tbuckley/cabot-search huggingface dataset:
ME-03 * BONE MARROW DERIVED MICROGLIA AND THEIR FUNCTION WITHIN TUMOR MICROENVIRONMENT
Authors: K. Burrell, S. Singh, S. Agnihotri, R. Hill, K. Aldape, G. Zadeh
Journal: Neuro-Oncology (2014)

We have previously demonstrated that BMDC are recruited to Glioblastoma Multiforme (GBM), in a highly tumor-growth and region-dependent pattern, demonstrating that the majority of BMDCs differentiate into inflammatory cells, MAC3 + , and CD11b+ IBA1+ microglia-like cells. The majority of microglia seen in GBM microenvironment are derived from the BMDC rather than being resident brain microglia. The role of microglial cells in GBMs remains unknown, with evidence supporting both an anti- and pro- tumorgenic function. In this study we aimed to understand the contribution of microglia to GBM growth and tumor vascularity. Chimeric mice with reconstituted green-fluorescent bone marrow were used to create intracranial GBM xenografts, by implanting red fluorescent glioma stem cells or U87 into the frontal lobe. Using a known inhibitor of microglial activation, minocycline, we show that treatment with this agent increased tumor cell growth and invasiveness and reduced animal survival compared to controls. We show that Minocycline decreases activation of microglia, inhibits the phagocytic activity of microglia in GBMs and decreases the perivascular localization of microglia. The mRNA expression profile of microglia isolated from the GBM microenvironment showed, through Ingenuity Pathway Analysis (IPA), a loss of engulfment and migration of cells and phaocytotic pathways in BM-derived microglia, additionally we see a reorganization of cytoskeletal pathways leading to an increase in the migration and invasiveness of GBM cells following treatment with Minocycline. We also have preliminary data to suggest that this property of Minocycline is dependent on VEGF levels, where in the context of low VEGF Minocycline does not provide a significant anti-angiogenic role. We demonstrate that microglia in GBM microenvironment, are primarily recruited and differentiated from the BM and not resident, and that these cells have an anti-tumorgenic functions, and inhibition of the activated microglia by Minocycline, results in a more invasive phenotype of GBM cells.
Pitfalls in Antiprotease Therapy of Emphysema
Authors: Gordon L. Snider, Edgar C. Lucey, Phillip J. Stone
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Many individuals with emphysema are unable to stop smoking despite the best efforts of specialists in smoking cessation. Because emphysema is a slowly progressive disease, it is rational to attempt to develop drugs for it. The hope is that drug therapy will slow the rate of decline of lung function, thereby delaying the onset of disability and prolonging life. The major emphasis in drug development has been on antiproteases having the ability to inhibit neutrophil elastase. There are a number of potential pitfalls in the development of such drugs. Although there is gathering evidence that elastin degradation is a part of the development of human emphysema, it is evident from studies in experimental emphysema that protease-antiprotease imbalance is not the only pathogenetic mechanism that gives rise to emphysema. There is strong evidence that human centrilobular and panacinar emphysema are different in pathogenesis. Indeed, airspace enlargement may be considered one of the stereotyped ways that the lung heals after a variety of injuries. There is accumulating evidence that macrophages as well as neutrophils may participate in elastolysis; antiproteases designed to inhibit neutrophil elastase may not inhibit the metalloproteases produced by macrophages. Some antiproteases may serve to transport elastase into the interstitium of the lung and actually increase the risk of emphysema. A process study of antiprotease therapy, using a measure of alteration of elastase burden of the lungs and urinary elastin peptides and desmosine measurements as markers of elastin degradation is now feasible. An outcome study of antiprotease therapy of emphysema should not be undertaken unless there is evidence from a process study that an antiprotease has biochemical efficacy and no unacceptable side effects.
Pulmonary inflammatory myofibroblastic tumour with unusual octreoscan uptake: two reports
Authors: F. Calabrese, A. Zuin, E. Brambilla, P. Zucchetta, F. Lunardi, M. Valente, F. Rea
Journal: European Respiratory Journal (2010)

To the Editors: 

Inflammatory myofibroblastic tumour (IMT) is a relatively uncommon lesion and occurs in nearly every site of the body. Patients with IMT are usually asymptomatic, with a solitary nodule or mass detected by routine chest radiograph 1. Many diagnostic procedures can be applied to make the diagnosis: computed tomography (CT) scan to outline nodule growth and perfusion, [18F]-2-fluoro-deoxy-D-glucose (FDG)-PET/CT scan to evaluate metabolic activity and 111In-Diethylene triamine pentaacetic acid (DTPA)-D-Phe1 scan (octreoscan) to investigate somatostatin analogue receptors, often present in a variety of neuroendocrine tumours (NETs).

We present two cases of pulmonary IMT clinically misdiagnosed as carcinoid tumours due to a positive octreoscan.

Case 1 was a 52-yr-old female former smoker who was admitted to our hospital with thoracic pain. The electrocardiogram was completely negative for angina or myocardial infarction. Chest radiograph and CT revealed a left hilar nodule, sharply circumscribed, slightly lobulated, with a mild homogeneous increase of density after enhancement. A whole-body FDG-PET/CT scan showed increased tracer uptake of the lung mass (standardised uptake value (SUV) 25) compatible with a malignant lesion. SUVmax was calculated 50 min after injection and normalised for body weight. After intravenous administration of 111 mBq of [111In]-octreotide, an abnormal, although low, uptake was present in the left lung hilar region (fig. 1a⇓). Bronchoscopy was negative. On the basis of the CT, FDG-PET/CT and octreoscan, a clinical/radiological diagnosis of a carcinoid tumour, most probably atypical, was postulated. The intraoperative frozen specimen excluded the diagnosis of …
The Matter of Mendelian Heredity
Authors: Merietta M. Cassle
Journal: JAMA (1965)

Modern genetics is often a maze of calculations and chemistry, and gaining a clear concept of basic genetic principles requires more than memorizing the three laws of Mendel. In this book, the authors emphasize development of a critical attitude toward genetic observations and data. Through analysis of the classic experiments by Mendel, Johannsen, Bateson, and Bumpus, the laws of genetics take form.  Written primarily as a university-level textbook, the book discusses the fundamental laws of heredity, cytogenetic events, gene action, and evolution. The chemical basis of heredity receives brief but adequate attention. The presentation of elementary statistics is particularly clear and concise. From the probabilities in the toss of a coin to the coefficient of variation, text and examples combine to make eloquent sense.  Easily read data tables and graphs supplement the text. While the diagrams of bivalent orientation in meiotic division are adequate, they are not easily understood. Accompanying
Hypovolemia in Shock Due to Acute Myocardial Infarction
Authors: HENRY S. LOEB, RAYMOND J. PIETRAS, JOHN R. TOBIN, ROLF M. GUNNAR
Journal: Circulation (1969)

Twelve patients with the clinical features of shock following acute myocardial infarction were treated with low molecular weight dextran (LMWD) as a plasma volume expander. Two of the patients had elevated central venous pressures (CVP), and neither responded favorably to plasma volume expansion. The remaining 10 patients had CVPs under 7 mm Hg prior to dextran infusion; five survived. Each survivor responded favorably to dextran infusion manifested by an increase in arterial pressure and cardiac index. The average increase in CVP in these patients was 1.0 mm Hg per 100 ml of dextran infused. The other five patients died either without recovering from shock or in chronic cardiac failure. These patients failed to show a significant increase in arterial pressure or cardiac index after dextran infusion; CVP increased by an average of 1.9 mm Hg per 100 ml infused. Hypovolemia must be considered in all patients in whom clinical evidence of shock develops as a complication of acute myocardial infarction, and if the CVP is normal or low, plasma volume expansion should be undertaken with caution. Increase in arterial pressure and evidence of improved cardiac index with little rise in CVP indicate a good response to the infusion and excellent prognosis for survival.
Retinoic acid receptor-related orphan receptor α-induced activation of adenosine monophosphate-activated protein kinase results in attenuation of hepatic steatosis
Authors: Eun-Jin Kim, Young-Sil Yoon, Suckchang Hong, Ho-Young Son, Tae-Young Na, Min-Ho Lee, Hyun-Jin Kang, Jinyoung Park, Won-Jea Cho, Sang-Gun Kim, Seung-Hoi Koo, Hyeung-geun Park, Mi-Ock Lee
Journal: Hepatology (2011)

There is increasing evidence that the retinoic acid receptor-related orphan receptor α (RORα) plays an important role in the regulation of metabolic pathways, particularly of fatty acid and cholesterol metabolism; however, the role of RORα in the regulation of hepatic lipogenesis has not been studied. Here, we report that RORα attenuates hepatic steatosis, probably via activation of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) and repression of the liver X receptor α (LXRα). First, RORα and its activator, cholesterol sulfate (CS), induced phosphorylation of AMPK, which was accompanied by the activation of serine-threonine kinase liver kinase B1 (LKB1). Second, the activation of RORα, either by transient transfection or CS treatment, decreased the TO901317-induced transcriptional expression of LXRα and its downstream target genes, such as the sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase. RORα interacted physically with LXRα and inhibited the LXRα response element in the promoter of LXRα, indicating that RORα interrupts the autoregulatory activation loop of LXRα. Third, infection with adenovirus encoding RORα suppressed the lipid accumulation that had been induced by a free-fatty-acid mixture in cultured cells. Furthermore, we observed that the level of expression of the RORα protein was decreased in the liver of mice that were fed a high-fat diet. Restoration of RORα via tail-vein injection of adenovirus (Ad)-RORα decreased the high-fat-diet-induced hepatic steatosis. Finally, we synthesized thiourea derivatives that activated RORα, thereby inducing activation of AMPK and repression of LXRα. These compounds decreased hepatic triglyceride levels and lipid droplets in the high-fat-diet-fed mice.We found that RORα induced activation of AMPK and inhibition of the lipogenic function of LXRα, which may be key phenomena that provide the beneficial effects of RORα against hepatic steatosis.
Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study
Authors: Donna E. Reece, Vaishali Sanchorawala, Ute Hegenbart, Giampaolo Merlini, Giovanni Palladini, Jean-Paul Fermand, Robert A. Vescio, Xiangyang Liu, Yusri A. Elsayed, Andrew Cakana, Raymond L. Comenzo
Journal: Blood (2009)
Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans
Authors: J. J. Carter, M. M. Madeleine, G. C. Wipf, R. L. Garcea, P. A. Pipkin, P. D. Minor, D. A. Galloway
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Propagation of poliovirus in monkey kidney cells led to the inadvertent contamination of poliovirus vaccines with simian virus 40 (SV40) between 1955 and 1963. Recent studies using polymerase chain reaction–based strategies have detected SV40 DNA in a large number of tumor types. The finding of SV40 DNA in tumors from individuals who are too young to have been exposed to SV40-contaminated vaccines has led to the suggestion that SV40 has become a prevalent transmissible human pathogen. To test this hypothesis, we screened human sera for antibodies to SV40 using direct and competitive enzyme-linked immunosorbent assays (ELISAs). Methods: An ELISA was developed using recombinant SV40 virus-like particles (VLPs) and was validated using sera from naturally infected macaques. VLPs of SV40 and the related ubiquitous human polyomaviruses, JCV and BKV, were used to screen human sera to determine the prevalence of SV40, JCV, and BKV antibodies among a normal population of control subjects (n = 487) and among case patients with either osteosarcoma (n = 122) or prostate cancer (n = 90). A competitive ELISA in which sera were pre-adsorbed with each type of VLP was used to identify cross-reactive antibodies. Correlations of reactivity among the three polyomavirus types were calculated using the Spearman correlation coefficient. All statistical tests were two-sided. Results: BKV and JCV antibodies were prevalent in all case patients and control subjects examined. In contrast, only 6.6% (46/699) of serum samples were positive for SV40 antibodies by ELISA; however, none of these samples could be confirmed as having authentic SV40 antibodies following pre-adsorption with JCV or BKV VLPs. Conclusion: These data indicate that some individuals have BKV and/or JCV antibodies that cross-react with SV40, but they do not provide support for SV40 being a prevalent human pathogen.
Endoproteolysis of Presenilin 1 and Accumulation of Processed Derivatives In Vivo
Authors: Gopal Thinakaran, David R Borchelt, Michael K Lee, Hilda H Slunt, Lia Spitzer, Grace Kim, Tamara Ratovitsky, Frances Davenport, Christer Nordstedt, Mary Seeger, John Hardy, Allan I Levey, Samuel E Gandy, Nancy A Jenkins, Neal G Copeland, Donald L Price, Sangram S Sisodia
Journal: Neuron (1996)
Abstract 1259: Gut microbiota and mucosal inflammation and colorectal neoplasia
Authors: Temitope O. Keku, Romin Bonakdar, Felix Araujo Perez, Amber N. McCoy, Patrick Edmundson, Kevin Smith
Journal: Cancer Research (2014)

Abstract Colorectal cancer (CRC) is a leading cause of cancer death in the United States. Chronic inflammation has been linked to colorectal neoplasia. More recent studies also implicate imbalances in the gut microbiota (bacteria) CRC. We sought to understand the relationship between the gut microbiota, mucosal inflammation and colorectal adenomas, CRC precursors. We hypothesized that the gut microbiota promotes inflammation via activation of mucosal immune cells to elevate adenoma risk. We examined the relationship between adherent gut bacteria, mucosal immune cells, namely T cells (CD4+ and CD8+), macrophages (CD11b+) and natural killer cells (CD57+) and adenomas in a case control study. Methods: Participants were consenting screening colonoscopy patients at UNC Hospitals without history or diagnosis of inflammatory bowel disease. Subjects were defined as cases (n=42) or controls (n=35) based on the presence or absence of adenomas. High throughput deep sequencing method was used to assess the microbiota in normal colonic mucosa of cases and controls. Immune cells were assessed by immunohistochemistry and automated image analysis using Aperio software. Differences in microbiota abundance or mucosal immune cell numbers between cases and controls were evaluated by t-tests. Diversity was measured by Shannon diversity. Correlation between bacteria and immune cells was performed using Spearman's correlation. Results: Cases had higher WHR than controls (p=0.0001). No difference was observed for age, sex, BMI among cases and controls. The abundance of several bacteria taxa differed significantly between cases and controls. We observed a positive relationship between mucosal immune cell density and adenomas. In particular, CD 4+ density and CD4/CD8 ratio were higher in cases than controls (CD4; 1.44 case, 0.69 control p = 0.001; CD4/CD8 1.66 case, 0.56 control, p= 0.002). There were no statistically significant differences in CD 57+, CD11b or CD 8+ cell density between cases and controls. The correlation patterns between the gut microbiota and immune cells differed markedly for cases and controls. There was a positive correlation between Proteobacteria and CD4 or CD4/CD8+ cells among cases but not controls. Conclusions: our results suggest that the gut bacteria and immune cells are interacting differently depending on adenoma status. These findings suggest activation of mucosal immune cells by bacteria may promote local inflammation and contribute to the etiology of colorectal cancer. Citation Format: Temitope O. Keku, Romin Bonakdar, Felix Araujo Perez, Amber N. McCoy, Patrick Edmundson, Kevin Smith. Gut microbiota and mucosal inflammation and colorectal neoplasia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1259. doi:10.1158/1538-7445.AM2014-1259
Radiation Sensitivity, H2AX Phosphorylation, and Kinetics of Repair of DNA Strand Breaks in Irradiated Cervical Cancer Cell Lines
Authors: Judit P. Banáth, Susan H. MacPhail, Peggy L. Olive
Journal: Cancer Research (2004)

Six human cervical cancer cell lines [five human papillomavirus (HPV) positive, one HPV negative] for induction and rejoining of DNA strand breaks and for kinetics of formation and loss of serine 139 phosphorylated histone H2AX (gammaH2AX). X-rays induced the same level of DNA breakage for all cell lines. By 8 hours after 20 Gy, <2% of the initial single-strand breaks remained and no double-strand breaks could be detected. In contrast, 24 hours after irradiation, gammaH2AX representing up to 30% of the initial signal still present. SW756 cells showed almost four times higher background levels of gammaH2AX and no residual gammaH2AX compared with the most radiosensitive HPV-negative C33A cells that showed the lowest background and retained 30% of the maximum level of gammaH2AX. Radiation sensitivity, measured as clonogenic-surviving fraction after 2 Gy, was correlated with the fraction of gammaH2AX remaining 24 hours after irradiation. A substantial correlation with gammaH2AX loss half-time measured over the first 4 hours was seen only when cervical cell lines were included in a larger series of p53-deficient cell lines. Interestingly, p53 wild-type cell lines consistently showed faster gammaH2AX loss half-times than p53-deficient cell lines. We conclude that cell line-dependent differences in loss of gammaH2AX after irradiation are related in part to intrinsic radiosensitivity. The possibility that the presence of gammaH2AX foci may not always signify the presence of a physical break, notably in some tumor cell lines, is also supported by these results.
Military Medicine's Role Continues in Bosnia
Authors: Phil Gunby
Journal: JAMA (1996)

IT APPEARS that US military medicine will be at work in Bosnia-Herzegovina beyond the 1-year stay, originally expected to end December 20,1996, that had been announced for American troops participating in the North Atlantic Treaty Organization (NATO) peace-enforcement effort. Some 5000 US soldiers moved into the former Yugoslavia last month from bases in Germany. This, the Pentagon says, is the covering force for withdrawal of 15 800 US military people, many of whom were in place December 20,1995, when the 52000-troop NATO force assumed the peace-enforcement duties from the United Nations (<i>JAMA</i>. 1996;275:24). The new arrivals are expected to stay until mid-March 1997, although some diplomats contend that NATO forces will have to remain in the region for at least 2 more years if the civil war is not to resume. Military physicians are watching the newcomers closely until they acclimatize, because the tick season does not end until later
Amiodarone or an Implantable Cardioverter–Defibrillator for Congestive Heart Failure
Authors: Gust H. Bardy, Kerry L. Lee, Daniel B. Mark, Jeanne E. Poole, Douglas L. Packer, Robin Boineau, Michael Domanski, Charles Troutman, Jill Anderson, George Johnson, Steven E. McNulty, Nancy Clapp-Channing, Linda D. Davidson-Ray, Elizabeth S. Fraulo, Daniel P. Fishbein, Richard M. Luceri, John H. Ip
Journal: New England Journal of Medicine (2005)

Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients.We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause.The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class.In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.
One in 100 US deaths is related to sexual behaviour
Authors: Jeanne Lenzer
Journal: BMJ (2005)

More than one in every 100 deaths in the United States can be attributed to sexual behaviour, according to a new study ( Sexually Transmitted Infections 2005;81:38-40). Rates of illness and premature death attributable to sexual behaviour in the United States are triple the rates in other wealthy nations, the authors say.

Using updated data from the 1996 US burden of disease study, the researchers reported that 29 782 deaths in 1998 could be attributed to sexual behaviour, constituting 1.3% of all deaths in the United States that year. They calculated a total of more than one million disability adjusted life years (DALYs) in 1998 and more than 20 …
Relationships between free cadmium ion activity in seawater, cadmium accumulation and subcellular distribution, and growth in polychaetes.
Authors: K D Jenkins, B M Sanders
Journal: Environmental Health Perspectives (1986)

We have examined the relationships between Cd ion activity [Cd2+], in seawater, Cd accumulation and subcellular distribution and growth in the polychaete Neanthes arenaceodentata. Organisms were exposed for 3 weeks to a range of [Cd2+] in a Cd-chelate buffer system. Cadmium accumulation and growth were monitored weekly for each exposure group and subcellular Cd distributions were determined at the end of the 3-week period. We found Cd associated with all of the subcellular fractions except the very low molecular weight ligands. Total Cd accumulation was greatest at day 7 and decreased over time in all but the highest [Cd2+] where it remained constant. For each point in time, however, there was a linear relationship between total Cd and [Cd2+] in seawater. Linear relationships were also observed between [Cd2+] and Cd loading in each subcellular ligand pool. Specific growth rates varied with both [Cd2+] and time in a nonlinear manner.