tbuckley/cabot-search huggingface dataset:
Impact of Islet Autoimmunity on the Progressive β-Cell Functional Decline in Type 2 Diabetes
Authors: Barbara M. Brooks-Worrell, Edward J. Boyko, Jerry P. Palmer
Journal: Diabetes Care (2014)

Cross-sectional studies have suggested that islet autoimmunity may be more prevalent in type 2 diabetes (T2D) than previously appreciated and may contribute to the progressive decline in β-cell function. In this study, we longitudinally evaluated the effect of islet autoimmune development on the progressive β-cell dysfunction in T2D patients.Twenty-three T2D patients negative for islet autoantibodies (GAD antibody and insulinoma-associated protein 2) and islet-specific T cells were evaluated prospectively for up to 36 months. We investigated the percentage of patients who developed islet autoantibodies (Ab+) and/or islet-reactive T cells (T+) and the effect of the islet autoimmunity on fasting and glucagon-stimulated C-peptide responses. We defined positive islet autoimmunity as Ab+ and/or T+ for at least two study visits.Of the 23 patients, 6 (26%) remained negative for islet autoimmunity (Ab-T-), 14 (61%) developed Ab+ and/or T+, and 3 (13%) were unclassifiable because they developed islet autoimmunity at only one study visit. Islet Ab+ was observed to be less stable than islet-specific T-cell responses. Development of islet autoimmunity was significantly associated with a more rapid decline in fasting (P < 0.0001) and glucagon-stimulated (P < 0.05) C-peptide responses.These pilot data suggest that the development of islet autoimmunity in T2D is associated with a significantly more rapid β-cell functional decline.
RII AND RIII TYPE RESISTANCE OF PLASMODIUM FALCIPARUM TO COMBINATION OF MEFLOQUINE AND SULFADOXINE/PYRIMETHAMINE IN INDONESIA
Authors: StephenL. Hoffman, AnthonyJ. Dimpudus, JamesR. Campbell, HarijaniA. Marwoto, Nono Sukri, Diet Rustama, NarainH. Punjabi, H.S. Oetomo, Syahrial Harun, P. Heizmann, LarryW. Laughlin
Journal: The Lancet (1985)
CD19+CD21low B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome
Authors: Zoya Kuzmina, Katharina Krenn, Ventzislav Petkov, Ulrike Körmöczi, Roman Weigl, Arno Rottal, Peter Kalhs, Margit Mitterbauer, Lothar Ponhold, Gerhard Dekan, Hildegard T. Greinix, Winfried F. Pickl
Journal: Blood (2013)
The Changing Role of Dissection in Medical Education
Authors: S. Ryan Gregory, Thomas R. Cole
Journal: JAMA (2002)

played by Cary Grant, is followed everywhere by a large, silent man.The man is with him as he addresses an anatomy class, as he conducts the student orchestra, as he stands over a patient in the operating room.The man speaks only at rare moments, each crucial, coming to Noah's aid as the voice of wisdom, of conscience, or of the past.When Noah is finally challenged by a university tribunal to defend his relationship with the odd man he calls "my friend," the story comes out: the man is a convicted murderer, executed by hanging and sent 20 years earlier to Noah, a medical student who needed "a cadaver of my own."The "cadaver" awakened as soon as Noah stuck a gloved finger in his mouth, and has never since left his side.Early experiences in the anatomy laboratory underpin later practice in ways that are not easy to articulate.The knowledge gained there guides diagnosis, allows us to link phenomena that seem on the body's surface to be unrelated, and gives us fluency in a discourse that lets us to describe what is happening to our patients.Visualizing the structures hidden beneath the skin allows us to identify conditions otherwise beyond our grasp.Although the overwhelming bulk of the knowledge we use to care for patients is learned outside the lab, and the centrality of the experience wanes even by the end of first year, what we learn in anatomy lab is somehow, quietly, always there.In this issue of MSJAMA, literature professor John Bender recounts his season as an outsider in the lab and describes how the process serves as a ritual entry into the medical profession.Beyond the technical knowledge it affords, anatomy lab links us to the past and begins our socialization to future practice.We dissect knowing that we are making the same cuts and seeking the same structures as physicians centuries earlier.But today, we pride ourselves on taking more from the experience, on engaging with the gift that is the donation.Samantha Stewart and Rita Charon describe anatomy study as an initial confrontation with life and death that will follow us throughout our careers, and discuss a way these early lessons might be retrieved.S. Ryan Gregory and Thomas Cole describe the history of dissection across centuries, while Aaron Tward and Hugh Patterson account for the shift from grave robbing to cadaver donation in the United States.Finally, to launch our new creative writing section murmur, Matthew Ehrlich evaluates his cadaver's chief complaint.The first body in our care has neither the needs nor the agency of a patient, and yet for many of us, it is the body we will envision as we examine the intact surface of each patient who comes to us.Whether it is our initiation into "the professional tribe of physicians" (Bender), "the scientific method" (Gregory and Cole), or "the use of affective responses" (Stewart and Charon), anatomy lab is as much a part of how we see as what we know."The trouble with you, Elwell," Noah's ally says to his accuser at the end, "is you've never had a cadaver of your own."
Peptides and Aptamers Targeting HSP70: A Novel Approach for Anticancer Chemotherapy
Authors: Anne-Laure Rérole, Jessica Gobbo, Aurelie De Thonel, Elise Schmitt, Jean Paul Pais de Barros, Arlette Hammann, David Lanneau, Eric Fourmaux, Oleg Deminov, Olivier Micheau, Laurent Lagrost, Pierre Colas, Guido Kroemer, Carmen Garrido
Journal: Cancer Research (2011)

The inhibition of heat shock protein 70 (HSP70) is an emerging strategy in cancer therapy. Unfortunately, no specific inhibitors are clinically available. By yeast two-hybrid screening, we have identified multiple peptide aptamers that bind HSP70. When expressed in human tumor cells, two among these peptide aptamers-A8 and A17-which bind to the peptide-binding and the ATP-binding domains of HSP70, respectively, specifically inhibited the chaperone activity, thereby increasing the cells' sensitivity to apoptosis induced by anticancer drugs. The 13-amino acid peptide from the variable region of A17 (called P17) retained the ability to specifically inhibit HSP70 and induced the regression of subcutaneous tumors in vivo after local or systemic injection. This antitumor effect was associated with an important recruitment of macrophages and T lymphocytes into the tumor bed. Altogether, these data indicate that peptide aptamers or peptides that target HSP70 may be considered as novel lead compounds for cancer therapy.
A management algorithm for congenital erythropoietic porphyria derived from a study of 29 cases
Authors: R.P. Katugampola, A.V. Anstey, A.Y. Finlay, S. Whatley, J. Woolf, N. Mason, J.C. Deybach, H. Puy, C. Ged, H. de Verneuil, S. Hanneken, E. Minder, X. Schneider-Yin, M.N. Badminton
Journal: British Journal of Dermatology (2012)

Congenital erythropoietic porphyria (CEP) is an autosomal recessive photomutilating porphyria with onset usually in childhood, where haematological complications determine prognosis. Due to its extreme rarity and clinical heterogeneity, management decisions in CEP are often difficult.To develop a management algorithm for patients with CEP based on data from carefully characterized historical cases.A single investigator collated data related to treatments and their outcomes in 29 patients with CEP from the U.K., France, Germany and Switzerland.Six children were treated with bone marrow transplantation (BMT); five have remained symptomatically cured up to 11.5 years post-transplantation. Treatments such as oral charcoal, splenectomy and chronic hypertransfusion were either of no benefit or were associated with complications and negative impact on health-related quality of life. Lack of consistent genotype-phenotype correlation meant that this could not be used to predict disease prognosis. The main poor prognostic factors were early age of disease onset and severity of haematological manifestations.A management algorithm is proposed where every patient, irrespective of disease severity at presentation, should receive a comprehensive, multidisciplinary clinical assessment and should then be reviewed at intervals based on their predicted prognosis, and the rate of onset of complications. A BMT should be considered in those with progressive, symptomatic haemolytic anaemia and/or thrombocytopenia. Uroporphyrinogen III synthase genotypes associated with poor prognosis would additionally justify consideration for a BMT. Rigorous photoprotection of the skin and eyes from visible light is essential in all patients.
A Precedent for Modern Psychotherapeutic Techniques: One Thousand Years Ago
Authors: MOHAMMAD SHAFII
Journal: American Journal of Psychiatry (1972)

The author cites a 1,000-year-old case history of a young prince who manifested symptoms of psychotic depression associated with anorexia nervosa. The treatment of this patient by Avicenna, a Persian physician, set a precedent for some psychotherapeutic techniques currently in use. These include: communicating with the patient within his delusional system, creating an effective therapeutic milieu, and applying consultation techniques of community psychiatry.
Antibodies against Merozoite Surface Protein (Msp)-119 Are a Major Component of the Invasion-Inhibitory Response in Individuals Immune to Malaria
Authors: Rebecca A. O'Donnell, Tania F. de Koning-Ward, Rachel A. Burt, Moses Bockarie, John C. Reeder, Alan F. Cowman, Brendan S. Crabb
Journal: The Journal of Experimental Medicine (2001)

Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-119 from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-119, we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum–immune humans and P. chabaudi–immune mice. In some individual human sera, MSP-119 antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-119–based vaccines.
Cytokine responsiveness of CD8+ T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients
Authors: Richard G Everson, Richard M Jin, Xiaoyan Wang, Michael Safaee, Rudi Scharnweber, Dominique N Lisiero, Horacio Soto, Linda M Liau, Robert M Prins
Journal: Journal for ImmunoTherapy of Cancer (2014)

Immunotherapeutic approaches, such as dendritic cell (DC) vaccination, have emerged as promising strategies in the treatment of glioblastoma. Despite their promise, however, the absence of objective biomarkers and/or immunological monitoring techniques to assess the clinical efficacy of immunotherapy still remains a primary limitation. To address this, we sought to identify a functional biomarker for anti-tumor immune responsiveness associated with extended survival in glioblastoma patients undergoing DC vaccination.28 patients were enrolled and treated in two different Phase 1 DC vaccination clinical trials at UCLA. To assess the anti-tumor immune response elicited by therapy, we studied the functional responsiveness of pre- and post-vaccination peripheral blood lymphocytes (PBLs) to the immunostimulatory cytokines interferon-gamma (IFN-γ) and interleukin-2 (IL-2) in 21 of these patients for whom we had adequate material. Immune responsiveness was quantified by measuring downstream phosphorylation events of the transcription factors, STAT-1 and STAT-5, via phospho-specific flow cytometry.DC vaccination induced a significant decrease in the half-maximal concentration (EC-50) of IL-2 required to upregulate pSTAT-5 specifically in CD3(+)CD8(+) T lymphocytes (p < 0.045). Extended survival was also associated with an increased per cell phosphorylation of STAT-5 in cytotoxic T-cells following IL-2 stimulation when the median post/pre pSTAT-5 ratio was used to dichotomize the patients (p = 0.0015, log-rank survival; hazard ratio = 0.1834, p = 0.018). Patients whose survival was longer than two years had a significantly greater pSTAT-5 ratio (p = 0.015), but, contrary to our expectations, a significantly lower pSTAT-1 ratio (p = 0.038).Our results suggest that monitoring the pSTAT signaling changes in PBL may provide a functional immune monitoring measure predictive of clinical efficacy in DC-vaccinated patients.
Lipoprotein(a) in the Nephrotic Syndrome
Authors: CHANTAL DOUCET, VINCENT MOOSER, SOPHIE GONBERT, FRANC[COMBINING CEDILLA]OISE RAYMOND, JOHN CHAPMAN, CLAUDE JACOBS, JOËLLE THILLET
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Plasma levels of lipoprotein(a) (Lp(a)), an atherogenic particle, are elevated in kidney disease, which suggests a role of this organ in the metabolism of Lp(a). Additional evidence for a role of the kidney in the clearance of Lp(a) is provided by the fact that circulating N-terminal fragments of apolipoprotein(a) (apo(a)) are processed and eliminated by the renal route. To further understand the mechanism underlying such renal excretion, the levels of apo(a) fragments in plasma and urine relative to plasma Lp(a) levels were determined in patients with nephrotic syndrome ( n = 15). In plasma, the absolute (24.7 ± 20.4 versus 2.16 ± 2.99 μg/ml, P &lt; 0.0001) as well as the relative amounts of apo(a) fragments (4.6 ± 3.4% versus 2.1 ± 3.3% of total Lp(a), P &lt; 0.0001) were significantly elevated in nephrotic patients compared with a control, normolipidemic population. In addition, urinary apo(a) excretion in patients with nephrotic syndrome was markedly elevated compared with that in control subjects (578 ± 622 versus 27.7 ± 44 ng/ml per mg creatinine, P &lt; 0.001). However, the fractional catabolic rates of apo(a) fragments were similar in both groups (0.68 ± 0.67% and 0.62 ± 0.47% in nephrotic and control subjects, respectively), suggesting that increased plasma concentrations of apo(a) fragments in nephrotic subjects are more dependent on the rate of synthesis rather than on the catabolic rate. Molecular analysis of apo(a) immunoreactive material in urine revealed that the patterns of apo(a) fragments in nephrotic patients were distinct from those of control subjects. Full-length apo(a), large N-terminal apo(a) fragments similar in size to those present in plasma, as well as C-terminal fragments of apo(a) were detected in urine from nephrotic patients but not in urine from controls. All of these apo(a) forms were in addition to smaller N-terminal apo(a) fragments present in normal urine. This study also demonstrated the presence of Lp(a) in urine from nephrotic patients by ultracentrifugal fractionation. These data suggest that in nephrotic syndrome, Lp(a) and large fragments of apo(a) are passively filtered by the kidney through the glomerulus, whereas smaller apo(a) fragments are secreted into the urine.
Total Cavopulmonary Connection Flow With Functional Left Pulmonary Artery Stenosis
Authors: Kerem Pekkan, Hiroumi D. Kitajima, Diane de Zelicourt, Joseph M. Forbess, W. James Parks, Mark A. Fogel, Shiva Sharma, Kirk R. Kanter, David Frakes, Ajit P. Yoganathan
Journal: Circulation (2005)

Background— In our multicenter study of the total cavopulmonary connection (TCPC), a cohort of patients with long-segment left pulmonary artery (LPA) stenosis was observed (35%). The clinically recognized detrimental effects of LPA stenosis motivated a computational fluid dynamic simulation study within 3-dimensional patient-specific and idealized TCPC pathways. The goal of this study was to quantify and evaluate the hemodynamic impact of LPA stenosis and to judge interventional strategies aimed at treating it. Methods and Results— Simulations were conducted at equal vascular lung resistance, modeling both discrete stenosis (DS) and diffuse long-segment hypoplasia with varying degrees of obstruction (0% to 80%). Models having fenestrations of 2 to 6 mm and atrium pressures of 4 to 14 mm Hg were explored. A patient-specific, extracardiac TCPC with 85% DS was studied in its original configuration and after virtual surgery that dilated the LPA to 0% stenosis in the computer medium. Performance indices improved exponentially ( R 2 &gt;0.99) with decreasing obstruction. Diffuse long-segment hypoplasia was ≈50% more severe with regard to lung perfusion and cardiac energy loss than DS. Virtual angioplasty performed on the 3-dimensional Fontan anatomy exhibiting an 85% DS stenosis produced a 61% increase in left lung perfusion and a 50% decrease in cardiac energy dissipation. After 4-mm fenestration, TCPC baffle pressure dropped by ≈10% and left lung perfusion decreased by ≈8% compared with the 80% DS case. Conclusions— DS &lt;60% and diffuse long-segment hypoplasia &lt;40% could be considered tolerable because both resulted in only a 12% decrease in left lung perfusion. In contrast to angioplasty, a fenestration (right-to-left shunt) reduced TCPC pressure at the cost of decreased left and right lung perfusion. These results suggest that pre-Fontan computational fluid dynamic simulation may be valuable for determining both the hemodynamic significance of LPA stenosis and the potential benefits of intervention.
SIX WEEKS OF CORE STABILITY TRAINING REDUCES PEAK LANDING FORCE AMONG FEMALE CAPOEIRA ATHLETES
Authors: L Hayes, S Araujo, D Cohen
Journal: British Journal of Sports Medicine (2014)

Background Core stability training (CST) has increased in popularity among athletes and the general fitness population and is promoted as a means to reduce injury risk. In female athletes, an intervention combining CST and balance training reduced peak landing forces, a risk factor for anterior cruciate ligament (ACL) injuries. Less is known about the isolated effect on landing forces of a CST program comprised of a substantial proportion of static exercises. Objective To evaluate changes in peak landing force in a drop box jump test following a six week CST intervention. Design Intervention study. Setting Well trained Capoeira athletes. Participants 16 female athletes aged 27.3±3.7 years. Interventions Three isometric and three dynamic core stability exercises completed 3 times/week for 6 weeks. Main Outcome Measurements Peak landing forces during a drop jump pre- versus post-intervention. Results Peak landing force significantly decreased from pre- to post-intervention (2943±552 N vs. 1714±235 N respectively [P&lt;.001]). There was no significant change in body mass or jump height during the intervention (P=.528 and P=.877 respectively). Conclusions This study shows that in well-trained female athletes, the addition of a core stability training program that includes a substantial proportion of isometric exercises can reduce landing forces. High landing forces are associated with increased risk of ACL injuries and CST may therefore contribute to injury risk reduction in high risk athletes.
Analysis of genomic rearrangements associated with EGFRvIII expression suggests involvement of Alu repeat elements
Authors: Lori Frederick, Greg Eley, Xiao-Yang Wang, C. David James
Journal: Neuro-Oncology (2000)

We have developed a polymerase chain reaction (PCR)-based strategy for the synthesis and analysis of rearranged epidermal growth factor receptor (EGFR) fragments associated with the vIII mutant receptor expressed in glioblastomas with EGFR amplification. The sequencing of aberrant tumor fragments showed that intragenic deletion rearrangements consistently involve an approximately 600-bp region in intron 7 of EGFR and several rearrangement sites interspersed throughout the large (>100 kb) first intron of this gene. Examination of the intron 7 breakpoint region revealed an Alu repeat element, and all intron 7 rearrangement sites were located within or downstream of this repeat sequence. Analysis of intron 1 for similar sequences resulted in the identification of 11 sites containing> 80% homology with parts of the Alu element in intron 7. Reverse transcriptase-PCR and/or Western analysis of the tumors showed the presence of EGFRvIII cDNAs and/or proteins, respectively, in all cases for which a rearranged genomic fragment was generated by long-range PCR. Collectively, these data suggest that EGFR rearrangements, associated with the synthesis of the most common EGFR mutant, are mediated by a specific sequence element.
Brain Metabolism during Fasting*
Authors: O. E. Owen, A. P. Morgan, H. G. Kemp, J. M. Sullivan, M. G. Herrera, G. F. Cahill
Journal: Journal of Clinical Investigation (1967)

Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that beta-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism. A strikingly low respiratory quotient was also observed, suggesting a carboxylation mechanism as a means of disposing of some of the carbon of the consumed substrates.
Cancer cell: using inflammation to invade the host
Authors: José-Ignacio Arias, María-Angeles Aller, Jaime Arias
Journal: Molecular Cancer (2007)

Inflammation is increasingly recognized as an important component of tumorigenesis, although the mechanisms involved are not fully characterized. The invasive capacity of cancers is reflected in the classic metastatic cascade: tumor (T), node (N) and metastasis (M). However, this staging system for cancer would also have a tumoral biological significance. To integrate the mechanisms that control the inflammatory response in the actual staging system of cancer. It is considered that in both processes of inflammation and cancer, three successive phenotypes are presented that represent the expression of trophic functional systems of increasing metabolic complexity for using oxygen. While a malignant tumor develops it express phenotypes that also share the inflammatory response such as: an ischemic phenotype (anoxic-hypoxic), a leukocytic phenotype with anaerobic glycolysis and migration, and an angiogenic phenotype with hyperactivity of glycolytic enzymes, tumor proliferation and metastasis, and cachexia of the host. The increasing metabolic complexity of the tumor cell to use oxygen allows for it to be released, migrate and proliferate, thus creating structures of growing complexity. One aim of cancer gene therapy could be the induction of oxidative phosphorylation, the last metabolic step required by inflammation in order to differentiate the tissue that it produces.