tbuckley/cabot-search huggingface dataset:
Abstract 5265: Development of a microfluidic device for tagless analysis of cell surface proteins directing lung metastasis
Authors: Sri H. Vellanki, Robin L. Smith, Samir Tivari, Rajan Kumar, Robert Wieder
Journal: Cancer Research (2011)

Abstract Diagnostic analysis of the few tumor cells obtained by needle aspirates is currently limited to the cells’ morphologic characteristics. We are investigating tagless analysis of cell surface protein composition, when limited cell numbers are available, using a flow retardation microfluidic device. Expression of biologically significant cell surface proteins by individual cells is scored positive by achievement of flow retardation due to transient binding of cell surface proteins to cognizant antibodies immobilized on tandem patches of the channel. This permits repetitive queries of the same cell for several proteins that predict specific malignant behavior. We are adapting the model to LM2 cells, derived from lung metastases of MDA-MB-231 breast cancer cells, which selectively metastasize to the lung*. The original study identified 95 unique genes either overexpressed or underexpressed in LM2 cells compared to parental cells. Of these we identified three cell surface proteins, VCAM1, IL13RA2, and EMP1, as heterogeneously upregulated in a subset of LM2 cells and CXCR4, as downregulated in a subset of LM2 cells when compared with MDA-MB-231 cells. VCAM1 and IL13RA2 promote lung metastasis*. We sterile sorted LM2 cells into fractions expressing none, medium and high levels of these four proteins. We built a prototype microfluidic device able to retard the flow of streptavidin-coated silica oxide beads by immobilized biotin and used optical imaging and a tracking program for simultaneous analysis of multiple particles. We developed efficient and stable protein coating of microchannels and are generating patches with cognizant antibodies to these 4 antigens and to endothelial, macrophage, lymphocyte, fibroblast and endothelial cell markers as controls. We will correlate antigen expression levels with flow retardation efficiency. We will optimize shear rates affecting bond formation and shear stress affecting bond dissociation by optimizing velocity, viscosity, detergent and divalent cation concentrations to maximize cell separation. We will adapt the channel to select LM2 cells from excess controls in vitro and from tumor xenograft aspirates. *Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL and Massague J (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518-524. 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 5265. doi:10.1158/1538-7445.AM2011-5265
Cryptosporidiosis: An Outbreak Associated with Drinking Water Despite State-of-the-Art Water Treatment
Authors: Susan T. Goldstein
Journal: Annals of Internal Medicine (1996)

Objective: To determine the magnitude and source of an outbreak of cryptosporidiosis among persons with human immunodeficiency virus (HIV) infection and to determine whether the outbreak extended into the immunocompetent population. Design: Matched case–control study and environmental investigation. Setting: Clark County, Nevada. Participants: Adults with HIV infection (36 case-patients with laboratory-confirmed Cryptosporidium parvum infection and 107 controls), matched by physician or clinic and by CD4+ cell count category. Measurements: Potential risk factors for infection, death rates, and data on water quality. Results: Review of surveillance and microbiology records identified 3 cases of cryptosporidiosis in 1992 (the first year that cryptosporidiosis was reportable in Nevada), 23 cases in 1993, and 78 cases in the first quarter of 1994. Of the 78 laboratory-confirmed cases in the first quarter of 1994, 61 (78.2%) were in HIV-infected adults. Of these 61 adults, 32 (52.5%) had died by 30 June 1994; at least 20 of the 32 (62.5%) had cryptosporidiosis listed on their death certificates. In the case–control study, persons who drank any unboiled tap water were four times more likely than persons who drank only bottled water to have had cryptosporidiosis (odds ratio, 4.22 [95% CI, 1.22 to 14.65]; P = 0.02). For persons with CD4+ cell counts less than 100 cells/mm3, the association between tap water and cryptosporidiosis was even stronger (odds ratio, 13.52 [CI, 1.78 to 102.92]; P = 0.01). Additional data indicate that this outbreak also affected persons who were not infected with HIV. No elevated turbidity values or coliform counts and no Cryptosporidium oocysts were found in testing of source (Lake Mead) or finished (treated) water during the study period, but so-called presumptive oocysts were intermittently found after the investigation in samples of source water, filter backwash, and finished water. Conclusions: A cryptosporidiosis outbreak was associated with municipal drinking water, despite state-of-the-art water treatment and water quality better than that required by current federal standards. This outbreak highlights the importance of surveillance for cryptosporidiosis and the need for guidelines for the prevention of waterborne-Cryptosporidium infection among HIV-infected persons.
De Rerum Natura (The Nature of Things)
Authors: B. Twisselmann
Journal: BMJ (2009)

De Rerum Natura is science, including medical science, in verse. The Roman aristocrat Lucretius (99-55 bc) was a follower of the Greek philosopher Epicurus of Samos (341-27 bc). His narrative poem in six books was an attempt to publicise the Epicurean view of the universe in Rome. The underlying concept is that everything in the world, including human beings, consists of clusters of an infinite number of atoms (άτομον, or that which cannot be divided) that move around in an infinite void and in an unpredictable manner. Determinism is not a concept in this philosophy, and neither is immortality. These atoms vary in size, density, shape, speed, and concentration. Ambitious …
Lamivudine treatment for acute hepatitis B after liver transplantation
Authors: Pietro Andreone, Paolo Caraceni, Gian Luca Grazi, Luca Belli, Gian Luigi Milandri, Giorgio Ercolani, Elio Jovine, Antonia D'Errico, Pier Roberto Dal Monte, Gaetano Ideo, Domenico Forti, Alighieri Mazziotti, Antonino Cavallari, Mauro Bernardi
Journal: Journal of Hepatology (1998)
Senior staff should see all emergencies
Authors: J. Stevenson
Journal: BMJ (1994)

EDITOR,--The guidelines for the early management of patients with myocardial infarction raise several points and highlight some deficiencies in the care of emergencies in Britain.1 It is important to differentiate between treatment required by patients who present with cardiac arrest and that required by patients who present with symptoms of chest pain suggestive of myocardial infarction.

The best chance of survival after cardiac arrest in the community occurs when a bystander gives immediate and effective basic life support …
666. LV with Different Promoters Mediated Gene Expression in the Inner Ear
Authors: Maoli Duan, Anders Fridberger, Dongguang Wei, Cecilia Lundberg
Journal: Molecular Therapy (2005)

Introduction: Hearing loss is one of the most common diseases in our society affecting more than 10% of the population. The inner ear is unique organ compared to other system. First, the cochlea is a relatively isolated organ, which minimises unwanted effects on other tissues. The limited direct blood supply of the cochlea should also reduce the risk of immune responses. As the cochlea is fluid-filled, all functionally important cells are easily reached and a wide transfection of the cochlea is expected. These anatomic characteristics provide a beautiful model to carry out gene therapy in the inner ear since we can control the concentration using either a single injection or an osmotic pump to infuse genes into the cochlea chronically. The volume of perilymph and endolymph are charaderised in guinea pig, rat and mouse, the dosage can be controlled tightly and thus the risk of adverse effects a redecreased. Secondly, there is no other peripheral system in our body like the inner ear where so many genes have been cloned during past a few years. Rapid progress has been made in identifying hearing-related genes in the mouse. Thirdly, many transit factors and neurotrophins have been found coupled to development of the inner ear and even to survival of sensory cells of adult's inner ear against environmental damage such as noise trauma, ototoxic chemicals and ageing. However, we should keep in mind that gene delivery is critical key to make inner ear gene therapy success. At present, the main problem of gene therapy is the lack of efficient, specific and very safe gene delivery system. These bottlenecks are particular in the case for inner ear gene therapy. There is no report to show viral and non-viral vectors can target hair cells in vivo situation according to our knowledge. Thus, we will develop methods to see which vector can target hair cells and cochlear neurons in vivo.
So the Blind May See
Authors: David G. Cogan
Journal: New England Journal of Medicine (1969)

Engineering and medicine are locked into many projects to their mutual advantage and to the ultimate benefit of the patient. One of the less publicized but potentially most useful joint endeavors is the development of electronic devices for the blind. A recent conference* under the combined auspices of the Association for Computer Machinery, the Foundation for the Blind and the National Institute for Neurological Diseases and Stroke revealed several types of devices that are under current scrutiny.One is direct stimulation of the occipital cortex through implanted electrodes. The feasibility of this for human subjects was demonstrated two years ago, . . .
Expression of Nonmuscle Myosin Heavy Chain-B Isoform in the Vessel Wall of Porcine Coronary Arteries After Balloon Angioplasty
Authors: H. De Leon, N. A. Scott, F. Martin, L. Simonet, K. E. Bernstein, J. N. Wilcox
Journal: Circulation Research (1997)

Abstract Nonmuscle myosin heavy chain-B isoform (NMMHC-B) is expressed by proliferating vascular smooth muscle cells (SMCs), and its expression in primary lesions has been proposed to be predictive of restenosis after atherectomy. The present study was designed to study the time-course expression of NMMHC-B after angioplasty of porcine coronary arteries by in situ hybridization and immunohistochemistry. Domestic juvenile swine underwent percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending and circumflex coronary arteries with standard clinical angioplasty catheters. To identify proliferating cells, 5′-bromo-2′-deoxyuridine (BrdU) was administered and detected by immunohistochemistry on serial sections. Vessels were examined at 3, 7, and 14 days after balloon angioplasty, and uninjured coronary vessels were used as controls. Normal arteries showed hybridization to 35 S-labeled NMMHC-B riboprobes localized mainly in the medial layer. NMMHC-B expression in the adventitia was markedly increased 3 days after balloon angioplasty. Seven and 14 days after injury, NMMHC-B mRNA–containing cells were localized in the adventitia and neointima at the arterial injury site. Cell proliferation, as indicated by BrdU staining, colocalized with NMMHC-B mRNA expression 3 and 7 days after angioplasty. These data indicate that cells proliferating in the adventitia and neointima express NMMHC-B; however, its expression is not limited to the proliferative state, since NMMHC-B mRNA was also found in quiescent SMCs of normal coronary arteries and in nonproliferating adventitial and neointimal cells 14 days after angioplasty.
Cigarette Smoking and Ischaemic Heart Disease
Authors: B. Bronte-Stewart
Journal: BMJ (1961)

BRDITISH3RNA379Association, would receive a fresh impetus.Perhaps, as we have seen, our own B.M.A. Commonwealth Con- ference and Overseas Committee can take the initiative.But the overwhelming satisfaction of achieving this co-operation-and in what field is there more prospect of success than in medicine and health ?-would lie in the substantial step it would represent towards human brotherhood and co-operation.We are already, through the advent of the radio and the aeroplane, one world, for better or for worse.Here is a chance to emphasize the good in contrast to the many opportunities for evil.All the peoples of the world suddenly seem to have grasped the idea that they need not continue in hunger, poverty, ill-health, and ignorance.They know with Isaiah that every valley can be exalted and every mountain and hill laid low, and they are determined in action to bring about the changes they desire.The newly awakened countries may not know clearly what the good life is, or how to achieve it-any more perhaps than we do in the wealthier countries; but they do recognize some of the bad features of their present condition, as we do, and they will try to remedy them.They see in technology the way to grow more food, secure more shelter, and gradually to ameliorate their lot.How proper it is for us, who for the moment- perhaps a very fleeting moment-know a little more about these things, to wish to help; how dismal our failure if we sit at ease in our Zions and do nothing.In terms of practical politics and even of self-interest it may be better to lend a hand-when and where it is wanted-while the brief opportunity is there.It is not only in medicine and health that Commonwealth-wide co-operation is promising.The British Association meeting at Cardiff in September, 1960, talked about food production and mouths to be fed on the world scale.It was obviously again " one world " where mutual interdependence and co-operation seemed desirable, indeed inescapable.Progress in agriculture and in health go very much together, the one helping
Practice Guidelines-Reply
Authors: Robert H. Brook
Journal: JAMA (1990)

<h3>In Reply.—</h3> Developing valid practice guidelines is emotionally difficult and intellectually challenging, and I am appreciative of Dr Woolf's and Mr Goldschmidt's comments on my article. Unfortunately, parts of my article appear to be misinterpreted. In particular, Dr Woolf argues that I recommended that guidelines be used by insurers, courts, etc. I argued that they might be used by these agencies. If physicians aggressively pursue the development of valid practice guidelines and modify their practices to reflect their content, then such use might be unnecessary. It might be even in physicians' interest for each of us to contribute $100 per year to the development of publicly available and valid practice guidelines that would shape the future of American medicine. Willingness to help finance this activity might help convince the public that physicians want to use guidelines, as Dr Woolf suggests, for the purpose of continuing improvement. In terms of the
Fortnightly Review: Pressure sores
Authors: R K Vohra, C N McCollum
Journal: BMJ (1994)

Pressure sores have defied the best attempts of medical and nursing staff since they were first described in Egyptian mummies.'They are defined as a localised area of tissue damage resulting either from direct pressure on the skin causing pressure ischaemia or from shearing forces causing mechanical stress to the tissues.The pathophysiology remains poorly understood.2Pressure sores are painful, unsightly, difficult to treat, and costly.The estimated cost of caring for pressure sores is £150 million a year in the United Kingdom and more than $3 billion in the United States.34A full thickness sacral sore typically involves substantial expenditure in staff time, dressing materials, drugs, and special pressure relieving beds during hospital inpatient care over many months; the estimated total cost per patient is £26 000.' Also, there is the cost to patients in lost income, productivity, and independence, which the patients and their relatives increasingly attempt to recover from health authorities by litigation.67 PrevalenceThe prevalence of pressure sores among hospital inpatients in the United Kingdom is 7-8%; it may be even higher in community medicine.89Elderly people are particularly susceptible, with 70% of all pressure sores occurring in patients aged over 70 years.'0Younger patients usually have an underlying neuro- logical disorder, and patients with cerebral palsy, multiple sclerosis, and spinal cord lesions are par- ticularly susceptible: up to 85% of paraplegics develop a pressure sore."-'3Wheelchair users are also at a special risk, and around a quarter will develop a sore.'
Malignant Polyps: Are They Sheep in Wolves' Clothing?
Authors: Ronald L. Koretz
Journal: Annals of Internal Medicine (1993)

One of the arguments supporting the concept that benign adenomatous polyps of the colon degenerate into cancer is the observation of malignancy in polypoid growths known to have been present for years. Although a latent phase--the duration of time between the initial development of a malignancy and the subsequent occurrence of a clinical problem--must exist, this argument implies that this time span is not many years. If both the prevalence of malignant polyps and the incidence of consequent symptomatic colon cancer were known, the average latent phase could be calculated. In order to estimate this prevalence, I used autopsy data; the estimate was validated using independent data fro three colonoscopic screening studies. The annual incidence of all colon cancer in the United States is approximately 150,000 cases. I estimate that 725,000 people in the United States harbor at least one malignant polyp. Even if all 150,000 cases of colon cancer were associated with symptoms and began as malignant polyps, the average latent phase is 4.8 years. Because some colon cancers are removed while the patient is still asymptomatic (discovered on screening examination) and because at least some colon cancers arise de novo from the mucosa, the average latent phase must be even longer. These estimates suggest that it cannot be assumed that the histologic finding of cancer in a polyp that has been observed for many years represents "malignant degeneration" of a previously benign neoplasm; such a malignancy may have had that histologic characteristic from the start. Further, histologically ominous lesions (malignant polyps) may often have prolonged benign clinical courses.
Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis
Authors: A. C Ford, N. J Talley, B. M R Spiegel, A. E Foxx-Orenstein, L. Schiller, E. M M Quigley, P. Moayyedi
Journal: BMJ (2008)

<b>Objective</b> To determine the effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome. <b>Design</b> Systematic review and meta-analysis of randomised controlled trials. <b>Data sources</b> Medline, Embase, and the Cochrane controlled trials register up to April 2008. <b>Review methods</b> Randomised controlled trials comparing fibre, antispasmodics, and peppermint oil with placebo or no treatment in adults with irritable bowel syndrome were eligible for inclusion. The minimum duration of therapy considered was one week, and studies had to report either a global assessment of cure or improvement in symptoms, or cure of or improvement in abdominal pain, after treatment. A random effects model was used to pool data on symptoms, and the effect of therapy compared with placebo or no treatment was reported as the relative risk (95% confidence interval) of symptoms persisting. <b>Results</b> 12 studies compared fibre with placebo or no treatment in 591 patients (relative risk of persistent symptoms 0.87, 95% confidence interval 0.76 to 1.00). This effect was limited to ispaghula (0.78, 0.63 to 0.96). Twenty two trials compared antispasmodics with placebo in 1778 patients (0.68, 0.57 to 0.81). Various antispasmodics were studied, but otilonium (four trials, 435 patients, relative risk of persistent symptoms 0.55, 0.31 to 0.97) and hyoscine (three trials, 426 patients, 0.63, 0.51 to 0.78) showed consistent evidence of efficacy. Four trials compared peppermint oil with placebo in 392 patients (0.43, 0.32 to 0.59). <b>Conclusion</b> Fibre, antispasmodics, and peppermint oil were all more effective than placebo in the treatment of irritable bowel syndrome.
Effects of human mast cell tryptase and eosinophil granule proteins on the kinetics of blood clotting
Authors: Michael Samoszuk, Mark Corwin, Stanley L. Hazen
Journal: American Journal of Hematology (2003)

Abstract Hypereosinophilic syndromes are often associated with thrombosis through unclear mechanisms, and mastocytosis has been associated with a variety of bleeding disorders. The present studies were aimed at defining the roles and interactions of eosinophil and mast cell constituents on the kinetics of blood clotting as measured by thromboelastograms. Eosinophil granule proteins and purified eosinophil peroxidase markedly reduced the anticoagulant properties of the mast cell tryptase/heparin complex. Moreover, eosinophil peroxidase by itself functioned as a powerful procoagulant and also inhibited the anticoagulant actions of heparin in a chromogenic assay for antithrombin III/factor Xa activity. The anticoagulant activity of the tryptase/heparin complex was attributable exclusively to the associated heparin and not to the intrinsic enzymatic activity of tryptase. Eosinophil granule proteins also strongly inhibited the enzymatic activity of tryptase in the presence of hydrogen peroxide, thus implicating a critical role for eosinophil peroxidase. We conclude that eosinophil granule proteins and eosinophil peroxidase both function as powerful procoagulants and also inhibit the anticoagulant and enzymatic activities of mast cell tryptase. The present results thus provide a mechanistic rationale for the well‐established link between certain eosinophilic inflammatory disorders and hypercoagulant states. They also suggest that eosinophils may play an important role in neutralizing the anticoagulant activity of mast cell tryptase/heparin in various diseases. Am. J. Hematol. 73:18–25, 2003. © 2003 Wiley‐Liss, Inc.
Characterization of H+ efflux pathways in rat hepatocytes
Authors: Sawkat M. Anwer, Kathleen Nolan
Journal: Hepatology (1988)

A pH-stat method was used to characterize H + efflux pathways in hepatocytes in order to determine if Na + / H + and Ca ++ /H + exchange are involved in H + efflux from hepatocytes under basal conditions and if cyclic AMP analogs affect Na + /H + exchange. Total H + efflux of freshly prepared hepatocytes ranged from 10 to 15 nmoles per min per mg protein. A part of total H + efflux (35 to 50%) was dependent on extracellular Na + . This Na + -dependent H + efflux was (i) inhibited by amiloride with a half-maximal effect at 0.3 m M , (ii) inhibited by ouabain, (iii) dependent on extracellular pH and (iv) characterized by a K m of 15 ± 3 m M Na + and a Vmax of 9 ± 0.07 nmoles per min per mg protein. Amiloride, ouabain and replacement of Na + by choline also decreased intracellular pH determined from equilibrium distribution of dimethyloxazolidinedione. Li + could partially substitute for Na + in Na + -dependent H + efflux and in maintaining intracellular pH. Efflux of CO 2 and lactic acid from hepatocytes represented 80% of Na + -independent H + efflux. Efflux of H + in the presence and absence of Na + was not significantly altered by extracellular Ca ++ (&lt;10 μ M and 1.0 m M ). Thus, Ca ++ /H + exchange is unlikely to contribute significantly to total H + efflux from hepatocytes. Cyclic AMP analogs, dibutyryl cyclic AMP and 8-bromo cyclic AMP, inhibited amiloride-sensitive Na + -dependent H + efflux, and dibutyryl cyclic AMP decreased intracellular pH. These results indicate that (i) both Na + -independent and Na + -dependent mechanisms are involved in H + efflux from hepatocytes, (ii) Na + -dependent H + efflux represents Na + /H + exchange and is involved in maintaining intracellular pH and (iii) cyclic AMP analogs decrease intracellular pH by inhibiting Na + /H + exchange.