80 ng/mL) compared to stable state (AUC, 0.938; P<0.001). There was no correlation between the level of KL-6 and the treatment response. Among the patients followed-up without treatment (n=38), KL-6 level was higher in the patients whose disease was progressed compared to the patients remained in stable condition (AUC, 0.794; P=0.037) and higher frequency of reduction in lung function. Furthermore, univariate Cox hazard regression analysis showed KL-6 (HR, 1.003; P<0.001) was a significant predictors of survival. The patients with high level of KL-6 (≥1005.40 ng/mL) had shorter survival compared to those with low levels of KL-6 (median survival: 46 vs. 77 months respectively) (AUC, 0.801).

Conculusions: Our retrospective study suggested that blood level of KL-6 can be used as a marker of disease activity and prognostic predictor in the patients with RA-IP. More study in large number of the patients is warranted.
Reply: Severe Vitamin D Deficiency: A Biomarker of Exacerbation Risk?
Authors: Ken M. Kunisaki, Dennis E. Niewoehner, John E. Connett
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

From the Authors:

Heulens and colleagues hypothesize that patients with 25-hydroxyvitamin D (25[OH]D) blood levels greater than 40 ng/ml are likely to be vitamin D supplement users. Although this is a well-reasoned hypothesis, vitamin D supplementation data were not collected in our study (1), so we cannot confirm or refute this hypothesis.

In regard to exclusion of supplement users from observational studies, we agree that supplement use has been associated with many other confounders such as engagement in other healthy behaviors, better adherence to medications, and higher educational status (2–4). Such associations tend to overestimate the potential benefits of dietary supplements, and we found no such potential benefit, making health user bias unlikely. Conversely, Heulens and colleagues suggest that vitamin D supplement users in our study may have had more severe chronic obstructive pulmonary disease (COPD) and therefore biased our results toward the null hypothesis. Again, without supplement data, we cannot perform a formal analysis to address this issue of potential confounding by indication. However, the 107 patients with 25(OH)D greater than or equal to 40 ng/ml had a mean FEV1, the most commonly used marker of COPD severity, that was not different from those at lower 25(OH)D levels (Table 1).



TABLE 1.

MEAN FEV1 PERCENT PREDICTED, STRATIFIED BY BASELINE PLASMA 25(OH)D LEVEL IN THE COPD CLINICAL RESEARCH NETWORK AZITHROMYCIN TRIAL



Randomized controlled trials (RCTs) remain the gold standard for evaluating the effects of medical interventions, and the null results of Lehouck and colleagues’ well-designed RCT in 182 patients with COPD suggest no effect of vitamin D supplementation on COPD exacerbation risk (5). Their post hoc subgroup analysis of 30 patients with 25(OH)D levels less than 10 ng/ml and our post hoc observational data are consistent in suggesting a potential effect of vitamin D on exacerbation rate in patients with COPD with severe vitamin D deficiency. However, placebo-controlled RCT confirmation of these hypothesis-generating data is not ethical due to well-documented skeletal health benefits of vitamin D supplementation in patients with such profoundly low 25(OH)D levels (6).
Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases
Authors: V L Kinnula
Journal: Thorax (2005)

Cigarette smoke causes significant oxidant stress which is further enhanced by recruitment and activation of inflammatory cells to the lung. Polymorphisms in some detoxification enzymes are thought to increase the risk of developing chronic obstructive pulmonary disease (COPD), but the ultimate role of genetic variability in antioxidant and/or detoxification enzymes in COPD remains obscure. Some antioxidant enzymes are inducted, but the extent of induction is insufficient to protect the lung/alveolar epithelium against cigarette smoke. Exogenous antioxidants such as vitamins do not seem to protect against cigarette smoke related lung injury. Glutathione related synthetic drugs such as N-acetylcysteine have shown some benefits, but they may have pro-oxidant side effects. Synthetic compounds with superoxide dismutase and catalase activities have shown promising results in animal models against a variety of oxidant exposures including cigarette smoke in the lung. These results are in agreement with studies highlighting the importance of alveolar antioxidant protection mechanisms in oxidant stress and their inducibility. These new drugs need to be tested in cigarette smoking related lung injury/inflammation since inflammation/oxidant stress can continue after discontinuation of smoking.
Cure of Experimental Human Malignant Mesothelioma in Athymic Mice by Diphtheria Toxin
Authors: Vic Raso, John McGrath
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Cure of Experimental Human Malignant Mesothelioma in Athymic Mice by Diphtheria Toxin Get access Vic Raso, Vic Raso Search for other works by this author on: Oxford Academic PubMed Google Scholar John McGrath John McGrath Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 8, 19 April 1989, Pages 622–627, https://doi.org/10.1093/jnci/81.8.622 Published: 19 April 1989 Article history Received: 24 October 1988 Revision received: 17 January 1989 Accepted: 27 January 1989 Published: 19 April 1989
Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement.
Authors: M K Pangburn, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1980)

The reaction of [14C]methylamine with native human C3 led to the stoichiometric incorporation of methylamine, loss of hemolytic activity, and the concomitant exposure of a sulfhydryl group that could be labeled with [14C]iodoacetamide. Both labeled sites were located in the C3d portion of the alpha-chain, which is known to contain the metastable binding of C3b. The methylamine-modified C3 [C3(CH3NH2)] was shown to exhibit many of the functional properties of C3b, although the C3a portion of the molecule remained covalently attached. C3(CH3NH2) bound Factor B and beta 1H, and could be cleaved by C3b inactivator in the presence of beta 1H. C3(CH3NH2) added to human serum caused activation of the alternative pathway and consumption of C3. In presence of Factors B and D and Mg++, C3(CH2NH2) formed a C3 convertase. The convertase-forming material could be removed from solution by anti-C3a Sepharose and the preformed convertase was completely inhibited by purified antibody to C3a. This antibody did not affect the function of the C3 convertase that contained C3b. Similar functional properties were exhibited by C3 exposed for short periods of time to relatively low concentrations of chaotropic reagents, such as KSCN or guanidine. These results suggest that the initial C3 convertase of the alternative pathway may be formed from native C3, without proteolysis, by the attack of a variety of nucleophiles including water. The C3 convertase formed from this altered C3 then generates by proteolytic cleavage the initial metastable C3b that is capable of attaching to receptive surfaces. Conversion of C3 to C3b exposes one sulfhydryl residue as does modification of C3 with methylamine. When the C3d portion of C3b bound to zymosan particles via the metastable binding site was treated with radiolabeled methylamine, the fragment was released from the particles in radiolabeled form. These findings are consistent with the concept that native C3 contains an active carbonyl group, probably in the form of a thioester, which can either react with water to form functionally C3b-l;ike C3 or, upon enzymatic conversion of C3 to C3b, allows C3b to form an ester bond with hydroxyl groups on the target surface.
The Effects of Dominant and Nondominant Unilateral ECT as Compared to Bilateral ECT
Authors: J. MCANDREW, B. BERKEY, C. MATTHEWS
Journal: American Journal of Psychiatry (1967)

Electroconvulsive treatments were administered to 24 patients, each receiving one of three variations of electrode placement—dominant hemisphere, nondominant hemisphere, or bilateral. A battery of psychological tests administered to each patient before and after ECT revealed findings that fail to support previous investigations indicating that unilateral electrode placement results in fewer or less severe organic side effects than does bilateral electrode placement.
Aspects of student health. Counselling and the student.
Authors: B Thorne
Journal: BMJ (1976)

dependency" and identified a need for short-term terminal nursing.At Barry 890, of the patients died, the average lerigth of stay before death being 10-6 days, while at Oxford 15-2% of the patients died with a mean stay of 15-4 days.We have provided descriptive information on the running of a typical community hospital and shown that such a unit can be run effectively and within the constraints laid down by an operational policy whereby a high turnover is maintained.The major problem, however, is in identifying groups of patients who may be effectively treated in the community hospital.Certain groups may readily be identified as suitable for care, such as short-stay terminal patients and patients admitted for family nursing relief.Other groups, however, such as acute medical admissions and postoperative transfers are more difficult to define.Despite this problem, which may be only partially resolved by evidence derived from randomised controlled trials on the outcome of care, the community hospital adds a valuable dimension to primary care.
Exacerbation of Collagen Antibody-Induced Arthritis in Transgenic Mice Overexpressing Peroxiredoxin 6
Authors: Dae Hwan Kim, Dong Hun Lee, Mi Ran Jo, Dong Ju Son, Mi Hee Park, Chul Ju Hwang, Ju Ho Park, Dong Yeon Yuk, Do Young Yoon, Young‐Suk Jung, Youngsoo Kim, Jae Hwang Jeong, Sang Bae Han, Jin Tae Hong
Journal: Arthritis & Rheumatology (2015)

Objective Peroxiredoxin 6 plays important and complex roles in the process of inflammation, but its role in the development of rheumatoid arthritis (RA) remains unclear. We undertook this study to investigate the roles and mechanisms of peroxiredoxin 6 in the development of collagen antibody–induced arthritis (CAIA) and antigen‐induced arthritis (AIA) in peroxiredoxin 6–overexpressing transgenic mice, in peroxiredoxin 6–transfected RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and in synoviocytes from arthritis patients. Methods CAIA and AIA were induced using standard methods. Peroxiredoxin 6–transfected RAW 264.7 cells, macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and synoviocytes from arthritis patients were used to study proinflammatory responses and mechanisms. Clinical scores and histopathologic changes were determined in peroxiredoxin 6–overexpressing transgenic mice and wild‐type (WT) mice with CAIA or AIA. Generation of nitric oxide (NO), expression of inducible NO synthase and cyclooxygenase 2, and activity of NF‐κB and activator protein 1 (AP‐1) were determined in cultured macrophages and synoviocytes as well as in joint tissue from mice by Western blotting, electrophoretic mobility shift assay, and immunohistochemical analysis. Results Development of CAIA and AIA and proinflammatory responses were more exacerbated in peroxiredoxin 6–overexpressing transgenic mice than in WT mice. Overexpression of peroxiredoxin 6 increased lipopolysaccharide‐induced inflammatory responses in RAW 264.7 cells, in macrophages isolated from peroxiredoxin 6–overexpressing transgenic mice, and in synoviocytes from arthritis patients, and this was accompanied by up‐regulation of the JNK pathway. Moreover, a JNK inhibitor completely blocked RA development and proinflammatory responses. Conclusion Our findings suggest that overexpression of peroxiredoxin 6 might promote development of RA through NF‐κB and AP‐1 activity via the JNK pathway.
Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis
Authors: Marcel Leist, Barbara Single, Anna F. Castoldi, Simone Kühnle, Pierluigi Nicotera
Journal: The Journal of Experimental Medicine (1997)

Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP). Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged. Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis. Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation.
Bone marrow necrosis in lymphoma studied by magnetic resonance imaging
Authors: David E. Weissman, William G. Negendank, Ayad M. Al‐Katib, Mitchell R. Smith
Journal: American Journal of Hematology (1992)

Abstract We used magnetic resonance imaging (MRI) to examine the extent of necrosis in the marrow space in three patients with iymphoma who had necrosis in bone marrow biopsies taken from the posterior iliac crest. Two of the patients had multiple focal lesions observed in the spine, pelvis, and femurs. These lesions had MRI characteristics of fluid‐filled necrosis within marrow or Iymphoma. The third patient exhibited a unique pattern of anatomically extensive marginated lesions otherwise typical of avascular necrosis of bone. These cases provide evidence that MRI can document the extent of necrosis within the marrow space and can differentiate two distinct patterns of necrosis. © 1992 Wiley‐Liss, Inc.