tbuckley/cabot-search huggingface dataset:
Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity
Authors: Stavros Konstantinides, Katrin Schäfer, Stefan Koschnick, David J. Loskutoff
Journal: Journal of Clinical Investigation (2001)

Obesity is associated with increased cardiovascular morbidity and mortality and with elevated circulating levels of the satiety factor leptin. This study provides evidence for a direct link between leptin and the risk for thrombotic complications in obese individuals. For example, although arterial injury provokes thrombosis in both lean and obese (ob/ob) mice, the time to complete thrombotic occlusion is significantly delayed in the ob/ob mice, and the thrombi formed are unstable and frequently embolize. The ob/ob mice lack leptin, and intraperitoneal administration of leptin to these mice before injury restores the phenotype of lean mice by shortening the time to occlusion, stabilizing the thrombi, and decreasing the patency rate. The thrombi that form when leptin receptor-deficient obese (db/db) mice are injured also are unstable. However, in this instance, leptin has no effect. Platelets express the leptin receptor, and leptin potentiates the aggregation of platelets from ob/ob but not db/db mice in response to known agonists. These results reveal a novel receptor-dependent effect of leptin on platelet function and hemostasis and provide new insights into the molecular basis of cardiovascular complications in obese individuals. The results suggest that these prothrombotic properties should be considered when developing therapeutic strategies based on leptin.
Promoting Thiol Expression Increases the Durability of Antitumor T-cell Functions
Authors: Pravin Kesarwani, Amir A. Al-Khami, Gina Scurti, Krishnamurthy Thyagarajan, Navtej Kaur, Shahid Husain, Quan Fang, Osama S. Naga, Patricia Simms, Gyda Beeson, Christina Voelkel-Johnson, Elizabeth Garrett-Mayer, Craig C. Beeson, Michael I. Nishimura, Shikhar Mehrotra
Journal: Cancer Research (2014)

Abstract Ex vivo–expanded CD8+ T cells used for adoptive immunotherapy generally acquire an effector memory-like phenotype (TEM cells). With regard to therapeutic applications, two undesired features of this phenotype in vivo are limited persistence and reduced antitumor efficacy, relative to CD8+ T cells with a central memory-like phenotype (TCM cells). Furthermore, there is incomplete knowledge about all the differences between TEM and TCM cells that may influence tumor treatment outcomes. Given that TCM cells survive relatively longer in oxidative tumor microenvironments, we investigated the hypothesis that TCM cells possess relatively greater antioxidative capacity than TEM cells. Here, we report that TCM cells exhibit a relative increase compared with TEM cells in the expression of cell surface thiols, a key target of cellular redox controls, along with other antioxidant molecules. Increased expression of redox regulators in TCM cells inversely correlated with the generation of reactive oxygen and nitrogen species, proliferative capacity, and glycolytic enzyme levels. Notably, T-cell receptor–transduced T cells pretreated with thiol donors, such as N-acetyl cysteine or rapamycin, upregulated thiol levels and antioxidant genes. A comparison of antitumor CD8+ T-cell populations on the basis of surface thiol expression showed that thiol-high cells persisted longer in vivo and exerted superior tumor control. Our results suggest that higher levels of reduced cell surface thiols are a key characteristic of T cells that can control tumor growth and that profiling this biomarker may have benefits to adoptive T-cell immunotherapy protocols. Cancer Res; 74(21); 6036–47. ©2014 AACR.
RAID: a valid tool to quantify the impact of rheumatoid arthritis. But what impact will it have on the core set for trials?
Authors: Maarten Boers
Journal: Annals of the Rheumatic Diseases (2011)

In the context of measurement of health status, “impact” is a relatively new term that encompasses the patient's perspective on the disease.1 The importance of patient-reported outcomes has traditionally been recognised within the rheumatology community, as evidenced by their presence in the core set of end points for rheumatoid arthritis (RA) clinical trials formulated at the first Outcome Measures in Rheumatology Initiative (OMERACT) conference in 1992.2 However, patients and researchers present at the OMERACT 6 conference in 2002 noted that the patient perspective was not adequately covered by the three core set measures: pain, physical function and patient global assessment.3 Domains deemed important but not covered included fatigue, sleep quality and well-being.

More recently, researchers from Bristol have suggested that the impact of a disease or its components is dependent on three interdependent concepts: severity, importance and self-management.4 Severity and importance are relatively well-known components that have already been incorporated in so-called “personal preference” tools such as the McMaster-Toronto Arthritis (MACTAR) scale that asks patients to rank their five most important activities and subsequently tracks changes in the ability to perform these activities over time.5 Self-management is a new angle brought in by the patients that is really self evident once named, but rarely mentioned before let alone measured in trials. For example, the impact of a disease flare in RA could be expressed in: the total severity (how bad is it?); the importance (are joints that I really need affected?); and the ability to cope (can I still do what I need to do?).

Therefore, it is a happy occasion that …
Effect of exercise on dilution estimates of extravascular lung water and on the carbon monoxide diffusing capacity in normal adults.
Authors: C A Goresky, J W Warnica, J H Burgess, B E Nadeau
Journal: Circulation Research (1975)

Previous studies in exercising animals have demonstrated that the extravascular lung water accessible to measurement by dilution methodology increases in the transition from rest to low-level exercise and thereafter does not change with progress to high-level exercise. In normal humans, similar systematic examination is essential to provide a background for the interpretation of changes in measured extravascular lung water in pathophysiological states. Moreover, such an examination might provide new insight into the mechanisms underlying the change in the pulmonary diffusing capacity with exercise. We therefore measured both the pulmonary extravascular lung water (by use of the triple indicator-dilution technique) and the diffusing capacity for carbon monoxide in 11 subjects, seated on an exercise bicycle, at rest and usually during two levels of exercise. The central blood volume increased by 50% with a tripling of the cardiac output. The accessible lung water increased from an average of 2.16 g/kg to 2.55 g/kg in the transition from rest to low-level exercise, but it did not increase further at the higher level of exercise. The simultaneously measured diffusing capacity for carbon monoxide (single breath and steady state) continued to increase over the whole range of cardiac outputs. We infer that the proportion of the pulmonary parenchyma perfused by blood flow increases slightly in the transition from rest to low-level exercise but increases no further at the higher level of exercise. The continued increase in the pulmonary diffusing capacity over the range in which the estimated lung water values do not change appears to imply that part of this increase may be blood flow dependent rather than dependent on the recruitment of additional surface for exchange.
Henoch-Schonlein purpura due to food sensitivity.
Authors: B W Robinson
Journal: BMJ (1977)

<h3>Background</h3> Pregnancy in women with Rheumatic Diseases (RD) is of high risk and requires a close communication between the rheumatologist, obstetrician, and all other specialists involved.It may have an effect on the natural history of autoimmune disease, a phenomenon that is particularly relevant in Systemic Lupus Erythematous (SLE) and Rheumatoid Arthritis (RA). Additionally, there are consequences that autoimmune disease may yield throughout the course of conception and gestation. <h3>Objectives</h3> To describe the epidemiological characteristics of patients seen at the Clinic of Pregnancy and Rheumatic Diseases (Clínica de Embarazo y Enfermedades Reumáticas, CEER) located in the Jose E. Gonzalez University Hospital in Mexico. <h3>Methods</h3> We conducted a descriptive transversal study of a cohort of 50 adult patients that attended CEER; which were categorised within three consultation groups (reproductive age, with a present or future desire to become pregnant, pregnant or in postpartum period). All patients were evaluated by the Maternal-Fetal Medicine and Rheumatology department. CEER was created in, August 2017 and provided medical follow up for newly pregnant patients, those already pregnant, and patients in the immediate postpartum period. Epidemiological data was collected. <h3>Results</h3> Of the 50 patients, 8 (16%) with a present or future desire to become pregnant, 24 (48%) pregnant, just only one presented gestational diabetes; and 18 (36%) were in the immediate postpartum period. The median age was 32 years (<i>SD=6.16</i>). The 18 births were live births obtained by caesarean section, 8 (55.8%) were pre-term (<i>&lt;37</i> WG) and none presented eclampsia or preeclampsia. Of the patients, 22 (44%) had a diagnosis of RA, 10 (20%) had SLE, 10 (20%) had Antiphospholipid Syndrome, and the remaining 8 (16%) had other diagnoses (table 1). Only 18 (36%) had previous abortions. <h3>Conclusions</h3> The evaluation of patients with RD requires a close follow-up, which is why the population of reproductive age with RD must be seen early on. Considering that our results revealed a high percentage of preterm live births medical attention must be provided from the preconception to the postpartum period. <h3>References</h3> [1] Ching Soh May, Nelson-Piercy Catherine, High Risk pregnancy and the rheumatologist. Rheumatology. 2015;54(4): 572–587 [2] Alvarez-Nemegyei J. Cervantes-Diaz MT, Avila-zapata F, et al. Desenlace obstétrico antes y después del inicio de la artritis reumatoide. Rev Mex Imss2011;49:599–604 <h3>Disclosure of Interest</h3> None declared
Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes.
Authors: J Rugtveit, P Brandtzaeg, T S Halstensen, O Fausa, H Scott
Journal: Gut (1994)

Mucosal specimens from active Crohn's disease (ileum, n = 6; colon, n = 6), active ulcerative colitis (n = 9), normal ileum (n = 6), and normal colon (n = 6) were subjected to paired immunofluorescence staining for characterisation of macrophage subsets in situ. In the normal state, only few CD68+ macrophages (< 10%) expressing the myelomonocytic L1 antigen (calprotectin) were seen. In inflamed mucosa, especially near small vessels, the CD68+L1+ fraction increased with the degree of inflammation, near ulcers to median 65% (range 35-91%). Cells reactive with the monoclonal antibody RFD7 were also increased in inflammation but less than 5% of them costained for L1 antigen. It is concluded that L1 producing macrophages are distinct from the RFD7+ subset and probably recently recruited from peripheral blood monocytes. Like granulocytes, L1+ macrophages may be important in non-specific defence, providing calprotectin with putative anti-microbial and anti-proliferative properties.
Variants in ZNF365 isoform D are associated with Crohn's disease
Authors: T. Haritunians, M. R. Jones, D. P. B. McGovern, D. Q. Shih, R. J. Barrett, C. Derkowski, M. C. Dubinsky, D. Dutridge, P. R. Fleshner, A. Ippoliti, L. King, E. Leshinsky-Silver, A. Levine, G. Y. Melmed, E. Mengesha, E. A. Vasilauskas, S. Ziaee, J. I. Rotter, S. R. Targan, K. D. Taylor
Journal: Gut (2011)

<h3>Objective</h3> Genome-wide association studies have identified multiple Crohn9s disease (CD) susceptibility loci, including association with non-coding intergenic single-nucleotide polymorphisms (SNPs) at 10q21. <h3>Design</h3> To fine-map the 10q21 locus, the authors genotyped 86 SNPs in 1632 CD cases and 961 controls and performed single-marker and conditional analyses using logistic regression. <h3>Results</h3> Association with CD risk spanning 11 SNPs (p&lt;0.001) was observed. The most significant association observed was at the non-synonymous SNP, rs7076156 (Ala62Thr), in <i>ZNF365</i>. The alanine allele was over-represented in CD (p=5.23×10<sup>−7</sup>; OR=1.39 (95% CI 1.22 to 1.58)); allele frequency of 76% in CD and 69.7% in controls). Conditional analysis on rs7076156 nullified all other significant associations, suggesting that this is the causative variant at this locus. Four isoforms of <i>ZNF365</i> have previously been identified, and rs7076156 is located in an exon unique to <i>ZNF365</i> isoform D. The authors demonstrated, using reverse transcription-PCR, expression of ZNF365D in intestinal resections from both CD subjects and controls. Markedly reduced mean expression levels of ZNF365D were identified in Epstein–Barr virus-transformed lymphoblastoid cell lines from CD subjects homozygous for the risk allele (Ala). A whole-genome microarray expression study further suggested that the Ala62Thr change in <i>ZNF365</i> isoform D is related to differential expression of the genes <i>ARL4A</i>, <i>MKKS</i>, <i>RRAGD</i>, <i>SUMF2</i>, <i>TDR1</i> and <i>ZNF148</i> in CD. <h3>Conclusions</h3> Collectively, these data support the hypothesis that the non-synonymous Ala62Thr SNP, rs7076156, underlies the association between 10q21 and CD risk and suggest that this SNP acts by altering expression of genes under the control of <i>ZNF365</i> isoform D.
Mole Self-grip Wrench
Authors: A. C. Bingold
Journal: BMJ (1958)

<h3>Abstract</h3> Encounters among bacteria and their viral predators (bacteriophages) are among the most common ecological interactions on Earth. Further, these encounters are likely to occur predominantly within surface-bound communities that microbes most often occupy in natural environments. These communities, termed biofilms, are spatially constrained such that interactions become limited to near neighbors; diffusion of solutes and particulates is reduced; and there is pronounced heterogeneity in nutrient access and physiological state. It is appreciated from prior, abstracted theory that phage-bacteria interactions are fundamentally different in spatially structured contexts, as opposed to well-mixed liquid culture. Spatially structured communities are predicted to promote the protection of susceptible host cells from phage exposure, and thus weaken selection for phage resistance. The details and generality of this prediction in realistic biofilm environments, however, are not known. Here we explore phage-host interactions using experiments and simulations that are tuned to represent the essential elements of biofilm communities. Our simulations show that in biofilms, the coexistence of susceptible and phage-resistant bacteria is highly robust to a large array of conditions, including background growth rate, cost of phage resistance, mechanism of phage resistance, and phage diffusivity. We characterize the population dynamics underlying this coexistence, and we show that coexistence is recapitulated in an experimental model of biofilm growth measured with confocal microscopy. Our results provide a clear view into the dynamics of phage-resistance in biofilms, with single-cell resolution of the underlying cell-virion interactions, linking the predictions of canonical theory to realistic models and <i>in vitro</i> experiments of biofilm growth. <h3>Importance</h3> In the natural environment, bacteria most often live in communities bound to one another by secreted adhesives. These communities, or biofilms, play a central role in biogeochemical cycling, microbiome functioning, wastewater treatment, and disease. Wherever there are bacteria, there are also viruses that attack them, called phages. Interactions between bacteria and phages are likely to occur ubiquitously in biofilms. We show here, using simulations and experiments, that biofilms will almost universally allow phage-susceptible bacteria to be protected from phage exposure, if they are growing alongside other cells that are phage-resistant. This result has implications for the fundamental ecology of phage-bacterial interactions, as well as the development of phage-based antimicrobial therapeutics.
Ovariotomy on a Patient in her 85th Year
Authors: J. P. Bush
Journal: BMJ (1894)

The three cases which follow are all that have occurred in my practice since that date, external hernia, and malignant disease of the rectum being excluded.CASE I. Tttberculous Peritonitis: Obstruction of Ileum: Operation: Relief: Death one month later from Apoplexy.-S.B., aged 50, a labourer, was ad- mitted to the Crewkerne Hospital on May 28th, 1892.He had been suffer- ing for two or three months from symptoms of chronic intestinal obstruc- tion, with increasing emaciation.On admission the obstruction had been absolute for a week with fmecal vomiting for two days.Laparotomy was at once performed, and disclosed dry contracting tuberculosis of the peritoneum.The matting of the intestines was particularly dense in the right lower segment, and immediately above the right ileo-caecal valve the bowel was so dragged and kinked as to be completely obstructed.Some troublesome dissection so far remedied matters that the intestinal
Prospective Study of Rituximab in Chemotherapy-Dependent Human Immunodeficiency Virus–Associated Multicentric Castleman's Disease: ANRS 117 CastlemaB Trial
Authors: Laurence Gérard, Alice Bérezné, Lionel Galicier, Véronique Meignin, Martine Obadia, Nathalie De Castro, Christine Jacomet, Renaud Verdon, Isabelle Madelaine-Chambrin, Emmanuelle Boulanger, Sylvie Chevret, Felix Agbalika, Eric Oksenhendler
Journal: Journal of Clinical Oncology (2007)

Single-agent chemotherapy is usually effective in HIV-associated multicentric Castleman's disease (MCD). However, in most patients, chemotherapy cannot be discontinued.To evaluate the efficacy of four weekly rituximab infusions (375 mg/m(2)) after discontinuation of chemotherapy in HIV-associated MCD, 24 patients were enrolled onto a prospective open-label trial.At study entry, the median time from MCD diagnosis was 21 months. All patients had stable disease on chemotherapy and were dependent on chemotherapy for a median time of 13 months. The median CD4 cell count was 270 x 10(6)/L, and the plasma HIV RNA was less than 50 copies/mL in 18 patients. One patient died with progressive disease at day 15, and 23 patients completed the four cycles of rituximab. Sustained remission (SR) off treatment at day 60 (primary end point) was achieved in 22 patients (92%). From day 60 to day 365, one patient died with acute respiratory failure of undetermined origin, and four patients experienced relapse. Seventeen patients (71%) were alive in SR at day 365 without specific treatment, and the overall survival rate was 92% (95% CI, 71% to 98%). Rituximab was well tolerated, and the majority of adverse events were mild to moderate infections. Mild exacerbation of Kaposi's sarcoma (KS) lesions was observed in eight of 12 patients with previous KS.Rituximab was both effective and safe in HIV-infected patients with chemotherapy-dependent MCD.
Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)
Authors: Christian Möller, Sten Dreborg, Hosne A Ferdousi, Susanne Halken, Arne Høst, Lars Jacobsen, Antti Koivikko, Dieter Y Koller, Bodo Niggemann, Lene A Norberg, Radvan Urbanek, Erkka Valovirta, Ulrich Wahn
Journal: Journal of Allergy and Clinical Immunology (2002)
The magnitude of the bradycardia induced by face immersion in patients convalescing from myocardial infarction
Authors: B. A. GOODEN, G. HOLDSTOCK, J. R. HAMPTON
Journal: Cardiovascular Research (1978)

Twenty patients who had suffered myocardial infarction within the previous 3 to 13 days performed face immersion with breath-holding. The maximum reduction in heart rate was 17± 9 beats·min−1 (mean± SD). When compared with 24 patients without evidence of ischaemic heart disease, they behaved more like younger patients (22 ± 6) than patients in the same age range (7 ± 6). A greater vagal response for age after infarction may reflect persistent hypersensitivity of a reflex designed to protect the myocardium during cardiogenic shock.
A Burst of miRNA Innovation in the Early Evolution of Butterflies and Moths
Authors: Shan Quah, Jerome H.L. Hui, Peter W.H. Holland
Journal: Molecular Biology and Evolution (2015)

MicroRNAs (miRNAs) are involved in posttranscriptional regulation of gene expression. Because several miRNAs are known to affect the stability or translation of developmental regulatory genes, the origin of novel miRNAs may have contributed to the evolution of developmental processes and morphology. Lepidoptera (butterflies and moths) is a species-rich clade with a well-established phylogeny and abundant genomic resources, thereby representing an ideal system in which to study miRNA evolution. We sequenced small RNA libraries from developmental stages of two divergent lepidopterans, Cameraria ohridella (Horse chestnut Leafminer) and Pararge aegeria (Speckled Wood butterfly), discovering 90 and 81 conserved miRNAs, respectively, and many species-specific miRNA sequences. Mapping miRNAs onto the lepidopteran phylogeny reveals rapid miRNA turnover and an episode of miRNA fixation early in lepidopteran evolution, implying that miRNA acquisition accompanied the early radiation of the Lepidoptera. One lepidopteran-specific miRNA gene, miR-2768, is located within an intron of the homeobox gene invected, involved in insect segmental and wing patterning. We identified cubitus interruptus (ci) as a likely direct target of miR-2768, and validated this suppression using a luciferase assay system. We propose a model by which miR-2768 modulates expression of ci in the segmentation pathway and in patterning of lepidopteran wing primordia.
Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis.
Authors: I Miyajima, D Dombrowicz, T R Martin, J V Ravetch, J P Kinet, S J Galli
Journal: Journal of Clinical Investigation (1997)

We attempted to elicit active anaphylaxis to ovalbumin, or passive IgE- or IgG1-dependent anaphylaxis, in mice lacking either the Fc epsilonRI alpha chain or the FcR gamma chain common to Fc epsilonRI and Fc gammaRI/III, or in mice lacking mast cells (KitW/ KitW-v mice), and compared the responses to those in the corresponding wild-type mice. We found that the FcR gamma chain is required for the death, as well as for most of the pathophysiological changes, associated with active anaphylaxis or IgE- or IgG1-dependent passive anaphylaxis. Moreover, some of the physiological changes associated with either active, or IgG1-dependent passive, anaphylactic responses were significantly greater in Fc epsilonRI alpha chain -/- mice than in the corresponding normal mice. Finally, while both KitW/KitW-v and congenic +/+ mice exhibited fatal active anaphylaxis, mast cell-deficient mice exhibited weaker physiological responses than the corresponding wild-type mice in both active and IgG1-dependent passive systemic anaphylaxis. Our findings strongly suggest that while IgE antibodies and Fc epsilonRI may influence the intensity and/or kinetics of some of the pathophysiological changes associated with active anaphylaxis in the mouse, the mortality associated with this response can be mediated largely by IgG1 antibodies and Fc gammaRIII.