tbuckley/cabot-search huggingface dataset:
The role of neutrophils in myocardial ischemia–reperfusion injury
Authors: J Jordan
Journal: Cardiovascular Research (1999)

Reperfusion of ischemic myocardium is necessary to salvage tissue from eventual death. However, reperfusion after even brief periods of ischemia is associated with pathologic changes that represent either an acceleration of processes initiated during ischemia per se, or new pathophysiological changes that were initiated after reperfusion. This 'reperfusion injury' shares many characteristics with inflammatory responses in the myocardium. Neutrophils feature prominently in this inflammatory component of postischemic injury. Ischemia-reperfusion prompts a release of oxygen free radicals, cytokines and other proinflammatory mediators that activate both the neutrophils and the coronary vascular endothelium. Activation of these cell types promotes the expression of adhesion molecules on both the neutrophils and endothelium, which recruits neutrophils to the surface of the endothelium and initiate a specific cascade of cell-cell interactions, leading first to adherence of neutrophils to the vascular endothelium, followed later by transendothelial migration and direct interaction with myocytes. This specific series of events is a prerequisite to the phenotypic expression of reperfusion injury, including endothelial dysfunction, microvascular collapse and blood flow defects, myocardial infarction and apoptosis. Pharmacologic therapy can target the various components in this critical series of events. Effective targets for these pharmacologic agents include: (a) inhibiting the release or accumulation of proinflammatory mediators, (b) altering neutrophil or endothelial cell activation and (c) attenuating adhesion molecule expression on endothelium, neutrophils and myocytes. Monoclonal antibodies to adhesion molecules (P-selectin, L-selectin, CD11, CD18), complement fragments and receptors attenuate neutrophil-mediated injury (vascular injury, infarction), but clinical application may encounter limitations due to antigen-antibody reactions with the peptides. Humanized antibodies and non-peptide agents, such as oligosaccharide analogs to sialyl Lewis, may prove effective in this regard. Both nitric oxide and adenosine exhibit broad spectrum effects against neutrophil-mediated events and, therefore, can intervene at several critical points in the ischemic-reperfusion response, and may offer greater benefit than agents that interdict at a single point in the cascade. The understanding of the molecular processes regulating actions of neutrophils in ischemic-reperfusion injury may be applicable to other clinical situations, such as trauma, shock and organ or tissue (i.e. vascular conduits) transplantation.
Molecular pathways to Parkinson’s disease
Authors: Ming Guo
Journal: Molecular Neurodegeneration (2012)

Results Genetic studies suggest that PINK1 and parkin function in a common genetic pathway with PINK1 positively regulating parkin. The PINK1/parkin pathway regulates mitochondrial dynamics by positively regulating drp1 and negatively regulating mitofusin. Mammalian cell-based studies suggest that the PINK1/parkin may regulate mitochondrial quality control via mitophagy. How autophagy intersects with mitochondrial dynamics in vivo will be discussed.
Regulation of adenylyl cyclase in LTP
Authors: Erik D. Roberson, J. David Sweatt
Journal: Behavioral and Brain Sciences (1995)

Abstract Our results on hippocampal long-term potentiation are considered in the context of Xia et al.'s hypothesis. Whereas the target article proposes presynaptic PKC involvement in adenylyl cyclase activation by phosphorylation of nenromodulin, we suggest an additional postsynaptic role involving RC3/nenrogranin. Finally, we examine the possibility that the adenylyl cyclase mutant mouse may display normal learning with a selective impairment of memory.
Betulinic Acid, a Catalytic Inhibitor of Topoisomerase I, Inhibits Reactive Oxygen Species–Mediated Apoptotic Topoisomerase I–DNA Cleavable Complex Formation in Prostate Cancer Cells but Does Not Affect the Process of Cell Death
Authors: Agneyo Ganguly, Benubrata Das, Amit Roy, Nilkantha Sen, Somdeb Bose Dasgupta, Sibabrata Mukhopadhayay, Hemanta K. Majumder
Journal: Cancer Research (2007)

Abstract The ubiquitious enzyme topoisomerase I can be targeted by drugs which turn these enzymes into cellular poisons and subsequently induce cell death. Drugs like staurosporine, which do not target topoisomerase I directly, can also lead to stabilization of topoisomerase I–DNA cleavable complexes by an indirect process of reactive oxygen species (ROS) generation and subsequent oxidative DNA damage. In this study, we show that betulinic acid, a catalytic inhibitor of topoisomerases, inhibits the formation of apoptotic topoisomerase I–DNA cleavable complexes in prostate cancer cells induced by drugs like camptothecin, staurosporine, and etoposide. Although events like ROS generation, oxidative DNA damage, and DNA fragmentation were observed after betulinic acid treatment, there is no topoisomerase I–DNA cleavable complex formation, which is a key step in ROS-induced apoptotic processes. We have shown that betulinic acid interacts with cellular topoisomerase I and prohibits its interaction with the oxidatively damaged DNA. Using oligonucleotide containing 8-oxoguanosine modification, we have shown that betulinic acid inhibits its cleavage by topoisomerase I in vitro. Whereas silencing of topoisomerase I gene by small interfering RNA reduces cell death in the case of staurosporine and camptothecin, it cannot substantially reduce betulinic acid–induced cell death. Thus, our study provides evidence that betulinic acid inhibits formation of apoptotic topoisomerase I–DNA complexes and prevents the cellular topoisomerase I from directly participating in the apoptotic process. [Cancer Res 2007;67(24):11848–58]
In vitro autoantibody production by normal adult and cord blood B cells.
Authors: D S Pisetsky, D F Jelinek, L M McAnally, C F Reich, P E Lipsky
Journal: Journal of Clinical Investigation (1990)

To investigate the repertoire of autoantibodies in humans, anti-DNA and rheumatoid factor (RF) production in vitro was assessed in cultures of adult peripheral blood B cells and neonatal umbilical venous blood B cells. B cells were stimulated under various culture conditions, using an immobilized monoclonal anti-CD3 antibody and adult T cells or Staphylococcus aureus (SA) in the presence or absence of adult T cells or factors derived from mitogen-stimulated adult T cells as polyclonal B cell activators. Total IgM, as well as IgM anti-DNA and RF, were assessed by ELISA. Total IgM production was induced from adult and neonatal B cells with SA plus T cell factors, as well as anti-CD3-stimulated T cells. RF was induced from adult and cord blood B cells by either mode of stimulation, whereas significant anti-DNA production was observed only when B cells were stimulated with anti-CD3-activated T cells. These results confirm the presence of B cell precursors for autoantibodies in the preimmune as well as normal adult repertoire, and indicate that the production of anti-DNA and RF appears to be regulated independently.
“Failure to Communicate” due to Forgetting “Marriage Vow”?
Authors: John S. Torday
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

I have followed the debate between Drs. Lenfant and Macklem, two highly respected leaders in the field of lung biology, which came to a head recently in this journal (1, 2). As a member of the lung research community for more than 30 years, I share their concerns. I am afraid though that they still have not focused on the key element in the “failure to communicate” (3): biology has been sacrificed on the altar of reductionist molecular biology (an oxymoron). The genes that have been identified by the Human Genome Project (HGP) are merely the end result of evolution that forms the basis for the mechanisms of physiology. These genes must be seen within their biologic context to discern cause and effect (4). The processes of development, homeostasis, and repair, which are studied in contemporary biology, are “snapshots” of the ongoing evolutionary process, particularly after the Cambrian Burst, given that only 1% of today’s species survived that event. Like the physicists, we too need to consider initial conditions to know where we are going as a species. Without working models of lung biology that vertically integrate genes in pathways that integrate cell–cell communication leading to development, homeostasis, and repair (5), we may never effectively extricate ourselves from the morass of information exploding in a processless void. Metaphorically, it is like grinding up a painting, analyzing its chemical composition, and expecting to understand what the artist intended to communicate. I thought we had learned this lesson from the endocrinologists, who finally realized that ligand– receptor relationships must be seen within their biologic context. After all, that is how steroid receptors were first discovered (6), by observing the fate of the estrogen receptor within the context of the estrus cycle of the rat uterus. I believe that we are currently at the same stage of scientific interrogation that we were 40 years ago when biochemistry was the tool being used to leverage pathophysiology. In the postHGP era, we need to apply molecular biology to biology, not the other way around. The lack of attention to biological principles has caused the “failure to communicate” between the basic scientists and the translators. Using Dr. Macklem’s divorce metaphor (7), marriages sometimes fail because the partners grow apart; perhaps we can counsel this marriage by putting biology back into the relationship between science and medicine.
A NEW GRAPHIC URINE CHARTFOR THE URINE FINDINGS IN DIABETES MELLITUS.
Authors: FRANK SMITHIES
Journal: JAMA (1907)

<h3>[From the Medical Clinic of the University Hospital.]</h3> The chart here reproduced was designed (1) to facilitate the keeping of a concise record of the urine findings in diabetes mellitus; (2) to show the effects of treatment, by diet and medication, on the amount and character of the urine; (3) to show by curves the relation of the various urine findings to each other, and (4) to enable students to better appreciate the progress of the disease in respect to the urine and to perceive the modifying factors more readily. The chart has been made as simple as possible for the number of facts it embraces. A glance will show the general arrangement. It is printed on millimeter ruled paper. The sheets are of convenient size for filing in patients' histories. Appropriate headings permit the sheets to follow the course of the disease in a given patient over an extended
Health and environmental consequences of the world trade center disaster.
Authors: Philip J Landrigan, Paul J Lioy, George Thurston, Gertrud Berkowitz, L C Chen, Steven N Chillrud, Stephen H Gavett, Panos G Georgopoulos, Alison S Geyh, Stephen Levin, Frederica Perera, Stephen M Rappaport, Christopher Small
Journal: Environmental Health Perspectives (2004)

The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperreactivity. Evaluation of 10,116 firefighters showed exposure-related increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on 11 September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster.
A comparison of estimated maximal oxygen uptake in 9 and 10 year old schoolchildren in Tanzania and Norway
Authors: A Aandstad, S Berntsen, R Hageberg, L Klasson-Heggebø, S A Anderssen
Journal: British Journal of Sports Medicine (2006)

Objective: To compare estimated maximal oxygen uptake (V˙O 2max ) in Tanzanian and Norwegian children, by using the same bicycle protocol in both samples. Methods: Maximal oxygen uptake was estimated from an indirect maximal watt cycle ergometer test in 156 rural boys and girls in Tanzania. Similarly aged urban Norwegian boys and girls (n = 379) who underwent the same test were used for comparison. The Tanzanian children also participated in a 20 metre shuttle run test and a test of bicycle skill. The Tanzanian children were tested at altitude (∼1800 metres), while the Norwegian children were tested at sea level. Results: In the cycle ergometer test, estimated relative V˙O 2max was similar in Tanzanian and Norwegian boys, while Tanzanian girls had 8% lower estimated V˙O 2max compared with Norwegian girls (p&lt;0.001). Only one third of the Tanzanian children were able to ride a conventional bicycle. Excluding subjects not able to ride a bicycle, there was no difference in estimated V˙O 2max between Norwegian and Tanzanian children. The Tanzanian boys and girls reached significantly higher estimated V˙O 2max in the shuttle run test compared with the cycle ergometer test (p&lt;0.001). Conclusions: Tanzanian and Norwegian children attained similar relative V˙O 2max in the cycle ergometer test. However, the comparison was hampered by differences in altitude and the poor cycle ergometer skills in the Tanzanian children, both of which probably underestimated their V˙O 2max .
Radiation-Induced Myositis Mimicking Chest Wall Tumor Invasion in Two Patients With Lung Cancer
Authors: Hiroko Tomita, Tamotsu Kita, Katsumi Hayashi, Shigeru Kosuda
Journal: Clinical Nuclear Medicine (2012)

Two patients with lung cancer who had undergone stereotactic body radiation therapy (SBRT) exhibited increased F-18 FDG uptake in the chest wall after 6 months and 18 months, respectively, after SBRT. The prescribed dose of 50 Gy to the planning target volume was delivered on 4 consecutive days in each patient. It is important for nuclear medicine physicians to be familiar with F-18 FDG PET/CT findings ascribed to radiation-induced myositis in lung cancer patients treated with SBRT so that an appropriate differential diagnosis can be established.
Comparative Effectiveness of Alternative Prostate-Specific Antigen–Based Prostate Cancer Screening Strategies
Authors: Roman Gulati, John L. Gore, Ruth Etzioni
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits. Objective: To evaluate comparative effectiveness of alternative PSA screening strategies. Design: Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies. Data Sources: National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality. Target Population: A contemporary cohort of U.S. men. Time Horizon: Lifetime. Perspective: Societal. Intervention: 35 screening strategies that vary by start and stop ages, screening intervals, and thresholds for biopsy referral. Outcome Measures: PSA tests, false-positive test results, cancer detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved. Results of Base-Case Analysis: Without screening, the risk for prostate cancer death is 2.86%. A reference strategy that screens men aged 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%. A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%. Results of Sensitivity Analysis: Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions. Limitation: The model is a simplification of the natural history of prostate cancer, and improvement in survival due to screening is uncertain. Conclusion: Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives. Primary Funding Source: National Cancer Institute and Centers for Disease Control and Prevention.
Genomic alterations reveal potential for higher grade transformation in follicular lymphoma and confirm parallel evolution of tumor cell clones
Authors: Marianne Brodtkorb Eide, Knut Liestøl, Ole Christian Lingjærde, Marit E. Hystad, Stine H. Kresse, Leonardo Meza-Zepeda, Ola Myklebost, Gunhild Trøen, Hege Vangstein Aamot, Harald Holte, Erlend Bremertun Smeland, Jan Delabie
Journal: Blood (2010)
Experience with a Catheter-Based Ultrasound Probe in the Bile Duct and Pancreas
Authors: F. Gress, Y. K. Chen, S. Sherman, T. Savides, S. Zaidi, P. Jaffe, G. Lehman, M. J. Wonn, R. Hawes
Journal: Endoscopy (1995)

Complete examination of the biliary tree and pancreatic duct may be difficult or unsuccessful using conventional imaging instruments. The purpose of this study was to evaluate the cannulation success rate, clinical utility, and safety of a new catheter-based ultrasound probe (CBUSP) used in the biliary tree and pancreas.The probes used in this study are manufactured by Microvasive (Watertown, MA, U.S.A.) and were 6.2 Fr in diameter, operated at 12.5 MHz. Thirty-six patients (11 with malignant bile-duct strictures, 12 with benign bile-duct strictures, two with bile duct stones, three with pancreatic duct strictures, one with a pancreatic cyst, one with pancreas divisum, three with sphincter of Oddi dysfunction, and three normal) underwent examination with a CBUSP.Cannulation was successful in all 36 patients. The hepatic artery and portal vein could be visualized with the probe in the proximal bile duct in 81% and 94% of the cases, respectively. The portal vein could not be adequately visualized in any patients when the probe was in the distal bile duct. The mean thickness of the normal bile duct wall was 0.17 cm, and the mean wall thicknesses proximal to a benign and malignant stricture were 0.16 and 0.17 cm, respectively. The mean thicknesses of benign and malignant biliary strictures were 0.32 cm and 0.31 cm, respectively (not significant). Eight of 12 benign biliary strictures (67%) and five of 11 malignant strictures (45%) were symmetrical. However, no obvious differences could be identified between benign and malignant biliary strictures. There were no catheter related complications.Further catheter modifications are needed, but it appears to be feasible to assess vascular invasion in cholangiocarcinoma and to characterize biliary strictures in a way that may be able to influence therapy options in some patients. The currently available CBUSP cannot distinguish between benign and malignant strictures. However, with technical modifications, this may be possible in the future. The clinical usefulness of CBUSP in the pancreas awaits further investigation, but pancreatic imaging is feasible.
The American College of Physicians Award Lecture: Heterogenicity of Peptide Hormones Revealed by Radioimmunoassays.
Authors: Solomon A. Berson
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971The American College of Physicians Award Lecture: Heterogenicity of Peptide Hormones Revealed by Radioimmunoassays.Solomon A. Berson, M.D.Solomon A. Berson, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-843_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWithin the past decade radioimmunoassays have been developed for most of the peptide hormones. Recent studies have explored the state of these hormones in plasma and endocrine glands. Unlike the thyroidal and steroidal hormones that circulate largely or partly as protein-bound complexes, the peptide hormones appear to be free in the plasma, notwithstanding earlier suggestions that they too may be bound to plasma proteins. Evidence has accumulated, however, that peptide hormones may be present in at least two forms in plasma. Heterogenicity of plasma parathyroid hormone was detected by differences in reaction with different antisera. Proinsulin in plasma was shown... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 843-843KeywordsBlood plasmaEndocrine physiologyHormonesParathyroid hormonePeptide hormonesPlasma proteinsRadioimmunoassaysSteroid hormonesThyroid hormones Issue Published: 1 May 1971 PDF downloadLoading ...