tbuckley/cabot-search huggingface dataset:
Hyperpolarised 3He MRI versus HRCT in COPD and normal volunteers: PHIL trial
Authors: E. J. R. van Beek, A. M. Dahmen, T. Stavngaard, K. K. Gast, C. P. Heussel, F. Krummenauer, J. Schmiedeskamp, J. M. Wild, L. V. Søgaard, A. E. Morbach, L. M. Schreiber, H-U. Kauczor
Journal: European Respiratory Journal (2009)

The aim of the present study was to apply hyperpolarised (HP) 3 He magnetic resonance imaging (MRI) to identify patients with chronic obstructive pulmonary disease (COPD) and α 1 -antitrypsin deficiency (α 1 -ATD) from healthy volunteers and compare HP 3 He MRI findings with high-resolution computed tomography (HRCT) in a multicentre study. Quantitative measurements of HP 3 He MRI (apparent diffusion coefficient (ADC)) and HRCT (mean lung density (MLD)) were correlated with pulmonary function tests. A prospective three centre study enrolled 122 subjects with COPD (either acquired or genetic) and age-matched never-smokers. All diagnostic studies were completed in 94 subjects (52 with COPD; 13 with α 1 -ATD; 29 healthy subjects; 63 males; and 31 females; median age 62 yrs). The consensus assessment of radiologists, blinded for other test results, estimated nonventilated lung volume (HP 3 He MRI) and percentage diseased lung (HRCT). Quantitative evaluation of all data for each centre consisted of ADC (HP 3 He MRI) and MLD measurements (HRCT), and correlation with forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) indicating airway obstruction, and the diffusing capacity of the lung for carbon monoxide ( D L,CO ) indicating alveolar destruction. Using lung function tests as a reference, regional analysis of HP 3 He MRI and HRCT correctly categorised normal volunteers in 100% and 97%, COPD in 42% and 69% and α 1 -ATD in 69% and 85% of cases, respectively. Direct comparison of HP 3 He MRI and CT revealed 23% of subjects with moderate/severe structural abnormalities had only mild ventilation defects. In comparison with lung function tests, ADC was more effective in separating COPD patients from healthy subjects than MLD (p&lt;0.001 versus 0.038). ADC measurements showed better correlation with D L,CO than MLD (r = 0.59 versus 0.29). Hyperpolarised 3 He MRI correctly categorised patients with COPD and normal volunteers. It offers additional functional information, without the use of ionising radiation whereas HRCT gives better morphological information. We showed the feasibility of a multicentre study using different magnetic resonance systems.
S1P2, the G Protein–Coupled Receptor for Sphingosine-1-Phosphate, Negatively Regulates Tumor Angiogenesis and Tumor Growth <i>In vivo</i> in Mice
Authors: Wa Du, Noriko Takuwa, Kazuaki Yoshioka, Yasuo Okamoto, Koichi Gonda, Kazushi Sugihara, Akiyoshi Fukamizu, Masahide Asano, Yoh Takuwa
Journal: Cancer Research (2010)

Abstract Sphingosine-1-phosphate (S1P) has been implicated in tumor angiogenesis by acting through the Gi-coupled chemotactic receptor S1P1. Here, we report that the distinct receptor S1P2 is responsible for mediating the G12/13/Rho-dependent inhibitory effects of S1P on Akt, Rac, and cell migration, thereby negatively regulating tumor angiogenesis and tumor growth. By using S1P2LacZ/+ mice, we found that S1P2 was expressed in both tumor and normal blood vessels in many organs, in both endothelial cells (EC) and vascular smooth muscle cells, as well as in tumor-associated, CD11b-positive bone marrow–derived cells (BMDC). Lewis lung carcinoma or B16 melanoma cells implanted in S1P2-deficient (S1P2−/−) mice displayed accelerated tumor growth and angiogenesis with enhanced association of vascular smooth muscle cells and pericytes. S1P2−/− ECs exhibited enhanced Rac activity, Akt phosphorylation, cell migration, proliferation, and tube formation in vitro. Coinjection of S1P2−/− ECs and tumor cells into wild-type mice also produced a relative enhancement of tumor growth and angiogenesis in vivo. S1P2−/− mice were also more efficient at recruiting CD11b-positive BMDCs into tumors compared with wild-type siblings. Bone marrow chimera experiments revealed that S1P2 acted in BMDCs to promote tumor growth and angiogenesis. Our results indicate that, in contrast to endothelial S1P1, which stimulates tumor angiogenesis, S1P2 on ECs and BMDCs mediates a potent inhibition of tumor angiogenesis, suggesting a novel therapeutic tactic for anticancer treatment. Cancer Res; 70(2); 772–81
Genetics of Major Psychiatric Disorders
Authors: Roland D. Ciaranello, Andrea L. Ciaranello
Journal: Annual Review of Medicine (1991)

We review recent studies on the inheritance of affective disorders and schizophrenia. Both groups of diseases have substantial genetic and nongenetic components, and their inheritance does not fit simple Mendelian models. Linkage studies implicate the Xp28 and 11p15 regions as potential disease loci in affective illness, and the 5q11-q13 region in schizophrenia. These conclusions are highly controversial, however, and must be viewed as extremely tentative.
Density of surface immunoglobulin and capping on rat B lymphocytes. I. Changes with aging.
Authors: B A Woda, J D Feldman
Journal: The Journal of Experimental Medicine (1979)

The rate of capping and shedding of cross-linked surface immunoglobulins (SIg) was slower in old Lewis rats (greater than 24 mo) than in young Lewis rats (3-4 mo). Analysis of spleen cell populations with the fluorescence-activated cell sorter indicated that with aging there was a loss of cells with a high density of SIg. Cells with the highest density of SIg capped and shed cross-linked SIg faster than cells with a low density of SIg. The alteration in density of SIg may account for the difference in capping kinetics. Colchicine treatment increased the rate of capping of lymphocytes from young animals, but had no effect on the capping kinetics of lymphocytes from old animals.
Oncologic Surveillance After Surgical Resection for Renal Cell Carcinoma: A Novel Risk-Based Approach
Authors: Suzanne B. Stewart-Merrill, R. Houston Thompson, Stephen A. Boorjian, Sarah P. Psutka, Christine M. Lohse, John C. Cheville, Bradley C. Leibovich, Igor Frank
Journal: Journal of Clinical Oncology (2015)

Purpose The appropriate duration of surveillance for renal cell carcinoma (RCC) after radical or partial nephrectomy remains unknown, and evidence to support current guidelines are lacking. Herein, we provide an approach to surveillance that balances the risk of recurrence versus the risk of non-RCC death. Patients and Methods We identified 2,511 patients who underwent surgery for M0 RCC between 1990 and 2008. Patients were stratified for analysis by pathologic stage (pT1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN1), relapse location (abdomen, chest, bone, and other), age (&lt; 50, 50 to 59, 60 to 69, 70-79 and ≥ 80 years), and Charlson comorbidity index (CCI; ≤ 1 and ≥ 2). Risks of disease recurrence and non-RCC death were estimated by using parametric models for time-to-failure with Weibull distributions. Surveillance duration was estimated at the point when the risk of non-RCC death exceeded the risk of recurrence. Results At a median follow-up of 9.0 years (interquartile range, 6.4 to 12.7 years), a total of 676 patients developed recurrence. By using a competing-risk model, vastly different surveillance durations were appreciated. Specifically, among patients with pT1Nx-0 disease and a CCI ≤ 1, risk of non-RCC death exceeded that of abdominal recurrence risk at 6 months in patients age 80 years and older but failed to do so for greater than 20 years in patients younger than age 50 years. For patients with pT1Nx-0 disease but a CCI ≥ 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already at 30 days after surgery, regardless of patient age. Conclusion We present an individualized approach to RCC surveillance that bases the duration of follow-up on the interplay between competing risk factors of recurrence and non-RCC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation.
Identification of Gene Mutations in Autosomal Dominant Polycystic Kidney Disease through Targeted Resequencing
Authors: Sandro Rossetti, Katharina Hopp, Robert A. Sikkink, Jamie L. Sundsbak, Yean Kit Lee, Vickie Kubly, Bruce W. Eckloff, Christopher J. Ward, Christopher G. Winearls, Vicente E. Torres, Peter C. Harris
Journal: Journal of the American Society of Nephrology (2012)

Mutations in two large multi-exon genes, PKD1 and PKD2, cause autosomal dominant polycystic kidney disease (ADPKD). The duplication of PKD1 exons 1–32 as six pseudogenes on chromosome 16, the high level of allelic heterogeneity, and the cost of Sanger sequencing complicate mutation analysis, which can aid diagnostics of ADPKD. We developed and validated a strategy to analyze both the PKD1 and PKD2 genes using next-generation sequencing by pooling long-range PCR amplicons and multiplexing bar-coded libraries. We used this approach to characterize a cohort of 230 patients with ADPKD. This process detected definitely and likely pathogenic variants in 115 (63%) of 183 patients with typical ADPKD. In addition, we identified atypical mutations, a gene conversion, and one missed mutation resulting from allele dropout, and we characterized the pattern of deep intronic variation for both genes. In summary, this strategy involving next-generation sequencing is a model for future genetic characterization of large ADPKD populations.
L-NAME aggravates pulmonary oxygen toxicity in rats
Authors: G Capellier, V Maupoil, A Boillot, JP Kantelip, L Rochette, J Regnard, F Barale
Journal: European Respiratory Journal (1996)

Exposure to high oxygen concentration leads to acute lung injury and death in rats after 72 h. The pathophysiology of this phenomenon relies on several mechanisms, including alteration of vascular reactivity, recruitment and activation of neutrophils and alveolar macrophages, production of cytokines and excess production of free radicals. In addition to its potent vasodilating effect, nitric oxide (NO) has also been reported to prevent free radical-mediated damage. We wanted to determine whether NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, might modulate oxygen toxicity. In rats exposed to continuous high oxygen concentration, we studied the effect of administration of 50 mg.kg-1 of intraperitoneal L-NAME twice a day on the first day of oxygen exposure. L-NAME resulted in earlier death, since 57% of the animals exposed to oxygen and injected with L-NAME died within 60 h as compared to 22% of the animals exposed to oxygen and treated with saline (p < 0.01). Haematocrit and bronchoalveolar lavage fluid protein were also significantly increased in animals exposed to oxygen and receiving L-NAME. The lung water content was higher in the oxygen-exposed groups (p < 0.01) and slightly decreased by L-NAME (p < 0.05). Thiobarbituaric acid reactive substances (TBARS) were elevated in plasma (p < 0.01) and decreased in lung (p < 0.001) of oxygen-exposed animals, but no significant effect of L-NAME was observed. NG-nitro-L-arginine methyl ester had a deleterious effect in rats exposed to hyperoxia, which might suggest that endogenous nitric oxide has a protective role against hyperoxia-induced pulmonary lesions.
Commensal-dependent expression of IL-25 regulates the IL-23–IL-17 axis in the intestine
Authors: Colby Zaph, Yurong Du, Steven A. Saenz, Meera G. Nair, Jacqueline G. Perrigoue, Betsy C. Taylor, Amy E. Troy, Dmytro E. Kobuley, Robert A. Kastelein, Daniel J. Cua, Yimin Yu, David Artis
Journal: The Journal of Experimental Medicine (2008)

Alterations in the composition of intestinal commensal bacteria are associated with enhanced susceptibility to multiple inflammatory diseases, including those conditions associated with interleukin (IL)-17–producing CD4+ T helper (Th17) cells. However, the relationship between commensal bacteria and the expression of proinflammatory cytokines remains unclear. Using germ-free mice, we show that the frequency of Th17 cells in the large intestine is significantly elevated in the absence of commensal bacteria. Commensal-dependent expression of the IL-17 family member IL-25 (IL-17E) by intestinal epithelial cells limits the expansion of Th17 cells in the intestine by inhibiting expression of macrophage-derived IL-23. We propose that acquisition of, or alterations in, commensal bacteria influences intestinal immune homeostasis via direct regulation of the IL-25–IL-23–IL-17 axis.
Excess Cancers Among HIV-Infected People in the United States
Authors: Hilary A. Robbins, Ruth M. Pfeiffer, Meredith S. Shiels, Jianmin Li, H. Irene Hall, Eric A. Engels
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Nearly 900 000 people in the United States are living with diagnosed human immunodeficiency virus (HIV) infection and therefore increased cancer risk. The total number of cancers occurring among HIV-infected people and the excess number above expected background cases are unknown.
Number of Patients Studied Prior to Approval of New Medicines: A Database Analysis
Authors: Ruben G. Duijnhoven, Sabine M. J. M. Straus, June M. Raine, Anthonius de Boer, Arno W. Hoes, Marie L. De Bruin
Journal: PLoS Medicine (2013)

At the time of approval of a new medicine, there are few long-term data on the medicine's benefit-risk balance. Clinical trials are designed to demonstrate efficacy, but have major limitations with regard to safety in terms of patient exposure and length of follow-up. This study of the number of patients who had been administered medicines at the time of medicine approval by the European Medicines Agency aimed to determine the total number of patients studied, as well as the number of patients studied long term for chronic medication use, compared with the International Conference on Harmonisation's E1 guideline recommendations.All medicines containing new molecular entities approved between 2000 and 2010 were included in the study, including orphan medicines as a separate category. The total number of patients studied before approval was extracted (main outcome). In addition, the number of patients with long-term use (6 or 12 mo) was determined for chronic medication. 200 unique new medicines were identified: 161 standard and 39 orphan medicines. The median total number of patients studied before approval was 1,708 (interquartile range [IQR] 968-3,195) for standard medicines and 438 (IQR 132-915) for orphan medicines. On average, chronic medication was studied in a larger number of patients (median 2,338, IQR 1,462-4,135) than medication for intermediate (878, IQR 513-1,559) or short-term use (1,315, IQR 609-2,420). Safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least 6 and 12 mo in 46.4% and 58.3% of new medicines, respectively. Among the 84 medicines intended for chronic use, 68 (82.1%) met the guideline recommendations for 6-mo use (at least 300 participants studied for 6 mo and at least 1,000 participants studied for any length of time), whereas 67 (79.8%) of the medicines met the criteria for 12-mo patient exposure (at least 100 participants studied for 12 mo).For medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy. Both safety and efficacy require continued study after approval. New epidemiologic tools and legislative actions necessitate a review of the requirements for the number of patients studied prior to approval, particularly for chronic use, and adequate use of post-marketing studies. Please see later in the article for the Editors' Summary.
Tendon involvement in patients with ochronosis: an ultrasonographic study
Authors: G Filippou, B Frediani, E Selvi, I Bertoldi, M Galeazzi
Journal: Annals of the Rheumatic Diseases (2008)

Ochronosis is the musculoskeletal manifestation of alcaptonuria, a rare autosomal recessive disorder with an estimated prevalence of below 1:250 000.1 Alcaptonuria is associated with deficient homogentisate 1,2-dioxygenase (HGO) activity in the liver,2 causing production of large quantities of homogentisic acid (HGA). In urine and tissues, HGA oxidises to benzoquinones, which in turn form melanin-like polymers. Tendons are sites of ochronotic pigment deposition because of their high collagen content.3 Several cases of tendon and ligament ruptures in alcaptonuria have been reported.1 4 5 To our knowledge, no studies have been carried out regarding tendon pathology in ochronosis. Ultrasonography (US) is an inexpensive, repeatable, non-invasive exam that permits accurate visualisation of tendons and ligaments. Our …
Discrepancies between morphologic and functional changes in cardiac allograft vasculopathy, assessment by serial intracoronary ultrasound and Doppler studies
Authors: V. Klauss, C. Spes, K.-H. Henneke, J. Rieber, A. Kü, H. Sinzker, E. Roger, F. Wemer, J. Metz, C. Weber, P. Uberfuhr, K. Theisen, B. Reichart
Journal: Journal of the American College of Cardiology (1998)
Prostaglandin-Like Substances Appearing in Canine Renal Venous Blood During Renal Ischemia
Authors: JOHN C. McGIFF, KEITH CROWSHAW, NORBERTO A. TERRAGNO, ANDREW J. LONIGRO, JAMES C. STRAND, MARY ANNE WILLIAMSON, JAMES B. LEE, KEVIN K. F. NG
Journal: Circulation Research (1970)

Renal prostaglandins (PC s ) might mediate an antihypertensive function of the kidney. The blood-superfused organ technique possesses the sensitivity (threshold &lt; 0.4 ng/ml blood) and specificity required for identification of PGs in blood. Induction of unilateral renal ischemia in 14 chloraloseanesthetized dogs reduced renal blood flows from a mean value of 257 to 109 ml/min on the ischemic side and from 250 to 209 ml/min on the contralateral side. Concomitantly, PG-like substances were detected by assay organs in the venous blood of ischemic (13 experiments) and contralateral (11 experiments) kidneys. In one experiment, in a spontaneously hypertensive dog, PGs were not detected during renal ischemia. Renal venous blood and renal medullary tissue were extracted for acidic lipids and assayed for PG-like substances. Extracts of venous blood collected during renal ischemia and extracts of renal medulla yielded substances with biological activity indistinguishable from PG-like substances or PG standards. Chromatographic characterization of PG-like substances suggests that they are predominantly a mixture of PGE 2 and PGF 2α .
Meta-Analysis in Clinical Research
Authors: KRISTAN A. L'ABBÉ
Journal: Annals of Internal Medicine (1987)

Meta-analysis is the process of combining study results that can be used to draw conclusions about therapeutic effectiveness or to plan new studies. We review important design and statistical issues of this process. The design issues include protocol development, objectives, literature search, publication bias, measures of study outcomes, and quality of the data. The statistical issues include consistency (homogeneity) of study outcomes, and techniques for pooling results from several studies. Guidelines are provided to assess the quality of meta-analyses based on our discussion of the design and statistical issues. Limitations and areas for further development of this approach are discussed; researchers should come to a general agreement on how to conduct meta-analysis. As an explicit strategy for summarizing results, meta-analysis may help clinicians and researchers better understand the findings of clinical studies.
ELECTRON MICROSCOPIC STUDIES ON STREPTOCOCCI
Authors: John Swanson, Emil C. Gotschlich
Journal: The Journal of Experimental Medicine (1973)

The location of Group A carbohydrate in the streptococcal cell wall has been studied by several ultrastructural techniques. The findings, based largely on use of ferritin- and horseradish peroxidase-conjugated antibodies, are interpreted as demonstrating a discrete laminar distribution of the group-specific polysaccharide. This carbohydrate layer is located on the outermost surface of the cell wall in organisms lacking protein cell wall antigens.
Art: 1 of 48
Authors: Sabreena Malik
Journal: BMJ (2006)

Sasha Consiglio's 1 of 48 display is certainly more than the dolls, flowers, and pink paint that first strike the viewer. Each of the plastic female forms depicts an emotion felt by the artist's mother, retired nurse Jennifer Conway, as she progressed though the various stages of non-Hodgkin's lymphoma. The number 48 is also significant in another respect: when Mrs Conway asked for her test results in February 2003, she was told she was only one of 48 people waiting and would have to be patient.

Australian born Consiglio, who also works in a tattoo parlour, uses barbed wire, string, tape, bandages, and tentacles around the dolls' eyes, mouths, necks, arms, wrists, torsos, legs, and feet to portray Mrs Conway feeling trapped and strangled. The old dolls—some missing legs, heads, and hair— come from friends, family, charity shops, and car boot sales. I had never seen so many toy squids/octopuses before—placing them over the faces and in the hair of some of the dolls certainly had the powerful, suffocating effect Consiglio intended.​intended.



Figure 1

In a Barbie world



The dolls that I felt stood out most were doll 48, which, resembling Jesus on the crucifix, has nails through its hands and wire tying its feet together, and doll 11, whose upper thorax has been cut out and painted red. In general Consiglio intends the drips of red paint to symbolise shed tears rather than blood.

This is the second time 1 of 48 has been on display in York. In 2003, as part of an exhibition called Dolly Mixtures—which included 16 abandoned dolls in glass fronted baby-sized coffins—Consiglio's work was promptly removed from the bar in which it was showing after customers complained. A few of these coffins, along with another doll piece, Love Me, are on display again now with 1 of 48.

Jennifer Conway's lymphoma is currently in remission.
The monoclonal anti-CD25 antibody basiliximab for the treatment of progressive systemic sclerosis: an open-label study
Authors: M. O. Becker, C. Bruckner, H. U. Scherer, N. Wassermann, J. Y. Humrich, L. G. Hanitsch, U. Schneider, A. Kawald, K. Hanke, G. R. Burmester, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2010)

Systemic sclerosis (SSc) is characterised by skin fibrosis together with a dysfunction of the immune system and vasculopathy. Until now, only a few accepted treatment options have existed for patients with progressive disease.1 A similar skin fibrosis is seen in graft-versus-host disease, an immunologically mediated disease in recipients of haematological stem cells.2 In graft-versus-host disease, targeting of CD25-positive lymphocytes with a monoclonal antibody (basiliximab) has been shown to reduce its syptoms and complications.3 CD25 is the cluster designation for the high-affinity interleukin-2 receptor expressed on T and B lymphocytes after their activation. Activated lymphocytes are also thought to play a role in the pathogenesis of SSc as patients have elevated serum interleukin-2 receptor levels and the levels correlate with mortality and disease duration.4 5 As we had already treated one rapidly progressive SSc patient refractory to other forms of treatment with the monoclonal antibody basiliximab,6 we started a …