tbuckley/cabot-search huggingface dataset:
B‐CAM/LU expression and the role of B‐CAM/LU activation in binding of low‐ and high‐density red cells to laminin in sickle cell disease
Authors: Qin Zen, Milena Batchvarova, Christina A. Twyman, Christine E. Eyler, Huiling Qiu, Laura M. De Castro, Marilyn J. Telen
Journal: American Journal of Hematology (2004)

Abstract Red blood cells from patients with sickle cell disease (SS RBC) adhere to laminin and over‐express the high‐affinity laminin receptor basal cell adhesion molecule/Lutheran protein (B‐CAM/LU). This receptor has recently been shown to undergo activation in vitro through a protein kinase A‐dependent mechanism. Low‐density SS RBC express two‐thirds more B‐CAM/LU than high‐density SS RBC. However, high‐density SS RBC have been identified as most adherent to laminin under flow conditions. We investigated the ability of low‐ and high‐density SS RBC to interact with laminin under various conditions and explored factors that might be responsible for the differences in B‐CAM/LU–laminin interaction between high‐ and low‐density SS RBC. We confirmed that high‐density SS RBC adhere to laminin more strongly than low‐density SS RBC under flow conditions. However, low‐density SS RBC bind soluble laminin most strongly and are the most adherent to laminin under static conditions. Soluble recombinant Lutheran extracellular domain protein completely blocked SS RBC adhesion to laminin under both static and flow conditions. The protein kinase A inhibitor 14‐22 amide inhibited adhesion to laminin during flow by high‐density SS RBC from patients with strongly adherent cells but had no effect on adhesion observed after a static phase. Deletion of the cytoplasmic domain of B‐CAM as well as mutation of the juxtamembranous tyrosine residue failed to reduce B‐CAM‐mediated adhesion to laminin by transfected MEL cells. These studies confirm that B‐CAM/LU is the most critical receptor mediating adhesion to laminin under both static and flow conditions. Dense SS RBC are most adherent to laminin despite bearing fewer laminin receptors, apparently due to a reversible protein kinase A‐dependent process that is unlikely to involve direct phosphorylation of B‐CAM/LU. Our results also suggest that the nature of the interaction of B‐CAM/LU with laminin may be different under static and flow conditions. Am. J. Hematol. 75:63–72, 2004. © 2004 Wiley‐Liss, Inc.
177. Analysis of the High Shear Cell Lysis Device and the Air-Mixed Neutralization Column Used in the Recovery of Plasmid DNA from E. coli Cells
Authors: Sriram Ramakrishnan, Hugo Gonzalez, Henry L. Hebel
Journal: Molecular Therapy (2005)

Low-shear, alkaline-lysis procedures for cell lysis have been well-described in the literature. These methods avoid mechanical damage to the plasmid and other impurities. Further, low-shear methods for lysate neutralization and subsequent removal of solids is typically performed by mechanical means, such as filtration or centrifugation. However, these solid removal methods are limited by their inability to be scaled-up or involve laborious and numerous time-consuming steps. Liquid recovery has also been very inefficient in cases of filtration. Methods developed at ADViSYS, Inc., for such cell lysis and neutralization of cell lysate have defied conventional knowledge for shear-sensitive steps. Cell lysis is achieved through the use of a high-shear imparting emulsifier that effectively lyses the cells. Subsequent neutralization of the cell lysate is achieved by using a bubble column mixer that promotes the mixing of the lysed cells with the neutralization solution using air sparging. The mixing action is created by these upward flowing air bubbles and the entrapment of micro-bubbles aids in the further removal of solids.
Effect of Dietary Energy Restriction on Vascular Density during Mammary Carcinogenesis
Authors: Henry J. Thompson, John N. McGinley, Nicole S. Spoelstra, Weiqin Jiang, Zongjian Zhu, Pamela Wolfe
Journal: Cancer Research (2004)

Abstract Inhibition of mammary carcinogenesis by dietary energy restriction is associated with a decrease in cell proliferation and the induction of apoptosis. Although changes in the metabolism of insulin-like growth factor I and glucocorticoids have been proposed to modulate these cellular processes, limitations in blood supply could induce similar effects. To investigate this possibility, female Sprague Dawley rats were given an injection of 1-methyl-1-nitrosourea and fed purified diets ad libitum or at 60% ad libitum intake, i.e., 40% dietary energy restriction. Premalignant mammary pathologies and mammary adenocarcinomas obtained from these rats were processed for vascular density analysis via CD-31 immunostaining. Vascular density, measured as vessels/unit area, of premalignant mammary pathologies and adenocarcinomas from dietary energy restriction rats was reduced 31 and 39%, respectively (P &amp;lt; 0.01). This effect, which was observed in a 50-μm wide band of tissue surrounding each pathology, was exerted on blood vessels &amp;gt; 25 μm2. Conversely, intratumoral vascular density was unaffected by dietary energy restriction. cDNA microarray and Western blot analyses of adenocarcinomas for evidence of dietary energy restriction-mediated effects on vascularization revealed that only the level of vascular endothelial growth factor receptor protein Flk-1 was significantly reduced (P &amp;lt; 0.001). It appears that dietary energy restriction imposes limitations in the supply of blood to developing pathologies, an effect that could directly inhibit the carcinogenic process. The vascular density data imply that dietary energy restriction inhibited the growth of endothelial cells but leave unresolved the question of whether dietary energy restriction had a specific effect on angiogenesis. The factors that account for the failure of dietary energy restriction to limit intratumoral vascularization are not obvious and merit additional investigation.
No laughing matter
Authors: Douglas Kamerow
Journal: BMJ (2007)

The writer, director, and actor Michael Moore has cleverly woven the funniest, saddest, and most gruesome of more than 25 000 healthcare horror stories submitted to his website into a powerful and affecting film. Sicko will inflame his supporters as well as his detractors.

In the film's opening scene a man without insurance sutures a gaping wound on his own leg with what looks like a regular needle and thread. We then hear from an uninsured man who cut off the tips of two fingers with a saw. As it was not a life threatening illness and he had no insurance, the hospital told him he could pay $12 000 (£6000; €9000) to reattach his ring finger or $60 000 for his middle finger, or both. “Ever the romantic,” Moore quips, “he chose the ring finger.”

But Moore's real target in the movie is not the amorphous healthcare “system” in the United States or even the government. The villains are the large health insurance companies that sell coverage but then use all manner of tactics to worm out of paying for needed care, leading to discomfort, suffering, …
Informing Physicians About Promising New Treatments for Severe Disease
Authors: Gail S. Cairns
Journal: JAMA (1990)

To the Editor.—  We agree with Drs Steinbrook and Lo 1 that increasing the detailed information in unconventional communications indeed can provide timely and useful information to physicians. Our experience shows that diagnostic information may be transmitted quickly. In January 1990, Epidemic Intelligence Service Officer Kelly J. Henning, MD, identified practitioners' need for additional clinical information on the newly recognized tryptophan-associated eosinophilia-myalgia syndrome.  The decision was made to publish an emergency alert issue of City Health Information , the monthly epidemiologic bulletin of the New York City Department of Health. We were at press within 24 hours with an issue that described clinical, laboratory, and roentgenographic findings in the first 96 cases of eosinolphilia-myalgia syndrome in New York State. Copies were mailed to New York City's 24 000 physicians and to 8000 other health care providers within the next 2 weeks. In addition, the department's public health advisers hand carried the
A New Year's resolution after a lost decade
Authors: D J Weatherall
Journal: BMJ (2003)

For the universities of the rich world to forge real partnerships with the developing world 

All in all, 2003 has not been the best of years. The war in Iraq has been followed by the further destabilisation of the Middle East; the spin doctoring activities of government on both sides of the Atlantic have left their populations increasingly distrustful of politicians; and, closer to home, we have been regaled almost daily by stories of a dysfunctional healthcare system and the incompetence of doctors. Yet buried beneath all this gloom, and only rarely mentioned by the media, is the disturbing fact that over the past 10 years the already huge gap in the economic standing and state of health between the poor and rich countries of the world has widened even further. For many in the developing world it has been a decade of lost opportunity.

Although during the 1990s gross domestic product per head in the developing countries grew by 1.6% a year, and the proportion of people living on less than $1 a day fell from 29% to 23%, most of this progress was made in Asia.1 In other regions the number of poor people increased, even though the overall proportion in extreme poverty has fallen.1 Furthermore, 150 million children in low and middle income economies are still suffering from malnourishment, and, unless the situation improves, a similar number will be …
Identification of promoter activity and differential expression of transcripts encoding the murine stromelysin-1 gene in renal cells
Authors: Jerry Yee, Gerald S. Kuncio, Basant Bhandari, Fuad S. Shihab, Eric G. Neilson
Journal: Kidney International (1997)

Stromelysin-1, matrix metalloproteinase-3 (MMP-3), is an important endopeptidase selectively expressed by somatic cells in organ tissues. The renal tubulointerstitium, for example, comprises tubular epithelium and interstitial fibroblasts forming the principal mass of the kidney. We observed that mRNA encoding stromelysin-1 is detectable in murine renal fibroblasts, but not in proximal tubular epithelium. Transcripts measured by RNase protection assay in renal fibroblasts increase following exposure to phorbol ester, and thereafter, activated stromelysin-1 protein can be detected in culture media by Western blotting. A 6.4 Kb genomic clone containing the putative stromelysin-1 promoter was isolated and a relevant 2.1 Kb PstI restriction fragment including 2.1 Kb of the immediate 5'-flanking region was sequenced on both strands. Two transcriptional start sites were identified by primer extension; the major start site corresponded to a previously established position in the rat promoter, and a second undescribed minor transcriptional start site was located 16 bp upstream of the primary site. A HiNF-A chromatin-activating element at -106 bp was found in the early promoter region of pR336 and an active AP-1 site at -72 bp with an Ets/PEA-3 motif at -203 bp was suggested by transient transfection of luciferase minigenes into renal fibroblasts responsive to phorbol ester. This Ets element was identical to a site in the early promoter of the fibroblast-specific gene FSP1. A baseline enhancement in activity of pR336 in fibroblasts was further observed with the addition of 5' flanking sequence out to -1980 bp. This additional region of flanking sequence contains two modular regions: one of multiple PEA-3 elements between -684 bp and -1955 bp and a second region between -1929 bp and -1980 bps containing a second AP-1 site at -1929 bp, a MBF-1/ MEP-1 metal binding site, and a PPAR peroxisome proliferator element at -1950 bp. Our findings implicate a gene structure with expected activity in a mesenchymal phenotype. The PKC-dependent regulation of the stromelysin-1 gene supports the notion that it may be modulated during inflammation or tissue remodeling.
Likelihood Ratios to Determine 'Does This Patient Have Appendicitis?': Comment and Clarification
Authors: Atle Klovning
Journal: JAMA (1997)

<h3>To the Editor.</h3> —At the Second Nordic Workshop on Evidence-Based Health Care in Oslo, Norway, in June 1997, our group worked on the JAMA article on appendicitis.<sup>1</sup>I tried to calculate the positive LR by using the numbers provided in Table 3 in the formula<sup>2</sup>(sensitivity/[1-specificity]) and calculated, for example, a positive LR of 1.59 vs 3.76 in the article for rigidity and a LR positive of 1.72 vs 7.31 to 8.46 in the article for right lower quadrant pain. The numbers appear to be wrong. The authors alternatively could have presented the findings as a summary of receiver operating characteristic curves, which might have been easier to interpret.
Prognostic factors in acute respiratory distress syndrome: a retrospective multivariate analysis including prone positioning in management strategy
Authors: Christophe Venet, Stephane Guyomarc'h, Juliette Pingat, Christophe Michard, Silvy Laporte, Monique Bertrand, Pierre Gery, Dominique Page, Regine Vermesch, Jean Claude Bertrand, Fabrice Zeni
Journal: Intensive Care Medicine (2003)
Perioperative Use of Selective Serotonin Reuptake Inhibitors and Risks for Adverse Outcomes of Surgery
Authors: Andrew D. Auerbach, Eric Vittinghoff, Judith Maselli, Penelope S. Pekow, John Q. Young, Peter K. Lindenauer
Journal: JAMA Internal Medicine (2013)

Importance: Single-site studies have described an association between use of selective serotonin reuptake inhibitors (SSRIs) and adverse outcomes of surgery.Multicenter studies including a broad range of surgical procedures that explore rare outcomes, such as bleeding and mortality, and that account for indications for administration of SSRIs are needed.Objective: To determine whether perioperative use of SSRIs is associated with adverse outcomes of surgery in a national sample of patients.Design: Retrospective study of patients 18 years or older who underwent major surgery from January 1, 2006, through December 31, 2008, at 375 US hospitals.We used multivariable hierarchical models to estimate associations between SSRI use and our outcomes.Pharmacy data were used to determine whether a patient received an SSRI in the perioperative period.Setting: Three hundred seventy-five US hospitals.Participants: Five hundred thirty thousand four hundred sixteen patients 18 years or older.Exposure: Perioperative use of SSRIs. Main Outcomes and Measures:In-hospital mortality, length of stay, readmission at 30 days, bleeding events, transfusions, and incidence of ventricular arrhythmias.Results: Patients receiving SSRIs were more likely to have obesity, chronic pulmonary disease, or hypothyroidism (P Ͻ.001 for each) and more likely to have depression (41.0%vs 6.2%, PϽ.001).After adjustment, patients receiving SSRIs had higher odds of in-hospital mortality (adjusted odds ratio, 1.20 [95% CI, 1.07-1.36]),bleeding (1.09 [1.04-1.15]),and readmission at 30 days (1.22 [1.18-1.26]).Similar results were observed in propensitymatched analyses, although the risk of inpatient mortality was attenuated among patients with depression.Sensitivity analyses suggest that, to invalidate our results, an unmeasured covariate would have to have higher prevalence and be more strongly associated with mortality than any covariate included in our models. Conclusions and Relevance:Receiving SSRIs in the perioperative period is associated with a higher risk for adverse events.Determining whether patient factors or SSRIs themselves are responsible for elevated risks requires prospective study.
Diagnostic biopsy for hepatocellular carcinoma in cirrhosis: useful, necessary, dangerous, or academic sport?
Authors: J Scholmerich
Journal: Gut (2004)

At present, in experienced hands, ultrasound guided biopsy using either cut needles or fine needle aspiration, seems to be technically appealing and most effective for diagnosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the eighth most frequent tumour entity worldwide (one million per year). The incidence in the USA and elsewhere has increased, which is probably due to the rise in the incidence of hepatitis C virus infection. A number of cohort studies have shown that surveillance using abdominal ultrasound (US) improves management of HCC developing in cirrhotic patients as it allows early detection and application of potentially curative treatments.1 Thus far it is not entirely clear whether surveillance increases survival as no randomised controlled trials have been conducted to answer this question. However, as eventually curative treatments such as resection, ablation, and in particular liver transplantation have emerged as effective means of treating HCC as long as it is not too large and too widespread, early diagnosis seems to be a reasonable goal in improving the poor prognosis of this cancer.2–4 Interestingly, it has recently been shown by comparison of time periods that besides being part of the more recent cohort, tumour staging was the only independent predictor of survival.1 Thus it seems obvious that detection of early carcinoma in liver cirrhosis would be a reasonable goal. Progress made in recent years regarding imaging, in particular spiral computed tomography and using the increased vascularity of HCC, allowing for better scanning protocols, has increased the detection rate significantly. In addition, magnetic resonance imaging has become the diagnostic procedure of choice in some institutions. However, most experts still advocate liver biopsy.5–11

In addition, improved US techniques such as contrast enhancement with and without Doppler ultrasonography12,13 may improve early diagnosis further. However, no adequate …
Abstract B67: Metadherin mediates osteosarcoma invasion and metastasis
Authors: Limin Zhu, Adrianna S. Buford, Yanwen Yang, Pingyu Zhang, Wei-Lien Wang, Dennis P. Hughes
Journal: Cancer Research (2013)

Abstract Osteosarcoma is the most common type of bone malignancy in children. It is a highly invasive mesenchymal tumor in which metastasis accounts for the vast majority of mortality and morbidity in patients. Understanding the mechanisms controlling metastasis in osteosarcoma and developing novel therapeutic options targeting metastasis are essential for improving patient survival in this disease. Recent studies have shown that Metadherin (MTDH) plays a key role in mediating metastasis in a variety of human cancers. This study examined the role of MTDH in osteosarcoma metastasis and elucidated the mechanisms underlying its oncogenic activity. We used western blot, qPCR, and flow cytometry to measure the expression of MTDH in a panel of osteosarcoma cell lines. Patient-derived osteosarcoma samples were also examined for MTDH expression using immunohistochemistry. In parallel experiments we used MTDH-specific shRNA to down-regulate endogenous MTDH expression, and blocked cell surface MTDH by anti-MTDH antibodies. The impact of MTDH inhibition was assessed in vitro using migration assays and matrigel invasion assays. We also developed an osteosarcoma orthotopic xenograft model of NOD/SCID/IL2Rγ-deficient mice through intratibial injection of osteosarcoma cells with or without MTDH knockdown to study the relationship between MTDH expression and pulmonary metastatic potential of osteosarcoma cells. Compared to normal human osteoblasts, all osteosarcoma cell lines tested displayed elevated MTDH expression as shown by western blot, qPCR and flow cytometry analyses. MTDH knockdown reduced migration and decreased invasion in matrigel. Inhibition of cell surface MTDH with an anti-MTDH antibody targeting the extracellular domain of MTDH also profoundly impeded osteosarcoma cell motility and invasiveness in vitro. In an orthotopic xenograft mouse model using CCHD cells, inhibition of MTDH delayed primary tumor growth and prohibited pulmonary metastasis. All mice in the control group developed lung metastases while fewer than 20% of the mice in the MTDH-knockdown group showed sign of metastasis at six weeks after inoculation. MTDH knockdown also reduced mean lung weight and mean number of pulmonary metastasis. Immunohistochemical analysis of tumor samples showed that lung metastases had elevated MTDH expression level compared to primary tumors. Altogether these studies suggested that MTDH plays a critical role in promoting pulmonary metastasis of osteosarcoma and may serve as an attractive target for therapeutic intervention. Citation Format: Limin Zhu, Adrianna S. Buford, Yanwen Yang, Pingyu Zhang, Wei-Lien Wang, Dennis P. Hughes. Metadherin mediates osteosarcoma invasion and metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B67.
Increased amino acid clearance and urea synthesis in a patient with glucagonoma.
Authors: T P Almdal, H Heindorff, L Bardram, H Vilstrup
Journal: Gut (1990)

Fasting concentrations, clearance of exogenous infused amino acids, and lean body mass were studied in a patient with glucagonoma syndrome (fasting glucagon = 380 pmol/l, normal range 15-45 pmol). The fasting concentrations of all amino acids were reduced. The clearances of alanine, arginine, glycine, isoleucine, leucine, lysine, methionine, proline, serine, threonine, and tyrosine were increased. The urea synthesis rate during amino acid infusion was 27 mumols/kg per minute (normal range 20-24 mumols/kg per minute). The lean body mass of the patients was reduced to 59% of the expected value. It is suggested that the weight loss of patients with glucagonoma syndrome is partly due to increased hepatic conversion of amino acid nitrogen to urea nitrogen, resulting in decreased blood amino acid concentration, and secondary to this, organ protein catabolism, as shown by the decreased lean body mass.
Autopsy-Determined Causes of Death After Cardiac Valve Replacement
Authors: Frederick J. Schoen, Jack L. Titus, Gerald M. Lawrie
Journal: JAMA (1983)

We reviewed records of 378 patients who died after cardiac valve replacement and underwent autopsy at The Methodist Hospital, Houston, from 1962 through 1979. Patients were divided according to postoperative interval at death: within 30 days (early) or 30 days to ten years (late). Early deaths (279 patients) were due almost exclusively to cardiovascular abnormalities or operative complications (94%). Only 6% of early deaths were caused by prosthesis-associated complications. In contrast, late deaths (99 patients) were valve related in 47% of cases, including complete thrombotic occlusion or systemic thromboembolism (21%), prosthetic valve endocarditis (14%), valve dehiscence (6%), anticoagulation-related hemorrhage (3%), and mechanical degeneration (2%). Nine percent of late deaths were unrelated to cardiovascular disease. Thus, while early deaths primarily reflected the severity of preexisting or associated cardiovascular disease, prosthesis-associated complications were an important cause of late death after cardiac valve replacement.
IMPORTANCE OF THE SIZE OF STOMACH AND STOMA IN GASTRO-ENTEROSTOMIES
Authors: EDWARD L. JENKINSON
Journal: JAMA (1934)

Considerable has been written during the past fifteen years on gastro-enterostomy. Much has been said about the indications, contraindications, location and size of the stoma. Straus has done some excellent work on the preparation of the stomach prior to a gastro-enterostomy.  The importance of the position of the stoma has been stressed by many writers. Many have advised that the opening be placed at the most dependent part of the stomach, while others have found that the location of the stoma was of little importance if the most important indication for the gastro-enterostomy was present; namely, pyloric obstruction. There seems to be quite universal agreement among surgeons that obstruction at the pylorus or in the first part of the duodenum is the most important indication for a gastro-enterostomy. It is in this type of case that the best results are obtained. Frequent fluoroscopic observations lead one to believe that the