tbuckley/cabot-search huggingface dataset:
The Phenomenon of Famine
Authors: Nevin S. Scrimshaw
Journal: Annual Review of Nutrition (1987)

Famines are sustained, extreme shortages of food among discrete populations sufficient to cause high rates of mortality. Signs and symptoms of prolonged food deprivation include loss of fat and subcutaneous tissue, depression, apathy, and weakness, which progress to immobility and death of the individual, often from superimposed respiratory or other infections. The social consequences of famines are disruption from mass migrations of people in search of food, breakdown of social behavior, abandonment of cooperative effort, loss of personal pride and sense of family ties, and finally a struggle for individual survival. Famines have been common ever since the development of agriculture made human settlements possible. Food shortages due to crop failures caused by natural disasters including poor weather, insect plagues, and plant diseases; crop destruction due to warfare; and enforced starvation as a political tool are by no means the only causative factors. Many of the worst famines have been due to poor distribution of existing food supplies, either because of inequities that result in a lack of purchasing power on the part of the poor or because of political interference with normal distribution or relief movements of food. Europe and Asia, which in the past experienced frequent severe famines, sometimes with deaths in the hundreds of thousands or millions, have now largely eliminated famines through social and technological change. However, in Africa, political and social factors have destroyed the capacity of many populations to survive drought-induced variations in local food supplies and prices. Thus, famines are due to varying combinations of inadequacy of food supplies for whatever reason and the inability of populations to acquire food because of poverty, civil disturbances, or political interference. Despite the role of natural causes, the conclusion is inescapable that modern famines, like most of those in history, are man-made.Famines are sustained, extreme shortages of food among discrete populations sufficient to cause high rates of mortality. Crop failures caused by natural disasters including poor weather, insect plagues, and plant diseases; crop destruction due to warfare; and enforced starvation as a political tool are some causative factors of famine. However, modern famines, like most of those throughout history, are manmade. Many of the worst famines have been due to the poor distribution of existing food supplies, either because of inequities which result in a lack of purchasing power among the poor or because of political interference with the normal distribution or relief movements of food. Europe and Asia used to experience frequent severe famines, but have employed social and technological change to largely eliminate them. Political and social factors in Africa, however, have destroyed the capacity of many populations to survive drought-induced variations in local food supplies and prices.
Robert Basil Woodd-Walker
Authors: B. Woodd-Walker
Journal: BMJ (2012)

Nitric oxide-donating aspirin (NO-aspirin), representing a new concept in the development of more efficacious nonsteroidal anti-inflammatory drugs, consists of traditional aspirin bearing -ONO<sub>2</sub>, which releases NO. Conventional aspirin prevents human colon cancer, but its toxicity precludes its application as a chemopreventive agent. NO-aspirin seems safer and in cultured cancer cells it is &gt;1000-fold more potent than aspirin. To determine the mechanism by which NO-aspirin inhibits cell growth, we studied its effect on mitogen-activated protein kinase (MAPK) signaling in HT-29 human colon cancer cells. NO-aspirin stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 and Akt only marginally. The greatest increases in phosphorylation were seen in cJun NH<sub>2</sub>-terminal kinase (JNK) and p38 MAP kinases, which were observed as early as 5 min and after 1 h of treatment, averaged more than 10-fold over control. The activation of JNK and p38 was accompanied by large increases in the phosphorylation of the downstream transcription factors cJun and activating transcription factor 2 (ATF-2). We used specific MAPK inhibitors, small interfering (siRNA) gene silencing methods, and dominant-negative cJun to determine the relevance of these phosphorylation events to the ability of NO-aspirin to inhibit colon cancer cell growth. Only the dual inhibitor of p38 and JNK and the use of combined siRNA silencing of p38 and cJun abrogated the ability of NO-aspirin to block cell growth. Our data indicate that NO-aspirin is dependent on both the p38 and the JNK MAP kinase pathways for its ability to inhibit the growth of colon cancer cells.
In Vitro Sensitivity to Ultraviolet B Light and Skin Cancer Risk: A Case–Control Analysis
Authors: Li-E Wang, Ping Xiong, Sara S. Strom, Leonard H. Goldberg, Jeffrey E. Lee, Merrick I. Ross, Paul F. Mansfield, Jeffrey E. Gershenwald, Victor G. Prieto, Janice N. Cormier, Madeleine Duvic, Gary L. Clayman, Randal S. Weber, Scott M. Lippman, Christopher I. Amos, Margaret R. Spitz, Qingyi Wei
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established. Methods: We assessed in vitro UVB-induced chromatid breaks in a hospital-based case–control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher ( P = .001 and P <.001, respectively), but that in CMM case patients (mean = 0.30 breaks per cell, 95% CI = 0.28 to 0.33) was not ( P = .22). A frequency of chromatid breaks per cell above the median of control subjects was associated with nearly threefold increased risks for BCC (OR = 2.78, 95% CI = 1.79 to 4.30) and SCC (OR = 2.62, 95% CI = 1.50 to 4.60), but not with an increased risk of CMM. A dose–response relationship was evident between mutagen sensitivity and risk for both BCC ( Ptrend <.001) and SCC ( Ptrend <.001). Multiplicative interactions between mutagen sensitivity and sun exposure variables on risk, particularly for sunburn in BCC and hair color, tanning ability, and family history of skin cancer in SCC, were seen for NMSC but not CMM. Conclusions: UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM.
The feasibility of airways hyperresponsiveness as an inclusion criterion for studies on childhood asthma
Authors: A.W.A. Kamps, M.J. Visser, T.W. de Vries, W.M.C. van Aalderen, D.S. Postma, P.L.P. Brand
Journal: European Respiratory Journal (2001)

The feasibility of moderately severe airway hyperresponsiveness (AH) was examined as an inclusion criterion for clinical trials in asthmatic children. During the baseline period of a long-term clinical trial in asthmatic children, maintenance therapy with fluticasone (200 µg·day −1 ) was stopped for a maximum of 8 weeks and methacholine challenges were performed at 2-week intervals or earlier if the patients' condition deteriorated. Patients were eligible to continue the study if the provocative dose of methacholine causing a 20% fall in forced expired volume in one second (FEV 1 ) (PD 20 ) was &lt;80 µg. Fifty-one per cent of the children did not develop a PD 20 &lt;80 µg after withdrawal of fluticasone. Patients with or without a PD 20 &lt;80 µg did not differ in duration of asthma, duration of treatment, or peak flow variation. Patients with a PD 20 &lt;80 µg had higher levels of total and specific immunoglobulin-E, and lower levels of FEV 1 and mean maximal expiratory flow than patients with a PD 20 ≥80 µg. Forty-four per cent of the patients with a PD 20 ≥80 µg did not have any symptoms during the wash-out period and 39% of these patients remained free from symptoms during one year follow-up. The results of this study suggest that recruiting asthmatic children for clinical trials may be difficult if airways hyperresponsiveness is used as the sole inclusion criterion.
Abuse of pentazocine.
Authors: C G Nicol
Journal: BMJ (1978)

intracranial metastases is well documented4-8 47-80 O of unselected patients with intracranial metastases may be expected to obtain symptomatic relief with cranial irradiation5-8 and about 120o are still alive and active one year later.These results are obtained without the stress to the patient of a major operation.We hope these details will encourage the general physician to consider irradiation as a palliative measure for patients with cerebral metastases.
5-(N,N-dimethyl)amiloride-sensitive Na-Li exchange in isolated specimens of human atrium.
Authors: H H Rasmussen, R D Harvey, E J Cragoe, R E ten Eick
Journal: Journal of Clinical Investigation (1988)

To examine if a transmembrane Na-Li exchange similar to that reported to occur in human blood cells can be demonstrated in the heart, we incubated specimens of human atrium in cold (2-3 degrees C) Li-Tyrode's solution. The Li-loaded, Na-depleted specimens were then transferred to warm (30 degrees C) Na-Tyrode's solution. After transfer the membrane potential hyperpolarized to a level more negative than the equilibrium potential for K+. The hyperpolarization was inhibited by acetylstrophanthidin or K+-free solution indicating that it was due to current produced by the Na, K-pump responding to a Na load. This suggested that intracellular Li+ had been exchanged for Na+. The hyperpolarization was abolished by 10 microM 5-(N,N-dimethyl)amiloride while 10 microM bumetanide had no effect, findings that are consistent with the notion that the exchange of intracellular Li+ for extracellular Na+ occurs via an operational mode of the Na-H exchanger rather than being mediated through a mechanism involving the Na/K/2Cl cotransporter.
Combination therapy for hepatitis B
Authors: A M Di Bisceglie
Journal: Gut (2002)

Hepatitis B virus is a major cause of morbidity and mortality worldwide. Effective therapies were first introduced in the mid-1980s but frequent and sometimes severe side effects limit their use. Combination therapy represents the future of treatment for chronic hepatitis B, probably consisting of two or more nucleoside analogues although interferon may form part of some combinations. New drugs acting by different antiviral mechanisms may be particularly potent in combination.
Platelet glycoprotein IIb. Chromosomal localization and tissue expression.
Authors: P F Bray, J P Rosa, G I Johnston, D T Shiu, R G Cook, C Lau, Y W Kan, R P McEver, M A Shuman
Journal: Journal of Clinical Investigation (1987)

The GPIIb-IIIa complex functions as a receptor for cytoadhesive proteins on the platelet surface. Both GPIIb and GPIIIa are synthesized by a human erythroleukemia (HEL) cell line. We isolated several cDNA clones by screening a HEL cell cDNA library with an oligonucleotide derived from amino acid sequence of GPIIb. Nucleotide and amino acid sequences were determined from 703 bp of one of these clones. Amino acid sequence of purified platelet GPIIb peptides confirmed the identity of the clone. The cDNA encodes the carboxyl terminus of the large (alpha) subunit of GPIIb and all of the smaller (beta) subunit of GPIIb. By hybridizing the cDNA directly to chromosomes separated by dual laser chromosome sorting, the gene for GPIIb was mapped to chromosome 17. Northern blot analysis showed a approximately 3.4-kb GPIIb mRNA in HEL cells. We also compared the amino acid sequences determined from eight additional platelet GPIIb peptides with the derived amino acids from a published HEL cell GPIIb cDNA, and the platelet and HEL cell proteins appear to be the same. Despite previous reports that vascular endothelial cells and monocytes contain GPIIb, no GPIIb mRNA was observed in either type of cell. Thus, GPIIb appears to be specific for the platelet-megakaryocyte membrane and is distinct from the alpha subunits of the adhesion receptors in other normal tissues.
Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome
Authors: S Fukudo, T Nomura, M Hongo
Journal: Gut (1998)

Background —Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals. Aims —To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH. Subjects —Ten IBS patients diagnosed by Rome criteria and 10 healthy controls. Methods —CRH (2 μg/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. Results —CRH induced motility of the descending colon in both groups (p&lt;0.001) and induced greater motility indexes in IBS patients than in controls (p&lt;0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p&lt;0.05). CRH induced significant increases in plasma ACTH levels in both groups (p&lt;0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p&lt;0.001). Conclusion —Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH.
Low-dose anti-IgE therapy in patients with atopic eczema with high serum IgE levels
Authors: Benedetta Belloni, Mahzad Ziai, Annick Lim, Brigitte Lemercier, Martin Sbornik, Stephan Weidinger, Christian Andres, Christina Schnopp, Johannes Ring, Rüdiger Hein, Markus Ollert, Martin Mempel
Journal: Journal of Allergy and Clinical Immunology (2007)
Home environmental intervention benefits urban children with atopic asthma
Authors: K S Srinivasan
Journal: Thorax (2004)

▴ Morgan WJ, Crain EF, Gruchalla RS, et al . Results of a home-based environmental intervention among urban children with asthma. N Engl J Med2004;351:1068–80 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes. It is difficult to reduce these triggers and previous studies have not shown any significant decrease in morbidity. In this randomised controlled trial of an environmental intervention over 1 year, 937 children (age 5–11 … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DMorgan%26rft.auinit1%253DW.%2BJ.%26rft.volume%253D351%26rft.issue%253D11%26rft.spage%253D1068%26rft.epage%253D1080%26rft.atitle%253DResults%2Bof%2Ba%2BHome-Based%2BEnvironmental%2BIntervention%2Bamong%2BUrban%2BChildren%2Bwith%2BAsthma%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa032097%26rft_id%253Dinfo%253Apmid%252F15356304%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa032097&link_type=DOI [3]: /lookup/external-ref?access_num=15356304&link_type=MED&atom=%2Fthoraxjnl%2F59%2F12%2F1040.atom [4]: /lookup/external-ref?access_num=000223733900006&link_type=ISI
PRMT5 Is Required for Lymphomagenesis Triggered by Multiple Oncogenic Drivers
Authors: Yan Li, Nilesh Chitnis, Hiroshi Nakagawa, Yoshiaki Kita, Shoji Natsugoe, Yi Yang, Zihai Li, Mariusz Wasik, Andres J.P. Klein-Szanto, Anil K. Rustgi, J. Alan Diehl
Journal: Cancer Discovery (2015)

Protein arginine methyltransferase 5 (PRMT5) has been implicated as a key modulator of lymphomagenesis. Whether PRMT5 has overt oncogenic function in the context of leukemia/lymphoma and whether it represents a therapeutic target remains to be established. We demonstrate that inactivation of PRMT5 inhibits colony-forming activity by multiple oncogenic drivers, including cyclin D1, c-MYC, NOTCH1, and MLL-AF9. Furthermore, we demonstrate that PRMT5 overexpression specifically cooperates with cyclin D1 to drive lymphomagenesis in a mouse model, revealing inherent neoplastic activity. Molecular analysis of lymphomas revealed that arginine methylation of p53 selectively suppresses expression of crucial proapoptotic and antiproliferative target genes, thereby sustaining tumor cell self-renewal and proliferation and bypassing the need for the acquisition of inactivating p53 mutations. Critically, analysis of human tumor specimens reveals a strong correlation between cyclin D1 overexpression and p53 methylation, supporting the biomedical relevance of this pathway.We have identified and functionally validated a crucial role for PRMT5 for the inhibition of p53-dependent tumor suppression in response to oncogenic insults. The requisite role for PRMT5 in the context of multiple lymphoma/leukemia oncogenic drivers suggests a molecular rationale for therapeutic development.
P189 Mitochondrial dysfunction in muscle and airway compartments in COPD: preliminary findings:
Authors: G Haji, C Wiegman, M Patel, P Kemp, I Adcock, F Chung, M Polkey
Journal: Thorax (2013)

<h3>Introduction &amp; Rationale</h3> Oxidative stress may underlie both pulmonary and non-pulmonary manifestations of COPD and may result from mitochondrial dysfunction. We hypothesised that if oxidative stress arose from the lung and ‘spilled over’ to cause non-pulmonary disease (e.g. skeletal muscle weakness) then greater evidence of mitochondrial dysfunction should be evident in the lung. <h3>Objectives</h3> We measured mitochondrial function in endobronchial and skeletal muscle biopsies from COPD patients and healthy smokers matched for smoking history, age and sex. <h3>Methods and Measurements</h3> We have so far biopsied 4 control smokers with normal FEV<sub>1</sub> and FEV<sub>1</sub>/FVC ratio, and 4 GOLD II COPD patients out of a planned total of 40. Bronchoscopy with endobronchial biopsies (EB) and percutaneous muscle biopsy of the vastus lateralis (VL) were obtained on the same day; additional phenotypic measurements included lung function, quadriceps strength and 6-minute walk (6MW) distance. Mitochondria were isolated and mitochondrial reactive oxygen species (ROS) and membrane potential (MP) were measured using MitoSOX Red and the carbocyanine dye JC-1 respectively and intracellular ROS determined by 2’-7’-dichlorofluorescin diacetate (DCF) staining. <h3>Results</h3> GOLD stage II COPD patients had reduced lung function, quadriceps strength and 6MW test despite a similar smoking history. There was increased mitochondrial and intracellular ROS in both skeletal muscle and bronchial biopsies of COPD patients compared to controls. There was a trend for reduced MP in COPD EB mitochondria. <h3>Conclusion</h3> The presence of excessive ROS in cells from a lung and a non-lung compartment support the existence of a generalised dysfunction of mitochondria in established COPD resulting in increased mitochondrial oxidative stress.
Antibodies to C reactive protein
Authors: B J Rosenau
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> C reactive protein (CRP) is a known indicator of inflammation. Serum CRP is often raised in patients with inflammatory conditions. <b>Objective:</b> To determine whether individuals make antibodies to CRP and whether this might affect serum CRP concentrations. <b>Methods:</b> An enzyme linked immunosorbent assay was developed for the detection of antibodies to CRP. Specificity of the reaction was determined by inhibition of the reaction. <b>Results:</b> Sera from 413 patients were tested and 25 were found to be positive, particularly in patients with rheumatic diseases. Levels of anti-CRP did not correlate with serum CRP levels. <b>Conclusions:</b> The presence of low CRP levels may not reflect the presence of antibodies to CRP.
Molecular Pathways: Dysregulated Glutamatergic Signaling Pathways in Cancer
Authors: Todd D. Prickett, Yardena Samuels
Journal: Clinical Cancer Research (2012)

The neurotransmitter glutamate interacts with glutamate receptor proteins, leading to the activation of multiple signaling pathways. Dysfunction in the glutamatergic signaling pathway is well established as a frequent player in diseases such as schizophrenia, Alzheimer disease, and brain tumors (gliomas). Recently, aberrant functioning of this pathway has also been shown in melanoma. In both glioma and melanoma, glutamate secretion stimulates tumor growth, proliferation, and survival through activation of the mitogen-activated protein kinase and phosphoinositide 3-kinase/Akt pathways. In the future, extracellular glutamate levels and glutamatergic signaling may serve as biological markers for tumorigenicity and facilitate targeted therapy for melanoma. .
Change in Estimated GFR Associates with Coronary Heart Disease and Mortality
Authors: Kunihiro Matsushita, Elizabeth Selvin, Lori D. Bash, Nora Franceschini, Brad C. Astor, Josef Coresh
Journal: Journal of the American Society of Nephrology (2009)

Kidney function predicts cardiovascular and all-cause mortality, but little is known about the association of changes in estimated GFR (eGFR) with clinical outcomes. We investigated whether 3- and 9-yr changes in eGFR associated with risk for coronary heart disease (CHD) and all-cause mortality among 13,029 participants of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for baseline covariates including eGFR in Cox proportional hazards models, the quartile of participants with the greatest annual decline (annual decline ≥5.65%) in eGFR were at significantly greater risk for CHD and all-cause mortality (hazard ratio 1.30 [95% confidence interval 1.11 to 1.52] and 1.22 [95% confidence interval 1.06 to 1.41], respectively) compared with the third quartile (annual decline between 0.33 and 0.47%). We observed similar results when we analyzed 9-yr changes in eGFR. Adjustment for covariates at the second eGFR used to estimate change reduced the association with CHD but not with mortality. Among participants with stage 3 chronic kidney disease, an increase in eGFR during the first 3 yr also associated with a higher risk for mortality, perhaps as a result of clinical instability. In conclusion, a steeper than average decline in eGFR associates with a higher risk for CHD and all-cause mortality. Increases in eGFR among participants with chronic kidney disease associate with similar increased risks.