tbuckley/cabot-search huggingface dataset:
Regulating Syringe Exchange Programs: A Cautionary Note
Authors: Don C. Des Jarlais
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Recent estimates of new human immunodeficiency virus (HIV) seroconversions in the United States suggest that the plurality of new infections are associated with illicit drug injection.<sup>1</sup>Syringe-exchange programs (SEPs) are a common method for reducing HIV risk behavior among injecting drug users (IDUs) in other countries, but have remained quite controversial in the United States. There are many methodological difficulties in conducting and interpreting syringe-exchange evaluations. Nevertheless, reviews of evaluation studies,<sup>2,3</sup>as well as more recently published data,<sup>4,5</sup>suggest that SEPs may be able to substantially reduce HIV risk behavior in the United States. For SEPs to have a large impact on risk behavior, however, the scale of service would have to be greatly expanded. (By our most recent estimates, there are 41 SEPs in the United States, providing services to less than 5% of IDUs.) Large-scale expansion would almost certainly require additional public
The preparation of the chronic hyper-endotoxemia experimental animal model by means of a drug delivery system
Authors: Sachiro Kakinoki, Kouji Yukutake, Isao Kaetsu, Kumao Uchida, Kouichi Sutani, Takuya Kosumi, Norio Usui, Takeo Yonekura, Akio Kubota, Harumasa Ohyanagi
Journal: Journal of Controlled Release (2001)
Neural Wiskott-Aldrich syndrome protein modulates Wnt signaling and is required for hair follicle cycling in mice
Authors: Anna Lyubimova, John J. Garber, Geeta Upadhyay, Andrey Sharov, Florentina Anastasoaie, Vijay Yajnik, George Cotsarelis, Gian Paolo Dotto, Vladimir Botchkarev, Scott B. Snapper
Journal: Journal of Clinical Investigation (2010)

The Rho family GTPases Cdc42 and Rac1 are critical regulators of the actin cytoskeleton and are essential for skin and hair function. Wiskott-Aldrich syndrome family proteins act downstream of these GTPases, controlling actin assembly and cytoskeletal reorganization, but their role in epithelial cells has not been characterized in vivo. Here, we used a conditional knockout approach to assess the role of neural Wiskott-Aldrich syndrome protein (N-WASP), the ubiquitously expressed Wiskott-Aldrich syndrome-like (WASL) protein, in mouse skin. We found that N-WASP deficiency in mouse skin led to severe alopecia, epidermal hyperproliferation, and ulceration, without obvious effects on epidermal differentiation and wound healing. Further analysis revealed that the observed alopecia was likely the result of a progressive and ultimately nearly complete block in hair follicle (HF) cycling by 5 months of age. N-WASP deficiency also led to abnormal proliferation of skin progenitor cells, resulting in their depletion over time. Furthermore, N-WASP deficiency in vitro and in vivo correlated with decreased GSK-3beta phosphorylation, decreased nuclear localization of beta-catenin in follicular keratinocytes, and decreased Wnt-dependent transcription. Our results indicate a critical role for N-WASP in skin function and HF cycling and identify a link between N-WASP and Wnt signaling. We therefore propose that N-WASP acts as a positive regulator of beta-catenin-dependent transcription, modulating differentiation of HF progenitor cells.
Abstract 1429: Role of monocyte chemotactic protein-1 (MCP-1) in the tumor microenvironment.
Authors: Lilia Y. Kucheryavykh, Aixa F. Rivera-Pagán, Kimberleve Rolón-Reyes, Serguey N. Skatchkov, Misty J. Eaton
Journal: Cancer Research (2013)

Abstract Glioblastomas, the most malignant form of gliomas, harbor multiple cell types. In particular, microglial cells can contribute up to 30% of a brain tumor mass, and can promote glioma cell growth and dispersal. The purpose of the present study was to test the hypothesis that glioma cells recruit nearby microglia through an MCP-1-mediated mechanism and enhance their production of MCP-1 in the tumor microenvironment. We evaluated the role of MCP-1 on glioma cell proliferation and invasion. Consistent with previous studies in rat models (Platten et al., 2003), we found that U-87 and A-172 human glioma cells promote microglial migration towards the glioma environment using a modified Boyden chamber migration assay. Furthermore, this effect was decreased after immunoneutralization of MCP-1 released from glioma cells. Additionally, using an antibody array we found that U-87 or A-172 glioma cell conditioned medium stimulates a 7-10 fold increase of MCP-1 release by microglia by 24 hours. We next analyzed the consequences of elevated MCP-1 on the invasiveness and proliferation of glioma cells. Using standard invasion assays with or without microglia in a lower compartment, we demonstrated that microglia significantly increased invasion of glioma cells, but this effect was not blocked by MCP-1 immunoneutralization. This suggests that the stimulatory effect of microglia on glioma invasion was due to some other factor such as release of matrix metalloproteinases (MMPs). In contrast, microglia increased U-87 and A-172 glioma cell proliferation within 72 hours and MCP-1 immunoneutralization reversed this proliferative effect of microglia in both cell lines. Based on these results, we propose that glioma cells release low levels of MCP-1 to recruit nearby microglia and enhance the production of MCP-1. This increased secretion of MCP-1 from microglial cells recruits more microglial cells into the tumor and stimulate glioma progression. A variety of substances released by microglia in tumor microenvironment, including cytokines, growth factors, proteases and extracellular matrix components could lead to increased proliferation and invasiveness of glioma cells. Supported by G11 HD052352, G12 RR03035, 8G12MD007583-27, U54 NS039408 and by the UCC Pilot Project Program Citation Format: Lilia Y. Kucheryavykh, Aixa F. Rivera-Pagán, Kimberleve Rolón-Reyes, Serguey N. Skatchkov, Misty J. Eaton. Role of monocyte chemotactic protein-1 (MCP-1) in the tumor microenvironment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1429. doi:10.1158/1538-7445.AM2013-1429
Aspirin-Induced Depression of Glomerular Filtration Rate in Normal Humans: Role of Sodium Balance
Authors: RICHARD S. MUTHER
Journal: Annals of Internal Medicine (1981)

The renal clearance of endogenous creatinine, inulin and para-aminohippurate was measured in 10 healthy human volunteers taking aspirin during severe dietary sodium restriction (10 meq/d) to clarify the clinical significance and pathophysiology of aspirin-induced changes in renal function. Sodium restriction alone had no effect on renal clearances but did increase plasma renin activity and urinary prostaglandin E excretion. The addition of aspirin decreased the urinary clearance of prostaglandin E but not plasma renin activity, and caused a significant fall in both endogenous creatinine (from 92.3 +/- 4.1 SE ml/min . 1.73 m2 body surface area to 80.8 +/- 4.4 mL/min . 1.73 m2, p = 0.02) and inulin (from 95.3 +/- 7.0 mL/min . 1.73 m2 to 80.9 +/- 7.0 mL/min . 1.73 m2, p less than 0.001). The fall in inulin clearance was directly related to the salicylate level. The clearance of para-aminohippurate showed only a slight, statistically insignificant decline with aspirin. The results of this study suggest that aspirin-induced depression of glomerular filtration rate may be independent of total renal plasma flow. Aspirin should be used cautiously, with careful attention to dosage, in sodium-restricted patients whose glomerular filtration rate may, in part, be under the homeostatic control of renal prostaglandins.
Exploration of Panviral Proteome: High-Throughput Cloning and Functional Implications in Virus-host Interactions
Authors: Xiaobo Yu, Xiaofang Bian, Andrea Throop, Lusheng Song, Lerys Del Moral, Jin Park, Catherine Seiler, Michael Fiacco, Jason Steel, Preston Hunter, Justin Saul, Jie Wang, Ji Qiu, James M. Pipas, Joshua LaBaer
Journal: Theranostics (2014)

Throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms.The systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic treatment of a viral infection, and mechanisms of host biology.With more than 2,000 viral genomes sequenced, only a small percent of them are well investigated.The access of these viral open reading frames (ORFs) in a flexible cloning format would greatly facilitate both in vitro and in vivo virus-host interaction studies.However, the overall progress of viral ORF cloning has been slow.To facilitate viral studies, we are releasing the initiation of our panviral proteome collection of 2,035 ORF clones from 830 viral genes in the Gateway® recombinational cloning system.Here, we demonstrate several uses of our viral collection including highly efficient production of viral proteins using human cell-free expression system in vitro, global identification of host targets for rubella virus using Nucleic Acid Programmable Protein Arrays (NAPPA) containing 10,000 unique human proteins, and detection of host serological responses using micro-fluidic multiplexed immunoassays.The studies presented here begin to elucidate host-viral protein interactions with our systemic utilization of viral ORFs, high-throughput cloning, and proteomic technologies.These valuable plasmid resources will be available to the research community to enable continued viral functional studies.
Abstract LB-9: Intersection of Notch and ERBB signalling in melanoma
Authors: Barbara Bedogni
Journal: Cancer Research (2011)

Abstract Malignant melanoma is an aggressive malignancy of the melanocytes. The incidence rates for melanoma are steadily increasing and melanoma has now become the most common form of cancer among young adults between the ages of 25 and 29 years old. Because melanomas are highly resistant to the majority of therapies, the survival rate for patients with metastatic disease is less than 15%. There is a clear need for novel more effective therapies. Identification of the signaling pathways that are altered in melanoma provides opportunities for the development of novel targeted therapies. The Notch pathway is an evolutionary conserved signaling cascade that has an essential role in embryonic development but is inappropriately active in various types of cancers. Studies from our group and others have shown that hyper activation of Notch1 is an early event in melanocyte transformation and modulates both growth and metastasis in melanoma. We have found a new interaction between Notch1 and neuregulin1 (NRG1) signaling that plays a role in melanoma. Neuregulin1 is the ligand for ERBB3, a member of the Epidermal Growth Factor family of receptors that are involved in the genesis and progression of a number of cancers. Notch1 binds to the NRG1 promoter thereby modulating NRG1 expression and consequently the activation of the ERBB3 pathway. Inhibition of either NRG1 or ERBB3 activity in melanoma cells lead to cell growth inhibition and tumor growth delay similar to Notch1 inhibition. Mechanistically, these effects are dependent on the accumulation of p27 following either NRG1 or Notch1 down regulation. In addition, we find that NRG1/ERBB3 signaling influences Notch1 activation likely through the modulation of the Notch ligands Jaggged-1 (JAG-1) and Delta like 3 (Dll3), thus providing a feed forward regulatory loop linking the two pathways. Taken together, our findings underline a new, previously undescribed interaction between Notch1 and NRG1/ERBB3 in melanoma. Our goal is to investigate the mechanisms by which these two oncogenic signaling pathways intersect to promote a highly aggressive disease phenotype and to provide experimental evidence that the targeting of Notch and ERBB signaling is a tractable and effective approach to treat forms of melanoma that may be resistant to current available therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-9. doi:10.1158/1538-7445.AM2011-LB-9
Lipid transfer proteins and 2S albumins as allergens
Authors: Elide A. Pastorello, Valerio Pravettoni, Chiara Trambaioli, Carlo Pompei, Oreste Brenna, Laura Farioli, Amedeo Conti
Journal: Allergy (2001)

Plant lipid transfer proteins, a widespread family of proteins, have been recently identified as important food allergens. Their common structural features, such as eight conserved cysteines forming disulfide bridges, basic isoelectric point and high similarity in amino acid sequence, are the basis of allergic clinical cross‐reactivity. This has been demonstrated for the LTP allergens of the Prunoideae subfamily, whose similarity is about 95% as demonstrated for the purified allergens of peach, apricot, plum and apple. A relevant aspect is the existence of sequence homology of LTPs of botanically unrelated foods, as demonstrated for LTPs of maize and peach. A class of food allergens of well recognized clinical importance is that of seed storage 2S albumins. They have been identified in the most diffused edible seeds and nuts, such as mustard, sesame, Brazil nut, walnut and peanut. In particular, a strong correlation between IgE‐binding to these proteins and food‐induced anaphylaxis has been demonstrated for Brazil nut and sesame seeds.
The presentation of raised intracranial pressure in children with spina bifida and the importance of integrated follow up.
Authors: P Tomlinson
Journal: BMJ (1984)

older reports of coexistent tuberculosis and cancer in a breast would today be regarded as a non-infective accompaniment of the tumour, but unquestionably there are occasional instances of proved tuberculosis in a cancerous breast (although of no statistical relevance, this association was present in two of the six cases of proved tuberculous mastitis in the table).It is essential to avoid mistaking the noninfective granulomatous reaction in a cancerous breast for tuberculosis or any other infective condition and so delaying diagnosis of the associated tumour.
Prevention of Coronary Artery Disease
Authors: A Leaf, T J Ryan
Journal: New England Journal of Medicine (1990)

Cardiologic practices are an important contributor to the cost of medical care today. Combining the high prevalence of cardiovascular disease with medical and surgical interventions that involve expensive forms of technology creates high costs. There has been much discussion of how to improve the quality of cardiologic practices, even with the hope of reducing medical costs. Some cardiologic procedures have been carefully evaluated, such as coronary-artery bypass surgery1 2 3 and coronary angioplasty with thrombolytic therapy.4 5 6 7 All efforts to define a high quality of practice and the best uses for the abundant and expensive forms of technology are to the good. What . . .
Technetium-99m MDP Demonstration of Neoplastic Lesions Involving Bone and Adjacent Soft Tissues
Authors: JOHN MATHEWS, JAMES D. SLAVIN, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1986)

Four patients are presented with malignant tumors involving both bone and adjacent soft tissue. In each of these neoplasms (two representing adenocarcinoma of the prostate, and one each of squamous cell carcinoma of lung and chondrosarcoma), the lesions were detected by accumulation of Tc-99m MDP. Involvement of both bone and soft tissue was confirmed by CT examination or surgery. It is probable that the lesions originated in bone and then extended to soft tissue.
Relation of Mean Right Atrial Pressure to Echocardiographic and Doppler Parameters of Right Atrial and Right Ventricular Function
Authors: Sherif F. Nagueh, Helen A. Kopelen, William A. Zoghbi
Journal: Circulation (1996)

Background A paucity of data exists as to the relation of mean right atrial pressure (RAP) to Doppler parameters of right atrial and ventricular filling. Furthermore, whether echocardiographic parameters of right atrial and right ventricular function and inferior vena cava improve the relation of Doppler filling dynamics with RAP has not been explored. Methods and Results Doppler and echocardiographic studies were performed simultaneously with measurements of mean RAP in consecutive patients who either had a central venous catheter in the Intensive Care Unit or underwent catheterization of the right side of the heart. The initial population consisted of 35 patients with a mean age (±SD) of 60±15 years; 34% were on mechanical ventilation. Mean RAP averaged 9±5.7 mm Hg (range, 2 to 28 mm Hg). Among tricuspid inflow parameters, the strongest relation with RAP was observed with the ratio of early to late velocity ( r =.66). For hepatic venous flow, systolic filling wave indexes had the best relation with atrial pressure, the highest being for systolic filling fraction ( r =−.86). Weaker relations were noted with the use of right atrial volumes, right ventricular function, and inferior vena caval diameters. The addition of any of these variables did not improve the relation of systolic filling fraction with RAP. The regression equation (RAP=21.6−24 systolic filling fraction) was tested prospectively in the estimation of atrial pressure in 50 patients. The correlation coefficient was .89 in the prospective group and .88 in the total group of 85 patients. The mean difference between predicted and actual pressures in the whole population was −0.2±2.6 mm Hg. The sensitivity and specificity for mean RAP&gt;8 mm Hg were 86% and 92%, respectively. Conclusions Among echocardiographic and Doppler parameters of right atrial and right ventricular function, hepatic venous flow dynamics relate best to mean atrial pressure and can be used clinically to estimate mean RAP.
Hepatitis C and injecting drug use in prisons
Authors: A J McBride, I M Ali, W Cleee
Journal: BMJ (1994)

Kurds were suspects as far as the regime was concerned.This is exactly what the Turkish government thinks of its Kurdish people: every Kurd is a suspect and terrorist.The number of Kurdish people coming to Britain as asylum seekers has increased since the escalation of Turkish military and police operations in Kurdistan.Many of them have been imprisoned and tortured, and they have been subjected to or have witnessed other kinds of state organised violence.Many have lost families, friends, jobs, status, and belongings.The impact of these traumatic life events and losses must be considerable on their mental health and social fuctioning.General practitioners and psychiatrists therefore need to be aware of the histories of their Kurdish patients.The plight of Kurdish people should not be forgotten.
The camKK2/camKIV relay is an essential regulator of hepatic cancer
Authors: Fumin Lin, Kathrina L. Marcelo, Kimal Rajapakshe, Cristian Coarfa, Adam Dean, Nathaniel Wilganowski, Holly Robinson, Eva Sevick, Karl‐Dimiter Bissig, Lauren C. Goldie, Anthony R. Means, Brian York
Journal: Hepatology (2015)

Hepatic cancer is one of the most lethal cancers worldwide. Here, we report that the expression of Ca 2+ /calmodulin‐dependent protein kinase kinase 2 (CaMKK2) is significantly up‐regulated in hepatocellular carcinoma (HCC) and negatively correlated with HCC patient survival. The CaMKK2 protein is highly expressed in all eight hepatic cancer cell lines evaluated and is markedly up‐regulated relative to normal primary hepatocytes. Loss of CaMKK2 function is sufficient to inhibit liver cancer cell growth, and the growth defect resulting from loss of CaMKK2 can be rescued by ectopic expression of wild‐type CaMKK2 but not by kinase‐inactive mutants. Cellular ablation of CaMKK2 using RNA interference yields a gene signature that correlates with improvement in HCC patient survival, and ablation or pharmacological inhibition of CaMKK2 with STO‐609 impairs tumorigenicity of liver cancer cells in vivo . Moreover, CaMKK2 expression is up‐regulated in a time‐dependent manner in a carcinogen‐induced HCC mouse model, and STO‐609 treatment regresses hepatic tumor burden in this model. Mechanistically, CaMKK2 signals through Ca 2+ /calmodulin‐dependent protein kinase 4 (CaMKIV) to control liver cancer cell growth. Further analysis revealed that CaMKK2 serves as a scaffold to assemble CaMKIV with key components of the mammalian target of rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway and thereby stimulate protein synthesis through protein phosphorylation. Conclusion : The CaMKK2/CaMKIV relay is an upstream regulator of the oncogenic mammalian target of rapamycin/ribosomal protein S6 kinase, 70 kDa, pathway, and the importance of this CaMKK2/CaMKIV axis in HCC growth is confirmed by the potent growth inhibitory effects of genetically or pharmacologically decreasing CaMKK2 activity; collectively, these findings suggest that CaMKK2 and CaMKIV may represent potential targets for hepatic cancer. (H epatology 2015;62:505–520
Ballistocardiograms in Coarctation of the Aorta
Authors: Herbert R. Brown, Marvin J. Hoffman, Vincent DeLalla
Journal: New England Journal of Medicine (1949)

THE recent interest in coarctation of the aorta can be attributed to the development of a surgical treatment eliminating the stenotic area.1 2 3 In recent years the number of reported cases has steadily increased. This apparent increased incidence probably represents a new awareness leading to a much more frequent diagnosis of a condition that was formerly a medical curiosity. The incidence of coarctation as given by Levine4 is 0.05 per cent of the population.In large measure the diagnosis depends first upon thinking of the possibility of this condition and secondly on a few additional procedures indicated to aid in establishing . . .
Agencies act to avert "public health catastrophe" in wake of floods in Pakistan
Authors: P. Moszynski
Journal: BMJ (2010)

Relief teams responding to Pakistan’s worst flooding in generations are being hampered by massive infrastructural damage that has left the worst hit areas unreachable except by air.

Health workers are warning of the risk of waterborne diseases as continuing heavy monsoon rains threaten to cause further damage downstream. 

Millions of people have been affected, and 1500 people have already died as a result of floods, local news agencies report. One of the worst hit areas is the province of Khyber Pakhtunkhwa (formerly the North West Frontier Province).⇓ This area has seen hundreds of thousands of people displaced by a recent Pakistan army campaign against suspected Taliban insurgents.



Meanwhile the World Health Organization has reported an increasing number of cases of …