tbuckley/cabot-search huggingface dataset:
Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit.
Authors: J A Dent, M Galbusera, Z M Ruggeri
Journal: Journal of Clinical Investigation (1991)

In this report we demonstrate that proteolytic cleavage of the constituent subunit is one of the causes determining the heterogeneous size distribution of plasma von Willebrand factor (vWf) multimers. As shown by two-dimensional nonreduced/reduced agarose/polyacrylamide gel electrophoresis, the structure of circulating vWf molecules may deviate from that represented by assemblage of a variable number of identical subunits. Indeed, even though the largest multimers in normal plasma appear to be composed predominantly of intact 225-kD subunits, those of intermediate and smaller size contain also 189-, 176-, and 140-kD proteolytic fragments. Different subunit composition patterns are repeated regularly in multimers of increasing molecular mass, yielding series of bands with similar structure. One of these series consists of molecules without evidence of proteolytic fragmentation, and its smallest member appears to be a dimer of 225-kD subunits. Type IIA von Willebrand disease, characterized by absence of the largest multimers, displays a pattern wherein the fragments of 176 and 140 kD are relatively increased, that of 189 kD is markedly decreased or absent, but the composition of individual multimers is otherwise similar to that of species seen also in normal plasma. In contrast to those in the circulation, all normal platelet vWf multimers contain only intact subunit. These results suggest that proteolytic cleavage of plasma vWf subunits occurs after release from cellular sites, whereas platelet vWf stored in alpha-granules is protected from proteolysis. These findings provide information that may be relevant for understanding the normal processing of vWf multimers and for elucidating the pathogenesis of some of the congenital and acquired structural abnormalities of this molecule.
BACTERIA ON FRUIT
Authors: J. T. Smeall
Journal: BMJ (1932)

JOURNAL:he typical gravis pellicle and granular deposit, while 28 ,howed uniform turbidity, and therefore resembled mitis.In 195 strains there was failure to ferment starch and glycogen (mitis), but in broth only 118 gave the typical mitis appear- ance, 14 showed pellicle and deposit, while 63 gave a deposit but no pellicle.We also observed colony differences on as " starch-fermenting type.
Coronary collateral function during exercise.
Authors: C Eng, R E Patterson, S F Horowitz, D A Halgash, A D Pichard, J Midwall, M V Herman, R Gorlin
Journal: Circulation (1982)

A totally occluded coronary vessel subtending a noninfarcted, entirely collateral-dependent myocardial region (NIECDMR) provides an opportunity to assess collateral perfusion during exercise stress. Collateral function was determined by analysis of exercise thallium-201 myocardial perfusion images from 31 patients who had at least one NIECDMR (total 41 NIECDMRs) documented during catheterization. Twenty-two of 41 NIECDMRs manifested exercise-induced perfusion defects and 19 were normally perfused. The exercise-negative NIECDMRs were further categorized: Group 1 NIECDMRs (n = 13) were associated with defects in other myocardial regions supplied by diseased vessels and were considered negative relative to other jeopardized regions; group 2 NIECDMRs (n = 6) were not associated with exercise-induced defects in other myocardial regions, which suggests that collateral perfusion was adequate during maximal exercise. Regions supplied by a diseased left anterior descending coronary artery manifested exercise defects regardless of collaterals, possibly because these regions were larger and required more perfusion. Angiographic indexes of collateral function did not clearly predict exercise results.
A Model for Continuing Comprehensive Care in A University Hospital General Medical Clinic.
Authors: Timm A. Zimmerman
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971A Model for Continuing Comprehensive Care in A University Hospital General Medical Clinic.Timm A. Zimmerman, M.D., James F. Wallace, M.D.Timm A. Zimmerman, M.D.Search for more papers by this author, James F. Wallace, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-836_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMost university hospitals are well-known for their scholarly research programs and sophisticated teaching of modern medicine. Increasingly, however, they are being criticized for providing few examples of comprehensive continuing medical care for students and physicians-in-training. Nowhere is this deficiency more conspicuous than in the general medical outpatient clinics. Differently utilized, these facilities might provide an ideal opportunity for relevant training of students and physicians in the field of internal medicine. Factors responsible for the inability of a typical university hospital general medical clinic to provide comprehensive continuing medical care include lack of physician continuity, insufficient physician interest or ability in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Timm A. Zimmerman, M.D.; James F. Wallace, M.D.Affiliations: Seattle, Wash. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 836-836KeywordsHospital medicineOutpatient clinics ePublished: 1 December 2008 Issue Published: 1 May 1971 PDF downloadLoading ...
Accidental Deaths, Saved Lives, and Improved Quality
Authors: Troyen A. Brennan, Atul Gawande, Eric Thomas, David Studdert
Journal: New England Journal of Medicine (2005)

The authors argue that despite the success of the patient-safety movement in attracting the attention of the public and the medical profession, the Institute of Medicine's goal of reducing deaths from medical errors by 50 percent has not been achieved. They believe the greatest promise will come not from a focus on preventing accidental deaths but from dedication to evidence-based interventions to deliver more effective medical care.
Regulation of the costimulator B7, not class II major histocompatibility complex, restricts the ability of murine kidney tubule cells to stimulate CD4+ T cells.
Authors: D T Hagerty, B D Evavold, P M Allen
Journal: Journal of Clinical Investigation (1994)

The proximal segment of murine kidney tubule cells (KTC) constitutively expresses low levels of class II major histocompatibility complex (MHC) that are upregulated during local and systemic inflammation. It is not known if KTC also express the costimulator molecules necessary for them to productively participate in immune responses and stimulate T cells. To answer this question, we studied the ability of KTC to present antigens to four Th1 clones. KTC did not induce T cell proliferation to specific antigen, superantigen, or concanavalin A. However, T cell receptors did engage the peptide/MHC ligand presented by KTC, as indicated by T cell enlargement and upregulation of interleukin-2 receptor expression. Importantly, KTC failed to express the Th1 costimulator, B7, as detected by fluorescence cytometry and reverse transcription polymerase chain reaction. We directly demonstrated that lack of B7 expression accounted for at least part of the KTC presentation defect, in that a KTC line transfected with the cDNA for B7 stimulated T cell proliferation to antigen. Our results suggest that epithelial cells expressing class II MHC have developed mechanisms to prevent costimulator expression and limit parenchymal tissue destruction. Failure of class II-expressing epithelial cells to limit costimulator expression may be an important component of organ-specific autoimmunity.
Pulmonary asbestosis and autoimmunity.
Authors: A Toivanen
Journal: BMJ (1976)

have reported values of 25-hydroxycholecalciferol of over 749 nmol/l (300 ng/ml) in vitamin D intoxication, and the value in the present case was even greater.It is not clear how much calciferol was being ingested, but the lack of response of the hypercalcaemia to treatment with prednisolone could have been due to consumption of a very high dose.
Performance assessment is here to stay
Authors: Anna Walker
Journal: BMJ (2004)

The Healthcare Commission has inherited the ratings task for 2003-4 and has recently advised that the number of breaches will now be measured as a percentage of the total number of patients a trust treats. 2Our analysis shows that trusts need to monitor constantly the statistical rigour of the performance indicators used to assess them.We thank L Parker for help with the statistical analyses and M F Laker for advice.
BLOOD GROUP ACTIVITY OF ALLERGENIC PREPARATIONS
Authors: L. BERRENS, C. L. H. GUIKERS, J. VAN RIJSWIJK‐VERBEEK
Journal: Allergy (1975)

Haemagglutination-inhibition studies showed that several different allergenic preparations exhibit A and B blood group activity. Most products displayed A-specificity, less often B-specificity; the inhibition titers were usually low. No correlation was evident between isoagglutination-inhibition titers and the complement-consuming capacity or skin-reactivity of the allergens. Absorption of A- and B-isoagglutinins from human serum did not affect the complement consumption by house dust allergens. Hapten-inhibition studies confirmed the non-participation of blood group antibodies in allergen-induced complement consumption. The observed inhibition by D-glucosamine is attributed to a partial structural homology with the lysine-sugar site on house dust allergens.
A guide to research partnerships for pragmatic clinical trials
Authors: K. E. Johnson, C. Tachibana, G. D. Coronado, L. M. Dember, R. E. Glasgow, S. S. Huang, P. J. Martin, J. Richards, G. Rosenthal, E. Septimus, G. E. Simon, L. Solberg, J. Suls, E. Thompson, E. B. Larson
Journal: BMJ (2014)

#### Summary points

Pragmatic clinical trials are comparative effectiveness studies conducted in real-world settings to answer questions relevant to patients, clinicians, and healthcare decision makers. In contrast, explanatory clinical trials study how treatments or interventions work in carefully controlled settings and study populations, often to investigate a biological hypothesis or test a drug or device to meet regulatory requirements. The pragmatic approach requires unique methods to achieve the goal of identifying sustainable, generalizable, evidence based ways to improve healthcare.1 2 3 4 5 While previous authors addressed statistical considerations,6 little guidance is available on the methods for establishing partnerships between researchers and the people and processes in usual care settings that are necessary to conduct a pragmatic clinical trial. Based on insights from an initiative to accelerate pragmatic research,7 this article summarizes best practices for researchers and partners in healthcare systems as they establish collaborative relationships, develop research questions, and implement sustainable pragmatic clinical trials.

A recent example …
Chest Wall Metastasis of Ileal Carcinoid Tumor Detected With In-111 Octreotide Scan
Authors: Bedri Seven, Erhan Varoglu, Kerim Cayir, Mustafa Yildirim, Omer Onbas, Fatih Alper, Mustafa Koplay, Umran Yildirim
Journal: Clinical Nuclear Medicine (2006)

Carcinoid tumors are potentially malignant, generally being related to regional lymph node and liver metastases. Rarely, metastases to other sites such as the breast have been reported. Radiolabeled peptide analogs such as In-111 octreotide play a useful role in the localization and potentially in the management of carcinoid tumors and their distant metastases. The authors report a case of ileal carcinoid tumor with unusual presentation of a chest wall metastasis. Chest radiograph was normal. Thoracic CT scanning showed a soft tissue mass in the chest wall. In-111 octreotide scintigraphy revealed increased uptake in the anterior chest wall and liver. A biopsy of the lesion showed carcinoid tumor.
Meta-analysis of trials of prophylactic antibiotics for children with measles: inadequate evidence
Authors: F. Shann
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To assess whether antibiotics should be given to all children with measles in communities with a high case fatality rate. <b>Design:</b> Meta-analysis of randomised controlled trials that compared routine antibiotic prophylaxis with no antibiotic treatment or selective treatment of pneumonia or sepsis. <b>Subjects:</b> Six trials of children admitted to hospital with measles: five in Glasgow, London, or New York between 1939 and 1954; and one in India in 1967. <b>Main outcome measures:</b> Incidence of pneumonia or sepsis, and mortality. <b>Results:</b> All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia or sepsis in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia or sepsis was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls (exact odds ratio 4.0, mid-P corrected 95% confidence interval 0.5 to 101.6). <b>Conclusion:</b> The quality of the trials reviewed was poor, and they provide weak evidence for giving antibiotics to all children with measles. Available evidence suggests that, when mortality from measles is high, all children with measles should be treated with vitamin A but antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis. <h3>Key messages</h3> Since many deaths from measles in young children are caused by bacterial pneumonia it might be sensible to give antibiotics to all children with measles where there is high case mortality, but there has been no systematic evaluation of such a policy Six randomised controlled trials of prophylactic antibiotics in children with measles were found All trials were poorly designed and preceded the introduction of vitamin A for measles Prophylactic antibiotics had little or no effect on mortality from measles In communities with mortality from measles of 1% or more, all children with measles should be treated with vitamin A but antibiotics should be given only if a child has clinical signs of pneumonia or sepsis
Physician Heal Thyself!
Authors: Joseph R. Cruse
Journal: JAMA (1989)

Before postgraduate courses on addiction, before there were 3000 members in the American Society for Addiction Medicine, before medical student scholarship programs in addictions, before curricula changed to include alcoholism as a "primary disease," and before extensive impaired-MD programs were in place, it was easy to ignore the alcoholism in our patients. In a 1940s<i>JAMA</i>review of<i>Alcoholics Anonymous</i>, a book used by its members as a guide to living and remaining alcohol free, the reviewer stated that the book "was of little redeeming value." It took 35 years for the first million copies to be sold and ten additional years for the next 10 million to be sold. Now 2500 to 3000 are sold every day of the year. For years, the attitude of the medical profession paralleled that of the<i>JAMA</i>reviewer, except for physicians who looked upon alcoholism as a disease and who utilized Alcoholics Anonymous
Tumeurs anorectales: faisabilité de la cytoponction ganglionnaire sous échoendoscopie
Authors: L Vercambre, E Assenat, F Bibeau, M Latournerie, R Altwegg, P Rouanet, P Senesse
Journal: Endoscopy (2008)

Introduction: Dans le cancer du rectum et de l'anus, le statut ganglionnaire est déterminant pour le choix thérapeutique (HAS 2005, Thésaurus SNFGE). Celui-ci reste difficile à appréhender en raison de notre incapacité à préciser le statut histologique des ganglions visualisés en imagerie.
Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration<i>in vitro</i>and<i>in vivo</i>
Authors: Daan van Poll, Biju Parekkadan, Cheul H. Cho, François Berthiaume, Yaakov Nahmias, Arno W. Tilles, Martin L. Yarmush
Journal: Hepatology (2008)

Orthotopic liver transplantation is the only proven effective treatment for fulminant hepatic failure (FHF), but its use is limited because of organ donor shortage, associated high costs, and the requirement for lifelong immunosuppression. FHF is usually accompanied by massive hepatocellular death with compensatory liver regeneration that fails to meet the cellular losses. Therefore, therapy aimed at inhibiting cell death and stimulating endogenous repair pathways could offer major benefits in the treatment of FHF. Recent studies have demonstrated that mesenchymal stem cell (MSC) therapy can prevent parenchymal cell loss and promote tissue repair in models of myocardial infarction, acute kidney failure, and stroke through the action of trophic secreted molecules. In this study, we investigated whether MSC therapy can protect the acutely injured liver and stimulate regeneration. In a D-galactosamine–induced rat model of acute liver injury, we show that systemic infusion of MSC-conditioned medium (MSC-CM) provides a significant survival benefit and prevents the release of liver injury biomarkers. Furthermore, MSC-CM therapy resulted in a 90% reduction of apoptotic hepatocellular death and a three-fold increment in the number of proliferating hepatocytes. This was accompanied by a dramatic increase in the expression levels of 10 genes known to be up-regulated during hepatocyte replication. Direct antiapoptotic and promitotic effects of MSC-CM on hepatocytes were demonstrated using in vitro assays. Conclusion: These data provide the first clear evidence that MSC-CM therapy provides trophic support to the injured liver by inhibiting hepatocellular death and stimulating regeneration, potentially creating new avenues for the treatment of FHF.
Spatial Regulation of RhoA Activity during Pancreatic Cancer Cell Invasion Driven by Mutant p53
Authors: Paul Timpson, Ewan J. McGhee, Jennifer P. Morton, Alex von Kriegsheim, Juliane P. Schwarz, Saadia A. Karim, Brendan Doyle, Jean A. Quinn, Neil O. Carragher, Mike Edward, Michael F. Olson, Margaret C. Frame, Valerie G. Brunton, Owen J. Sansom, Kurt I. Anderson
Journal: Cancer Research (2011)

The ability to observe changes in molecular behavior during cancer cell invasion in vivo remains a major challenge to our understanding of the metastatic process. Here, we demonstrate for the first time, an analysis of RhoA activity at a subcellular level using FLIM-FRET (fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer) imaging in a live animal model of pancreatic cancer. In invasive mouse pancreatic ductal adenocarcinoma (PDAC) cells driven by mutant p53 (p53(R172H)), we observed a discrete fraction of high RhoA activity at both the leading edge and rear of cells in vivo which was absent in two-dimensional in vitro cultures. Notably, this pool of active RhoA was absent in noninvasive p53(fl) knockout PDAC cells, correlating with their poor invasive potential in vivo. We used dasatanib, a clinically approved anti-invasive agent that is active in this model, to illustrate the functional importance of spatially regulated RhoA. Dasatanib inhibited the activity of RhoA at the poles of p53(R172H) cells in vivo and this effect was independent of basal RhoA activity within the cell body. Taken together, quantitative in vivo fluorescence lifetime imaging illustrated that RhoA is not only necessary for invasion, but also that subcellular spatial regulation of RhoA activity, as opposed to its global activity, is likely to govern invasion efficiency in vivo. Our findings reveal the utility of FLIM-FRET in analyzing dynamic biomarkers during drug treatment in living animals, and they also show how discrete intracellular molecular pools might be differentially manipulated by future anti-invasive therapies.
P672A crucial role of TLT2 ligation to exaggerated interleukine-8/macrophage inhibitory protein-2 following myocardial ischemia in rat
Authors: N R Hadi, N G Yousif
Journal: Cardiovascular Research (2014)

Background: The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of evidence suggests that inflammatory mediators could play a crucial role in ischemia-reperfusion injury. Furthermore, ischemia-reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines, which could be lethal for the cardiomyocytes. TREM-like Transcript 2 (TLT2) is a transmembrane receptor expressed on B cells, macrophages and neutrophils in the rat and human. Methods and Results: Left anterior descending artery (LAD) occlusion was performed on wild-type rat. Animals were treated with TLT2 mAb immediately after LAD ligation. After 3-days post-ischemia, triphenyltetrazolium chloride staining was performed and infarct size was measured by planimetry. MCP-1, TNF-a, IL-6 expression were determined by ELIZA. chemiluminescence system it was shown that TLT2 ligation increases the the proinflammatory response specially TNF-a, IL-6 and MCP-1 in both plasma and cardiac tissue after regional cardiac ischemia. Transwell assays have been used to determine the effect that TLT2 mAb on rat neutrophil chemotaxis. Data demonstrate that TLT2 ligation increases migration in response to chemotactic stimuli, IL-8, and MIP-2. Conclusion: TLT2 mAb treatment potentiates chemotaxis in response to regional cardiac ischemia
Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function.
Authors: Y Saito, K Nakao, K Nishimura, A Sugawara, K Okumura, K Obata, R Sonoda, T Ban, H Yasue, H Imura
Journal: Circulation (1987)

Synthetic alpha-human atrial natriuretic polypeptide was infused in patients with congestive heart failure (CHF) (New York Heart Association class III or IV) and in those without CHF. The infusion of atrial natriuretic polypeptide (ANP) at a rate of 0.1 microgram/kg/min significantly decreased pulmonary capillary wedge pressure and increased stroke volume index in all of the patients with CHF, whereas it decreased pulmonary capillary wedge pressure but caused no significant change in stroke volume index in the patients without CHF. Concomitant significant reductions in total systemic resistance were observed in both groups of patients. The ANP infusion significantly increased the urine volume, the excretion of sodium, and endogenous creatinine clearance in the patients without CHF. In the patients with CHF, it also showed a tendency to increase all these variables, but the urine volume did not correlate with the reduction in pulmonary capillary wedge pressure. The ANP infusion also decreased plasma aldosterone concentrations in these patients, although no significant difference was observed in the decrement of the plasma aldosterone concentration in the patients with and those without CHF. These findings indicate that the ANP infusion improves left ventricular function in patients with CHF, and suggest that this improvement results mainly from the vasodilating activity of ANP.