tbuckley/cabot-search huggingface dataset:
H-2 effects on cell-cell interactions in the response to single non-H-2 alloantigens. I. Donor H-2D region control of H-7.1-immunogenicity and lack of restriction in vivo.
Authors: P J Wettstein, G Haughton, J A Frelinger
Journal: The Journal of Experimental Medicine (1977)

Genes in the H-2 complex regulate the relative immunogenicity of the H-7.1 histocompatibility alloantigen, as measured by survival times of H-7.1-incompatible skin grafts in vivo. The gene controlling relative rejectability of H-7.1-incompatible grafts has been mapped to the H-2D region. H-7.1-incompatible skin grafts donated by H-2Db donors were rejected significantly more rapidly by H-2a/H-2b heterozygous recipients than similar H-7.1-incompatible grafts donated by H-2Dd donors. Further, there was absolutely no evidence of H-2 restriction in cytotoxic effector activity. In vivo cross-priming, as indicated by accelerated secondary graft rejection, was extensive. The efficiency of cross-priming was dependent upon the primary and secondary graft donor H-2 haplotypes.
The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial
Authors: S Keating, S Suciu, T de Witte, R Zittoun, F Mandelli, A Belhabri, S Amadori, W Fibbe, E Gallo, G Fillet, B Varet, G Meloni, A Hagemeijer, P Fazi, G Solbu, R Willemze
Journal: Leukemia (2003)
A CASE OF HUMAN GLANDERS
Authors: F.H. JACOB, HUBERT M. TURNBULL, Joseph A. Arkwright, Gertrude M. Dobrashian
Journal: British Journal of Dermatology (1921)

Journal Article A CASE OF HUMAN GLANDERS Get access F.H. JACOB, M.D., M.R.C.P. Lond., F.H. JACOB, M.D., M.R.C.P. Lond. Director of the Pathological Institute of the London Hospital Search for other works by this author on: Oxford Academic Google Scholar HUBERT M. TURNBULL, M.A., D.M., HUBERT M. TURNBULL, M.A., D.M. Director of the Pathological Institute of the London Hospital Search for other works by this author on: Oxford Academic Google Scholar Joseph A. Arkwright, M.A., M.D., Joseph A. Arkwright, M.A., M.D. Assistant Bacteriologist, Lister Institute Search for other works by this author on: Oxford Academic Google Scholar Gertrude M. Dobrashian, M.B., B.S. Gertrude M. Dobrashian, M.B., B.S. Pathologist, Nottingham Municipal Laboratory Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 33, Issue 2, 1 February 1921, Pages 39–55, https://doi.org/10.1111/j.1365-2133.1921.tb09019.x Published: 01 February 1921
P26 Respiratory Patient Preference and Satisfaction Rapidly Evaluated with Tablet PC Using the 18-Element Consultation Specific Questionnaire (CSQ): Comparison with Surgical Patients
Authors: J Beeston, AK Datta
Journal: Thorax (2012)

<h3></h3> Patient perspective is important for quality assessment of service offered by hospitals and individual clinicians, evidenced by annual surveys required by the Care Quality Commission for all English NHS Acute Trusts. Patient satisfaction has been measured in consultations in Primary Care<sup>1</sup>. However as yet unanswered, is which aspects of consultations do patients value most, and whether this preference is dependent on patient type and mode of presentation. We used a tablet PC (Customer Research Technologies) or paper questionnaires for 106 respiratory outpatients (<b>RO</b>), 100 respiratory inpatients (<b>RI</b>, 38% male) and 102 urology inpatients (<b>UI</b>, 67% male) to answer 18 questions of the CSQ<sup>1</sup> on 5 point categorical scales for how important they value aspects of the consultation (very important – not at all important) &amp; how well that aspect was achieved (strongly agree – strongly disagree) in a teaching hospital over 10 weeks. Median (range) age was 68(26–91) years and 64 (20–90) years respectively and length of stay was 7 (1–93) and 4 (1–90) days respectively for <b>RI</b> and <b>UI</b> respectively. Anonymised questionnaires on the tablet PC were completed in median (range) 264 (142–775) secs. Outcome score correlated with importance in for <b>RI</b> and <b>UI</b> (Pearson correlation coefficient, PCC, 0.90 and 0.81 respectively) but not for <b>RO</b> (PCC 0.56) Questions were clustered into General satisfaction (3Q), Professional care (6Q), Depth of relationship (6Q) and Length of consultation (3Q) domains. Fig.1 shows for each domain and each patient type, percentage of total possible scores and importance evaluated. Scores for all three patient categories were higher for general satisfaction and professional care than for depth of relationship and length of consultation. Depth of relationship was regarded as least important by all three patient categories. We conclude patients value clinicians checking questions with them and being told about their treatment most and suggest doctors place more emphasis on this and on depth of relationship with patients. New technology allows preferences to be ascertained and analysed rapidly and accurately in a time constrained health service. <h3>Reference</h3> Kinnersley P et. al. (1996) A comparison of methods for measuring patient satisfaction with consultations in Primary Care, Family Practise, 13, 41–52.
<i>PADI4</i> polymorphism predisposes male smokers to rheumatoid arthritis
Authors: Yuta Kochi, Mohamed M Thabet, Akari Suzuki, Yukinori Okada, Nina A Daha, René E M Toes, Tom W J Huizinga, Keiko Myouzen, Michiaki Kubo, Ryo Yamada, Yusuke Nakamura, Kazuhiko Yamamoto
Journal: Annals of the Rheumatic Diseases (2010)

To elucidate the differential role of peptidyl arginine deiminase 4 (PADI4) polymorphism in rheumatoid arthritis (RA) between Asian and European populations, possible gene-environmental interactions among the PADI4 polymorphism, sex and smoking status were analysed.Three independent sets of case-control samples were genotyped for single-nucleotide polymorphisms in PADI4; Japanese samples (first set, 1019 RA patients, 907 controls; second set, 999 RA patients, 1128 controls) using TaqMan assays and Dutch samples (635 RA patients, 391 controls) using Sequenom MassARRAY platform. The association of PADI4 with RA susceptibility was evaluated by smoking status and sex in contingency tables and logistic regression models.In the first set of Japanese samples, PADI4 polymorphism (rs1748033) showed a greater risk in men (OR(allele) 1.39; 95% CI 1.10 to 1.76; p(trend)=0.0054) than in women and in ever-smokers (OR(allele) 1.25; 95% CI 1.02 to 1.53; p(trend)=0.032) than in never-smokers. Moreover, the highest risk was seen in male ever-smokers (OR(allele) 1.46; 95% CI 1.12 to 1.90; p(trend)=0.0047). Similar trends were observed in the second set of Japanese samples as well as in Dutch samples.PADI4 polymorphism highly predisposes male smokers to RA, and the genetic heterogeneity observed between Asian and European populations may be partly explained by differences in smoking prevalence among men.
Decreased axial bone mineral density in perimenopausal women with rheumatoid arthritis--a population based study.
Authors: H Kroger, R Honkanen, S Saarikoski, E Alhava
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--Although periarticular osteoporosis is a well-recognised phenomenon in rheumatoid arthritis (RA), there is considerable controversy over whether RA is associated with more generalised osteoporosis. The aetiology of this bone loss is probably multifactorial, including both life-style risk factors and disease-related determinants. Population-based studies on bone mineral density (BMD) in RA have not previously been conducted, and the purpose of the present cross-sectional population-based study was to determine whether patients with RA are at an increased risk of having osteoporosis. Furthermore, the determinants of BMD in RA patients were investigated. METHODS--BMD at the spine and femoral neck was measured in 143 women with RA. The control group consisted of 1611 women with no disease or taking any drugs known to affect bone metabolism. The study population was a random stratified sample from the Kuopio Osteoporosis Study, which included all perimenopausal women aged 47-56 years residing in Kuopio Province, Eastern Finland in 1989 (n = 14,220). The mean age of the patients at the time of densitometry was 53.7 years. RESULTS--The mean (SD) spinal and femoral neck BMD was significantly lower in patients with RA compared with controls [spine: 1.067 (0.161) v 1.129 (0.157) g/cm2, p &lt; 0.001; femoral neck: 0.851 (0.136) v 0.932 (0.123) g/cm2, p &lt; 0.001]. Analysis of variance showed that at the spine the difference was significant only in patients having corticosteroid treatment, whereas at the femoral neck patients with non-steroid treatment also had significantly lower BMD. When confounding factors were corrected, no significant difference could be found between non-steroid and corticosteroid treated patients with RA, suggesting that the independent effect of corticosteroids on BMD is only minimal. Multiple regression analysis found age, weight and functional grade to be significant predictors of spinal BMD (R2 = 0.403, p &lt; 0.001). In the femoral neck weight, cumulative corticosteroid dose and functional grade were significant predictors of BMD (R2 = 0.410, p &lt; 0.001). CONCLUSIONS--RA is associated with generalised osteoporosis. The physical impairment and body weight are the major determinants of both spinal and femoral bone mass in RA patients. The cumulative corticosteroid dose was also a significant determinant of femoral neck BMD. However, the independent effect of corticosteroids is questionable because the use of corticosteroids may be an indicator of more severe disease.
PM-09 * REGULATION OF MEDULLOBLASTOMA FORMATION BY Gfi1 AND Gfi1B
Authors: C. Lee, P. A. Northcott, T. Zichner, P. Lichter, J. O. Korbel, S. M. Pfister, R. J. Wechsler-Reya
Journal: Neuro-Oncology (2014)

Medulloblastoma (MB) is the most common malignant brain tumor in children. Genomic studies have identified four molecular subgroups: WNT, SHH, Group 3, and Group 4. Among these, Group 3 tumors are the most aggressive and the most frequently fatal. Aside from amplification or overexpression of the MYC oncogene (which is insufficient for tumorigenesis on its own), oncogenic drivers for Group 3 MB remain largely unidentified. Recently, whole genome sequencing of primary MB samples identified a series of disparate genomic structural variants restricted to Groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Using an orthotopic transplantation model, we show that Gfi1 and Gfi1B can cooperate strongly with Myc to transform neural stem cells and drive MB formation in mice. The resulting tumors are highly invasive and proliferative, and exhibit histological and molecular characteristics consistent with human Group 3 MB. These studies suggest that Gfi1 and Gfi1B may be important drivers of tumorigenesis in Group 3 MB. Our ongoing studies are focused on understanding the molecular mechanisms by which Gfi1 and Gfi1B contribute to tumor formation. Specifically, we are using proteomic approaches to examine the cofactors that bind to Gfi proteins and mediate their effects, and a combination of expression profiling and chromatin immunoprecipitation-sequencing (ChIP-Seq) to identify the molecular targets of these transcription factors in MB. In addition, we have created conditional Gfi1-expressing mice to determine whether these proteins are required for tumor maintenance. Finally, we are using cells from our animal models to identify therapeutic agents that inhibit the growth of Gfi-activated tumors in vitro and in vivo. These studies will provide key insights into the biology of Group 3 MB and help identify novel approaches to therapy.
Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.
Authors: H Kubagawa, L B Vogler, J D Capra, M E Conrad, A R Lawton, M D Cooper
Journal: The Journal of Experimental Medicine (1979)

IgA myeloma proteins of kappa- and lambda-types were isolated from two patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B-cell differentiation. Our results (a) confirm that B lymphocyte precursors in IgA plasma-cell myelomas are involved in the malignant process, (b) show that B lymphocytes of the malignant clone include those expressing each of the major heavy-chain isotypes, mu, delta, gamma, and alpha, and (c) provide strong circumstantial evidence that pre-B-cell members of the malignant clone are also increased in frequency. T cells expressing idiotypic determinants were not detected. These findings argue that the initial oncogenic event may occur in a B-stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre-B-cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. We discuss other implications of these findings and speculate that all of the various phenotypes of B-lineage malignancies may result from oncogenic processes affecting stem cell targets.
Ruptured hepatic aneurysm in systemic lupus erythematosus.
Authors: C N McCollum, M E Sloan, A M Davison, G R Giles
Journal: Annals of the Rheumatic Diseases (1979)

We report on a patient with systemic lupus erythematosus (SLE) who suffered catastrophic haemorrhage following rupture of an intrahepatic aneurysm. The association between hepatic artery aneurysm and SLE has not been recorded previously, but we have found evidence from the literature that there may be an association between autoagressive disorders and this surgical emergency.
A Randomized Clinical Trial Comparing Breakfast, Dinner, or Bedtime Administration of Insulin Glargine in Patients With Type 1 Diabetes
Authors: Andreas Hamann, Stephan Matthaei, Christoph Rosak, Louise Silvestre
Journal: Diabetes Care (2003)

OBJECTIVE—Insulin glargine (Lantus), a long-acting human insulin analog, provides effective glycemic control when administered at bedtime. This open-label, randomized, parallel group, multicenter study investigated whether insulin glargine is equally effective if administered before breakfast, before dinner, or at bedtime. RESEARCH DESIGN AND METHODS—Patients with type 1 diabetes on basal-bolus therapy (n = 378, 18–68 years, HbA1c 5.5–9.8%) were treated with once-daily individually titrated insulin glargine in combination with prandial insulin lispro for 24 weeks. RESULTS—Baseline characteristics were similar in the three groups (overall age 40.9 ± 11.9 years, diabetes duration 17.3 ± 11.5 years). Median total daily insulin dose was similar at baseline (0.65, 0.65, and 0.66 IU/kg for breakfast, dinner, and bedtime, respectively) and remained relatively constant over the study period; however, the insulin glargine–to–total insulin dose ratio increased more in the breakfast group than in the dinner and bedtime groups. A similar reduction of adjusted mean HbA1c from baseline to end point occurred in all patients (7.6–7.4, 7.6–7.5, and 7.6–7.5% for breakfast, dinner, and bedtime, respectively), and a similar percentage achieved HbA1c &amp;lt;7.0% at end point in all groups (29.5, 29.8, and 25.8%, respectively). The 24-h blood glucose profiles in relation to injection time were similar in all groups. The incidences of total symptomatic and severe hypoglycemia did not differ between the three treatment groups; however, nocturnal hypoglycemia occurred in significantly fewer patients in the breakfast group (59.5%) compared with the dinner (71.9%) and bedtime (77.5%) groups (P = 0.005). CONCLUSIONS—These data suggest that insulin glargine, in combination with insulin lispro, is safe and effective when administered before breakfast, before dinner, or at bedtime.
Preferences for cancer investigation: a vignette-based study of primary-care attendees
Authors: Jonathan Banks, Sandra Hollinghurst, Lin Bigwood, Tim J Peters, Fiona M Walter, Willie Hamilton
Journal: The Lancet Oncology (2014)

BackgroundThe UK lags behind many European countries in terms of cancer survival. Initiatives to address this disparity have focused on barriers to presentation, symptom recognition, and referral for specialist investigation. Selection of patients for further investigation has come under particular scrutiny, although preferences for referral thresholds in the UK population have not been studied. We investigated preferences for diagnostic testing for colorectal, lung, and pancreatic cancers in primary-care attendees.MethodsIn a vignette-based study, researchers recruited individuals aged at least 40 years attending 26 general practices in three areas of England between Dec 6, 2011, and Aug 1, 2012. Participants completed up to three of 12 vignettes (four for each of lung, pancreatic, and colorectal cancers), which were randomly assigned. The vignettes outlined a set of symptoms, the risk that these symptoms might indicate cancer (1%, 2%, 5%, or 10%), the relevant testing process, probable treatment, possible alternative diagnoses, and prognosis if cancer were identified. Participants were asked whether they would opt for diagnostic testing on the basis of the information in the vignette.Findings3469 participants completed 6930 vignettes. 3052 individuals (88%) opted for investigation in their first vignette. We recorded no strong evidence that participants were more likely to opt for investigation with a 1% increase in risk of cancer (odds ratio [OR] 1·02, 95% CI 0·99–1·06; p=0·189), although the association between risk and opting for investigation was strong when colorectal cancer was analysed alone (1·08, 1·03–1·13; p=0·0001). In multivariable analysis, age had an effect in all three cancer models: participants aged 60–69 years were significantly more likely to opt for investigation than were those aged 40–59 years, and those aged 70 years or older were less likely. Other variables associated with increased likelihood of opting for investigation were shorter travel times to testing centre (colorectal and lung cancers), a family history of cancer (colorectal and lung cancers), and higher household income (colorectal and pancreatic cancers).InterpretationParticipants in our sample expressed a clear preference for diagnostic testing at all risk levels, and individuals want to be tested at risk levels well below those stipulated by UK guidelines. This willingness should be considered during design of cancer pathways, particularly in primary care. The public engagement with our study should encourage general practitioners to involve patients in referral decision making.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.
Spontaneous production of fibroblast-activating factor(s) by synovial inflammatory cells. A potential mechanism for enhanced tissue destruction.
Authors: S M Wahl, D G Malone, R L Wilder
Journal: The Journal of Experimental Medicine (1985)

A characteristic feature of rheumatoid arthritis is hyperplasia of the synovial lining cells and fibroblasts, the source of tissue-degrading mediators, in association with the appearance and persistence of lymphocytes in affected joints. Diseased synovial tissue obtained at arthroscopy from 10 of 12 rheumatoid arthritis patients was found to release a factor(s) that could stimulate quiescent fibroblasts to proliferate in vitro. Mononuclear cells isolated from this synovial tissue and from the synovial fluid spontaneously produced fibroblast-activating factor(s) (FAF). In contrast, synovial tissue from patients with noninflammatory joint disease did not release FAF. By gel filtration, FAF was detected in two peaks (40,000 and 15,000 mol wt) that were consistent with the previously described peripheral blood T lymphocyte- and monocyte-derived factors with identical activity. The mononuclear cells were predominantly OKT3+/Leu-1+ T lymphocytes and OKM1+ cells of monocyte/macrophage lineage that expressed HLA-DR antigens, suggesting prior activation of these cells. Mononuclear cells isolated from the peripheral blood of these patients did not spontaneously secrete FAF. Lymphocytes and monocytes from the site of synovial inflammation appear to be activated in situ to produce factors that may contribute to the hyperplasia and overgrowth of the synovial membrane in rheumatoid arthritis.
Long-Term Balancing Selection at the Antiviral Gene OAS1 in Central African Chimpanzees
Authors: William Ferguson, Shira Dvora, Ronald W. Fikes, Anne C. Stone, Stéphane Boissinot
Journal: Molecular Biology and Evolution (2011)

Oligoadenylate synthetases (OAS) are interferon-induced enzymes that participate in the first line of defense against a wide range of viral infection in animals. Upon activation by viral double-stranded RNA, OAS synthesizes (2-5) oligoadenylates, which activate RNase L, leading to the nonspecific degradation of cellular and viral RNA. Some association studies in humans suggest that variation at one of the OAS genes, OAS1, could be influencing host susceptibility to viral infection. We assessed the diversity of OAS1 in hominoid primates with a focus on chimpanzees. We found that the OAS1 gene is extremely polymorphic in Central African chimpanzee and exhibits levels of silent and replacement diversity much higher than neutral regions of the chimpanzee genome. This level of variation strongly suggests that balancing selection is acting on OAS1, and indeed, this conclusion was validated by several tests of neutrality. We further demonstrated that balancing selection has been acting at this locus since the split between chimpanzees, humans, and gorillas (~8.6 Ma) and caused the persistence of two deeply divergent allelic lineages in Central African chimpanzees. These two groups of OAS1 alleles differ by a large number of amino acids (a.a.), including several a.a. putatively involved in RNA binding. It is therefore very likely that variation at the OAS1 locus affects the innate immune response of individuals to specific viral infection. Our data strongly suggest that interactions between viral RNA and OAS1 are responsible for the maintenance of ancestral polymorphisms at this locus for at least 13.2 My.