tbuckley/cabot-search huggingface dataset:
Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?
Authors: F. Violi, S. Basili, V. Raparelli, P. Chowdary, A. Gatt, A.K. Burroughs
Journal: Journal of Hepatology (2011)

Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers of platelet activation, and platelet count. Such changes have been considered particularly relevant in the bleeding complications that occur in cirrhosis. However, several studies have shown that routine diagnostic tests, such as platelet count, bleeding time, PFA-100, thromboelastography are not clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover, treatments used to increase platelet count or to modulate platelet function could potentially do harm. Consequently the optimal management of bleeding complications is still a matter of discussion. Moreover, in the last two decades there has been an increased recognition that not only bleeding but also thrombosis complicates the clinical course of cirrhosis. Thus, we performed a literature search looking at publications studying both qualitative and quantitative aspects of platelet function to verify which primary haemostasis defects occur in cirrhosis. In addition, we evaluated the contribution of qualitative and quantitative aspects of platelet function to the clinical outcome in cirrhosis and their therapeutic management according to the data available in the literature. From the detailed analysis of the literature, it appears clear that primary haemostasis may not be defective in cirrhosis, and a low platelet count should not necessarily be considered as an automatic index of an increased risk of bleeding. Conversely, caution should be observed in patients with severe thrombocytopenia where its correction is advised if bleeding occurs and before invasive diagnostic and therapeutic procedures.
Current Evidence on Healthy Eating
Authors: Walter C. Willett, Meir J. Stampfer
Journal: Annual Review of Public Health (2013)

Large nutritional epidemiology studies, with long-term follow-up to assess major clinical end points, coupled with advances in basic science and clinical trials, have led to important improvements in our understanding of nutrition in primary prevention of chronic disease. Although much work remains, sufficient evidence has accrued to provide solid advice on healthy eating. Good data now support the benefits of diets that are rich in plant sources of fats and protein, fish, nuts, whole grains, and fruits and vegetables; that avoid partially hydrogenated fats; and that limit red meat and refined carbohydrates. The simplistic advice to reduce all fat, or all carbohydrates, has not stood the test of science; strong evidence supports the need to consider fat and carbohydrate quality and different protein sources. This article briefly summarizes major findings from recent years bearing on these issues.
Impairment of Antigen-Presenting Cell Function in Mice Lacking Expression of Ox40 Ligand
Authors: Kazuko Murata, Naoto Ishii, Hiroshi Takano, Shigeto Miura, Lishomwa C. Ndhlovu, Masato Nose, Tetsuo Noda, Kazuo Sugamura
Journal: The Journal of Experimental Medicine (2000)

OX40 expressed on activated T cells is known to be an important costimulatory molecule on T cell activation in vitro. However, the in vivo functional significance of the interaction between OX40 and its ligand, OX40L, is still unclear. To investigate the role of OX40L during in vivo immune responses, we generated OX40L-deficient mice and a blocking anti-OX40L monoclonal antibody, MGP34. OX40L expression was demonstrated on splenic B cells after CD40 and anti-immunoglobulin (Ig)M stimulation, while only CD40 ligation was capable of inducing OX40L on dendritic cells. OX40L-deficient and MGP34-treated mice engendered apparent suppression of the recall reaction of T cells primed with both protein antigens and alloantigens and a significant reduction in keyhole limpet hemocyanin–specific IgG production. The impaired T cell priming was also accompanied by a concomitant reduction of both T helper type 1 (Th1) and Th2 cytokines. Furthermore, antigen-presenting cells (APCs) derived from the mutant mice revealed an impaired intrinsic APC function, demonstrating the importance of OX40L in both the priming and effector phases of T cell activation. Collectively, these results provide convincing evidence that OX40L, expressed on APCs, plays a critical role in antigen-specific T cell responses in vivo.
Arterial ketone body ratio in liver surgery
Authors: Keiji Matsushita, Seiji Kawasaki, Masatoshi Makuuchi
Journal: Hepatology (1994)

To evaluate the relevance of the hypothesis that the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate) can reflect the liver mitochondrial redox potential, we investigated the influence of ketone body metabolism in peripheral tissues on the arterial ketone body ratio during conditions in which no ketone body was available to the systemic circulation: during total clamping of the hepatoduodenal ligament in 37 patients undergoing partial hepatectomy and during the anhepatic phase in 14 liver transplant recipients. Changes in both the arterial acetoacetate and beta-hydroxybutyrate concentrations and arterial ketone body ratio varied markedly from patient to patient after clamping. Among 20 patients with hepatocellular carcinoma and associated chronic liver disease, arterial ketone body ratio 15 min after clamping was higher in 11 and lower in 9 than that before clamping. Of the remaining 17 patients with other types of tumor, arterial ketone body ratio was increased in 10 and decreased in 7 after clamping. Similar changes were observed in 14 recipients during the anhepatic phase of liver transplantation. Arterial ketone body ratio was increased in 7 recipients during the anhepatic phase compared with that at laparotomy, whereas it was lowered in the remaining 7. These results indicate that each of the two types of ketone body is metabolized in extrahepatic tissues to a different extent, varying among individual patients and disease conditions. We conclude that arterial ketone body ratio does not solely reflect the ratio of the amounts of acetoacetate to beta-hydroxybutyrate produced by the liver. This may make it difficult to use arterial ketone body ratio as an accurate parameter representing the redox state in liver mitochondria.
Brief Suppression of <i>Abcc8</i> Prevents Autodestruction of Spinal Cord After Trauma
Authors: J. Marc Simard, S. Kyoon Woo, Michael D. Norenberg, Cigdem Tosun, Zheng Chen, Svetlana Ivanova, Orest Tsymbalyuk, Joseph Bryan, Douglas Landsman, Volodymyr Gerzanich
Journal: Science Translational Medicine (2010)

Secondary injury that occurs after trauma to the spinal cord can be prevented by inhibiting expression of the gene that regulates a cation transporter.
T670X KIT Mutations in Gastrointestinal Stromal Tumors: Making Sense of Missense
Authors: T. Negri, G. M. Pavan, E. Virdis, A. Greco, M. Fermeglia, M. Sandri, S. Pricl, M. A. Pierotti, S. Pilotti, E. Tamborini
Journal: JNCI Journal of the National Cancer Institute (2009)

Chronic myeloid leukemia, gastrointestinal stromal tumors (GISTs), and idiopathic hypereosinophilic syndrome are associated with pathological deregulation of the tyrosine kinases BCR-ABL, KIT, and PDGFRA, respectively. Patients who become resistant to imatinib treatment often develop secondary mutations, the most common of which results in a substitution of isoleucine for threonine at the same location in the ATP-binding domain in all three kinases (in KIT this occurs at amino acid 670). We sought to determine why Thr is always replaced by Ile.All possible point mutations in the DNA triplet codon that could result in amino acid substitutions at Thr670 (Thr670Arg, Thr670Ile, Thr670Lys, Thr670Ala, Thr670Ser, Thr670Pro) were introduced by site-specific mutagenesis of the complementary DNA for a constitutively active, imatinib-sensitive form of the KIT receptor, Delta559/KIT. The resulting mutant KIT proteins were transiently expressed in COS1 African green monkey kidney cells grown with and without imatinib, and cell extracts were analyzed for KIT activation by immunoprecipitation and immunoblotting to determine autophosphorylation levels. We also performed molecular modeling to estimate the relative affinities of wild-type (Thr670) KIT and the KIT mutants for ATP and imatinib.Like the parental strain, Thr670Ala, Thr670Ser, and Thr670Lys mutants were inhibited by 5 microM imatinib, but in comparison, they were only weakly active and Thr670Pro and Thr670Arg were not active at all. Only the Thr670Ile mutant was fully active (autophosphorylated) and resistant to imatinib. These findings were consistent with computer modeling predictions that ranked these mutants Thr - Ile > Ala, Ser > Lys >> Pro according to their affinity for ATP but Thr > Ala, Ser > Lys >Pro - Arg - Ile according to their affinity for imatinib.This combination of in vitro and molecular modeling analyses shows why, among all possible amino acid substitutions at position 670 of KIT, only Ile is naturally selected as a resistance mutant in imatinib-treated GIST patients.
Anisotropy and polarization of space: Evidence from naïve optics and phenomenological psychophysics
Authors: Ivana Bianchi, Marco Bertamini
Journal: Behavioral and Brain Sciences (2013)

Abstract Additional evidence is presented concerning the anisotropy between vertical and horizontal encoding, which emerges from studies of human perception and cognition of space in plane mirror reflections. Moreover, it is suggested that the non-metric characteristic of polarization – that Jeffery et al. discuss with respect to gravity – is not limited to the vertical dimension.
Regulation of Regional Lung Perfusion by Nitric Oxide
Authors: Danguole Rimeika, Sven Nyrén, N. Peter Wiklund, Lotta Renström Koskela, Anders Tørring, Lars E. Gustafsson, Stig A. Larsson, Hans Jacobsson, Sten G. E. Lindahl, Claes U. Wiklund
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Improved oxygenation has previously been shown in patients with acute lung injury when ventilated in prone position. We hypothesized that this was due to higher regional production of nitric oxide in dorsocaudal lung regions. We measured nitric oxide synthase mRNA expression and nitric oxide production by citrulline assay in ventral and dorsal lung tissue from patients. In volunteers, regional lung perfusion in prone and supine postures was assessed by single photon emission computed tomography using (99m)Tc macroaggregated albumin before and after inhibition of nitric oxide synthase by N(G)-monomethyl-L-arginine infusion. Nitric oxide synthase mRNA expression and nitric oxide production were significantly higher in dorsal compared with ventral lung regions. In supine posture, lung perfusion was shifted to ventral parts during nitric oxide synthase inhibition, whereas in the prone posture lung perfusion remained unchanged. Our results suggest a role for endogenous nitric oxide in regulation of regional pulmonary perfusion.
Friend Virus-induced Reticulum Cell Sarcomas Grown in Vitro: Further Evidence for the Absence of Friend Virus
Authors: A. Howard Fieldsteel, Carole Kurahara, Peter J. Dawson
Journal: Cancer Research (1969)

Friend virus-induced reticulum cell sarcomas arising in BALB/c and BDF1 mice were grown in tissue culture and tested for the presence of Friend virus. Repeated tests in newborn BALB/c mice failed to detect infectious virus. Immunization with tissue cultures failed to protect mice against challenge with Friend virus or to induce detectable neutralizing antibody to the virus. Electron microscopy revealed small numbers of type-A particles which were thought to be unrelated to Friend virus. No type-C particles were seen. Virus-free cultures could be reinfected both in vivo and in vitro , but the virus again disappeared after prolonged culture. It was concluded that the cultures were free from infectious Friend virus and that the neoplastic properties of the tumor cells were not dependent upon its continued presence.
Netrin-1 Induces Apoptosis in Human Cervical Tumor Cells via the TAp73α Tumor Suppressor
Authors: Jean-Pierre Roperch, Karima El Ouadrani, Ann Hendrix, Shahin Emami, Olivier De Wever, Gerry Melino, Christian Gespach
Journal: Cancer Research (2008)

Abstract Netrins and their receptors deleted in colon cancer (DCC), neogenin, UNC5, and integrins are involved in axon guidance, epithelial morphogenesis, vascular pattering, cancer cell survival, invasion, tumor angiogenesis, and metastasis. Here, we considered the possible contribution of the p53-related apoptosis mediators p63 and p73 in the mechanisms underlying the antagonism between netrin-1 and DCC at the cell death control. We have showed that ectopic expression and external addition of netrin-1 in HeLa and HEK-293 cells with inactive p53 lead to impaired cell viability and induction of apoptosis. These responses were associated with up-regulation of the proapoptotic protein TAp73α, decreased Bcl-2/Bax ratio, and caspase-3 cleavage, with no change in protein levels of the antiapoptotic NH2-terminal–truncated ΔNp73α isoform, p73 adapter Yap-1 and p73 E3 ubiquitin ligase Itch, and p63, as well as the transcripts encoding p63, TAp73α, and ΔNp73α. However, the proteasome inhibitor MG132 potentiated, while DCC counteracted, netrin-1–induced TAp73α. Consistently, netrin-1 expression correlated with stabilization of the TAp73α protein and lower levels of TAp73α ubiquitination that was conversely enhanced by DCC, in a netrin-dependent manner. Our data indicate that netrin-1 selectively up-regulates TAp73α by preventing its ubiquitination and degradation. Targeted repression of p73α by shRNA reversed TAp73α and the apoptosis induced by netrin-1, and exacerbated the growth of HeLa tumor xenografts. Apoptosis induced by cisplatin was markedly enhanced in netrin-1 or DCC-expressing cells. Collectively, our data reveal that the transcriptionally active TAp73α tumor suppressor is implicated in the apoptosis induced by netrin-1 in a p53-independent and DCC/ubiquitin-proteasome dependent manner. [Cancer Res 2008;68(20):8231–9]
Leukocyte infection by the granulocytic ehrlichiosis agent is linked to expression of a selectin ligand
Authors: Jesse L. Goodman, Curtis M. Nelson, Marina B. Klein, Stanley F. Hayes, Brent W. Weston
Journal: Journal of Clinical Investigation (1999)

Human granulocytic ehrlichiosis (HGE) is an emerging tickborne illness caused by an intracellular bacterium that infects neutrophils. Cells susceptible to HGE express sialylated Lewis x (CD15s), a ligand for cell selectins. We demonstrate that adhesion of HGE to both HL60 cells and normal bone marrow cells directly correlates with their CD15s expression. HGE infection of HL60 cells, bone marrow progenitors, granulocytes, and monocytes was blocked by monoclonal antibodies against CD15s. However, these antibodies did not inhibit HGE binding, and anti-CD15s was capable of inhibiting the growth of HGE after its entry into the target cell. In contrast, neuraminidase treatment of HL60 cells prevented both HGE binding and infection. A cloned cell line (HL60-A2), derived from HL60 cells and resistant to HGE, was deficient in the expression of α-(1,3)fucosyltransferase (Fuc-TVII), an enzyme known to be required for CD15s biosynthesis. Less than 1% of HL60-A2 cells expressed CD15s, and only these rare CD15s-expressing cells bound HGE and became infected. After transfection with Fuc-TVII, cells regained CD15s expression, as well as their ability to bind HGE and become infected. Thus, CD15s expression is highly correlated with susceptibility to HGE, and it, and/or a closely related sialylated and α-(1,3) fucosylated molecule, plays a key role in HGE infection, an observation that may help explain the organism's tropism for leukocytes.
Aerobic fitness and obesity: relationship to cerebral white matter integrity in the brain of active and sedentary older adults
Authors: BL Marks, LM Katz, M Styner, JK Smith
Journal: British Journal of Sports Medicine (2010)

Objective Aerobic fitness (VO 2 peak) and obesity risk (OR) may impact brain health. This study examined hemispheric and segment specific relationships between VO 2 peak, OR and cerebral white-matter (CWM) integrity in the cingulum brain region in healthy older adults. Methods Fifteen subjects (66±6 years) completed VO 2 peak testing and MRI of the brain. OR was determined via body mass index (BMI) and abdominal girth. MRI analysis was performed with a structural 3D T1 MP-Rage and diffusion tensor imaging technique (DTI, 21 directions, repeated four times) on a 3.0 T MR imaging unit. CWM integrity indices, fractional anisotropy (FA) and mean diffusivity (MD), were computed from the tensors. The anterior, middle and posterior cingulum segments were analysed on both sides of the brain. Partial correlations (age and gender controlled) and standard multiple regressions were used to determine significant associations and unique contributions to CWM integrity. Results VO 2 peak was moderately related to FA in the left middle cingulum segment (r partial=0.573, p=0.041) and explained 28.5% of FA's total variance (p=0.10). Abdominal girth (r partial=−0.764, p=0.002) and BMI (r partial=−0.690, p=0.009) were inversely related to FA in the right posterior cingulum (RPC) segment. Abdominal girth and BMI uniquely explained 53.9% of FA's total variance (p=0.012) and 43.9% (p=0.040), respectively, in the RPC. Conclusion Higher aerobic fitness and lower obesity risk are related to greater CWM integrity but not in the same cingulum segments.
Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes.
Authors: P Sinnis, T E Willnow, M R Briones, J Herz, V Nussenzweig
Journal: The Journal of Experimental Medicine (1996)

Remnants of lipoproteins, intestinal chylomicrons, and very low density lipoprotein (VLDL), are rapidly cleared from plasma and enter hepatocytes. It has been suggested that remnant lipoproteins are initially captured in the space of Disse by heparan sulfate proteoglycans (HSPGs), and that their subsequent internalization into hepatocytes is mediated by members of the LDL-receptor gene family. Similarly to lipoprotein remnants, malaria sporozoites are removed from the blood circulation by the liver within minutes after injection by Anopheles mosquitoes. The sporozoite's surface is covered by the circumsporozoite protein (CS), and its region II-plus has been implicated in the binding of the parasites to glycosaminoglycan chains of hepatocyte HSPGs. Lactoferrin, a protein with antibacterial properties found in breast milk and neutrophil granules, is also rapidly cleared from the circulation by hepatocytes, and can inhibit the hepatic uptake of lipoprotein remnants. Here we provide evidence that sporozoites, lactoferrin, and remnant lipoproteins are cleared from the blood by similar mechanisms. CS, lactoferrin, and remnant lipoproteins compete in vitro and in vivo for binding sites on liver cells. The relevance of this binding event for sporozoite infectivity is highlighted by our demonstration that apoliprotein E-enriched beta-VLDI and lactoferrin inhibit sporozoite invasion of HepG2 cells. In addition, malaria sporozoites are less infective in LDL-receptor knockout (LDLR -/-) mice maintained on a high fat diet, as compared with littermates maintained on a normal diet. We conclude that the clearance of lipoprotein remnants and sporozoites from the blood is mediated by the same set of highly sulfated HSPGs on the hepatocyte plasma membrane.
Obsessive-Compulsive and Panic Symptoms in Patients With First-Admission Psychosis
Authors: Thomas Craig, Michael Y Hwang, Evelyn J Bromet
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The occurrence, persistence and specificity of the association between comorbid obsessive-compulsive and panic symptoms and three psychotic disorders—schizophrenia/schizoaffective disorder, bipolar disorder with psychosis, and major depression with psychosis—were examined in a first-admission, epidemiologically defined group of patients with psychotic symptoms. METHOD: The Structured Clinical Interview for DSM-III-R obsessive-compulsive and panic modules were administered at baseline and 24-month follow-up to patients with schizophrenia/schizoaffective disorder (N=225), bipolar disorder with psychosis (N=138), and major depression with psychosis (N=87) participating in the Suffolk County (N.Y.) Mental Health Project. The rates of subsyndromal symptoms and disorder criteria met were compared across the three psychosis groups. Recognition and treatment of anxiety symptoms at initial discharge and impact of the baseline presence of anxiety symptoms on 24-month clinical status were also examined. RESULTS: Obsessive-compulsive and panic symptoms were present at baseline in 10%–20% of all three groups. There was no specific association between obsessive-compulsive symptoms and any specific psychosis diagnosis; however, women with major depression with psychosis had a significantly higher rate of panic symptoms than the other two groups, and schizophrenia/schizoaffective disorder patients with baseline panic symptoms were significantly more likely to exhibit positive symptoms of psychosis after 24 months. CONCLUSIONS: The authors found no specific association between obsessive-compulsive symptoms and diagnosis early in the illness course, but the finding of an association between panic symptoms and psychotic depression among female patients and between baseline panic and positive psychotic symptoms in schizophrenia/schizoaffective disorder patients at 24 months suggests the need for further study.
Determining collateral ventilation during bronchoscopy: unanswered questions
Authors: Wolfgang Gesierich, Konstantinos Samitas, Juergen Behr
Journal: Thorax (2013)

In their recent review, Shah et al 1 made an excellent presentation of the latest perspectives of lung volume reduction with endobronchial valves, emphasising the importance of collateral ventilation (CV) and fissure analysis on selecting proper candidates, as shown in the VENT studies.2 ,3 The authors described representative cases of patients with positive and negative CV using the Chartis system4 and recommended that persistence of ﬂow after 5 min of balloon inﬂation, particularly where more than a litre of air has been expelled, suggests the presence of signiﬁcant CV.

Our centre has extensive experience in evaluating CV with Chartis. We agree with Dr Shah and colleagues on their clear definition of positive CV. We feel, however, that the accurate assessment of negative CV is not always …