tbuckley/cabot-search huggingface dataset:
The relative contribution of the CD28 and gp39 costimulatory pathways in the clonal expansion and pathogenic acquisition of self-reactive T cells.
Authors: N D Griggs, S S Agersborg, R J Noelle, J A Ledbetter, P S Linsley, K S Tung
Journal: The Journal of Experimental Medicine (1996)

The zona pellucida (ZP), an ovarian extracellular structure, contains three major glycoproteins: ZP1, ZP2, and ZP3. A ZP3 peptide contains both an autoimmune oophoritis-inducing T cell epitope and a B cell epitope that induces autoantibody to ZP. This study investigates two major T cell costimulation pathways in this disease model. Herein we show that blockage of glycoprotein (gp)39 and CD40 interaction with gp39 monoclonal antibody (mAb) results in the failure to induce both autoimmune oophoritis and autoantibody production. Inhibition of ligand binding to the CD28 receptor with the fusion protein, murine CTLA4-immunoglobulin (Ig), also results in failure to generate antibody to ZP and significantly reduces disease severity and prevalence. Surprisingly, the frequencies of antigen-specific T cells in anti-gp39 mAb-treated mice, CTLA4-Ig treated mice, and in mice given control hamster IgG or control fusion protein L6, were equivalent as determined by limiting dilution analysis (approximately equals 1:5,000). These T cells, which produced comparable amounts of interleukin 4 and interferon gamma in vitro, were able to transfer oophoritis to normal recipients. When anti-gp39 mAb and CTLA4-Ig were given together, the effect was additive, leading to inhibition of T cell activation as determined by in vitro proliferation and limiting dilution analysis (approximately equals 1:190,000); disease and antibody responses were absent in these mice. By studying these two costimulatory pathways in parallel, we have shown that autoimmune disease and autoantibody production are inhibitable by blocking either the gp39 or the CD28 pathway, whereas inhibition of clonal expansion of the effector T cell population occurs only when both pathways are blocked.
DEVELOPMENT, PERSISTENCE, AND SIGNIFICANCE OF TYPE 2, POLIOMYELITIS COMPLEMENT-FIXING ANTIBODY IN MAN
Authors: Jordi Casals, Peter K. Olitsky, Albert B. Sabin
Journal: The Journal of Experimental Medicine (1952)

Sera from 81 patients with a diagnosis of paralytic or non-paralytic poliomyelitis, and from 159 individuals of similar age groups giving no history of the disease, were tested with a high titered, complement-fixing poliomyelitis antigen of Type 2 (Lansing-like). The antigen consisted of brain tissue from newborn mice injected with the MEF1 strain of virus as previously adapted to these animals. The presence or absence of Type 2 neutralizing antibody in the sera under test was found not to affect the complement fixation. Positive reactions were obtained with 57 per cent of the sera deriving from non-paralytic patients and in 70 per cent from paralytics, when the specimens were tested at a dilution of 1:16. The complement-fixing antibody was often present in highest titer as early as 24 hours after the onset of poliomyelitis, and in almost all instances within 7 days. In about half of the patients a 4-fold or greater drop in titer occurred within 3 months, with little or no change in the others. The incidence of titers of 1:16 or higher with the control sera varied with the season of the year at which they were procured, 3 per cent of the winter samples proving positive and 13 per cent of the summer. The tests of sera from the group of patients from whom poliomyelitis virus was recovered, disclosed no significant differences between those having the paralytic and those having the non-paralytic disease. Type 1 (Brunhilde-like) strains of virus were recovered from many of the patients yielding positive tests, although they presented no evidence of previous or concurrent infection with Type 2 virus. This finding shows that Type 1 virus can give rise in patients to Type 2 complement-fixing antibody. The application of these data to the serologic diagnosis of poliomyelitis infection in man will of necessity be limited until information is obtained on the development, persistence, and significance of complement-fixation reactions with antigens deriving from Type 1 and Type 3 poliomyelitis strains.
The novel mitochondrial gene arrangement of the cattle tick, Boophilus microplus: fivefold tandem repetition of a coding region
Authors: N. J. Campbell, S. C. Barker
Journal: Molecular Biology and Evolution (1999)

We sequenced across all of the gene boundaries in the mitochondrial genome of the cattle tick, Boophilus microplus, to determine the arrangement of its genes. The mtDNA of B. microplus has a coding region, composed of tRNA(Glu) and 60 bp of the 3' end of ND1, that is repeated five times. Boophilus microplus is the first coelomate animal known to have more than two copies of a coding sequence. The mitochondrial genome of B. microplus has other unusual features, including (1) reduced T arms in tRNAs, (2) an AT bias in codon use, (3) two control regions that have evolved in concert, (4) three gene rearrangements, and (5) a stem-loop between tRNA(Gln) and tRNA(Phe). The short T arms and small control regions (CRs) of B. microplus and other ticks suggest strong selection for small genomes. Imprecise termination of replication beyond its origin, which can account for the evolution of tandem repeats of coding regions in other mitochondrial genomes, cannot explain the evolution of the fivefold repeated sequence in the mitochondrial genome of B. microplus. Instead, slipped-strand mispairing or recombination are the most plausible explanations for the evolution of these tandem repeats.
Gender verification--what purpose? What price?
Authors: J S Fox
Journal: British Journal of Sports Medicine (1993)

Gender verification -what purpose? what price?Against the background of mounting disquiet and opposition to the policv of gender verification of female competitors it is gratifying that the Council of the International Amateur Athletic Federation, meet- ing in Toronto in May 1992, determined that in future no 'so-called femininity tests' would be conducted at IAAF competitions.Howvever, the International Olvmpic Committee, the instigator of the sex test, has vet to see reason and relinquish its insistence upon the screening of all erstwhile female competitors in order that their gender mav be 'verified'.The newborn infant has its gender identified by the ritual inspection of its external genitalia by those assembled to supervise the birth.This crucial
Regulation of p53 Family Member Isoform ΔNp63α by the Nuclear Factor-κB Targeting Kinase IκB Kinase β
Authors: Aditi Chatterjee, Xiaofei Chang, Tanusree Sen, Rajani Ravi, Atul Bedi, David Sidransky
Journal: Cancer Research (2010)

Abstract The p53 family gene p63 plays an instrumental role in cellular stress responses including responses to DNA damage. In addition to encoding a full-length transcriptional activator, p63 also encodes several dominant inhibitory isoforms including the isoform ΔNp63α, the function of which is not fully understood. ΔNp63α is degraded in response to DNA damage, thereby enabling an effective cellular response to genotoxic agents. Here, we identify a key molecular mechanism underlying regulation of ΔNp63α expression in response to chemotherapeutic agents or tumor necrosis factor-α. We found that ΔNp63α interacts with IκB kinase (IKK), a multisubunit protein kinase that consists of two catalytic subunits, IKKα and IKKβ, and a regulatory subunit, IKKγ. The IKKβ kinase promotes ubiquitin-mediated proteasomal degradation of ΔNp63α, whereas a kinase-deficient mutant IKKβ-K44A fails to do so. Cytokine- or chemotherapy-induced stimulation of IKKβ caused degradation of ΔNp63α and augmented transactivation of p53 family–induced genes involved in the cellular response to DNA damage. Conversely, IKKβ inhibition attenuated cytokine- or chemotherapy-induced degradation of ΔNp63α. Our findings show that IKKβ plays an essential role in regulating ΔNp63α in response to extrinsic stimuli. IKK activation represents one mechanism by which levels of ΔNp63α can be reduced, thereby rendering cells susceptible to cell death in the face of cellular stress or DNA damage. Cancer Res; 70(4); 1419–29
PMO-189 Analysis of factors predictive of depth of insertion during double balloon enteroscopy
Authors: A Murino, M Nakamura, E J Despott, C Fraser
Journal: Gut (2012)

<h3>Introduction</h3> For many decades the small bowel (SB) has represented a blind area for endoscopists, until the recent introduction of double balloon enteroscopy (DBE) allowing SB investigation and therapy. At times achieving deep insertion can be particularly challenging. The aim of this study was to determine factors that might influence depth of insertion during DBE. <h3>Methods</h3> We retrospectively analysed 569 cases referred to our institute, a UK tertiary referral centre for DBE from February 2005 to October 2011. The maximum depth of insertion (MDI) was measured as described by May <i>et al.</i> History of abdomino-pelvic surgery, route of insertion, type of enteroscope, age, sedation or GA used and gender were considered influencing factors (IFs). Procedures were then divided into several subgroups according to the numbers IFs identified. <h3>Results</h3> Out of 569 procedures reviewed, 399 cases were selected for this study (F:M=159:240, mean age: 56 years). The mean MDI was 212 cm. 274 procedures were approached via the oral route, P5 and T5 enteroscopes were used in 189 and 210 procedures respectively and 146 patients had a history of abdomino-pelvic surgery. MDI was significantly affected by history of surgery (p <h3>Conclusion</h3> Our findings suggest that the MDI is significantly influenced by a history of abdomino-pelvic surgery, route of insertion and type of enteroscope used. Moreover the MDI tends to decrease if more than one factor is present. Based on these results, an estimation of likely insertion depth can be made prior to DBE and an appropriate strategy to achieve a successful outcome considered. <h3>Competing interests</h3> A Murino: Grant/Research Support from: Research Grant in deep enteroscopy released by Imotec/Fujinon, M Nakamura: None declared, E Despott: None declared, C Fraser: None declared.
Rheumatoid arthritis of the robust reaction type.
Authors: W H De Haas, W De Boer, F Griffioen, P Oosten-Elst
Journal: Annals of the Rheumatic Diseases (1974)

Louis Pasteur (1873): 'C'est ainsi que, suivant les con- stitutions et les temperaments, les maladies... atteignent ceux qui sont predisposes i les contracter' § In the course of 6 years a group of patients was isolated who were characterized by a curious dis- crepancy.On the one hand they showed a robust personality and a practically infinite capacity for work, but on the other hand they presented two unfavourable features, viz.substantial subcutaneous nodules (often the reason for referral) and a high titre in the Rose test.This type of reaction to rheu- matoid arthritis has been tentatively called the robust type (Figs 1,2).The present paper reports a study of some further properties seen in this type of patient. Patients1lNine male patients were studied in detail.All were married men, belonging to the working class.Their mean age was 56 5 yrs and the mean duration of their disease 9 yrs.All had classical rheumatoid arthritis with no concomitant disease, and none had been treated with corticosteroids or surgery.All were known to us for at least 2 years. Results(1) GENERAL IMPRESSION All patients gave an impression of vitality and energy.Their freedom of motion seemed unaffected and lacked the slow and guarded pattern typical of rheumatoid arthritis.The joints were, or at some period had been, moderately painful, but only rarely and briefly had some patients had to stop work.Joints of the shoulder girdle were affected in all patients.There was no evidence of neuropathy or vasculitis.Subcutaneous nodules were present at the elbows in all patients and in three cases also on the fingers; F I G. l a, b Male robust type; 54-year-old owner of plumber's shop.Never ab- sentfrom work.Nodulesdis- covered on routine examination.Refuses treatment.
Impact of Varicella Vaccination on Health Care Utilization
Authors: Fangjun Zhou
Journal: JAMA (2005)

Context Since varicella vaccine was first recommended for routine immunization in the United States in 1995, the incidence of disease has dropped substantially.However, national surveillance data are incomplete, and comprehensive data regarding outpatient as well as hospital utilization have not been reported.Objective To examine the impact of the varicella vaccination program on medical visits and associated expenditures. Design, Setting, and PatientsRetrospective population-based study examining the trends in varicella health care utilization, based on data from the MarketScan databases, which include enrollees (children and adults) of more than 100 health insurance plans of approximately 40 large US employers, from 1994 to 2002.Main Outcome Measures Trends in rates of varicella-related hospitalizations and ambulatory visits and direct medical expenditures for hospitalizations and ambulatory visits, analyzed using 1994 and 1995 as the prevaccination baseline. ResultsFrom the prevaccination period to 2002, hospitalizations due to varicella declined by 88% (from 2.3 to 0.3 per 100 000 population) and ambulatory visits declined by 59% (from 215 to 89 per 100 000 population).Hospitalizations and ambulatory visits declined in all age groups, with the greatest declines among infants younger than 1 year.Total estimated direct medical expenditures for varicella hospitalizations and ambulatory visits declined by 74%, from an average of $84.9 million in 1994 and 1995 to $22.1 million in 2002. ConclusionSince the introduction of the varicella vaccination program, varicella hospitalizations, ambulatory visits, and their associated expenditures have declined dramatically among all age groups in the United States.
Drug Release: Temporally Tunable, Enzymatically Responsive Delivery of Proangiogenic Peptides from Poly(ethylene glycol) Hydrogels (Adv. Healthcare Mater. 13/2015)
Authors: Amy H. Van Hove, Erin Antonienko, Kathleen Burke, Edward Brown, Danielle S. W. Benoit
Journal: Advanced Healthcare Materials (2015)

On p. 2002, D.S.W. Benoit and co-workers describe the first approach to temporally control enzymatically responsive drug release. The background shows the vascularization induced by the enzymatically responsive hydrogels, imaged using multiphoton fluorescence microscopy. Overlaid on this background are schematic depictions of hydrogels releasing drug slowly or quickly, depending on the enzymatically degradable linker use. A cell expressing enzymes is depicted showing the enzymatically mediated release.
Long-Term Follow-Up of the TIPS Early Detection in Psychosis Study: Effects on 10-Year Outcome
Authors: Wenche ten Velden Hegelstad, Tor K. Larsen, Bjørn Auestad, Julie Evensen, Ulrik Haahr, Inge Joa, Jan O. Johannesen, Johannes Langeveld, Ingrid Melle, Stein Opjordsmoen, Jan Ivar Rossberg, Bjørn Rishovd Rund, Erik Simonsen, Kjetil Sundet, Per Vaglum, Svein Friis, Thomas McGlashan
Journal: American Journal of Psychiatry (2012)

Objective: Early detection in first-episode psychosis confers advantages for negative, cognitive, and depressive symptoms after 1, 2, and 5 years, but longitudinal effects are unknown. The authors investigated the differences in symptoms and recovery after 10 years between regional health care sectors with and without a comprehensive program for the early detection of psychosis. Method: The authors evaluated 281 patients (early detection, N=141) 18 to 65 years old with a first episode of nonaffective psychosis between 1997 and 2001. Of these, 101 patients in the early-detection area and 73 patients in the usual-detection area were followed up at 10 years, and the authors compared their symptoms and recovery. Results: A significantly higher percentage of early-detection patients had recovered at the 10-year follow-up relative to usual-detection patients. This held true despite more severely ill patients dropping out of the study in the usual-detection area. Except for higher levels of excitative symptoms in the early-detection area, there were no symptom differences between the groups. Early-detection recovery rates were higher largely because of higher employment rates for patients in this group. Conclusions: Early detection of first-episode psychosis appears to increase the chances of milder deficits and superior functioning. The mechanisms by which this strategy improves the long-term prognosis of psychosis remain speculative. Nevertheless, our findings over 10 years may indicate that a prognostic link exists between the timing of intervention and outcome that deserves additional study.
Combining ATR Suppression with Oncogenic Ras Synergistically Increases Genomic Instability, Causing Synthetic Lethality or Tumorigenesis in a Dosage-Dependent Manner
Authors: Oren Gilad, Barzin Y. Nabet, Ryan L. Ragland, David W. Schoppy, Kevin D. Smith, Amy C. Durham, Eric J. Brown
Journal: Cancer Research (2010)

Previous studies indicate that oncogenic stress activates the ATR-Chk1 pathway. Here, we show that ATR-Chk1 pathway engagement is essential for limiting genomic instability following oncogenic Ras transformation. ATR pathway inhibition in combination with oncogenic Ras expression synergistically increased genomic instability, as quantified by chromatid breaks, sister chromatid exchanges, and H2AX phosphorylation. This level of instability was significantly greater than that observed following ATR suppression in untransformed control cells. In addition, consistent with a deficiency in long-term genome maintenance, hypomorphic ATR pathway reduction to 16% of normal levels was synthetic lethal with oncogenic Ras expression in cultured cells. Notably, elevated genomic instability and synthetic lethality following suppression of ATR were not due to accelerated cycling rates in Ras-transformed cells, indicating that these synergistic effects were generated on a per-cell-cycle basis. In contrast to the synthetic lethal effects of hypomorphic ATR suppression, subtle reduction of ATR expression (haploinsufficiency) in combination with endogenous levels of K-ras(G12D) expression elevated the incidence of lung adenocarcinoma, spindle cell sarcoma, and thymic lymphoma in p53 heterozygous mice. K-ras(G12D)-induced tumorigenesis in ATR(+/-)p53(+/-) mice was associated with intrachromosomal deletions and loss of wild-type p53. These findings indicate that synergistic increases in genomic instability following ATR reduction in oncogenic Ras-transformed cells can produce 2 distinct biological outcomes: synthetic lethality upon significant suppression of ATR expression and tumor promotion in the context of ATR haploinsufficiency. These results highlight the importance of the ATR pathway both as a barrier to malignant progression and as a potential target for cancer treatment.
Vitamin K2 Supplementation Improves Insulin Sensitivity via Osteocalcin Metabolism: A Placebo-Controlled Trial
Authors: Hyung Jin Choi, Juyoun Yu, Hosanna Choi, Jee Hyun An, Sang Wan Kim, Kyong Soo Park, Hak C. Jang, Seong Yeon Kim, Chan Soo Shin
Journal: Diabetes Care (2011)

Undercarboxylated osteocalcin (ucOC) is reported to function as an endocrine hormone, affecting glucose metabolism in mice (1,2). Vitamin K, which converts ucOC to carboxylated osteocalcin (cOC), has been suggested to regulate glucose metabolism by modulating osteocalcin and/or proinflammatory pathway (3–5).

We studied whether modulation of ucOC via vitamin K2 supplementation for 4 weeks affects β-cell function and/or insulin sensitivity in healthy young male subjects. Forty-two healthy young male volunteers received vitamin K2 (menatetrenone; 30 mg; Eisai Co., Japan) or placebo t.i.d. for 4 weeks. Frequently sampled intravenous glucose tolerance test was performed to determine insulin sensitivity index ( S i), acute insulin response to glucose (AIRg), and disposition index (DI) before and after treatment. Adiponectin, interleukin (IL)-6, C-reactive protein (CRP), ucOC, and cOC …
Power Line-Generated Electromagnetic Fields
Authors: C. Andrew L. Bassett
Journal: JAMA (1988)

To the Editor.—  I read the MEDICAL NEWS & PERSPECTIVES report on the power line controversy1with some dismay. Comparable items, appearing quite regularly in the lay press, already have caused unnecessary apprehension among patients who often interpret the termelectromagneticgenerically. Unfortunately, your reporter and others rarely attempt to delineate power line magnetic phenomena from those associated with diagnostic devices, such as magnetic resonance imaging, and therapeutic devices, such as those used to treat chronically non-united fractures or osteonecrosis.  Although there may be legitimate concerns about power lines, clearly they have not yet become a significant issue for magnetic resonance imaging. Furthermore, bone healing units have been in use for more than 15 years. During that time, more than 100 000 patients have been exposed safely to theseselectedmagnetic fields, which were based, originally, on naturally occurring, strain-generated potentials in bone. In fact, no untoward reactions from
Blood-on-a-Chip
Authors: Mehmet Toner, Daniel Irimia
Journal: Annual Review of Biomedical Engineering (2005)

▪ Abstract Accurate, fast, and affordable analysis of the cellular component of blood is of prime interest for medicine and research. Yet, most often sample preparation procedures for blood analysis involve handling steps prone to introducing artifacts, whereas analysis methods commonly require skilled technicians and well-equipped, expensive laboratories. Developing more gentle protocols and affordable instruments for specific blood analysis tasks is becoming possible through the recent progress in the area of microfluidics and lab-on-a-chip-type devices. Precise control over the cell microenvironment during separation procedures and the ability to scale down the analysis to very small volumes of blood are among the most attractive capabilities of the new approaches. Here we review some of the emerging principles for manipulating blood cells at microscale and promising high-throughput approaches to blood cell separation using microdevices. Examples of specific single-purpose devices are described together with integration strategies for blood cell separation and analysis modules.
Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial
Authors: Lila Bouadma, Charles-Edouard Luyt, Florence Tubach, Christophe Cracco, Antonio Alvarez, Carole Schwebel, Frédérique Schortgen, Sigismond Lasocki, Benoît Veber, Monique Dehoux, Maguy Bernard, Blandine Pasquet, Bernard Régnier, Christian Brun-Buisson, Jean Chastre, Michel Wolff
Journal: The Lancet (2010)
884 POLYCYSTIC LIVER DISEASE: A CLINICAL ANALYSIS OF 116 PATIENTS
Authors: D.B. de Koning, L. van Keimpema, R.H.M. te Morsche, A.P. van den Berg, P.L. Jansen, R.A. de Man, F. Nevens, B. van Hoek, J.P.H. Drenth
Journal: Journal of Hepatology (2008)