tbuckley/cabot-search huggingface dataset:
THE CAPILLARY SUPPLY IN NORMAL AND HYPERTROPHIED HEARTS OF RABBITS
Authors: R. A. Shipley, Louise J. Shipley, Joseph T. Wearn
Journal: The Journal of Experimental Medicine (1937)

1. During normal growth of the rabbit heart, muscle fibers enlarge, and the capillaries multiply so that a relatively constant capillary supply per unit of tissue is maintained from the time of birth to maturity. 2. In cardiac hypertrophy the muscle fibers enlarge, but the capillaries do not multiply and, as a result, the capillary supply per unit of tissue is reduced. 3. The decreased concentration of capillaries in the hypertrophied heart would constitute an impediment to the adequate exchange of metabolic substances, but the seriousness of the impediment cannot be estimated without further physiological data.
Optimizing Performance and Interpretation of Prostate Biopsy: A Critical Analysis of the Literature
Authors: Felix K.-H. Chun, Jonathan I. Epstein, Vincenzo Ficarra, Stephen J. Freedland, Rodolfo Montironi, Francesco Montorsi, Shahrokh F. Shariat, Fritz H. Schröder, Vincenzo Scattoni
Journal: European Urology (2010)
Recognitive specificity of human cytotoxic T lymphocytes. I. Antigen-specific inhibition of human cell-mediated lympholysis.
Authors: P M Sondel, F H Bach
Journal: The Journal of Experimental Medicine (1975)

The specificity of antigen recognition by in vitro sensitized human cytotoxic T lymphocytes (CTLs) has been studied using a sensitive cell-mediated lympholysis (CML) assay. Frequently, high levels of cytotoxicity are observed on third-party targets unrelated to sensitizing or responding cells; however, no cytotoxicity differing significantly from zero has been observed on targets autologous to the responding CTLs. This "cross-killing" of third-party target cells has been observed when stimulating and third-party cells bear no cross-reacting serologically defined (SD) antigens, thought to be the target antigens recognized by CTLs. CML-blocking studies, using unlabeled normal human lymphocytes to inhibit 51Cr release from radiolabeled target cells, have shown that cross-killing, even in the absence of shared SD determinants, results from CTLs recognizing antigens shared by the third-party targets and the initial stimulating population. Furthermore, these antigens have been mapped to the major histocompatibility complex (MHC). The ability of human CTLs to specifically recognize MHC-controlled antigens not detected serologically suggests that SD antigens may be recognized differently by alloantisera and CTLs, or that MHC antigens other than SD may be the targets of CTLs in CML.
Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells.
Authors: H V Raff, L J Picker, J D Stobo
Journal: The Journal of Experimental Medicine (1980)

Utilizing somatic cell hybridization, we have developed a monoclonal antibody that interacts only with cells of the monocyte/macrophage (M phi) line and not with other myeloid or lymphoid cells. This antibody detects a 120,000-dalton determinant present on 37 +/- 2.8% of the peripheral blood M phi from several (HLA-DR)-disparate individuals and only depicts a subpopulation (approximately 30%) of HLA-DR-bearing M phi from any single subject. Cytolytic removal of this subpopulation of HLA-DR-bearing cells markedly diminished antigen-induced T cell reactivity, a deficiency that can be reconstituted with autologous M phi but not with either their soluble products containing lymphocyte-activating factor or with intact HLA-DR-disparate M phi. Whereas M phi bearing both the 120,000-dalton determinant and HLA-DR serve as effective stimulators for autologous mixed lymphocyte reactions. M phi bearing only HLA-DR determinants do not. However, this latter population of M phi can stimulate proliferation among alloreactive T cells. These studies indicate that the Mac-120 monoclonal antibody detects a subpopulation of HLA-DR-bearing M phi that is required for the genetically restricted presentation of conventional antigen to reactive T cells. Within the M phi population, these Mac-120+ cells constitute the most effective stimulators for autologous mixed lymphocyte reactions.
Influence of cyclic loading on the nutrition of articular cartilage.
Authors: B P O'Hara, J P Urban, A Maroudas
Journal: Annals of the Rheumatic Diseases (1990)

Articular cartilage is avascular. Nutrients are transported to the cells mainly by diffusion from the synovial fluid. Nutrient transport is also sometimes thought to be assisted by movement of fluid in and out of cartilage in response to cyclic loading of the tissue (9pumping9). The influence of pumping on transport of solutes through cartilage was measured by subjecting plugs of human femoral head cartilage immersed in medium containing radioactive solutes to a simulated walking cycle of 2.8 MPa at 1 Hz. The rate of absorption or desorption of tracers from the cycled plugs was compared with that of unloaded control plugs. For small solutes (urea, NaI) fluid transport did not affect the rate of solute transport significantly. Most major nutrients, such as glucose and oxygen, are small solutes and thus nutrition should not be affected by pumping. The rate of desorption of a large solute (serum albumin), however, was increased by 30-100% in plugs subjected to cyclic loading.
Nine years' experience of physiological correction of tricuspid atresia: long-term results and current surgical approach.
Authors: J Ottenkamp, J Rohmer, J M Quaegebeur, A G Brom, F Fontan
Journal: Thorax (1982)

Fontan's correction has been performed without early death in 24 consecutive patients with tricuspid atresia. Eighteen patients had ventriculoarterial concordance (group I) and six discordance (group II). Late death related to infections occurred in three patients. The follow-up time in group I (16 survivors) ranges from 1 year 10 months to 7 years 5 months (mean 3 years 8 months) and in group II (five survivors) from 2 years 1 month to 5 years 6 months (mean 3 years 6 months). Early postoperative cardiac catheterisation showed arterial pulsatile pressure recordings in the pulmonary artery only in two patients in group I, in whom a valved conduit was used to connect the right atrial appendage with the outlet chamber. Patients with a valved conduit connected with either the pulmonary artery (group II) or the outlet chamber (two patients of group I) showed better preservation of right atrial contractions angiocardiographically and scored better in exercise tests than did patients with a non-valved conduit (14 patients of group I). In the latter patients evidence of regurgitant bloodflow from the outlet chamber into the right atrium was found. Reoperation was necessary in two patients. The outlet chambers showed a substantial increase in diameter after operation. No disturbances of kidney or liver function were found up to seven years after operation. The clinical condition has improved considerably in all survivors. It is concluded that the use of a valved conduit is preferable for connecting the pulmonary artery directly in cases of tricuspid atresia with ventriculoarterial discordance or the outlet chamber when there is ventriculoarterial concordance.
Emergency endoscopy cover: cost and benefits?
Authors: A. N. Barkun
Journal: Gut (2010)

The importance of the elapsed time between initial presentation of upper gastrointestinal bleeding (UGIB) and the performance of a gastroscopy remains poorly understood, despite being the focus of much research and consistent recommendations across societies.1–4 Furthermore, as in other areas of medicine, the improved efficacy observed in randomised controlled trials (RCTs) of patients presenting with non-variceal UGIB may not translate into similar benefits in a real-life setting. The national audit by Hearnshaw et al (published online) thus provides a plethora of important observational information, including insights into after-hours endoscopy.5 These new data need to be interpreted in light of existing guidelines and their supportive evidence. Although the evidence discussed below pertains to all patients presenting with UGIB, for the most part it does not specifically address patients with a high likelihood of bleeding from complications of portal hypertension (usually ∼10–15% of all patients with UGIB6 7).

A multidisciplinary approach with timely involvement of a trained endoscopist and endoscopy assistant is widely recommended1–4; such involvement may entail after-hours availability, since early endoscopy is the cornerstone of treatment for patients with acute non-variceal UGIB. Indeed, the performance of an early gastroscopy allows for safe and prompt discharge of patients classified as low risk, improves patient outcomes for patients classified as high risk and reduces resource utilisation for patients classified as either low or high risk.4 The definition of early endoscopy varies widely among studies, from 2 to 24 h after presentation to the emergency department.3 4 8 9 The improvement in outcomes attributable to performing endoscopic haemostasis in patients with high-risk endoscopic lesions has been shown.10–14 Yet it is important to realise that the benefits attributable to early endoscopy relate to both its diagnostic and therapeutic roles in managing patients with non-variceal UGIB.

Several …
Interleukin-2 Administration Alters the CD4+FOXP3+ T-Cell Pool and Tumor Trafficking in Patients with Ovarian Carcinoma
Authors: Shuang Wei, Ilona Kryczek, Robert P. Edwards, Linhua Zou, Wojciech Szeliga, Mousumi Banerjee, Marilyn Cost, Pui Cheng, Alfred Chang, Bruce Redman, Ronald B. Herberman, Weiping Zou
Journal: Cancer Research (2007)

Abstract Interleukin (IL)-2 is used in the immunotherapy of patients with certain cancer and HIV infection. IL-2 treatment reliably results in 16% to 20% objective clinical response rate in cancer patients, with significant durability of responses in selected patients. However, the mechanisms of therapeutic activity in responding versus nonresponding patients remain poorly understood. CD4+CD25+FOXP3+ regulatory T (Treg) cells contribute to immunosuppressive networks in human tumors. We treated 31 ovarian cancer patients with IL-2. We show that administration of IL-2 induces the proliferation of existent Treg cells in patients with ovarian cancer. The potency of Treg cell proliferation is negatively determined by the initial prevalence of Treg cells, suggesting that Treg cells are a factor for self-controlling Treg cell proliferation. After IL-2 cessation, the number of Treg cells more efficiently dropped in clinical responders than nonresponders. Furthermore, IL-2 treatment stimulates chemokine receptor CXCR4 expression on Treg cells, enables Treg cell migration toward chemokine CXCL12 in the tumor microenvironment, and may enforce Treg cell tumor accumulation. Our findings support the concept that administration of IL-2 numerically and functionally affects the Treg cell compartment. These data provide an important insight in evaluating the clinical benefit and therapeutic prediction of IL-2 treatment in patients with cancer. [Cancer Res 2007;67(15):7487–94]
Polymorphism of immunoglobulin enhancer element HS1,2A: allele *2 associates with systemic sclerosis. Comparison with HLA-DR and DQ allele frequency
Authors: D Frezza, V Giambra, B Tolusso, M De Santis, S Bosello, S Vettori, G Triolo, G Valentini, G Ferraccioli
Journal: Annals of the Rheumatic Diseases (2007)

To investigate the relationship of the polymorphic enhancer HS1,2 central to the 3' enhancer complex regulatory region (IgH3'EC) of the immunoglobulin heavy chain genes with systemic sclerosis (SSc) disease and compare it with HLA-DR and DQ associations.A total of 116 patients with SSc were classified as diffuse (dSSc) or limited (lSSc), and as carriers of antitopoisomerase I (anti-Scl70) or anticentromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analysed according to the genotypes.The analysis of genotypes for the four alleles of the HS1,2A enhancer showed an increased frequency of allele *2 in the SSc cohort highly significant versus controls (57% vs. 40%, p<0.0001). Considering the autoantibody pattern, we found that the frequency of the 2/2 genotype was increased in ACA+ patients (42%) and anti-Scl70+ patients (31%) compared with the control group (15%). The differences of allelic frequencies among dSSc versus lSSc or ACA+ versus anti-Scl70+ patients were not significant, although highly significant when comparing each subgroup with the control group. HLA-DRB1*11 and DQB1*03 associated with SSc. No association was seen between HS1,2A enhancer polymorphism and HLA alleles.These data confirm there was an increased risk of having SSc in carriers of allele *2, suggesting an intriguing function of this polymorphism for B-cell regulation.
Footprints of X-to-Y Gene Conversion in Recent Human Evolution
Authors: B. Trombetta, F. Cruciani, P. A. Underhill, D. Sellitto, R. Scozzari
Journal: Molecular Biology and Evolution (2009)

Different X-homologous regions of the male-specific portion of the human Y chromosome (MSY) are characterized by a different content of putative single nucleotide polymorphisms (SNPs), as reported in public databases. The possible role of X-to-Y nonallelic gene conversion in contributing to these differences remains poorly understood. We explored this issue by analyzing sequence variation in three regions of the MSY characterized by a different degree of X–Y similarity and a different density of putative SNPs: the PCDH11Y gene in the X-transposed (X–Y identity 99%, high putative SNP content); the TBL1Y gene in the X-degenerate (X–Y identity 86–88%, low putative SNP content); and VCY genes–containing region in the P8 palindrome (X–Y identity 95%, low putative SNP content). Present findings do not provide any evidence for gene conversion in the PCDH11Y and TBL1Y genes; they also strongly suggest that most putative SNPs of the PCDH11Y gene (and possibly the entire X-transposed region) are most likely X–Y paralogous sequence variants, which have been entered in the databases as SNPs. On the other hand, clear evidence for the VCY genes in the P8 palindrome having acted as an acceptor of X-to-Y gene conversion was obtained. A rate of 1.8 × 10−7 X-to-Y conversions/bp/year was estimated for these genes. These findings indicate that in the VCY region of the MSY, X-to-Y gene conversion can be highly effective to increase the level of diversity among human Y chromosomes and suggest an additional explanation for the ability of the Y chromosome to retard degradation during evolution. Present data are expected to pave the way for future investigations on the role of nonallelic gene conversion in double-strand break repair and the maintenance of Y chromosome integrity.
PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies
Authors: Benjamin J. Chen, Bjoern Chapuy, Jing Ouyang, Heather H. Sun, Margaretha G.M. Roemer, Mina L. Xu, Hongbo Yu, Christopher D.M. Fletcher, Gordon J. Freeman, Margaret A. Shipp, Scott J. Rodig
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed–Sternberg cells comprising classical Hodgkin lymphoma (CHL) and by malignant B cells comprising EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus- and immunodeficiency-associated tumors. Experimental Design: Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1. Results: Robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1. Conclusion: Certain aggressive B-cell lymphomas and virus- and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate methods to detect PD-L1 in FFPE tissue biopsies. Clin Cancer Res; 19(13); 3462–73. ©2013 AACR.
Mass Spectrometry–Based Metabolic Profiling Reveals Different Metabolite Patterns in Invasive Ovarian Carcinomas and Ovarian Borderline Tumors
Authors: Carsten Denkert, Jan Budczies, Tobias Kind, Wilko Weichert, Peter Tablack, Jalid Sehouli, Silvia Niesporek, Dominique Könsgen, Manfred Dietel, Oliver Fiehn
Journal: Cancer Research (2006)

Abstract Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or environmental changes. We have used a metabolite profiling approach to test the hypothesis that quantitative signatures of primary metabolites can be used to characterize molecular changes in ovarian tumor tissues. Sixty-six invasive ovarian carcinomas and nine borderline tumors of the ovary were analyzed by gas chromatography/time-of-flight mass spectrometry (GC-TOF MS) using a novel contamination-free injector system. After automated mass spectral deconvolution, 291 metabolites were detected, of which 114 (39.1%) were annotated as known compounds. By t test statistics with P &amp;lt; 0.01, 51 metabolites were significantly different between borderline tumors and carcinomas, with a false discovery rate of 7.8%, estimated with repeated permutation analysis. Principal component analysis (PCA) revealed four principal components that were significantly different between both groups, with the highest significance found for the second component (P = 0.00000009). PCA as well as additional supervised predictive models allowed a separation of 88% of the borderline tumors from the carcinomas. Our study shows for the first time that large-scale metabolic profiling using GC-TOF MS is suitable for analysis of fresh frozen human tumor samples, and that there is a consistent and significant change in primary metabolism of ovarian tumors, which can be detected using multivariate statistical approaches. We conclude that metabolomics is a promising high-throughput, automated approach in addition to functional genomics and proteomics for analyses of molecular changes in malignant tumors. (Cancer Res 2006; 66(22): 10795-804)
Pain in the Chest in a User of Cocaine
Authors: M. David Wiener
Journal: JAMA (1987)

<h3>History</h3> A 21-year-old man presented with pleuritic substernal chest pain of one hour's duration. The pain was exacerbated in a supine position and did not radiate. He denied fever, cough, vomiting, or palpitations. No history of blunt or penetrating trauma was obtained. Further questioning revealed that he was a recreational user of cocaine and had inhaled free-based cocaine via a pipe the previous evening and as recently as two hours before admission to the hospital. Physical examination demonstrated an anxious young man with a respiratory rate of 26 breaths per minute and shallow. He was afebrile with normal heart rate and blood pressure. His sternum was tender to palpation, and auscultation revealed precordial crepitus synchronous with systole (Hamman's sign<sup>1</sup>). The remainder of the physical examination showed no abnormality. His electrocardiogram showed sinus rhythm at a rate of 62 beats per minute. Posteroanterior and lateral roentgenograms of the chest were
Morphological characterisation of Crohn's disease fistulae
Authors: F Bataille
Journal: Gut (2004)

Fistulae are a common complication in up to 35% of all patients with Crohn's disease. Their therapy is difficult and frequently unsatisfactory. To date, no histological comparison of Crohn's disease fistulae with non-inflammatory bowel disease fistulae has been performed. In addition, Crohn's disease fistulae have not been well characterised morphologically.Eighty four fistulae from Crohn's disease patients were compared with 13 fistulae from controls. Haematoxylin-eosin staining, electron microscopy, and immunohistochemistry for panCytokeratin (epithelial cells), CD20 (B cells), CD45R0 (T cells), and CD68 (macrophages) were performed according to standard techniques. In addition, histopathological findings were compared with clinical and laboratory data.In 31.0% of controls and 27.4% of Crohn's disease specimens, fistulae had a lining of flattened intestinal epithelium without goblet cells or, in the case of cutaneous/perianal disease, narrow squamous epithelium. Non-epithelialised fistulae were covered by a thin layer of (myo)fibroblasts, focally forming a new basement membrane, as demonstrated by electron microscopy. All fistulae were surrounded by granulation tissue. Crohn's disease fistulae presented with central infiltration by CD45R0+ T cells, followed by a small band of CD68+ macrophages and dense accumulation of CD20+ B cells. In contrast, in controls, there was dense infiltration by CD68+ macrophages with only few CD20+ B cells and CD45R0+ T lymphocytes.Fistulae in Crohn's disease differ markedly from non-Crohn's disease fistulae with regard to their cellular composition. The presence of an epithelial lining in a subgroup of fistulae may be important for the therapeutic approach and healing process.
The Druggable Genome: Evaluation of Drug Targets in Clinical Trials Suggests Major Shifts in Molecular Class and Indication
Authors: Mathias Rask-Andersen, Surendar Masuram, Helgi B. Schiöth
Journal: The Annual Review of Pharmacology and Toxicology (2013)

The largest innovations within pharmaceutical development come through new compounds that have unique and novel modes of action. These innovations commonly involve expanding the protein space targeted by pharmaceutical agents. At present, information about drugs and drug targets is available online via public databases such as DrugBank and the Therapeutic Targets Database. However, this information is biased, understandably so, toward established drugs and drug-target interactions. To gain a better overview of the drug-targeted portion of the human proteome and the directions of current drug development, we developed a data set of clinical trial drug-target interactions based on CenterWatch's Drugs in Clinical Trials Database, one of the largest databases of its kind. Our curation identified 475 potentially novel clinical trial drug targets. This review aims to identify trends in drug development based on the potentially novel targets currently being explored in clinical trials.