tbuckley/cabot-search huggingface dataset:
Salt Accelerates Allograft Rejection through Serum- and Glucocorticoid-Regulated Kinase-1–Dependent Inhibition of Regulatory T Cells
Authors: Kassem Safa, Shunsuke Ohori, Thiago J. Borges, Mayuko Uehara, Ibrahim Batal, Tetsunosuke Shimizu, Ciara N. Magee, Roger Belizaire, Reza Abdi, Chuan Wu, Anil Chandraker, Leonardo V. Riella
Journal: Journal of the American Society of Nephrology (2015)

A high-salt diet (HSD) in humans is linked to a number of complications, including hypertension and cardiovascular events. Whether a HSD affects the immune response in transplantation is unknown. Using a murine transplantation model, we investigated the effect of NaCl on the alloimmune response in vitro and in vivo. Incremental NaCl concentrations in vitro augmented T cell proliferation in the settings of both polyclonal and allospecific stimulation. Feeding a HSD to C57BL/6 wild-type recipients of bm12 allografts led to accelerated cardiac allograft rejection, despite similar mean BP and serum sodium levels in HSD and normal salt diet (NSD) groups. The accelerated rejection was associated with a reduction in the proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) and a significant decrease in Treg proliferation, leading to an increased ratio of antigen-experienced CD4(+) T cells to Tregs in mice recipients of a HSD compared with mice recipients of a NSD. Because serum- and glucocorticoid-regulated kinase-1 (SGK1) has been proposed as a potential target of salt in immune cells, we fed a HSD to CD4(Cre)SGK1(fl/fl) B6-transplanted recipients and observed abrogation of the deleterious effect of a HSD in the absence of SGK1 on CD4(+) cells. In summary, we show that NaCl negatively affects the regulatory balance of T cells in transplantation and precipitates rejection in an SGK1-dependent manner.
Relationship between peak cardiac pumping capability and selected exercise‐derived prognostic indicators in patients treated with left ventricular assist devices
Authors: Djordje G. Jakovljevic, Emma J. Birks, Robert S. George, Michael I. Trenell, Petar M. Seferovic, Magdi H. Yacoub, David A. Brodie
Journal: European Journal of Heart Failure (2011)
DEVELOPMENT OF FOOD PREFERENCES
Authors: Leann L. Birch
Journal: Annual Review of Nutrition (1999)

Using a developmental systems perspective, this review focuses on how genetic predispositions interact with aspects of the eating environment to produce phenotypic food preferences. Predispositions include the unlearned, reflexive reactions to basic tastes: the preference for sweet and salty tastes, and the rejection of sour and bitter tastes. Other predispositions are (a) the neophobic reaction to new foods and (b) the ability to learn food preferences based on associations with the contexts and consequences of eating various foods. Whether genetic predispositions are manifested in food preferences that foster healthy diets depends on the eating environment, including food availability and child-feeding practices of the adults. Unfortunately, in the United States today, the ready availability of energy-dense foods, high in sugar, fat, and salt, provides an eating environment that fosters food preferences inconsistent with dietary guidelines, which can promote excess weight gain and obesity.
The Role of Grief and Fear in the Death of Kidney Transplant Patients
Authors: ROBERT M. EISENDRATH
Journal: American Journal of Psychiatry (1969)

Eight out of 11 patients who died following renal transplantation were noted to have suffered a sense of abandonment by their families or to have experienced panic and a sense of pessimism about the outcome of the operation, to a degree not observed among patients who survived. The author concludes that preoperative psychotherapy to help mobilize the hopeless patient's will to live may be necessary for his survival.
Clinical Feature and Progress of Contrast Media Anaphylaxis
Authors: Min-Hye Kim, Min-Suk Yang, Woo-Jung Song, So-Hee Lee, Sae-Hoon Kim, Hye-Ryun Kang, Heung-Woo Park, Sun-Sin Kim, Yoon-Seok Chang, Kyung-Up Min, You-Young Kim, Sang Heon Cho
Journal: Journal of Allergy and Clinical Immunology (2013)
Associated Loss of Fat-free Mass and Bone Mineral Density in Chronic Obstructive Pulmonary Disease
Authors: Charlotte E. Bolton, Alina A. Ionescu, Kathleen M. Shiels, Rebecca J. Pettit, Peter H. Edwards, Michael D. Stone, Lisette S. Nixon, William D. Evans, Timothy L. Griffiths, Dennis J. Shale
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

We hypothesized that in patients with chronic obstructive pulmonary disease, loss of fat-free mass (FFM) and loss of bone mineral density (BMD) were related to (1) each other and may be clinically inapparent, (2) urinary markers of cellular and bone collagen protein breakdown, and (3) severity of lung disease. Eight-one patients and 38 healthy subjects underwent dual-energy X-ray absorptiometry to determine body composition and BMD. Urinary protein breakdown markers, inflammatory mediators, and their soluble receptors were determined. Thirty-three patients had a low fat-free mass index (kg/m2), 17 of whom had a normal body mass index. Thirty-two percent of patients (13% of healthy subjects) had osteoporosis at the hip or lumbar spine. The marker of cellular protein breakdown was elevated in patients and related to lung disease severity and body composition. The marker of bone collagen breakdown was greater in patients with osteoporosis. Inflammatory mediators were elevated in patients. Loss of FFM and loss of BMD were related, occurred commonly, and could be subclinical in patients with chronic obstructive pulmonary disease. Loss of both was greatest with severe lung disease. Increased excretion of cellular and bone collagen protein breakdown products in those with low FFM and BMD indicates a protein catabolic state in these patients.
Spontaneous tool use and sensorimotor intelligence in<i>Cebus</i>compared with other monkeys and apes
Authors: Suzanne Chevalier-Skolnikoff
Journal: Behavioral and Brain Sciences (1989)

Abstract Spontaneous tool use and sensorimotor intelligence in Cebus were observed to determine whether tool use is discovered fortuitously and learned by trial-and-error or, rather, whether advanced sensorimotor abilities (experimentation and insight) are critical in its ontogeny and evolution.
Aberrant Splicing of Cyclin-Dependent Kinase–Associated Protein Phosphatase KAP Increases Proliferation and Migration in Glioblastoma
Authors: Yi Yu, Xiuli Jiang, Brad S. Schoch, Rona S. Carroll, Peter M. Black, Mark D. Johnson
Journal: Cancer Research (2007)

Abstract The cyclin-dependent kinase (Cdk)–associated protein phosphatase KAP is a dual-specificity phosphatase of which the only known function is to dephosphorylate Cdk2 and inhibit cell cycle progression. Paradoxically, we find increased KAP mRNA expression in malignant astrocytomas, which correlates with increasing histologic grade and decreased patient survival. We have resolved this apparent paradox with the discovery of aberrant KAP splicing in malignant astrocytomas that leads to increased expression of KAP-related transcripts but decreased KAP protein expression. In addition, the aberrant splicing generates a dominant negative KAP variant that increases proliferation. We provide the first evidence that KAP not only regulates proliferation but also inhibits migration by decreasing cdc2 mRNA and protein expression. The effect of KAP on cdc2 expression requires its phosphatase activity but does not involve direct dephosphorylation of cdc2. Thus, KAP regulates both cdc2-dependent migration and Cdk2-dependent proliferation, and its loss due to aberrant splicing increases malignancy in human gliomas. [Cancer Res 2006;67(1):130–8]
Tuberculosis in Students and Nurses
Authors: R. E. Verney
Journal: BMJ (1955)

LUNG CANCERM RNAL 929 cigarette smoking by each group of men, and comparing the relative figures with the relative death rates from lung cancer.The measure of agreement between the relative values of benzpyreine intake on assumption (2) and those for the standardized death rates (S.D.R.) in the various groups is such as to justify a working hypothesis that benzpyrene might be the agent responsible for the associations of lung cancer with both smoking and urban residence, and to encourage research into the amounts of this and other hydro- carbons in the air, both outside and inside buildings, in different localities.Summary in this field whether or not it is finally substantiated.In collecting the patients' histories on which this study is based many people have co-operated, and acknowledgment is made to the medical officers of health, doctors, and health visitors in the counties of Anglesey, Caernarvon, Denbigh, Flint, and Cheshire, and county boroughs of Liverpool and Chester; to the Management Committees of Bangor, Wrexham, Chester, and Broadgreen Hospitals; and to the patients and their relatives.
Microvessel Density as a Prognostic Factor in Women with Breast Cancer
Authors: Bernard Uzzan, Patrick Nicolas, Michel Cucherat, Gérard-Yves Perret
Journal: Cancer Research (2004)

Abstract We performed a meta-analysis of all 87 published studies linking intratumoral microvessel density (MVD), reflecting angiogenesis, to relapse-free survival (RFS) and overall survival (OS). With median MVD as cutoff, MVD impact was measured by risk ratio (RR) between the two survival distributions. Seventeen studies did not mention survival data or fit inclusion criteria. Twenty-two were multiple publications of the same series, leaving 43 independent studies (8936 patients). MVD was assessed by immunohistochemistry, using antibodies against factor VIII (27 studies; n = 5262), CD31 (10 studies; n = 2296), or CD34 (8 studies; n = 1726). MVD might be a better prognostic factor when assessed by CD31 or CD34 versus factor VIII (P = 0.11). For RFS, statistical calculations were performed in 25 studies (6501 patients). High MVD significantly predicted poor survival [RR = 1.54 for RFS and OS with the same 95% confidence interval (CI), 1.29–1.84]. Twenty-two studies analyzed separately lymph node-negative patients (n = 3580), for whom predictors of poor survival are requested. This latter meta-analysis included 15 studies for RFS (2727 patients) and 11 for OS (1926 patients). High MVD significantly predicted poor survival [RR = 1.99 for RFS (95% CI, 1.33–2.98) and RR = 1.54 for OS (95% CI, 1.01–2.33)]. Between-study variations could result from patient selection criteria, techniques to stain and count microvessels, and cutoff selection. MVD was a significant although weak prognostic factor in women with breast cancer. Standardization of MVD assessment is needed.
Elevated Erythropoietin Receptor and Transforming Growth Factor-β1 Expression in Stenotic Arteriovenous Fistulae Used for Hemodialysis
Authors: NAOKI IKEGAYA, TATSUO YAMAMOTO, AKIHIRO TAKESHITA, TAKUYA WATANABE, KATSUHIKO YONEMURA, TAKEHIKO MIYAJI, KAZUHISA OHISHI, MITSUYOSHI FURUHASHI, YUKITAKA MARUYAMA, AKIRA HISHIDA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The issue of whether recombinant human erythropoietin (rhEPO) increases thrombosis of arteriovenous (AV) fistulae used for hemodialysis remains unclear. Thrombosis often occurs at stenotic segments of fistulae where there is marked intimal hyperplasia and extracellular matrix accumulation. Increased expression of transforming growth factor-β1 (TGF-β1) has been shown to be involved in the development of atherosclerotic lesions by promoting intimal hyperplasia and extracellular matrix accumulation. To clarify the role of rhEPO in the development of stenosis of AV fistulae, this study examined expression of the erythropoietin receptor (EPO-R), TGF-β1, plasminogen activator inhibitor type 1 (PAI-1), cellular fibronectin containing an extra domain A (EDA+), and TGF-β1 mRNA, and assessed in situ rhEPO binding in tissue specimens from seven cutaneous veins and eight patent and seven stenosed portions of AV fistulae of patients undergoing dialysis. Prominent intimal hyperplasia was evident in the stenosed segments. Significant elevation in expression of EPO-R and TGF-β1 was noted in patent AV fistulae compared to the cutaneous veins. Significant enhancement of EPO-R and TGF-β expression was detected in the stenotic fistulae. Fibronectin EDA+ and PAI-1 expression was increased in intimal hyperplasia compared to patent fistulae and cutaneous veins. Elevated EPO-R expression was further confirmed by in situ binding of biotin-labeled rhEPO in stenosed tissue specimens. It is hypothesized that increased rhEPO binding due to elevated EPO-R expression contributes to the development of AV fistula stenosis caused by intimal hyperplasia and extracellular matrix accumulation in response to increased TGF-β1 expression in patients receiving hemodialysis.
Effect of a Preoperative Decontamination Protocol on Surgical Site Infections in Patients Undergoing Elective Orthopedic Surgery With Hardware Implantation
Authors: Serge P. Bebko, David M. Green, Samir S. Awad
Journal: JAMA Surgery (2015)

Surgical site infections (SSIs), commonly caused by methicillin-resistant Staphylococcus aureus (MRSA), are associated with significant morbidity and mortality, specifically when hardware is implanted in the patient. Previously, we have demonstrated that a preoperative decontamination protocol using chlorhexidine gluconate washcloths and intranasal antiseptic ointment is effective in eradicating MRSA in the nose and on the skin of patients.To examine the effect of a decontamination protocol on SSIs in patients undergoing elective orthopedic surgery with hardware implantation.A prospective database of patients undergoing elective orthopedic surgery with hardware implantation at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, was analyzed from October 1, 2012, to December 31, 2013. Cohort groups before and after the intervention were compared.Starting in May 2013, during their preoperative visit, all of the patients watched an educational video about MRSA decontamination and were given chlorhexidine washcloths and oral rinse and nasal povidone-iodine solution to be used the night before and the morning of scheduled surgery.Thirty-day SSI rates were collected according to the definitions of the Centers for Disease Control and Prevention National Nosocomial Infections Surveillance. Data on demographics, comorbidities such as chronic obstructive pulmonary disease and coronary artery disease, tobacco use, alcohol use, and body mass index were also collected. Univariate analysis was performed between the 2 groups of patients. Multivariate analysis was used to identify independent predictors of SSI.A total of 709 patients were analyzed (344 controls and 365 patients who were decolonized). Both groups were well matched with no significant differences in age, body mass index, sex, or comorbidities. All of the patients (100%) completed the MRSA decontamination protocol. The SSI rate in the intervention group was significantly lower (1.1%; 4 of 365 patients developed an SSI) than the SSI rate in the control group (3.8%; 13 of 344 patients developed an SSI) (P = .02). Multivariate logistic regression identified MRSA decontamination as an independent predictor of not developing an SSI (adjusted odds ratio, 0.24 [95% CI, 0.08-0.77]; P = .02).Our study demonstrates that preoperative MRSA decontamination with chlorhexidine washcloths and oral rinse and intranasal povidone-iodine decreased the SSI rate by more than 50% among patients undergoing elective orthopedic surgery with hardware implantation. Universal decontamination using this low-cost protocol may be considered as an additional prevention strategy for SSIs in patients undergoing orthopedic surgery with hardware implantation and warrants further study.
Phase II Clinical Experience With the Novel Proteasome Inhibitor Bortezomib in Patients With Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma
Authors: Owen A. O'Connor, John Wright, Craig Moskowitz, Jamie Muzzy, Barbara MacGregor-Cortelli, Michael Stubblefield, David Straus, Carol Portlock, Paul Hamlin, Elizabeth Choi, Otila Dumetrescu, Dixie Esseltine, Elizabeth Trehu, Julian Adams, David Schenkein, Andrew D. Zelenetz
Journal: Journal of Clinical Oncology (2004)

To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL).Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11. Patients were required to have received no more than three prior chemotherapy regimens, with at least 1 month since the prior treatment, 3 months from prior rituximab, and 7 days from prior corticosteroids; absolute neutrophil count more than 1,500/microL (500/microL if documented bone marrow involvement); and platelet count more than 50,000/microL.Twenty-six patients were registered, of whom 24 were assessable. Ten patients had follicular lymphoma, 11 had MCL, three had small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), and two had marginal zone lymphoma. The overall response rate was 58%, with one complete remission (CR), one unconfirmed CR (CRu), and four partial remissions (PR) among patients with follicular non-Hodgkin's lymphoma (NHL). All responses were durable, lasting from 3 to 24+ months. One patient with MCL achieved a CRu, four achieved a PR, and four had stable disease. One patient with MCL maintained his remission for 19 months. Both patients with marginal zone lymphoma achieved PR lasting 8+ and 11+ months, respectively. Patients with SLL or CLL have yet to respond. Overall, the drug was well tolerated, with only one grade 4 toxicity (hyponatremia). The most common grade 3 toxicities were lymphopenia (n = 14) and thrombocytopenia (n = 7).These data suggest that bortezomib was well tolerated and has significant single-agent activity in patients with certain subtypes of NHL.
Pulmonary infiltrates in non-HIV patients
Authors: P MURRAY
Journal: Thorax (2001)

Multidrug resistant tuberculosisWe read with interest the report by White and Moore-Gillon 1 on the resource implications of multidrug resistant tuberculosis (MDR-TB) in the UK.We studied the outcome of 44 HIV negative patients with MDR-TB admitted to two tertiary care tuberculosis units in the Netherlands between 1985 and 1998. 2 3 Most (38 patients) had pulmonary tuberculosis.The mean admission period was 164 days and all patients received an individually tailored combination of antituberculosis drugs for a mean period of 608 days.We estimated the cost of treatment per patient to be US$60 000 which included admission fee, costs for outpatient visits, and the costs of drug provision.Although we did not include cost of toxicity monitoring and additional procedures, our costs compare favourably with those of White et al 1 (mean £60 000) and Mahmoudi 4 (mean US$180 000).In the Netherlands the number of patients with tuberculosis resistant to any antituberculous drugs is limited to 11%, and only 0.6% of the bacilli are MDR.Between 1993 and 1997 only 43 cases of MDR-TB were identified, of which 28% had received previous treatment for tuberculosis (Index Tuberculosis 1998, Royal Netherlands Tuberculosis Association, The Hague, 2000).This suggests that transmission of MDR bacilli rather than inadequate treatment contributes to the resistance problem in the Netherlands.In poor resource countries, directly observed short course chemotherapy of tuberculosis is generally recommended to prevent the occurrence of MDR-TB.We feel that new rapid molecular methods for detecting resistance should be developed to limit the period of potential (nosocomial and community) transmission of MDR bacilli and thus prevent the emergence of MDR-TB.Such tests should then be made available to poor resource countries at an aVordable price.
From Integrated Genomics to Tumor Lineage Dependency
Authors: Levi A. Garraway, William R. Sellers
Journal: Cancer Research (2006)

Abstract In principle, genomic information derived from tumors should illuminate critical cellular dependencies that are tractable to therapeutic targeting; however, realizing this ideal remains difficult. Using an integrated analysis of high-resolution single nucleotide polymorphism maps and gene expression databases associated with the NCI60 collection cancer cell lines, we identified the transcription factor MITF as an amplified oncogene in melanoma that is critical for anchoring lineage dependence and malignant character. Similar combined genomic approaches may be useful in other cancer types to learn how critical regulators of tumor lineage are linked to genomic alterations in cancer cells. (Cancer Res 2006; 66(5): 2506-8)
Detection of GAD65-Reactive T-Cells in Type 1 Diabetes by Immunoglobulin-Free ELISPOT Assays
Authors: Reiko Kotani, Masao Nagata, Hiroaki Moriyama, Maki Nakayama, Katsumi Yamada, Shahead Ali Chowdhury, Sagarika Chakrabarty, Zhenzi Jin, Hisafumi Yasuda, Koichi Yokono
Journal: Diabetes Care (2002)

OBJECTIVE—To investigate the prevalence of β-cell autoantigen-reactive peripheral T-cells in type 1 diabetes, we developed an immunoglobulin-free enzyme-linked immunospot (ELISPOT) assay and assessed its usefulness for diagnosing this disease. RESEARCH DESIGN AND METHODS—Cellular immune responses to β -cell autoantigens were studied both by immunoglobulin-free proliferation assays and ELISPOT assays in 33 patients with type 1 diabetes and 15 patients with type 2 diabetes, compared with 23 healthy control subjects. Autoantibodies against GAD65 and IA-2 were measured by radioimmunoassay. RESULTS—Significant proliferative responses to GAD65 were observed in 10 of 31 (32.3%) type 1 diabetic patients (P &amp;lt; 0.05), whereas GAD65-reactive γ-interferon (IFN-γ)-secreting cells were detected in 22 of 33 patients (66.7%) by ELISPOT assay (P &amp;lt; 0.001). Of patients negative for both GAD65 and IA-2, five of six (83.3%) showed IFN-γ positivity in ELISPOT and two of five (40.0%) showed significant proliferation against GAD65. CONCLUSIONS—Using a newly developed ELISPOT assay, GAD-reactive T-helper 1 cells in PBMC of type 1 diabetic patients could be identified at a higher frequency than by the proliferation assay. Therefore, the immunoglobulin-free ELISPOT assay is an excellent tool for detecting T-cell reactivity to autoantigens with greater specificity and, in combination with β-cell autoantibody determination, will improve the diagnosis of type 1 diabetes.
Fate of Premalignant Clones during the Asymptomatic Phase Preceding Lymphoid Malignancy
Authors: Vincent Moulés, Carole Pomier, David Sibon, Anne-Sophie Gabet, Michal Reichert, Pierre Kerkhofs, Luc Willems, Franck Mortreux, Eric Wattel
Journal: Cancer Research (2005)

Abstract Almost all cancers are preceded by a prolonged period of clinical latency during which a combination of cellular events helps move carcinogen-exposed cells towards a malignant phenotype. Hitherto, investigating the fate of premalignant cells in vivo remained strongly hampered by the fact that these cells are usually indistinguishable from their normal counterparts. Here, for the first time, we have designed a strategy able to reconstitute the replicative history of the bona fide premalignant clone in an animal model, the sheep experimentally infected with the lymphotropic bovine leukemia virus. We have shown that premalignant clones are early and clearly distinguished from other virus-exposed cells on the basis of their degree of clonal expansion and genetic instability. Detectable as early as 0.5 month after the beginning of virus exposure, premalignant cells displayed a two-step pattern of extensive clonal expansion together with a mutation load ∼6 times higher than that of other virus-exposed cells that remained untransformed during the life span of investigated animals. There was no fixation of somatic mutations over time, suggesting that they regularly lead to cellular death, partly contributing to maintain a normal lymphocyte count during the prolonged premalignant stage. This equilibrium was finally broken after a period of 18.5 to 60 months of clinical latency, when a dramatic decrease in the genetic instability of premalignant cells coincided with a rapid increase in lymphocyte count and lymphoma onset.