tbuckley/cabot-search huggingface dataset:
Physical and Functional Links between Anion Exchanger-1 and Sodium Pump
Authors: Ya Su, Rafia S. Al-Lamki, Katherine G. Blake-Palmer, Alison Best, Zoe J. Golder, Aiwu Zhou, Fiona E. Karet Frankl
Journal: Journal of the American Society of Nephrology (2014)

Anion exchanger-1 (AE1) mediates chloride-bicarbonate exchange across the plasma membranes of erythrocytes and, via a slightly shorter transcript, kidney epithelial cells. On an omnivorous human diet, kidney AE1 is mainly active basolaterally in α-intercalated cells of the collecting duct, where it is functionally coupled with apical proton pumps to maintain normal acid-base homeostasis. The C-terminal tail of AE1 has an important role in its polarized membrane residency. We have identified the β1 subunit of Na(+),K(+)-ATPase (sodium pump) as a binding partner for AE1 in the human kidney. Kidney AE1 and β1 colocalized in renal α-intercalated cells and coimmunoprecipitated (together with the catalytic α1 subunit of the sodium pump) from human kidney membrane fractions. ELISA and fluorescence titration assays confirmed that AE1 and β1 interact directly, with a Kd value of 0.81 μM. GST-AE1 pull-down assays using human kidney membrane proteins showed that the last 11 residues of AE1 are important for β1 binding. siRNA-induced knockdown of β1 in cell culture resulted in a significant reduction in kidney AE1 levels at the cell membrane, whereas overexpression of kidney AE1 increased cell surface sodium pump levels. Notably, membrane staining of β1 was reduced throughout collecting ducts of AE1-null mouse kidney, where increased fractional excretion of sodium has been reported. These data suggest a requirement of β1 for proper kidney AE1 membrane residency, and that activities of AE1 and the sodium pump are coregulated in kidney.
Inhibition of Integrin α2β1 Ameliorates Glomerular Injury
Authors: Corina M. Borza, Yan Su, Xiwu Chen, Ling Yu, Stacey Mont, Sergei Chetyrkin, Paul Voziyan, Billy G. Hudson, Paul C. Billings, Hyunil Jo, Joel S. Bennett, William F. DeGrado, Beate Eckes, Roy Zent, Ambra Pozzi
Journal: Journal of the American Society of Nephrology (2012)

Mesangial cells and podocytes express integrins α1β1 and α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin α1β1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin α2β1 in renal injury is unclear. Here, we subjected wild-type and integrin α2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin α2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin α2β1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wild-type mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin α2-null, mesangial cells in vitro, demonstrating that its effects are integrin α2β1-dependent. Taken together, these results indicate that integrin α2β1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria.
Inflammation in Atherosclerosis and Implications for Therapy
Authors: Rodolfo Paoletti, Antonio M. Gotto, David P. Hajjar
Journal: Circulation (2004)

Atherosclerosis is now understood to be a disease characterized by inflammation that results in a host of complications, including ischemia, acute coronary syndromes (unstable angina pectoris and myocardial infarction), and stroke. Inflammation may be caused by a response to oxidized low-density lipoproteins, chronic infection, or other factors; and markers of this process, such as C-reactive protein, may be useful to predict an increased risk of coronary heart disease. Thus, we believe that inflammatory processes may be potential targets of therapy in preventing or treating atherosclerosis and its complications.
Low molecular weight iron in guinea pig reticulocytes
Authors: Simeon Pollack, Theresa Campana, Janet Weaver
Journal: American Journal of Hematology (1985)

Abstract The low molecular weight iron found in the guinea pig reticulocyte has been partially characterized. On thin layer chromatography it is distinguishable from the iron complexes of a variety of nucleotides, sugars, and amino acids. On paper chromatography it comigrates with a 250‐nm absorbing, orcinol‐positive material. The eluted count peak contains phosphorus. Approximately 1 μg of iron is recovered from 1 ml of hemolyzed red cells. Preparation under nitrogen improves recovery of low molecular weight iron, suggesting that the iron is in the ferrous oxidation state.
Acupuncture, Trigger Points and Musculoskeletal Pain
Authors: B Hazleman
Journal: Annals of the Rheumatic Diseases (1990)

This is a handbook for patients, actual and potential, and for all lay readers with an interest in osteoporosis.It is written jointly by three American doctors, one a specialist, who share a Florida practice, and by one professional writer.Within its context it provides a comprehensive account of osteoporosis-what it is, how it should be managed, its risk factors, signs and symptoms, and plans for prevention and treatment from childhood to old age.It is profusely but clearly illustrated, readable, and informative.It might be argued that the benefits of high calcium intake and calcium supplementation are less well proved than the authors uncritically maintain.The minute details given of the calcium content of everything we eat might, therefore, lead to unnecessary obsessions on the patients' part.Nevertheless, the book is judicious in its recommendations for therapy and treads a fair line between accepted and experimental treatment.Other details include a simple description of quantitative computed tomography and even the exact calcium content of every 'dish' available at McDonalds and Burger King!The flavour is therefore transatlantic, and one disadvantage to British readers is the limitation of all drug names to American proprietary preparations.Despite this, it
HIV-1 Induces Cytotoxic T Lymphocytes in the Cervix of Infected Women
Authors: Luwy Musey, Yuxiang Hu, Linda Eckert, Michael Christensen, Tobi Karchmer, M. Juliana McElrath
Journal: The Journal of Experimental Medicine (1997)

Although T lymphocytes are present in the genital mucosa, their function in sexually transmitted diseases is unproven. To determine if cervical T cells mediate HIV-specific cytolysis, mononuclear cells in cytobrush specimens from HIV-1-infected women were stimulated in vitro with antigen. Resultant cell lines lysed autologous targets expressing HIV-1 proteins in 12/19 (63%) subjects, and these responses were detected intermittently on repeated visits. All 8 subjects with blood CD4+ counts ⩾500 cells/μl had HIV-1-specific cervical CTL, whereas only 4/11 with counts &amp;lt;500 cells/μl had detectable responses (P = 0.008). Class II MHC– restricted CD4+ CTL clones lysed targets expressing Env gp41 or infected with HIV-1. Class I MHC-restricted CD8+ clones recognized HIV-1 Gag- or Pol-expressing targets, and the epitopes were mapped to within 9–20 amino acids. Comparisons of intra-individual cervical and blood CTL specificities indicate that epitopes recognized by CTL in the cervix were commonly recognized in the blood. These studies provide the first definitive evidence for an MHC-restricted effector function in human cervical lymphocytes.
Pattern of end-of-life decisions in two Tunisian intensive care units: the role of culture and intensivists’ training
Authors: Islem Ouanes, Néji Stambouli, Fahmi Dachraoui, Lamia Ouanes-Besbes, Samir Toumi, Faouzi Ben Salem, Mourad Gahbiche, Fekri Abroug
Journal: Intensive Care Medicine (2012)
Metformin and Cancer: Mounting Evidence Against an Association
Authors: Samy Suissa, Laurent Azoulay
Journal: Diabetes Care (2014)

Metformin, a biguanide derived from the French lilac, has become the preferred first-line therapy for the treatment of type 2 diabetes (1). This drug is inexpensive, has an excellent safety profile, and can be safely combined with other antidiabetes agents (2). As a result, it has become the most widely prescribed antidiabetes drug worldwide.

In addition to metformin’s well-established antidiabetes effects, there has been considerable interest in its antitumor properties. Such interest started from a short report of an observational study published in 2005 that suggested that the use of metformin was associated with a 23% decreased risk of any cancer (3). Since then, a large number of observational studies have been published with several “corroborating” a possible decreased incidence of cancer with this drug (4). In parallel, several laboratory studies have also suggested that metformin has antineoplastic activity, although doses used in such experiments were typically higher than the conventional doses used in the treatment of type 2 diabetes (5). Nonetheless, this apparent convergence of evidence from both observational and laboratory studies has led some to call for large randomized clinical trials (RCTs) of metformin in cancer prevention and treatment (6–9). However, a careful assessment of the observational studies conducted to date point to some important time-related biases that systematically exaggerated the reported antitumor effects of metformin (10).

Time-related biases, such as immortal time bias, time window bias, and time lag bias, have been previously described in studies of diabetes treatment (10) and in other therapeutic areas (11–14). These biases result from not properly classifying exposure during the follow-up of a cohort study or from …
Hospital Report Cards for Hospital-Acquired Pressure Ulcers: How Good Are the Grades?
Authors: Jennifer A. Meddings, Heidi Reichert, Tim Hofer, Laurence F. McMahon
Journal: Annals of Internal Medicine (2013)

Value-based purchasing programs use administrative data to compare hospitals by rates of hospital-acquired pressure ulcers (HAPUs) for public reporting and financial penalties. However, validation of these data is lacking.To assess the validity of the administrative data used to generate HAPU rates by comparing the rates generated from these data with those generated from surveillance data.Retrospective analysis of 2 million all-payer administrative records from 448 California hospitals and quarterly hospitalwide surveillance data from 213 hospitals from the Collaborative Alliance for Nursing Outcomes (as publicly reported on the CalHospitalCompare Web site).196 acute care hospitals with at least 6 months of available administrative and surveillance data.Nonobstetric adults discharged in 2009.Hospital-specific HAPU rates were computed as the percentage of discharged adults (from administrative data) or examined adults (from surveillance data) with at least 1 stage II or greater HAPU (HAPU2+). Categorization of hospital performance based on administrative data was compared with the grade assigned when surveillance data were used.When administrative data were used, the mean hospital-specific HAPU2+ rate was 0.15% (95% CI, 0.13% to 0.17%); when surveillance data were used, the rate was 2.0% (CI, 1.8% to 2.2%). Among the 49 hospitals with HAPU2+ rates in the highest (worst) quartile from administrative data, use of the surveillance data set resulted in performance grades of "superior" for 3 of these hospitals, "above average" for 14, "average" for 15, and "below average" for 17.Data are from 1 state and 1 year.Hospital performance scores generated from HAPU2+ rates varied considerably according to whether administrative or surveillance data were used, suggesting that administrative data may not be appropriate for comparing hospitals.Agency for Healthcare Research and Quality.
Parapsychology: Science of the anomalous or search for the soul?
Authors: James E. Alcock
Journal: Behavioral and Brain Sciences (1987)

Although there has been over a century of formal empirical inquiry, parapsychologists have clearly failed to produce a single reliable demonstration of “paranormal,” or “psi,” phenomena. Although many parapsychological research projects have been carried out under what have been described as well-controlled conditions, this does not by itself make a science, for unless and until it can be demonstrated that paranormal phenomena really exist, there is no subject matter around which a science can develop. Indeed, parapsychologists have not even succeeded in developing a reasonable definition of paranormal phenomena that does not involve, or imply, some aspect of mind-body dualism. Moreover, parapsychology has developed several principles (such as the experimenter effect) which can be used to explain away failures, and the use of these principles contributes to making the psi-hypothesis unfalsifiable.The “anything goes” attitude in parapsychology, which seems to lend credence to virtually any “paranormal” claim, serves to weaken the credibility of parapsychological endeavors in the eyes of critics. This general willingness to suspend doubt is another indication that parapsychology is more than the quest to explain anomalous experiences, as is claimed. It is argued in this paper that parapsychological inquiry reflects the attempt to establish the reality of a nonmaterial aspect of human existence, rather than a search for explanations for anomalous phenomena.
HEMOGLOBIN AND PLASMA PROTEIN
Authors: F. S. Robscheit-Robbins, S. C. Madden, A. P. Rowe, A. P. Turner, G. H. Whipple
Journal: The Journal of Experimental Medicine (1940)

Given healthy dogs, fed abundant iron and a limited protein diet, with sustained anemia due to simple bleeding, we can study the capacity of each animal to produce new hemoglobin and plasma protein. Some dogs can produce much hemoglobin and enough new plasma protein to maintain the plasma protein concentration at approximately a low normal level. It is probable that their plasma protein producing capacity is not fully extended (Table 2). Other dogs (Table 5) can produce the same amount of hemoglobin but a hypoproteinemia develops and continues which should mean a maximal stimulus to produce new plasma protein. In such dogs we have strong stimuli to produce simultaneously new hemoglobin and new plasma protein. The ratio of plasma protein to hemoglobin varies from 40 to 60 per cent. The total new formed blood protein may amount to 30 to 40 per cent of the total diet protein intake which shows that some dogs have remarkable capacity to conserve and use diet protein. In this emergency of simultaneous depletion of hemoglobin and plasma protein levels, the dog gives preference to hemoglobin manufacture no matter what one of the listed food proteins is tested.
Can you feel the real paper?
Authors: Mats Börjesson, Magnus Forssblad, Jón Karlsson
Journal: British Journal of Sports Medicine (2015)

Welcome to the third annual Swedish theme issue of BJSM ! The Swedish Society of Exercise and Sports Medicine (SFAIM) is proud of the ongoing collaboration with BJSM , and we are happy to continue to offer our members the journal online, as part of their national membership benefits.

Today, new discoveries have many ways of finding a wide audience including through e-journals, the web, Twitter and Facebook. This maximises dissemination, which can only be a good thing. Yet in this age of new technology, a print journal such as BJSM may have more to offer than ever before. We highlight a few advantages of the old ‘paper journal’. 

1.  The paper journal does not need a power supply. You might say that the internet and computer can work on batteries. But, consider a nice holiday, out sunbathing in the archipelago, far from any electrical source. The batteries never run out in paper journals!

2.  In addition, in the sun, on said island, without protection for your screen, the paper journal offers superior viewing; something that is always a problem with any kind of screen…

3.  In case of wet weather, protecting iPads and computers is a …
The preventive effect of uncarboxylated osteocalcin against free fatty acid-induced endothelial apoptosis through the activation of phosphatidylinositol 3-kinase/Akt signaling pathway
Authors: Chang Hee Jung, Woo Je Lee, Jenie Yoonoo Hwang, Min Jung Lee, So Mi Seol, Yun Mi Kim, Yoo La Lee, Joong-Yeol Park
Journal: Metabolism (2013)
Tories urge patients to complain to health secretary over cancer leaflets
Authors: A. O'Dowd
Journal: BMJ (2010)

The UK Conservative party is encouraging patients to write to the health secretary for England, Andy Burnham, to complain about a recent distribution of leaflets concerning cancer treatment, which it claims were a “shameful” example of scaremongering.

As part of its campaign for the UK general election on 6 May the Labour party has issued 250 000 postcards, addressed to individuals, warning them that their access to and speed of treatment for cancer would be affected badly if the Conservatives were to win the election.

Labour has, in turn, completely rejected the Tories’ claim that it targeted the leaflets at patients with cancer.

The cards warn that the guarantees that …
Angiogenic Response Caused by Oncolytic Herpes Simplex Virus–Induced Reduced Thrombospondin Expression Can Be Prevented by Specific Viral Mutations or by Administering a Thrombospondin-Derived Peptide
Authors: Manish Aghi, Samuel D. Rabkin, Robert L. Martuza
Journal: Cancer Research (2007)

Abstract Wild-type (WT) herpes simplex virus (HSV) causes some pathology, such as ocular keratitis, by increasing infected tissue vascularity, possibly reflecting altered angiogenic factor expression in infected cells. Oncolytic HSVs possess specific mutations enabling selective replication in tumor cells. We investigated whether this ability to enhance infected tissue vascularity is retained in oncolytic HSV, which could be an undesirable effect of oncolytic HSVs that may need to be addressed when treating tumors with oncolytic HSVs. s.c. tumors derived from U87 human glioma cells in athymic mice were treated with oncolytic HSVs G207 or G47Δ in the presence or absence of a recombinant protein composed of the three type-1 repeats (3TSR) of thrombospondin-1 (TSP-1). Real-time reverse transcription-PCR and Western blot of infected cultured cells measured angiogenic factor expression. Microvessel density was assessed using immunofluorescence. G207-treated U87 s.c. tumors had elevated microvessel densities compared with saline- and G47Δ-treated tumors, and G207 treatment caused delayed tumor growth resumption. G207-infected U87 and U373 cells exhibited reduced protein, not mRNA, expression of angiogenesis inhibitors TSP-1 and thrombospondin-2 (TSP-2). 3TSR restored the G207-treated tumor microvessel density to the low level of G47Δ-treated tumors and prevented delayed growth resumption. Oncolytic HSV G207 thus retains the ability of WT HSV to increase infected tissue vascularity. In infected tumors, this increased vascularity is mediated by reduced TSP-1 and TSP-2 levels and causes delayed tumor growth resumption. Incorporating viral mutations, such as those seen in G47Δ or administering thrombospondin-derived peptides, counteracts the angiogenic effect of oncolytic HSV and should be considered when designing oncolytic HSV therapies. [Cancer Res 2007;67(2):440–4]
Rho/Rho-Kinase Pathway in Brain Stem Contributes to Blood Pressure Regulation via Sympathetic Nervous System
Authors: Koji Ito, Yoshitaka Hirooka, Koji Sakai, Takuya Kishi, Kozo Kaibuchi, Hiroaki Shimokawa, Akira Takeshita
Journal: Circulation Research (2003)

Recent studies have demonstrated that the Rho/Rho-kinase pathway plays an important role in various cellular functions, including actin cytoskeleton organization and vascular smooth muscle contraction. This pathway is also present in the central nervous system and is involved in the maintenance of dendritic spines and axon outgrowth and in the regulation of neurotransmitter release. However, its role in central blood pressure regulation is unknown. In the present study, blockade of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem by microinjection of a specific Rho-kinase inhibitor decreased blood pressure, heart rate, and renal sympathetic nerve activity in both Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). However, the magnitude of decreases in these variables was greater in SHR than in WKY rats. In addition, an adenovirus vector encoding dominant-negative Rho-kinase decreased blood pressure, heart rate, and urinary norepinephrine excretion in both WKY rats and SHR in an awake and free-moving state. The magnitude of decreases in these variables was also greater in SHR than in WKY rats. Furthermore, membrane RhoA expression and Rho-kinase activity in the NTS were enhanced in SHR compared with WKY rats. These observations indicate that the Rho/Rho-kinase pathway in the NTS contributes to blood pressure regulation via the sympathetic nervous system in vivo and suggest that activation of this pathway is involved in the central mechanisms of hypertension.
A single-nucleotide polymorphism tagging set for human drug metabolism and transport
Authors: Kourosh R Ahmadi, Mike E Weale, Zhengyu Y Xue, Nicole Soranzo, David P Yarnall, James D Briley, Yuka Maruyama, Mikiro Kobayashi, Nicholas W Wood, Nigel K Spurr, Daniel K Burns, Allen D Roses, Ann M Saunders, David B Goldstein
Journal: Nature Genetics (2004)
Do <i>MDM2</i> SNP309 and <i>TP53</i> R72P Interact in Breast Cancer Susceptibility? A Large Pooled Series from the Breast Cancer Association Consortium
Authors: Marjanka K. Schmidt, Scarlett Reincke, Annegien Broeks, Linde M. Braaf, Frans B.L. Hogervorst, Rob A.E.M. Tollenaar, Nichola Johnson, Olivia Fletcher, Julian Peto, Johanna Tommiska, Carl Blomqvist, Heli A. Nevanlinna, Catherine S. Healey, Alison M. Dunning, Paul D.P. Pharoah, Douglas F. Easton, Thilo Dörk, Laura J. Van't Veer
Journal: Cancer Research (2007)

Abstract Association studies in large series of breast cancer patients can be used to identify single-nucleotide polymorphisms (SNP) contributing to breast cancer susceptibility. Previous studies have suggested associations between variants in TP53 (R72P) and MDM2 (SNP309) and cancer risk. Data from molecular studies suggest a functional interaction between these genes. We therefore investigated the effect of TP53 R72P and MDM2 SNP309 on breast cancer risk and age at onset of breast cancer in a pooled series of 5,191 cases and 3,834 controls from the Breast Cancer Association Consortium (BCAC). Breast cancer risk was not found to be associated with the combined variant alleles [odds ratio (OR), 1.00; 95% confidence interval (95% CI), 0.81–1.23]. Estimated ORs were 1.01 (95% CI, 0.93–1.09) per MDM2 SNP309 allele and 0.98 (95% CI, 0.91–1.04) for TP53 R72P. Although we did find evidence for a 4-year earlier age at onset for carriers of both variant alleles in one of the breast cancer patient series of the BCAC (the German series), we were not able to confirm this effect in the pooled analysis. Even so, carriers of both variant alleles did not have different risk estimates for bilateral or estrogen receptor–positive breast cancer. In conclusion, in this large collaborative study, we did not find an association of MDM2 SNP309 and TP53 R72P, separately or in interaction, with breast cancer. This suggests that any effect of these two variants would be very small and possibly confined to subgroups that were not assessed in our present study. [Cancer Res 2007;67(19):9584–90]