tbuckley/cabot-search huggingface dataset:
The biology of tumor growth in the non-Hodgkin's lymphomas. A dual parameter flow cytometry study of 220 cases.
Authors: S E Shackney, A M Levine, R I Fisher, P Nichols, E Jaffe, W H Schuette, R Simon, C A Smith, S J Occhipinti, J W Parker
Journal: Journal of Clinical Investigation (1984)

Dual parameter flow cytometry studies (cell DNA content and electronic cell volume) were performed in 220 cases of non-Hodgkin's lymphoma. All cases were characterized as B or T cell malignancies, based on immunologic surface marker characteristics. Aneuploidy by flow cytometry was more common among the B cell lymphomas than among the T cell lymphomas, and was most common among the large B cell lymphomas and B cell lymphomas of intermediate size. Ploidy index distributions showed a prominent hyperdiploid peak, as well as tumor cell populations with near-tetraploid DNA contents. In serial studies, a decrease in ploidy index was observed in association with clinical and histologic transformation in one case. The highest S fractions were observed among the large and intermediate B cell lymphomas and among the aggressive T cell lymphomas. In clinical samples consisting of mixtures of diploid and aneuploid populations, the data on the aneuploid components could often be separated from other components of the mixture in multiparameter studies on the basis of the larger electronic cell volumes of the aneuploid cells. In each case, the aneuploid large cell component almost invariably had a higher S fraction than the residual component(s) of the mixture. Overall, the data are consistent with a model of clonal selection and clonal evolution in the lymphomas in which early cytogenetic abnormalities that involve little or no change in total cell DNA content are followed by cell tetraploidization that is associated with cytogenetic instability and chromosome loss over the course of time.
Translating Clinical Research into Clinical Practice: Impact of Using Prediction Rules To Make Decisions
Authors: Brendan M. Reilly, Arthur T. Evans
Journal: Annals of Internal Medicine (2006)

Clinical prediction rules, sometimes called clinical decision rules, have proliferated in recent years. However, very few have undergone formal impact analysis, the standard of evidence to assess their impact on patient care. Without impact analysis, clinicians cannot know whether using a prediction rule will be beneficial or harmful. This paper reviews standards of evidence for developing and evaluating prediction rules; important differences between prediction rules and decision rules; how to assess the potential clinical impact of a prediction rule before translating it into a decision rule; methodologic issues critical to successful impact analysis, including defining outcome measures and estimating sample size; the importance of close collaboration between clinical investigators and practicing clinicians before, during, and after impact analysis; and the need to measure both efficacy and effectiveness when analyzing a decision rule's clinical impact. These considerations should inform future development, evaluation, and use of all clinical prediction or decision rules.
Multiple cardiac proteasome subtypes differ in their susceptibility to proteasome inhibitors
Authors: A. Kloss, S. Meiners, A. Ludwig, B. Dahlmann
Journal: Cardiovascular Research (2009)

The proteasome is the proteolytically active core of the ubiquitin-proteasome system, which regulates vital processes and which can cause various diseases when it malfunctions. Therefore, the proteasome has become an attractive target for pharmaceutical interventions. Inhibition of the cardiac proteasome by specific proteasome inhibitors has been shown to attenuate cardiac hypertrophy and ischaemia reperfusion injury of the heart. We have resolved the cardiac proteasome into its subtypes and have addressed the key question of how proteasome inhibitors affect single cardiac proteasomal subtypes. The 20S proteasome from rat heart was dissected into three different subpopulations (groups I–III), each comprising 4–7 different subtypes. The major group (group II) comprises standard proteasome subtypes; the two minor subpopulations (groups I and III) contain intermediate proteasome subtypes. All subtypes exhibit chymotrypsin-, trypsin-, and caspase-like activity but to different degrees. We have tested the effect of two common proteasome inhibitors on the chymotrypsin-like activity of all subtypes: 20–30 nmol/L MG132 caused 50% inhibition of all subtypes from groups I and II, whereas 100 nmol/L was necessary to affect group III subtypes to the same extent. However, another inhibitor, bortezomib (VELCADE™), already used clinically, inhibited 50% of the activity of group III proteasome subtypes even below 20 nmol/L, a concentration showing almost no effect on group I and II proteasome subtypes. The caspase-like activity of group II proteasome subtypes was not affected by MG132 and was inhibited by bortezomib only at concentrations above 100 nmol/L. These data show that different inhibitors have differential inhibitory effects on the various cardiac proteasome subtypes. Different cardiac subtypes are inhibited by the same dose of proteasome inhibitor to a different extent.
Randomised trial of bandaging after sclerotherapy for varicose veins.
Authors: A J Batch, S S Wickremesinghe, M E Gannon, J A Dormandy
Journal: BMJ (1980)

The injection treatment of varicose veins has been practised for at least a century. The technique fell into disrepute in the early half of this century with the realisation that significant complications and recurrence could result from spreading thrombophlebitis and damage to adjacent previously unaffected segments of varicose vein (1, 7) and for many Years surgery was the treatment of choice. However, in 1963 Fegan (7) described the principles of successful compression sclerotherapy and his technique has been widely adopted since then. The basis of this technique involves the maintenance of firm uninterrupted compression for a minimum of 6 weeks, thereby preventing the formation and spread of thrombosis. As many patients find this period uncomfortable, some surgeons have modified Fegan’s original principle and shorten the period of bandages, but there have been no controlled studies to evaluate the importance of the period of compression. We therefore conducted a randomised prospective trial to compare the results of compression bandaging for 3 weeks and 6 weeks after sclerotherapy.
Chronic exposure to outdoor air pollution and lung function in adults
Authors: L J L Forbes, V Kapetanakis, A R Rudnicka, D G Cook, T Bush, J R Stedman, P H Whincup, D P Strachan, H R Anderson
Journal: Thorax (2009)

<h3>Background:</h3> The extent to which chronic exposure to outdoor air pollutants influences lung function in adults is unclear. The aim of this study was to measure the association between chronic exposure to outdoor air pollutants and adult lung function. <h3>Methods:</h3> The relationship between measures of lung function (forced expiratory volume in 1 s (FEV<sub>1</sub>) and FEV<sub>1</sub> as a percentage of forced vital capacity (FVC)) and average exposure to particulate matter &lt;10 μm in diameter, nitrogen dioxide, sulfur dioxide and ozone was examined in four representative cross-sectional surveys of the English population aged ⩾16 in 1995, 1996, 1997 and 2001. Year-specific estimates were pooled using fixed effects meta-analysis. <h3>Results:</h3> Greater exposure to particulate matter &lt;10 μm in diameter, nitrogen dioxide and sulfur dioxide was associated with lower adult FEV<sub>1</sub>. The size of the effect on population mean FEV<sub>1</sub> was about 3% for particulate matter &lt;10 μm, and 0.7% for nitrogen dioxide and sulfur dioxide, for a 10 μg/m<sup>3</sup> increase in pollutant concentration. The effects were most marked in men, older adults and ex-smokers. FEV<sub>1</sub> was not associated with ozone concentration. No associations were found between the pollutants and FEV<sub>1</sub> as a percentage of FVC. <h3>Conclusions:</h3> Chronic exposure to outdoor air pollution is associated with modestly reduced FEV<sub>1</sub> in adults.
Six-Minute Walk Distance in Chronic Obstructive Pulmonary Disease
Authors: Frank Sciurba, Gerard J. Criner, Shing M. Lee, Zab Mohsenifar, David Shade, William Slivka, Robert A. Wise
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The 6-minute walk test is used in clinical practice and clinical trials of lung diseases; however, it is not clear whether replicate tests need to be performed to assess performance. Furthermore, little is known about the impact of walking course layout on test performance. We conducted 6-minute walks on 761 patients with severe emphysema (mean ± SD FEV1% predicted = 26.3 ± 7.2) who were participants in the National Emphysema Treatment Trial. Four hundred seventy participants had repeated walks on a separate day. The second test was improved by an average of 7.0 ± 15.2% (66.1 ± 146 feet, p < 0.0001, by paired t test), with an intraclass correlation coefficient of 0.88 between days. The course layout had an effect on the distance walked. Participants tested on continuous (circular or oval) courses had a 92.2-foot longer walking distance than those tested on straight (out and back) courses. Course length had no significant effect on walking distance. The training effect found in these patients with severe emphysema is less than in previous reports of patients with chronic obstructive pulmonary disease. Furthermore, the layout of the track may influence the 6-minute walk performance.
PHARMACOGENOMICS OF ACUTE LEUKEMIA
Authors: Meyling H Cheok, Sanne Lugthart, William E. Evans
Journal: The Annual Review of Pharmacology and Toxicology (2006)

Over the past four decades, treatment of acute leukemia in children has made remarkable progress, from this disease being lethal to now achieving cure rates of 80% for acute lymphoblastic leukemia and 45% for acute myeloid leukemia. This progress is largely owed to the optimization of existing treatment modalities rather than the discovery of new agents. However, the annual number of patients with leukemia who experience relapse after initial therapy remains greater than that of new cases of most childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize medications and tailor treatment regimens to individual patients, with the goal of enhancing efficacy and safety through better understanding of the person's genetic makeup. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric acute leukemia. These include work using candidate-gene approaches, as well as genome-wide studies using haplotype mapping and gene expression profiling. These strategies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm.
Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation
Authors: J Berkes
Journal: Gut (2003)

The effects of pathogenic organisms on host intestinal epithelial cells are vast. Innumerable signalling pathways are triggered leading ultimately to drastic changes in physiological functions. Here, the ways in which enteric bacterial pathogens utilise and impact on the three major physiological functions of the intestinal epithelium are discussed: alterations in the structure and function of the tight junction barrier, induction of fluid and electrolyte secretion, and activation of the inflammatory cascade. This field of investigation, which was virtually non-existent a decade ago, has now exploded, thus rapidly expanding our understanding of bacterial pathogenesis. Through increased delineation of the ways in which microbes alter host physiology, we simultaneous gain insight into the normal regulatory mechanisms of the intestinal epithelium.
Progressive multifocal leucoencephalopathy in the rheumatic diseases: assessing the risks of biological immunosuppressive therapies
Authors: L. H. Calabrese, E. S. Molloy
Journal: Annals of the Rheumatic Diseases (2008)

Progressive multifocal leucoencephalopathy (PML) is a rare and often fatal opportunistic infection that has been well reported in patients with rheumatic diseases. The contributions of predisposing factors such as underlying disease and immunosuppressive drug selection are incompletely understood but it would appear that patients with systemic lupus erythematosus may be at highest risk. Natalizumab, a biological agent approved for multiple sclerosis and Crohn9s disease has the clearest pattern of small but definite risk. Although the risk due to rituximab is difficult to assess given the multiple confounders, continued vigilance is warranted. Rheumatologists need to become familiar with PML and feel able to help patients make shared and informed decisions about the risks when starting treatment with immunosuppressive therapies. In particular, rheumatologists need to be vigilant and pursue the diagnosis of PML in all patients with unexplained neurological signs or symptoms with clinical and MRI findings compatible with the diagnosis.
Diplochromosomes in a Goldfish Tumor
Authors: John J. Biesele
Journal: Cancer Research (1943)

(Received for publication February 8, 1943) It has been demonstrated recently that the predomi- nant mitotic figures in a number of mouse cancers contain diplochromosomes, which are made up of twice as many chromonemas as are chromosomes of embryonic or regenerating adult tissues and hence are twice as large (1). In lesser frequency are mitotic figures with chromosomes of normal size and those with polytene chromosomes of 4 or 8 times normal size. The mouse cancers studied included the fibro- sarcoma XG of Selle, Brindley, and Spies (7), which arose from transplanted liver cells of C3H mice bear- ing methylcholanthrene-induced tumors elsewhere on the body; tumor 10591A of the Roscoe B. Jackson Memorial Laboratory; Crocker mouse sarcoma 180; a spontaneous mammary carcinoma; and 6 primary methylcholanthrene-induced sarcomas of C3H mice. rods or short V's, and the diploid number approaches 90, very accurate counts were difficult to make. Oc- casionally hopeless jumbles of chromosomes were left unanalyzed, and sometimes chromatids were mistaken for whole chromosomes. For each mitotic figure, the width and average length of the chromosomes were computed with the aid of camera lucida drawings. Then, considering the metaphase chromosome as made up of a pair of cylinders (chromatids), the aver- age chromosome volume for each mitosis was calcu- lated. The volume of each figure or nucleus was reckoned as the average of the volumes of a short cylinder and an ellipsoid, after measurements had been made by means of the fine adjustment screw and a ruler beneath the mirror of the camera lucida. The results, incorporated in Table I, represent means of
Secondary skin cancer in nineteenth-century Britain
Authors: WILSON I.B. ONUIGBO
Journal: British Journal of Dermatology (1976)

Journal Article Secondary skin cancer in nineteenth‐century Britain Get access WILSON I.B. ONUIGBO WILSON I.B. ONUIGBO Department of Pathology, General Hospital, Enugu, Nigeria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue 4, 1 April 1976, Pages 457–466, https://doi.org/10.1111/j.1365-2133.1976.tb06126.x Published: 01 April 1976
Treating Chronic Idiopathic Thrombocytopenic Purpura -- A New Application of an Old Treatment
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1994)

Idiopathic thrombocytopenic purpura is a common problem in hematologic practice. The acute form of the disease, which affects mainly children, is almost always self-limited. The physician's role in these cases is to tide the patient over the attack, sometimes with a brief course of corticosteroids or intravenous immune globulin. Chronic idiopathic thrombocytopenic purpura is a far more troublesome disorder. The typical patient is a woman in her 30s who bruises easily and has gingival bleeding or epistaxis and, often, menorrhagia. Petechiae are prominent findings, but splenomegaly is not a feature of the disease. Dangerous spontaneous hemorrhage is unusual, even when . . .
Short-Term Effects of an Educational Program on Health-Seeking Behavior for Infections in Patients With Type 2 Diabetes
Authors: Leonie M.A.J. Venmans, Kees J. Gorter, Eelko Hak, Guy E.H.M. Rutten
Journal: Diabetes Care (2008)

The aim of this study was to assess the short-term effects of an educational program on (determinants of) self-reported health-seeking behavior for infections of the urinary tract (UTIs) and lower respiratory tract (LRTIs) in patients with type 2 diabetes.In a randomized controlled trial, 1,124 patients with type 2 diabetes aged between 44 and 85 years participated. The intervention consisted of a multifaceted educational program with an interactive meeting, a leaflet, a Web site, and a consultation with the diabetes care provider. The program focused on the needs of patients, apparent from a prior focus group and questionnaire study. The primary outcome measure was an indicator of health-seeking behavior for UTIs and LRTIs, defined as the proportion of participants with a positive score on at least seven of nine determinants, six from the Health Belief Model and the additional three domains of knowledge, need for information, and intention. The primary outcome was measured with questionnaires at baseline and after 5 months.Complete outcome data were available for 468 intervention group patients and 472 control group patients. In all, 68% of the intervention group patients attended the meeting. At baseline, 28% of the participants from the intervention group had a positive score on seven of the nine determinants, compared with 27% from the control group. After the educational program, these percentages were 53 and 32%, respectively (P < 0.001).Our educational program positively influenced determinants of health-seeking behavior for common infections in patients with type 2 diabetes.
Glucose Intolerance in Uremia
Authors: Ralph A. Defronzo, Jordan D. Tobin, John W. Rowe, Reubin Andres
Journal: Journal of Clinical Investigation (1978)

The relative contributions of impaired insulin secretion and of tissue insensitivity to insulin to the carbohydrate intolerance of uremia were investigated in 10 chronically uremic subjects. Two types of glucose-clamp experiments were performed in each patient before and after 10 wk of thrice weekly hemodialysis. In both types the blood glucose concentration was maintained at a constant level by the periodic adjustment of a variable glucose infusion with a negative feedback formula.Hyperglycemic clamp. The blood glucose concentration was acutely raised and maintained 125 mg/dl above basal levels for 2 h. Since the glucose concentration was held constant, the glucose infusion rate is an index of glucose metabolism (M). After dialysis M increased in all patients from an average of 4.23 to 6.30 mg/kg body wt per min (P < 0.001). The plasma insulin responses (I) both pre- and postdialysis were biphasic with an early burst within the first 2-5 min, followed by a phase of gradually increasing insulin concentration. After dialysis the plasma insulin response diminished slightly. Consequently, the M/I ratio, an index of tissue sensitivity to endogenous insulin, increased postdialysis in all subjects by an average of 92% (P < 0.01). Euglycemic clamp. The plasma insulin concentration was acutely raised and maintained by a primecontinuous insulin infusion. The blood glucose concentration was held constant at the basal level by a variable glucose infusion as above. M/I again is a measure of tissue sensitivity to insulin (exogenous) and increased in all patients postdialysis by an average of 57% (P < 0.01). In two patients hepatic glucose production was measured with tritiated glucose during the euglycemic clamp and declined by 84% predialysis. A similar decrease (82%) was observed postdialysis. Thus, both the hyperglycemic and euglycemic clamp techniques demonstrated tissue insensitivity to insulin to be the dominant carbohydrate defect in uremia. The surprising apparent lack of consistency in the change in beta cell response postdialysis is explained by the strong inverse correlation between beta cell sensitivity to glucose and tissue sensitivity to insulin (r = -0.920; P < 0.001). Those individuals who showed the most striking improvement in tissue sensitivity to insulin actually decreased their serum insulin response to hyperglycemia; those whose improvement in tissue sensitivity was more modest showed increases in beta cell responses.
Inducible chondrocyte-specific overexpression of BMP2 in young mice results in severe aggravation of osteophyte formation in experimental OA without altering cartilage damage
Authors: E N Blaney Davidson, E L Vitters, M B Bennink, P L E M van Lent, A P M van Caam, A B Blom, W B van den Berg, F A J van de Loo, P M van der Kraan
Journal: Annals of the Rheumatic Diseases (2014)

Objectives In osteoarthritis (OA) chondrocytes surrounding lesions express elevated bone morphogenetic protein 2 (BMP2) levels. To investigate the functional consequence of chondrocyte-specific BMP2 expression, we made a collagen type II dependent, doxycycline (dox)-inducible BMP2 transgenic mouse and studied the effect of elevated BMP2 expression on healthy joints and joints with experimental OA. Methods We cloned a lentivirus with BMP2 controlled by a tet-responsive element and transfected embryos of mice containing a collagen type II driven cre-recombinase and floxed rtTA to gain a mouse expressing BMP2 solely in chondrocytes and only upon dox exposure (Col2-rtTA-TRE-BMP2). Mice were treated with dox to induce elevated BMP2 expression. In addition, experimental OA was induced (destabilisation of the medial meniscus model) with or without dox supplementation and knee joints were isolated for histology. Results Dox treatment resulted in chondrocyte-specific upregulation of BMP2 and severely aggravated formation of osteophytes in experimental OA but not in control mice. Moreover, elevated BMP2 levels did not result in alterations in articular cartilage of young healthy mice, although BMP2-exposure did increase VDIPEN expression in the articular cartilage. Strikingly, despite apparent changes in knee joint morphology due to formation of large osteophytes there were no detectible differences in articular cartilage: none with regard to structural damage nor in Safranin O staining intensity when comparing destabilisation of the medial meniscus with or without dox exposure. Conclusions Our data show that chondrocyte-specific elevation of BMP2 levels does not alter the course of cartilage damage in an OA model in young mice but results in severe aggravation of osteophyte formation.