tbuckley/cabot-search huggingface dataset:
Psychophysical Evaluation for Visual Prosthesis
Authors: Gislin Dagnelie
Journal: Annual Review of Biomedical Engineering (2008)

Vision restoration through retinal, optic nerve, and cortical implants is no longer just the stuff of fantasy. The design and development of visual prostheses rapidly move from the engineering phase toward preclinical and clinical trials, yet the benchmarks to determine their efficacy in blind research subjects have received very little attention, and likewise the selection criteria and preparation of early recipients of these devices. This article examines the aspects of vision for which prostheses may be of help, the selection of early prosthesis wearers, and the pre- and postimplant evaluations required to assess safety and efficacy. I concentrate on the functional assessment, and particularly on psychophysical methodology, but also address other measures of safety and efficacy, as well as approaches to vision rehabilitation with visual prostheses. Finally, I speculate what roles the first few generations of visual prostheses may play, and emphasize the importance of using simulations to support the development and rehabilitation process.
Bleomycin-induced remodeling – Inflammation and fibrosis are developing in parallel during initiation
Authors: Kristina Rydell-Törmänen, Gunilla Westergren-Thorsson
Journal: European Respiratory Journal (2011)

Background: Pulmonary fibrosis is a facet of Diffuse Parenchymal Lung Disease and has been considered a sequel to chronic inflammation. Yet the relation between connective tissue and immune system during the initiation phase has not been thoroughly investigated. Our aim was to investigate the initiation phase and the interplay between immune system and connective tissue.

Methods: C57/Bl6 mice were given subcutaneous bleomycin injections (controls received saline) 3 times/week for 1, 2, 3 and 4 weeks. Following sacrifice, lungs were embedded in paraffin and 4 μm thick sections were used for analysis of lung parenchyma; Masson Trichrome (total collagen) and immunohistochemistry to detect neutrophils, macrophages and B-cells.

Results: Total collagen was significantly increased at 1, 2 and 4 weeks. A transient neutrophilia was found at 1w (2779±820 cells/mm2), but no difference compared to controls was found at 2, 3 and 4w. Macrophages were significantly increased at 2w (135±29 cells/mm2), whereas B-cells were significantly decreased at 3 and 4w, compared to controls.

Conclusions: Subcutaneous administration of bleomycin induced rapid pulmonary remodeling, exemplified by increased total collagen. The immune response was markedly different from the one following intratracheal administration, illustrated by the moderate and transient neutrophilia. Increase of macrophages at 2w in combination with decreased neutrophils suggests ongoing clearance. Decrease of B-cells may suggest migration to lymphoid organs, thus initiation of an adaptive immune response. In summary, we found fibrosis and inflammation occurring in parallel, both present early in the development of pulmonary fibrosis.
Role of ET-1 and GM-CSF on the differentiation potential of monocytes in systemic sclerosis
Authors: N. Binai, T. Hugle, J. van Laar
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Systemic sclerosis (SSc) is a rare but potentially life threatening connective tissue disease characterised by vasculopathy, inflammation, the production of autoantibodies and excessive fibrosis of skin and internal organs. Fibrosis is defined by an excess production of extracellular matrix (ECM) molecules predominantly of type I collagen. The main producers of collagen are myofibroblasts. These cells are characterised by the expression of α-SMA. Monocytes are one of the first cells that infiltrate inflamed or damaged tissue and they bear a high differentiation potential. Furthermore, in SSc it is suggested that monocytes are activated and play an important role in disease onset and progression. We postulate that monocytes can differentiate into myofibroblasts-like cells under the influence of soluble factors such as endothelin-1, IL-4 and GM-CSF which are elevated in SSc serum. <h3>Materials and methods</h3> To study the effect of ET-1 as well as GM-CSF and IL-4, we isolated monocytes from whole blood of healthy controls or SSc patients by ficoll and positive selection with CD14 beads. Monocytes were cultured in the presence of the above soluble factors over 14 days. Expression of α-SMA and type I collagen was then determined by Western blotting, qPCR and immunofluorescence. <h3>Results</h3> Monocytes from healthy individuals and SSc patients responded different to certain stimuli. In particular, we found that differentiation of healthy monocytes into α-SMA expressing cells is strictly dependent on GM-CSF. However, in patient monocytes ET-1 and IL-4 are also able to promote α-SMA expression but to a lesser extend than GM-CSF. Furthermore, we observed that type I collagen expression requires GM-GSF treatment but can be enhanced with costimulation of ET-1. <h3>Conclusions</h3> These data suggest that monocytes can differentiate into a myofibroblast-like phenotype and that SSc patient monocytes require a less complex stimulation to do so. Understanding the role of monocytes in fibrosis may contribute to the development of novel therapies for systemic sclerosis.
Female boxing in Italy: 2002–2007 report
Authors: Bianco Massimiliano, Sanna Nicola, Bucari Sante, Fabiano Carmela, V Palmieri, Zeppilli Paolo
Journal: British Journal of Sports Medicine (2009)

Objective To collect medical data on women's boxing. Design Cross-sectional and longitudinal study. Setting Medical examinations requested by Italian laws. Participants A retrospective study was conducted on all female boxing competitions in Italy from April 2001 to December 2007. Sixty-one amateur female boxers were evaluated longitudinally. Interventions (1) Retrospective study: All pre-/postmatch medical reports were analysed. (2) Prospective study: Breast, gynaecologic, brain, eyes, ear, nose and throat examinations were carried out. Main outcome measurements (1) Retrospective study: Any injury assessed before/after the match. (2) Prospective study: Health problems which could be related to boxing activity. Results (1) Retrospective study: Data from 5600 examinations were collected. Precompetition, a medical problem was recorded in three athletes (one conjunctiva hyperemia, one zygomatic bruise, one eyelid haematoma). Post competition, 51/2800 medical checks showed mild common injuries, such as soft tissue facial lesions, epistaxis and hand-wrist problems. Only one concussion was recorded with hospitalisation (for a thorough evaluation). Another athlete was hospitalised for a nasal fracture. (2) Prospective study: Two fibroadenomas, three ovarian cysts and one intramural uterine myoma were diagnosed. In four boxers, non-specific electroencephalographic abnormalities were detected, however, with a normal brain MRI in three (the fourth is still waiting for the radiologic procedure). Nasal septum deviation was common (42.6%) and a transmissive hypoacusia was observed in two athletes. No major eye injuries were reported. Conclusions Female boxing seems to be a safe sport with a very low incidence of events requiring hospitalisation. No specific diseases in female boxers could be observed, in particular regarding the breast and reproductive system.
Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study
Authors: R. M. Zagari, G. Bianchi-Porro, R. Fiocca, G. Gasbarrini, E. Roda, F. Bazzoli
Journal: Gut (2006)

Triple therapy is recommended for Helicobacter pylori eradication, yet consensus on the duration of treatment is lacking.
The Strength of Persistent Antigenic Stimulation Modulates Adaptive Tolerance in Peripheral CD4+ T Cells
Authors: Nevil J. Singh, Ronald H. Schwartz
Journal: The Journal of Experimental Medicine (2003)

The quantitative adaptation of receptor thresholds allows cells to tailor their responses to changes in ambient ligand concentration in many biological systems. Such a cell-intrinsic calibration of T cell receptor (TCR) sensitivity could be involved in regulating responses to autoantigens, but this has never been demonstrated for peripheral T cells. We examined the ability of monoclonal naive T cells to modulate their responsiveness differentially after exposure to fourfold different levels of persistent antigen stimulation in vivo. T cells expanded and entered a tolerant state with different kinetics in response to the two levels of stimulation, but eventually adjusted to a similar slow rate of turnover. In vivo restimulation revealed a greater impairment in the proliferative ability of T cells resident in a higher antigen presentation environment. We also observed subtle differences in TCR signaling and in vitro cytokine production consistent with differential adaptation. Unexpectedly, the system failed to similarly compensate to the persistent stimulus in vivo at the level of CD69 expression and actin polymerization. This greater responsiveness of T cells residing in a host with a lower level of antigen presentation allows us to demonstrate for the first time an intrinsic tuning process in mature T lymphocytes, albeit one more complex than current theories predict.
Micropuncture studies of the recovery phase of myohemoglobinuric acute renal failure in the rat
Authors: Donald E. Oken, Gerald F. DiBona, Franklin D. McDonald
Journal: Journal of Clinical Investigation (1970)

Micropuncture studies of the recovery phase of glycerol-induced myohemoglobinuric acute renal failure were performed in rats whose blood urea nitrogen (BUN) had fallen at least 20% below its peak value. The glomerular filtration rate (GFR) of individual nephrons in a single kidney in the recovery period generally either was in the normal range or minimal. Each animal's BUN concentration at the time of the study was inversely related to the proportion of functioning surface nephrons, but did not correlate with individual nephron GFR values. Proximal tubule fractional water absorption was significantly depressed as manifested by both depressed inulin (TF/P) values and supernormal volumes of collections, a finding which, in the absence of a urea-induced osmotic diuresis, suggests impaired sodium transport by the damaged nephron. The mean proximal tubule hydrostatic pressure in recovery was normal and there was little variation in pressure among functioning nephrons. It is concluded that recovery from this model of acute renal failure reflects the progressive recruitment of increasing numbers of functioning nephrons. The recovery of individual nephron glomerular filtration, once begun, was rapid and complete. No evidence could be adduced that the gradual return of renal function towards normal reflects a slow release of tubular obstruction or repair of disrupted tubular epithelium. Rather, recovery appeared to be directly attributable to the return of an adequate effective glomerular filtration pressure. Significant limitation in proximal tubule water absorption persisted after individual nephron GFR had returned to normal or supernormal values in this model of experimental acute renal failure in the rat, a finding which readily accounts for the diuresis associated with the recovery phase of this syndrome.
Allogeneic Lymphocytes Induce Tumor Regression of Advanced Metastatic Breast Cancer
Authors: Michael R. Bishop, Daniel H. Fowler, Donna Marchigiani, Kathleen Castro, Claude Kasten-Sportes, Seth M. Steinberg, Juan C. Gea-Banacloche, Robert Dean, Catherine K. Chow, Charles Carter, Elizabeth J. Read, Susan Leitman, Ronald Gress
Journal: Journal of Clinical Oncology (2004)

Allogeneic T lymphocytes can induce regression of metastatic breast cancer through an immune-mediated graft-versus-tumor (GVT) effect in murine models. To determine if a clinical GVT effect exists against metastatic breast cancer, allogeneic lymphocytes were used as adoptive cellular therapy after a reduced-intensity chemotherapy conditioning regimen and allogeneic hematopoietic stem-cell transplantation (HSCT) from human leukocyte antigen-matched siblings.Sixteen patients with metastatic breast cancer that had progressed after treatment with anthracyclines, taxanes, hormonal agents, and trastuzumab, received allogeneic HSCT. The reduced-intensity transplant conditioning regimen consisted of cyclophosphamide and fludarabine. To distinguish an immunological GVT effect from any antitumor effect of cytotoxic chemotherapy in the transplant-conditioning regimen, allogeneic T lymphocytes were removed from the stem-cell graft and were subsequently administered late postallogeneic HSCT. Allogeneic lymphocytes containing 1 x 10(6), 5 x 10(6), and 10 x 10(6) CD3(+) cells/kg were infused on days +42, +70, and +98 post-allogeneic HSCT, respectively.Objective tumor regressions occurred after day +28 post-allogeneic HSCT in six patients and were attributed to allogeneic lymphocyte infusions. Two of these responding patients had disease progression post-allogeneic HSCT before subsequent tumor regression. Tumor regressions occurred concomitantly with the establishment of complete donor T-lymphoid engraftment, were associated with the development of graft-versus-host disease (GVHD), and were abrogated by subsequent systemic immunosuppression for GVHD.Allogeneic lymphocytes can induce regression of advanced metastatic breast cancer. These results indicate that an immunological GVT effect from allogeneic lymphocytes exists against metastatic breast cancer and provide rationale for further development of allogeneic cellular therapy for this largely incurable disease.
The transcription factor lymphoid enhancer factor 1 controls invariant natural killer T cell expansion and Th2-type effector differentiation
Authors: Tiffany Carr, Veena Krishnamoorthy, Shuyang Yu, Hai-Hui Xue, Barbara L. Kee, Mihalis Verykokakis
Journal: The Journal of Experimental Medicine (2015)

Invariant natural killer T cells (iNKT cells) are innate-like T cells that rapidly produce cytokines that impact antimicrobial immune responses, asthma, and autoimmunity. These cells acquire multiple effector fates during their thymic development that parallel those of CD4+ T helper cells. The number of Th2-type effector iNKT cells is variable in different strains of mice, and their number impacts CD8 T, dendritic, and B cell function. Here we demonstrate a unique function for the transcription factor lymphoid enhancer factor 1 (LEF1) in the postselection expansion of iNKT cells through a direct induction of the CD127 component of the receptor for interleukin-7 (IL-7) and the transcription factor c-myc. LEF1 also directly augments expression of the effector fate–specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ. Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.
Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem.
Authors: E H Beachey, H Gras-Masse, A Tarter, M Jolivet, F Audibert, L Chedid, J M Seyer
Journal: The Journal of Experimental Medicine (1986)

The protective immunogenicity of a hybrid peptide containing tandem copies of types 5 and 24 epitopes was investigated. Carboxy-terminal peptides of the cyanogen bromide-derived fragment 7 (CB7) of type 24 M protein were chemically synthesized, and then extended to include the first 20 residues of the amino-terminus of type 5 M protein. When emulsified in CFA and injected into rabbits without conjugation to a carrier, each of the synthetic hybrid peptides, designated S-M5(1-20)-S-CB7(23-35)C and S-M5(1-20)-S-CB(19-34), evoked opsonic antibodies against both types 5 and 24 streptococci without raising heart tissue-crossreactive immunity. These results suggest that tandem hybrid peptides may provide a new approach to the development of multivalent vaccines, not only to different serotypes of group A streptococci but perhaps also to a variety of other infectious agents.
TYPE-SPECIFIC PROTECTION AND IMMUNITY FOLLOWING INTRANASAL INOCULATION OF MONKEYS WITH GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Robert F. Watson, Sidney Rothbard, Homer F. Swift
Journal: The Journal of Experimental Medicine (1946)

1. Nasopharyngeal carrier states of several weeks to several months duration were induced in the Macaca mulatta by the intranasal inoculation with matt strains of group A streptococci. 2. Following such a successful inoculation with a particular type of group A streptococcus, the animal was usually resistant to reimplantation with that same type for several months to a year or more, although reimplantation with a heterologous type could generally be easily effected. 3. This resistance was shown to be closely correlated with the antibodies directed toward the type-specific M antigen, not toward the T antigen of the strains employed. 4. A majority (83.8 per cent) of the animals in which intranasal inoculation was followed by successful implantation developed significant increases in the antistreptolysin O titres of their sera; and in a limited number of instances, type-specific agglutinins and bacteriostatic antibodies were demonstrable in the animals' sera following successful implantation. 5. Nasopharyngeal carrier states could not be induced with the glossy, avirulent variants of group A streptococci; these animals, moreover, failed to show antibody responses and were susceptible to implantation with the matt variants of the homologous glossy strains. 6. The findings are in accord with the known facts regarding immunity to group A streptococci gained through experiments on rodents; and the possible relationship of these observations to the problem of type-specific immunity in human beings is discussed.
Lumbosacral radiographic signs in patients with previous enteroarthritis or uroarthritis
Authors: A Mannoja
Journal: Annals of the Rheumatic Diseases (2004)

To investigate if there are differences in radiological findings in lumbosacral spine radiographs between different subgroups of patients with previous reactive arthritis.95 patients with previous enteroarthritis (n = 53), uroarthritis (n = 37), or Reiter's syndrome, aetiology unknown (n = 5) were included in the study. Lumbosacral radiographs were taken 7 to 38 years after the initial arthritis. Three independent observers read the radiographs. Spinal changes included squaring of vertebrae, Romanus lesions, syndesmophytes, and osteophytes. Sacroiliitis was recorded according to the New York and Stoke methods. Signs of enthesitis in the iliac crest and disc space narrowing were recorded. Interobserver reliability and intraobserver reproducibility were determined.23% of patients had grade 2-4 sacroiliitis (New York criteria) and 14% had syndesmophytes. There was more frequent sacroiliitis (32% v 13%) in uroarthritis than in enteroarthritis, and more syndesmophytes (mean 0.54 v 0.15 per patient; prevalence 24% v 6%, respectively). In other radiological features, no significant differences were present between the groups. In the material as a whole, patients with sacroiliitis of grade 2 or more had significantly less disc space narrowing both in patient comparisons (chi(2) test) and in numbers of spaces involved (Mann-Whitney test). Interobserver and intraobserver agreement, calculated using Cohen's kappa method, varied from 0.2 to 1.Syndesmophytes and sacroiliitis are more common in patients with previous uroarthritis than in those with previous enteroarthritis, but radiological findings in lumbosacral spine radiographs are characteristically similar.
Exome sequencing identifiesMUTYHmutations in a family with colorectal cancer and an atypical phenotype
Authors: Nuria Seguí, Matilde Navarro, Marta Pineda, Nicole Köger, Fernando Bellido, Sara González, Olga Campos, Silvia Iglesias, Rafael Valdés-Mas, Adriana López-Doriga, Marta Gut, Ignacio Blanco, Conxi Lázaro, Gabriel Capellá, Xose S Puente, Guido Plotz, Laura Valle
Journal: Gut (2014)

Ma et al 1 comprehensively assessed the association of previously reported genetic variants with colorectal cancer (CRC) risk. The meta-analyses revealed strong evidence for association with rare MUTYH variants, even when excluding cases with MUTYH-associated polyposis. An article by Nieuwenhuis et al 2 accurately defined the phenotypical features of MUTYH-associated polyposis. However, the study was performed on clinic-based series ascertained based on the inheritance model or the presence of polyps, which may miss additional phenotypes relevant to improve the disease characterisation and therefore, its genetic diagnosis. To illustrate this, we report a family with a clinical phenotype that resembled Lynch syndrome but was caused by MUTYH mutations.

To identify novel hereditary CRC genes, we studied an Amsterdam I family (hereditary non-polyposis CRC) with no mutations in the DNA mismatch repair (MMR) genes (figure 1, table 1). By exome sequencing performed on four cancer-affected (II.2, II.6, III.1 and III.6) and one cancer-free (III.5) family members, we identified a total of 11 unreported or rare heterozygous variants present in the cancer-affected individuals (see online supplementary table S1). One of them was MUTYH c.1147delC …
Mycoplasma pneumoniae Pneumonia
Authors: H. George Decancq
Journal: JAMA (1965)

THE ETIOLOGIC agent of most cold-agglutininpositive primary atypical pneumonias has been identified<sup>1</sup>as<i>Mycoplasma pneumoniae</i>. The roentgenographic findings are similar to those of bronchopneumonia<sup>2</sup>with an enlarged hilar shadow and exaggerated bronchial markings or patchy consolidation.<sup>3</sup>In approximately 50% of primary atypical pneumonia cases, the lesion is limited to a Single lobe<sup>4</sup>; however, these infiltrates rarely involve the entire lobe. True lobar or segmental pneumonia, which involves an entire lobe or segment, is usually caused by the pneumococcus organism,<i>Diplococcus pneumoniae</i>,<sup>5</sup>and is uncommonly seen in primary atypical pneumonia. This report describes an unusual case of<i>M pneumoniae</i>pneumonia which presented as lobar pneumonia, progressed to involve the entire right lung, and produced pleural effusion. <h3>Report of a Case</h3> A 13-year-old girl was admitted to the Children's Hospital of Pittsburgh with a five-day history of fever and a nonproductive cough. The fever was intermittent with