tbuckley/cabot-search huggingface dataset:
Kidney Preservation by Surface Cooling: Analysis of 130 Transplants
Authors: B. Hulme, M. E. Snell, J. R. Kenyon, K. Owen, W. S. Peart
Journal: BMJ (1972)

An analysis of 130 consecutive cadaveric renal transplants has shown the effectiveness of simple surface cooling of organs before transplantation. The primary graft failure rate was 10%, and kidneys could be stored for periods of up to 12 hours including warm ischaemia times of 150 minutes. Forty-eight patients received haemodialysis before transplantation and 78 patients received peritoneal dialysis. There were significant differences in the incidence of tubular necrosis in the two groups: these may have been linked to the differences in fluid and osmotic load presented to the transplants.
Renal Response to Electrical Stimulation in the Septum and Diencephalon of Rabbits
Authors: AMIN N. JURF, WILLIAM D. BLAKE
Journal: Circulation Research (1972)

The septum and diencephalon were electrically stimulated with stereotaxically placed bipolar, concentric electrodes in pentobarbital anesthetized rabbits with one kidney acutely denervated. Transient changes (30-60 seconds) in renal blood flow and urine flow were estimated with electromagnetic flowmeters and drop recorders and persistent changes (20-30 minutes) by clearance techniques. Hypothalamic stimulation, particularly in the perifornical region, caused increased blood pressure, reflex bradycardia (blocked by atropine), and intense renal vasoconstriction in the innervated kidney with a latency of about 2 seconds. In the denervated kidney renal blood flow increased with the rise in blood pressure but after 10-15 seconds decreased, possibly in response to catecholamines released from the adrenal glands. Clearance studies during hypothalamic stimulation showed persistent decreases in renal blood flow, glomerular filtration, maximal tubular transport of glucose and paraaminohippurate, and water and electrolyte excretion in the innervated kidney. The parallel decreases in the maximum tubular transport of glucose and glomerular filtration rate suggest nephron closure rather than flow redistribution as the major component of the response. Ventral thalamic and septal stimulation decreased blood pressure and renal blood flow in the denervated kidney to about the same extent. Ventral thalamic stimulation also decreased renal blood flow in the innervated kidney whereas septal stimulation transiently increased renal blood flow, suggesting inhibition of existing sympathetic vasoconstriction (not blocked by atropine). In clearance studies, effects of septal stimulation on the intact kidney (relative to the denervated kidney) were similar to the effects of acute denervation and consistent with redistribution of intrarenal blood flow.
Palmoplantar keratoderma and oral leucoplakia with cutaneous horn of the lips
Authors: C. Baykal, N. Savci, A. Kavak, S. Kurul
Journal: British Journal of Dermatology (2002)

Summary The inherited palmoplantar keratodermas (PPK) may be associated with a wide variety of other ectodermal abnormalities. The coexistence of PPK and leucoplakia may indicate the increased risk of oesophageal carcinoma in adult life. Cutaneous horn may develop over benign, precancerous, as well as malignant lesions, and frequently may be associated with actinic keratoses and Bowen's disease. On the other hand, the relationship of cutaneous horn and leucoplakia has been the subject of only a single case report. We present a case of PPK and diffuse oral leucokeratosis associated with relapsing cutaneous horn of the lips.
Letting Go of the Bear's Tail
Authors: Robert B. Van Cleve
Journal: JAMA (1966)

LONG-TERM anticoagulant therapy has been used for many years in conditions such as myocardial infarction in which there is a risk of thromboembolism. Several reports have questioned the usefulness of anticoagulants in preventing a recurrence of myocardial infarction.<sup>1-5</sup>Other studies have cast some doubt on the necessity of continuing such treatment for longer than a year following the infarction.<sup>6-8</sup> There is also considerable controversy regarding the recurrence of thromboembolic episodes following discontinuation of long-term anticoagulant therapy. Our experience with abrupt discontinuation of long-term anticoagulant therapy has been published elsewhere.<sup>9</sup>This paper concerns 149 patients whose long-term therapy with sodium warfarin (Coumadin Sodium) was discontinued and compares them to those whose anticoagulant therapy was continued in an effort to see if all patients should be maintained on this therapy indefinitely. <h3>Description of the Study</h3> A total of 191 patients who had been receiving sodium warfarin for an average
In defense of intuitive mathematical theories as the basis for natural number
Authors: David Barner
Journal: Behavioral and Brain Sciences (2008)

Abstract Though there are holes in the theory of how children move through stages of numerical competence, the current approach offers the most promising avenue for characterizing changes in competence as children confront new mathematical concepts. Like the science of mathematics, children's discovery of number is rooted in intuitions about sets, and not purely in analytic truths.
Associations of Total and High-Molecular-Weight Adiponectin With All-Cause and Cardiovascular Mortality in Older Persons
Authors: Jorge R. Kizer, David Benkeser, Alice M. Arnold, Kenneth J. Mukamal, Joachim H. Ix, Susan J. Zieman, David S. Siscovick, Russell P. Tracy, Christos S. Mantzoros, Christopher R. deFilippi, Anne B. Newman, Luc Djousse
Journal: Circulation (2012)

Background— Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk) and cohorts with prevalent cardiovascular disease, heart failure, or advanced age (higher risk). Methods and Results— In a population-based study of older adults, we examined the relationships of total and high-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: No cardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrial fibrillation (group 2); and heart failure/atrial fibrillation (group 3). We found significant differences in the associations with all-cause mortality across the groups. The association in group 1 was U-shaped; increasing levels of total adiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (hazard ratio=0.81 per 1 SD [95% confidence interval, 0.65–0.95]), but above this cut point, higher levels conferred greater risk (hazard ratio=1.19 [95% confidence interval, 1.12–1.27]). Further adjustment for diabetes mellitus or insulin resistance, protection against which has been proposed to mediate the beneficial relationships of adiponectin with outcome, attenuated the association in the lower range. There was no significant association in group 2, but in group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for group 2, and magnified the one for group 3 (hazard ratio=1.31 [1.15–1.50]). Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality. Conclusions— Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as it relates to older adults.
Inborn errors underlying herpes simplex encephalitis: From TLR3 to IRF3
Authors: Shen-Ying Zhang, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2015)

The Journal of Experimental MedicineAfter their inoculation by mosquitos and entry into the bloodstream, malaria sporozoites must cross the liver sinusoidal barrier to gain access to hepatocytes, where they can multiply as erythrocyte-infecting forms.In this issue, Cha et al. provide further evidence that Kupffer cells (KCs) offer a gateway for entry of sporozoites into the liver parenchyma and identify the receptor on the KCs that directs the passage of the parasite through this portal.A remarkably fruitful phage display strategy led to the identification of a peptide, P39, that bound to KCs.P39 strongly inhibited sporozoite entry into KCs in vitro and reduced liver infection in vivo.It was also shown to bind specifically to CD68, a heavily glycosylated transmembrane protein similar to LAMPs in its cellular distribution, sequence, and structure.Furthermore, the expression of CD68, at least in the liver, is confined to KCs.The function of CD68 as a receptor for sporozoite entry into KCs in vitro was supported by silencing, overexpression, and ectopic expression of the CD68 gene and by antibody inhibition.More critically, parasite liver burden in CD68 knockout mice was reduced by 71%, substantiating CD68 as a key receptor for sporozoite interaction with KCs in vivo, and KCs as the paramount gateway cells.Finally, CD68 knockout mice treated with clodronate to deplete KCs showed liver parasite burdens that were comparable to clodronate-treated, wild-type mice, which in turn had comparable infections to untreated wildtype mice.The authors conclude that CD68 serves as such an efficient gateway that sporozoite transit to the liver parenchyma proceeds as if the sinusoidal barrier did not exist.These findings still need to be reconciled with prior quantitative imaging studies that attribute a greater role for endothelial cells in sinusoid traversal and that reveal a negative impact of KCs on sporozoite survival.Beyond its function as a receptor for sporozoite entry, the nature and consequences of CD68 engagement need to be further explored.Does CD68-mediated sporozoite entry into KCs involve active penetration or phagocytosis?Is there damage to the host cell?Does CD68 engagement inhibit antigen presentation function and/or trigger release of antiinflammatory cytokines that contribute to the state of relative immune tolerance in the liver?And, crucially, what is the parasite ligand for CD68?Assuming its accessibility for antibody targeting in its native state, it would seem an ideal component of a pre-erythrocytic vaccine.
Tumor Vascular Response to Photodynamic Therapy and the Antivascular Agent 5,6-Dimethylxanthenone-4-Acetic Acid: Implications for Combination Therapy
Authors: Mukund Seshadri, Joseph A. Spernyak, Richard Mazurchuk, Susan H. Camacho, Allan R. Oseroff, Richard T. Cheney, David A. Bellnier
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Photodynamic therapy (PDT) is a clinically approved treatment for a variety of solid malignancies. 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is a potent vascular targeting agent that has been shown to be effective against a variety of experimental rodent tumors and xenografts and is currently undergoing clinical evaluation. We have previously reported that the activity of PDT against transplanted mouse tumors is selectively enhanced by DMXAA. In the present study, we investigated the in vivo tumor vascular responses to the two treatments given alone and in combination. Experimental Design: Vascular responses to (i) four different PDT regimens using the photosensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) at two different fluences (128 and 48 J/cm2) and fluence rates (112 and 14 mW/cm2), (ii) 5-aminolevulinic acid (ALA)–sensitized PDT (135 J/cm2 at 75 mW/cm2), (iii) DMXAA at a high (30 mg/kg) and low dose (25 mg/kg), and (iv) the combination of HPPH-PDT (48 J/cm2 at 112 mW/cm2) and low-dose DMXAA were studied in BALB/c mice bearing Colon-26 tumors. Results: PDT-induced changes in vascular permeability, determined using noninvasive magnetic resonance imaging with a macromolecular contrast agent, were regimen dependent and did not predict tumor curability. However, a pattern of increasing (4 hours after treatment) and then decreasing (24 hours after) contrast agent concentrations in tumors, seen after high-dose DMXAA or the combination of PDT and low-dose DMXAA, was associated with long-term cure rates of &amp;gt;70%. This pattern was attributed to an initial increase in vessel permeability followed by substantial endothelial cell damage (CD31 immunohistochemistry) and loss of blood flow (fluorescein exclusion assay). Low dose–rate PDT, regardless of the delivered dose, increased the level of magnetic resonance contrast agent in peritumoral tissue, whereas treatment with either DMXAA alone, or PDT and DMXAA in combination resulted in a more selective tumor vascular response. Conclusions: The observed temporal and spatial differences in the response of tumor vessels to PDT and DMXAA treatments could provide valuable assistance in the optimization of scheduling when combining these therapies. The combination of PDT and DMXAA provides therapeutically synergistic and selective antitumor activity. Clinical evaluation of this combination is warranted.
Expression of the Serpin Serine Protease Inhibitor 6 Protects Dendritic Cells from Cytotoxic T Lymphocyte–Induced Apoptosis
Authors: Jan Paul Medema, Danita H. Schuurhuis, Delphine Rea, Joost van Tongeren, Joan de Jong, Sandra A. Bres, Sandra Laban, René E.M. Toes, Mireille Toebes, Ton N.M. Schumacher, Bellinda A. Bladergroen, Ferry Ossendorp, J. Alain Kummer, Cornelis J.M. Melief, Rienk Offringa
Journal: The Journal of Experimental Medicine (2001)

Dendritic cells (DCs) play a central role in the immune system as they drive activation of T lymphocytes by cognate interactions. However, as DCs express high levels of major histocompatibility complex class I, this intimate contact may also result in elimination of DCs by activated cytotoxic T lymphocytes (CTLs) and thereby limit induction of immunity. We show here that immature DCs are indeed susceptible to CTL-induced killing, but become resistant upon maturation with anti-CD40 or lipopolysaccharide. Protection is achieved by expression of serine protease inhibitor (SPI)-6, a member of the serpin family that specifically inactivates granzyme B and thereby blocks CTL-induced apoptosis. Anti-CD40 and LPS-induced SPI-6 expression is sustained for long periods of time, suggesting a role for SPI-6 in the longevity of DCs. Importantly, T helper 1 cells, which mature DCs and boost CTL immunity, induce SPI-6 expression and subsequent DC resistance. In contrast, T helper 2 cells neither induce SPI-6 nor convey protection, despite the fact that they trigger DC maturation with comparable efficiency. Our data identify SPI-6 as a novel marker for DC function, which protects DCs against CTL-induced apoptosis.
VISTA Is an Immune Checkpoint Molecule for Human T Cells
Authors: J. Louise Lines, Eirini Pantazi, Justin Mak, Lorenzo F. Sempere, Li Wang, Samuel O'Connell, Sabrina Ceeraz, Arief A. Suriawinata, Shaofeng Yan, Marc S. Ernstoff, Randolph Noelle
Journal: Cancer Research (2014)

Abstract V-domain Ig suppressor of T cell activation (VISTA) is a potent negative regulator of T-cell function that is expressed on hematopoietic cells. VISTA levels are heightened within the tumor microenvironment, in which its blockade can enhance antitumor immune responses in mice. In humans, blockade of the related programmed cell death 1 (PD-1) pathway has shown great potential in clinical immunotherapy trials. Here, we report the structure of human VISTA and examine its function in lymphocyte negative regulation in cancer. VISTA is expressed predominantly within the hematopoietic compartment with highest expression within the myeloid lineage. VISTA-Ig suppressed proliferation of T cells but not B cells and blunted the production of T-cell cytokines and activation markers. Our results establish VISTA as a negative checkpoint regulator that suppresses T-cell activation, induces Foxp3 expression, and is highly expressed within the tumor microenvironment. By analogy to PD-1 and PD-L1 blockade, VISTA blockade may offer an immunotherapeutic strategy for human cancer. Cancer Res; 74(7); 1924–32. ©2013 AACR.
The leak and endobronchial peek
Authors: Mohammed H AlShati
Journal: Thorax (2014)

A 42-year-old man from Afghanistan was referred to hospital as a case of non-resolving pneumonia. He had fever and productive cough of thick white sputum for 4 months without response to antibiotics. There was no history of haemoptysis, sick contacts, recent travel, weight loss, substance abuse or HIV risk factors. He was a non-smoker with unremarkable family and environmental history.

On examination, he was febrile (temp=39.1°C) with stable haemodynamics. Oxygen saturation was 96% while breathing room air at rest and finger nail clubbing was absent. Chest auscultation revealed bronchial breathing on the left upper lung zone. The rest of his examination was unremarkable. Except for mild neutrophilic leukocytosis, complete blood count (CBC) was unremarkable. Moderate elevation of erythrocyte sedimentation …
Combined cDNA Array Comparative Genomic Hybridization and Serial Analysis of Gene Expression Analysis of Breast Tumor Progression
Authors: Jun Yao, Stanislawa Weremowicz, Bin Feng, Robert C. Gentleman, Jeffrey R. Marks, Rebecca Gelman, Cameron Brennan, Kornelia Polyak
Journal: Cancer Research (2006)

Abstract To identify genetic changes involved in the progression of breast carcinoma, we did cDNA array comparative genomic hybridization (CGH) on a panel of breast tumors, including 10 ductal carcinoma in situ (DCIS), 18 invasive breast carcinomas, and two lymph node metastases. We identified 49 minimal commonly amplified regions (MCRs) that included known (1q, 8q24, 11q13, 17q21-q23, and 20q13) and several uncharacterized (12p13 and 16p13) regional copy number gains. With the exception of the 17q21 (ERBB2) amplicon, the overall frequency of copy number alterations was higher in invasive tumors than that in DCIS, with several of them present only in invasive cancer. Amplification of candidate loci was confirmed by quantitative PCR in breast carcinomas and cell lines. To identify putative targets of amplicons, we developed a method combining array CGH and serial analysis of gene expression (SAGE) data to correlate copy number and expression levels for each gene within MCRs. Using this approach, we were able to distinguish a few candidate targets from a set of coamplified genes. Analysis of the 12p13-p12 amplicon identified four putative targets: TEL/ETV6, H2AFJ, EPS8, and KRAS2. The amplification of all four candidates was confirmed by quantitative PCR and fluorescence in situ hybridization, but only H2AFJ and EPS8 were overexpressed in breast tumors with 12p13 amplification compared with a panel of normal mammary epithelial cells. These results show the power of combined array CGH and SAGE analysis for the identification of candidate amplicon targets and identify H2AFJ and EPS8 as novel putative oncogenes in breast cancer. (Cancer Res 2006; 66(8): 4065-78)
C1q and Mannose Binding Lectin Engagement of Cell Surface Calreticulin and Cd91 Initiates Macropinocytosis and Uptake of Apoptotic Cells
Authors: Carol Anne Ogden, Aimee deCathelineau, Peter R. Hoffmann, Donna Bratton, Berhane Ghebrehiwet, Valerie A. Fadok, Peter M. Henson
Journal: The Journal of Experimental Medicine (2001)

Removal of apoptotic cells is essential for maintenance of tissue homeostasis, organogenesis, remodeling, development, and maintenance of the immune system, protection against neoplasia, and resolution of inflammation. The mechanisms of this removal involve recognition of the apoptotic cell surface and initiation of phagocytic uptake into a variety of cell types. Here we provide evidence that C1q and mannose binding lectin (MBL), a member of the collectin family of proteins, bind to apoptotic cells and stimulate ingestion of these by ligation on the phagocyte surface of the multifunctional protein, calreticulin (also known as the cC1qR), which in turn is bound to the endocytic receptor protein CD91, also known as the α-2-macroglobulin receptor. Use of these proteins provides another example of apoptotic cell clearance mediated by pattern recognition molecules of the innate immune system. Ingestion of the apoptotic cells through calreticulin/CD91 stimulation is further shown to involve the process of macropinocytosis, implicated as a primitive and relatively nonselective uptake mechanism for C1q- and MBL-enhanced engulfment of whole, intact apoptotic cells, as well as cell debris and foreign organisms to which these molecules may bind.
Azathioprine hepatotoxicity after liver transplantation
Authors: Martina Sterneck, Russell Wiesner, Nancy Ascher, John Roberts, Linda Ferrell, Jurgen Ludwig, John Lake
Journal: Hepatology (1991)

We report the first two cases of apparent azathioprine hepatotoxicity occurring after liver transplantation. The two patients exhibited jaundice, elevated serum transaminase activities and histopathological features of sinusoidal congestion and centrilobular hepatocellular degeneration 17 and 61 days after transplantation. After withdrawal of azathioprine, liver test results improved immediately in both patients. Recurrence of liver injury after another challenge with azathioprine was seen in the first case. Previously, fatal venoocclusive disease occurring after kidney transplantation had been attributed to azathioprine. Irreversible venoocclusive disease and the reversible hepatotoxicity described in this report (i.e., sinusoidal congestion with centrizonal necrosis) most likely represent different stages of hepatic endotheliitis caused by azathioprine. Thus early diagnosis of azathioprine hepatotoxicity is of great importance. (Hepatology 1991;14:806-810).
Purinergic receptors as future targets for treatment of functional GI disorders
Authors: G. Burnstock
Journal: Gut (2008)

The concept of purinergic signalling arose from experiments designed to find the identity of the non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter in the gut.1 However, it has taken many years for the more general importance of the various roles of ATP as a physiological messenger in the gut to be recognised. Later, after the concept of co-transmission was established, ATP, nitric oxide and vasoactive intestinal polypeptide were recognised as co-transmitters in NANC nerves, although the proportions vary in different gut regions. Following cloning experiments in the early 1990s, four subtypes of P1 (adenosine) receptors, seven subtypes of P2X ion channel receptors and eight subtypes of P2Y G-protein-coupled receptors have been recognised.2 Many of these purinoceptor subtypes have been identified on the myenteric, submucosal motor, sensory and interneurons involved in synaptic …