tbuckley/cabot-search huggingface dataset:
An intrinsic B cell defect is required for the production of autoantibodies in the lpr model of murine systemic autoimmunity.
Authors: E S Sobel, T Katagiri, K Katagiri, S C Morris, P L Cohen, R A Eisenberg
Journal: The Journal of Experimental Medicine (1991)

Mice homozygous for the gene lpr develop marked lymphadenopathy and a spectrum of autoantibodies closely resembling that of human systemic lupus erythematosus. The unusual T cell phenotype of the expanded lymphocyte population and the T-dependence of several antibodies in this strain have suggested that primary T cell abnormalities underlie the autoimmune syndrome. Using double chimeras, we now show that expression of the lpr gene in B cells is absolutely necessary for autoantibody production. Combinations of anti-Thy 1.2 + C' treated bone marrow from congenic strains of C57BL/6 mice, differing only at the immunoglobulin heavy chain (Igh) and lpr loci, were transferred into lethally irradiated B6/lpr mice. Double chimerism was documented by allotype-specific surface IgD and IgM immunofluorescence assay of peripheral blood and by allotype-specific enzyme-linked immunosorbent assay for total IgM in serum. Despite the presence of both +/+ and lpr B cells, IgM and IgG2a anti-chromatin as well as IgM anti-IgG were entirely the products of lpr B cells. Total serum IgG2a and IgG1 were also dominated by the lpr phenotype but not to the same extent. A similar experiment using B6/lpr-Igha recipients confirmed these findings. Additional experiments in which B6/lpr recipients were infused with ratios of donor bone marrow favoring B6.C20 +/+ over B6/lpr showed that even though +/+ B cells were overrepresented, autoantibodies were only of the lpr allotype. In addition, in the presence of lpr B cells, normal B cells showed little response to an exogenous, T cell-dependent antigen. The data thus indicate that lpr B cells manifest an intrinsic abnormality which is essential for autoantibody production in the lpr model.
Development and application of a rapid rehabilitation system for reconstruction of maxillofacial soft-tissue defects related to war and traumatic injuries
Authors: Shi-zhu Bai, Zhi-hong Feng, Rui Gao, Yan Dong, Yun-peng Bi, Guo-feng Wu, Xi Chen
Journal: Military Medical Research (2014)

The application of a maxillofacial prosthesis is an alternative to surgery in functional-aesthetic facial reconstruction. Computer aided design/computer aided manufacturing has opened up a new approach to the fabrication of maxillofacial prostheses. An intelligentized rapid simulative design and manufacturing system for prostheses was developed to facilitate the prosthesis fabrication procedure.The rapid simulation design and rapid fabrication system for maxillofacial prostheses consists of three components: digital impression, intelligentized prosthesis design, and rapid manufacturing. The patients' maxillofacial digital impressions were taken with a structured-light 3D scanner; then, the 3D model of the prostheses and their negative molds could be designed with specific software; lastly, with resin molds fabricated by the rapid prototyping machine, the prostheses could be produced directly and quickly.Fifteen patients with maxillofacial defects received prosthesis rehabilitation provided by the established system. The total clinical time used for each patient was only 4 hours over 2 appointments on average. The contours of the prostheses coordinated properly with the appearance of the patients, and the uniform-thickness border sealed well to adjacent tissues. All of the patients were satisfied with their prostheses.The rapid simulative rehabilitation system of maxillofacial defects is approaching completion. It could provide an advanced technological solution for the Army in cases of maxillofacial defect rehabilitation.
PERCENTAL RELATIONSHIP BETWEEN BLOOD SUGAR AND SPINAL FLUID SUGAR IN MENTAL DISEASE
Authors: E. P. Johns, G. H. Stevenson
Journal: American Journal of Psychiatry (1938)

A study is presented of the relationship existing between simultaneous fasting spinal fluid sugar and blood sugar. A definite correlation between the blood sugar and spinal fluid sugar is indicated. In a group of 46 control patients the mean percental relationship was found to be 62 with a standard deviation of 7. In schizophrenia no deviation from the control series was encountered. In manic depressive psychosis the mean percental value for the entire group was within the normal range but there were marked individual variations particularly in patients in the manic phase. In general paresis, admission specimens showed low mean percental values, which tended to approximate the control series following treatment.
Comparison of the Cystic Fibrosis Questionnaire with the St George's Respiratory Questionnaire in adult patients with cystic fibrosis
Authors: Markus Hofer, Astrid Hirt, Thomas Kurowski, Annette Boehler
Journal: European Respiratory Journal (2012)

Background 

The Cystic Fibrosis Questionnaire (CFQ-R) is widely use in out-come studies. Nevertheless, correlation with pulmonary function test (PFT) is weak, namely in mild to moderate impairment.

Aim 

To prospective evaluated the accuracy of the CFQ-R with PFT (FEV1, obstructive ventilation defined as ratio FEV1 to vital capacity (FEV1/FVC), and hyperinflation defined as ratio residual volume to total lung capacity (RV/TLC)) and to compare it with the St George's Respiratory Questionnaire (SGRQ).

Methods 

Clinical data including PFT were collected. CFQ-R and SGRQ were obtained. Spearman correlation was performed.

Results 

32 patients (13 females) with a mean age of 29±11y, body-mass index (BMI) of 22.3±3.4kg/m2, FEV1 of 67±29%, FEV1/VC of 0.67±0.14 and RV/TLC of 0.46±0.15 are evaluated. Results of CFQ-R were: physical well-being 74±25, vitality 59±23, emotion 79±19, eating 93±20, treatment burden 75±19, health perception 72±24, social role 72±18, body image 73±24, role 73±24 weight 77±32, respiration 68±19 and digestion 79±23. Total score of SGQR was 23±17, with following subdomains: symptom 44±25, activity 25±23, impact 15±14. PFT was strongly correlated (p<0.0001) with SGQR activity (FEV1 rho=-0.67) and total score (-0-68), moderately correlated (p<0.005) with CFQ-R physical (0.63) and SGQR symptom score (-0.59) and weakly correlated (p<0.01) with CFQR treatment burden (0.54), health perception (0.57) and role (0.55).

Conclusions 

In adult CF patients CFQ-R is only moderately correlated with pulmonary function. In contrast, the SGQR, initial developed for patients with chronic obstructive pulmonary diseases showed a better correlation with PFT.
Why do general practitioners prescribe antibiotics for sore throat? Grounded theory interview study
Authors: S. Kumar
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives:</b> To understand why general practitioners prescribe antibiotics for some cases of sore throat and to explore the factors that influence their prescribing. <b>Design:</b> Grounded theory interview study. <b>Setting:</b> General practice. <b>Participants:</b> 40 general practitioners: 25 in the maximum variety sample and 15 in the theoretical sample. <b>Results:</b> General practitioners are uncertain which patients will benefit from antibiotics but prescribe for sicker patients and for patients from socioeconomically deprived backgrounds because of concerns about complications. They are also more likely to prescribe in pressured clinical contexts. Doctors are mostly comfortable with their prescribing decisions and are not prescribing to maintain the doctor-patient relationship. <b>Conclusions:</b> General practitioners have reduced prescribing for sore throat in response to research and policy initiatives. Further interventions to reduce prescribing would need to improve identification of patients at risk of complications and be workable in busy clinical situations. <h3>What is already known on this topic</h3> Prescribing of antibiotics for sore throat has fallen in the past 10 years General practitioners overestimate patients9 expectations for antibiotics <h3>What this study adds</h3> General practitioners are uncertain who benefits most from antibiotics for sore throat and are particularly concerned about complications Maintaining the doctor-patient relationship was not the primary reason for prescribing antibiotics Doctors are mostly comfortable with their antibiotic prescribing for sore throat
Sleeping sickness in Uganda: a thin line between two fatal diseases
Authors: Kim Picozzi, EricM Fèvre, Martin Odiit, Mark Carrington, Mark C Eisler, Ian Maudlin, Susan C Welburn
Journal: BMJ (2005)

To determine, through the use of molecular diagnostic tools, whether the two species of parasite that cause human African trypanosomiasis have become sympatric.Blood sampling of all available patients between June 2001 and June 2005 in central Uganda and between July and September 2003 in northwest Uganda and analysis of subcounty sleeping sickness records in Uganda between 1985 and 2005.Sleeping sickness treatment centres in central and northwest Uganda and in south Sudan.Patients presenting at the treatment centres and diagnosed as having sleeping sickness.Classification of parasites from patients from each disease focus as either Trypanosoma brucei rhodesiense (acute form) or T b gambiense (chronic form).Blood from 231 patients with sleeping sickness in central Uganda and from 91 patients with sleeping sickness in northwest Uganda and south Sudan were screened for T b rhodesiense (detection of SRA gene) and T b gambiense (detection of TgsGP gene). All samples from central Uganda were classified as T b rhodesiense, and all samples from northwest Uganda and south Sudan were identified as T b gambiense.The two focuses of human African trypanosomiasis remain discrete, but the area of Uganda affected by the acute form of human sleeping sickness has increased 2.5-fold since 1985, spreading to three new districts within the past five years through movement of infected livestock. Without preventive action targeted at the livestock reservoir of this zoonotic disease, it is likely that the two disease focuses will converge. This will have a major impact on diagnosis and treatment of this neglected disease. Real time monitoring is recommended, using molecular diagnostic tools (at a regional surveillance centre, for example) targeted at both livestock and human patients.
Utility of quantitative T-cell responses versus unstimulated interferon- for the diagnosis of pleural tuberculosis
Authors: K. Dheda, R. N. van Zyl-Smit, L. A. Sechi, M. Badri, R. Meldau, S. Meldau, G. Symons, P. L. Semple, A. Maredza, R. Dawson, H. Wainwright, A. Whitelaw, Y. Vallie, P. Raubenheimer, E. D. Bateman, A. Zumla
Journal: European Respiratory Journal (2009)

The clinical utility of antigen-specific interferon (IFN)-γ release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-γ levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.®TB, QuantiFERON®-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.®TB: 86, 60, 84 and 64%, respectively; QuantiFERON®-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-γ: 97, 100, 100 and 94%, respectively. Unstimulated IFN-γ was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.
Atypical mycobacteriosis in a lung transplant recipient
Authors: S Baldi, M Rapellino, E Ruffini, A Cavallo, M Mancuso
Journal: European Respiratory Journal (1997)

Although mycobacterial infections are more frequent in lung transplant recipients than in other solid organ recipients only occasional reports of infection from atypical Mycobacteria have been reported in patients receiving lung transplantation. We present a case of pleural and cutaneous infection due to Mycobacterium fortuitum in a double-lung transplant recipient. The infection was rapidly responsive to therapy with a two drug regimen and no reduction of immunosuppression was necessary.
Melanoma-associated naevi: precursors or coincidence?
Authors: S. Kraft, H. Tsao
Journal: British Journal of Dermatology (2015)

Individuals with multiple melanocytic naevi have an elevated melanoma risk, and approximately 20–30% of melanomas are histologically associated with naevi.1,2 Naevus‐associated melanomas occur in younger patients, and are often located on the trunk and of the superficial spreading type.1,2,3,4 Melanomas at sites of chronic sun damage and acral melanomas are usually not associated with naevi.1,2,4 Melanoma‐associated naevi sometimes present a practical problem for the dermatopathologist, because they may be difficult to distinguish from melanoma and complicate determination of Breslow thickness. The prognostic significance of a naevus found in association with melanoma is still unclear. However, this may be due to differences in study design. A recent large, controlled study suggests that there is no prognostic difference.2 An interesting and controversial topic is whether melanomas arise from associated naevi or whether they develop de novo – with just a coincidental association. The aforementioned different properties of naevus‐associated melanomas, along with studies showing nonrandom association of naevi with melanomas,5 suggest that associated naevi may indeed represent precursors for these melanomas. However, causal proof is lacking. In addition, the risk for malignant transformation of naevi is extremely low.4 Naevus‐associated melanomas also pose a clinical challenge. If all melanomas arose from precursor naevi and if most patients harbour only a limited number of moles, then prophylactic removal of naevi could have an impact on melanoma outcome. However, the majority of melanomas do not emerge from the naevic compartment and most at‐risk individuals have a large number of naevi. Thus, the signal‐to‐noise ratio for clinical detection of naevus‐associated melanomas is quite low.
Thrombopoietin-deficiency, DIC, thrombocyte consumption, and thrombocytopenia in cirrhosis
Authors: M Peck-Radosavljevic, M Wichlas, J Zacherl, G Stiegler, P Stohlawetz, S Panzer, R Steininger, P Ferenci, J Pidlich, A Gangl
Journal: Journal of Hepatology (1998)
Treatment of Nonmetastatic Rhabdomyosarcoma in Childhood and Adolescence: Third Study of the International Society of Paediatric Oncology—SIOP Malignant Mesenchymal Tumor 89
Authors: Michael C.G. Stevens, Annie Rey, Nathalie Bouvet, Caroline Ellershaw, Françoise Flamant, Jean Louis Habrand, H. Basil Marsden, Helene Martelli, Jose Sanchez de Toledo, Richard D Spicer, David Spooner, Marie Jose Terrier-Lacombe, Adrian van Unnik, Odile Oberlin
Journal: Journal of Clinical Oncology (2005)

To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy.Five hundred three previously untreated patients aged from birth to 18 years, recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage.Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy.Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).
Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus.
Authors: D E Kelley, L J Mandarino
Journal: Journal of Clinical Investigation (1990)

The diminished ability of insulin to promote glucose disposal and storage in muscle has been ascribed to impaired activation of glycogen synthase (GS). It is possible that decreased glucose storage could occur as a consequence of decreased glucose uptake, and that GS is impaired secondarily. Muscle glucose uptake in 15 diabetic subjects was matched to 15 nondiabetic subjects by maintaining fasting hyperglycemia during infusion of insulin. Leg muscle glucose uptake, glucose oxidation (local indirect calorimetry), release of glycolytic products, and muscle glucose storage, as well as muscle GS and pyruvate dehydrogenase (PDH) were determined before and during insulin infusion. Basal leg glucose oxidation and PDH were increased in the diabetics. Insulin-stimulated leg glucose uptake in the diabetics (8.05 +/- 1.41 mumol/[min.100 ml leg tissue]) did not differ from controls (5.64 +/- 0.37). Insulin-stimulated leg glucose oxidation, nonoxidized glycolysis, and glucose storage (2.48 +/- 0.27, 0.68 +/- 0.15, and 5.04 +/- 1.34 mumol/[min.100 ml], respectively) were not different from controls (2.18 +/- 0.12, 0.62 +/- 0.16, and 2.83 +/- 0.31). PDH and GS in noninsulin-dependent diabetes mellitus (NIDDM) were also normal during insulin infusion. When diabetics were restudied after being rendered euglycemic by overnight insulin infusion, GS and PDH were reduced compared with hyperglycemia. Thus, fasting hyperglycemia is sufficient to normalize insulin-stimulated muscle glucose uptake in NIDDM, and glucose is distributed normally to glycogenesis and glucose oxidation, possibly by normalization of GS and PDH.
Cross-Reactivity between Swine Leukocyte Antigen and Human Anti–HLA-Specific Antibodies in Sensitized Patients Awaiting Renal Transplantation
Authors: Inmaculada Díaz Varela, Pilar Sánchez Mozo, Alberto Centeno Cortés, Clara Alonso Blanco, Francisco Valdés Cañedo
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Xenotransplantation is increasingly viewed as a promising way to alleviate the problem of patients who have alloreactive lymphocytotoxic antibodies and therefore tend to accumulate on the waiting list for renal transplantation. One barrier to xenotransplantation in these patients could be the hyperacute or acute vascular rejection as a result of preexisting anti-HLA antibodies that recognize swine leukocyte antigens. The cross-reactivity of sera from 98 patients with pig lymphocytes was studied by flow cytometry. After absorption of xenoreactive natural antibodies (XNA), isotype, class, and antibody specificity causing a positive cross-match (XM) were determined. For nonsensitized patients, all of the antibody binding to pig lymphocytes was due to XNA, which were removed by pig red blood cells absorption. In contrast, in sensitized patients, after removal of XNA, pig lymphocyte XM remained positive. There was no correlation between antibody binding to pig lymphocytes and Ig isotype (IgG or IgM) or HLA class-specific antibodies. For testing evidence that class II–specific antibodies were responsible for antibody binding to pig lymphocytes, HLA class I–specific antibodies were absorbed with pooled human platelets. It was confirmed that HLA class II–specific antibodies were responsible for the positive pig XM, but the strength of the positive XM was weaker than the strength caused by HLA class I–specific antibodies. Sera with multiple specificities (plurispecific sera) displayed a greater frequency of cross-reactivity with swine leukocyte antigens (<i>P</i> &lt; 0.05). Seven of 11 highly immunized patients without cross-reactivity IgG with porcine lymphocytes showed positive XM before an IgM was used. The results demonstrate the cross-reactive nature of HLA antibodies and therefore point out the need to perform a prospective XM after absorption of XNA in presensitized individuals. E-mail: idv@udc.es
LY2109761 Attenuates Radiation-Induced Pulmonary Murine Fibrosis via Reversal of TGF-β and BMP-Associated Proinflammatory and Proangiogenic Signals
Authors: Paul Flechsig, Monika Dadrich, Sebastian Bickelhaupt, Jürgen Jenne, Kai Hauser, Carmen Timke, Peter Peschke, Eric W. Hahn, Hermann-Josef Gröne, Jonathan Yingling, Michael Lahn, Ute Wirkner, Peter E. Huber
Journal: Clinical Cancer Research (2012)

Radiotherapy is used for the treatment of lung cancer, but at the same time induces acute pneumonitis and subsequent pulmonary fibrosis, where TGF-β signaling is considered to play an important role.We irradiated thoraces of C57BL/6 mice (single dose, 20 Gy) and administered them a novel small-molecule TGF-β receptor I serine/threonine kinase inhibitor (LY2109761) orally for 4 weeks before, during, or after radiation. Noninvasive lung imaging including volume computed tomography (VCT) and MRI was conducted 6, 16, and 20 weeks after irradiation and was correlated to histologic findings. Expression profiling analysis and protein analysis was conducted in human primary fibroblasts.Radiation alone induced acute pulmonary inflammation and lung fibrosis after 16 weeks associated with reduced life span. VCT, MRI, and histology showed that LY2109761 markedly reduced inflammation and pulmonary fibrosis resulting in prolonged survival. Mechanistically, we found that LY2109761 reduced p-SMAD2 and p-SMAD1 expression, and transcriptomics revealed that LY2109761 suppressed expression of genes involved in canonical and noncanonical TGF-β signaling and downstream signaling of bone morphogenetic proteins (BMP). LY2109761 also suppressed radiation-induced inflammatory [e.g., interleukin (IL)-6, IL-7R, IL-8] and proangiogenic genes (e.g., ID1) indicating that LY2109761 achieves its antifibrotic effect by suppressing radiation-induced proinflammatory, proangiogenic, and profibrotic signals.Small-molecule inhibitors of the TGF-β receptor I kinase may offer a promising approach to treat or attenuate radiation-induced lung toxicity or other diseases associated with fibrosis.