tbuckley/cabot-search huggingface dataset:
The Problem with Cell Phones ... or Maybe Not
Authors: W. K. A. Yung
Journal: Neuro-Oncology (2010)

It's a popular topic … and a baffling question, to boot. Do cellular phones cause brain tumors?

Cell phones (or mobile phones, if you prefer) are ubiquitous. In the United States, current population about 307 million, there are more than 279 million wireless subscribers, say Inskip et al.1 in this issue of Neuro-Oncology; even allowing for users with multiple accounts (say, for work and personal use), that number is staggering. Worldwide, the story is the same: one study reports that there are now 4.6 billion subscribers,2 and another reports that about 50% of the world population (or some 3.3 billion people) were users in 2007.3 Yes, there is some variability in the numbers, but if cell phone use causes or even just elevates the risk for brain tumors … well, you get the picture: we will have plenty of patients for clinical trials.

Do cell phones generate enough RF (radiofrequency) electromagnetic radiation to induce gene mutations and thus increase the risk of brain tumors? The evidence so far is equivocal. Some studies have shown an overall increase in incidence among long-term users, some an increase in only certain histologic types of brain tumors, and some no increase at all or—oddly—a reduction in incidence. Two recent meta-analyses both came down on the side of suggesting that there may be evidence of a link.3,4 So far, no one seems to be able to muster much more conclusiveness than that.

Such analyses have been hindered by methodological inconsistency, potential bias, and reporting and recall inaccuracies—no surprise given the relative youth of the cell phone as a technology in widespread use and the intrinsic difficulties of analyzing epidemiologic events that may take years or even decades to evolve. Similar hindrances impede progress in understanding the risk of late effects from radiotherapy, for instance. And let's not even start on whether anthropogenic global warming is fact or fiction!

We have some hope that the questions about a cell phone–brain tumor link will be answered, eventually. After all, it took years of study for people to accept that lead-based paint could contribute to impaired IQ and that smoking increases the risk of lung cancer. What is required are time and evidence. Neuro-Oncology cannot alter the laws of physics and so can have no effect on the former, but we can contribute to the body of knowledge.

In this issue, we do so by publishing the aforementioned article by Inskip et al.,1 who have delved into the records of the Surveillance, Epidemiology, and End Results (SEER) database to gain more insight. Although this evidence is drawn from just the United States, its insights should be applicable worldwide, as biologic processes know no national borders.
Antithrombotic Effects of Recombinant Human, Active Site–Blocked Factor VIIa in a Rabbit Model of Recurrent Arterial Thrombosis
Authors: Paolo Golino, Massimo Ragni, Plinio Cirillo, Davide D’Andrea, Annalisa Scognamiglio, Amelia Ravera, Chiara Buono, Mirella Ezban, Nicola Corcione, Francesco Vigorito, Mario Condorelli, Massimo Chiariello
Journal: Circulation Research (1998)

Abstract —The extrinsic coagulation pathway is activated when circulating factor VII (FVII) gains access to tissue factor (TF) exposed as a consequence of vascular injury. Increasing evidence indicates that this TF-dependent activation of the coagulation plays an important role in the pathophysiology of intravascular thrombus formation. In the present study, we tested the effects of recombinant human, active site–blocked activated FVII (FVIIai) in a rabbit model of carotid artery thrombosis. Cyclic flow variations (CFVs), due to recurrent thrombus formation, were obtained in stenotic rabbit carotid arteries with endothelial injury. Carotid blood flow velocity was measured by a Doppler flow probe. After 30 minutes of CFVs, the animals received FVIIai (100 μg · kg −1 · min −1 intracarotid infusion for 10 minutes, n=9). If CFVs were abolished, animals were followed for 30 additional minutes, after which recombinant human activated FVII (FVIIa) was infused into the carotid artery (100 μg · kg −1 · min −1 for 10 minutes) to determine whether FVIIai could be displaced from TF by FVIIa, thus restoring CFVs. To establish the duration of action of FVIIai, an additional group of animals received FVIIai at the same dose as above, and after CFVs were inhibited, they were followed until CFVs were restored or for up to 6 hours. To determine whether CFVs could be restored by epinephrine after their abolition with FVIIai, increasing doses of epinephrine were administered to a third group of 6 animals. FVIIai abolished CFVs in 8 of 9 rabbits ( P &lt;.01). This effect was reversible, as FVIIa administration restored CFVs in all animals. Prothrombin times and activated partial thromboplastin times did not change significantly throughout the study. One single 10-minute infusion exerted complete antithrombotic effects for at least 6 hours, despite the fact that at this time point, plasma FVIIai levels were well below threshold concentrations. Epinephrine restored CFVs in 3 of 6 animals in which CFVs were inhibited by FVIIai. FVIIai exerts potent antithrombotic effects in this model; these effects were prolonged even after FVIIai was almost completely cleared from the circulation, probably as a result of the tight binding of FVIIai to TF. Thus, FVIIai might represent an antithrombotic substance of potential interest.
The novel<i>CTSC</i>homozygous nonsense mutation p.Lys106X in a patient with Papillon-Lefèvre syndrome with all permanent teeth remaining at over 40 years of age
Authors: T. Kobayashi, K. Sugiura, T. Takeichi, M. Akiyama
Journal: British Journal of Dermatology (2013)

Funding sources: This study was supported in part by Grant‐in‐Aid for Scientific Research (C) 23591617 (to K.S.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Grant‐in‐Aid for Scientific Research (A) 23249058 (to M.A.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the 'Research on Measures for Intractable Diseases' Project: Matching Fund Subsidy (H23‐028) from the Ministry of Health, Labour and Welfare of Japan. Conflicts of interest: None declared. Dear Editor, Papillon–Lefèvre syndrome (PLS; OMIM 245000) is a rare autosomal recessive genodermatosis caused by mutations in CTSC1 and characterized by palmoplantar keratoderma, psoriasiform lesions over the extensor surface of extremities and severe gingivitis followed by loss of teeth.2 3 CTSC encodes cathepsin C, a lysosomal cysteine protease required for the activation of granule‐associated serine proteases in inflammatory cells.1 Seventy‐seven distinct CTSC mutations have been identified, most of which are missense mutations that alter protein folding and function (Human Gene Mutation Database; Institute of Medical Genetics, Cardiff University, Cardiff, U.K.). Here, we show a novel homozygous nonsense mutation, p.Lys106X, which results in a deficiency of the mutant mRNA because of nonsense‐mediated mRNA decay in a patient with PLS who has the atypical clinical feature of retention of all the permanent teeth at age > 40 years.
Total unilateral pulmonary sequestration
Authors: M. Bates
Journal: Thorax (1968)

A case is described of a baby boy aged 7 months who was found to have total sequestration of the right lung, the right main bronchus communicating with the lower end of the oesophagus. This was discovered during investigation for supposed asthma, as the child had wheezed since birth. No episodes of cyanosis or difficulties with feeding had occurred. The embryological considerations are discussed and reasons are given to account for this abnormality which must have occurred at the 5-mm. stage of development. This child is probably the first reported case of total pulmonary sequestration which has survived childbirth and subsequent pneumonectomy and now, when 6 years old, appears to have a reasonable life ahead.
Synovial plasma cells in rheumatoid arthritis. Electron microscope and immunofluorescence studies.
Authors: G V Orlovskaya, P Y Muldiyarov, I S Kazakova
Journal: Annals of the Rheumatic Diseases (1970)

Ghadially and Roy, 1967), who have given minute description of the ultrastructural changes in the synovial lining layer.The fine structural details of the subsynovial tissue, in particular in the plasma cells have not been so carefully described.Norton and Ziff (1966) demonstrated a group of plasma cells but did not comment on their submicroscopical features.It is the purpose of this paper to describe the ultra- structural changes in rheumatoid synovial plasmo- cytes which are known to be the cellular sites of rheumatoid factor formation (Mellors, Heimer, Corcos, and Korngold, 1959; Mellors, Nowoslawski, Korngold, and Sengson, 1961; Kazakova, Orlov- skaya, and Pavlov, 1967).Preliminary reports on this subject have already been published (Orlov- skaya, 1969; Orlovskaya, Muldiyarov, and Kaza- kova, 1969). Material and methodsTwenty synovial membrane biopsies were obtained at synovectomy from the knee joints of patients with sero- positive rheumatoid arthritis.Specimens were removed from the regions where the synovial membrane showed marked villous proliferation, which have been found by previous immunofluorescent studies to contain rheuma- toid factor (Kazakova and others, 1967).The tissue samples were divided into two parts for immunofluorescent study and electron microscopy.copyright.
The Longitudinal Course of Borderline Psychopathology: 6-Year Prospective Follow-Up of the Phenomenology of Borderline Personality Disorder
Authors: Mary C. Zanarini, Frances R. Frankenburg, John Hennen, Kenneth R. Silk
Journal: American Journal of Psychiatry (2003)

The syndromal and subsyndromal phenomenology of borderline personality disorder was tracked over 6 years of prospective follow-up.The psychopathology of 362 inpatients with personality disorders was assessed with the Revised Diagnostic Interview for Borderlines (DIB-R) and borderline personality disorder module of the Revised Diagnostic Interview for DSM-III-R Personality Disorders. Of these patients, 290 met DIB-R and DSM-III-R criteria for borderline personality disorder and 72 met DSM-III-R criteria for other axis II disorders (and neither criteria set for borderline personality disorder). Most of the borderline patients received multiple treatments before the index admission and during the study. Over 94% of the total surviving subjects were reassessed at 2, 4, and 6 years by interviewers blind to previously collected information.Of the subjects with borderline personality disorder, 34.5% met the criteria for remission at 2 years, 49.4% at 4 years, 68.6% at 6 years, and 73.5% over the entire follow-up. Only 5.9% of those with remissions experienced recurrences. None of the comparison subjects with other axis II disorders developed borderline personality disorder during follow-up. The patients with borderline personality disorder had declining rates of 24 symptom patterns but remained symptomatically distinct from the comparison subjects. Impulsive symptoms resolved the most quickly, affective symptoms were the most chronic, and cognitive and interpersonal symptoms were intermediate.These results suggest that symptomatic improvement is both common and stable, even among the most disturbed borderline patients, and that the symptomatic prognosis for most, but not all, severely ill borderline patients is better than previously recognized.
Doxorubicin Release: Hybrid Organic Nanotubes with Dual Functionalities Localized on Cylindrical Nanochannels Control the Release of Doxorubicin (Adv. Healthcare Mater. 6/2012)
Authors: Wuxiao Ding, Naohiro Kameta, Hiroyuki Minamikawa, Momoyo Wada, Toshimi Shimizu, Mitsutoshi Masuda
Journal: Advanced Healthcare Materials (2012)

Novel cylindrical nanocapsules, with tunable inner surface, enable controlled release of the encapsulated anticancer drug doxorubicin. On page 699, M. Masuda and co-workers develop such nanocapsules with dual functionalities (–COOH and benzyloxycarbonyl) localized on their cylindrical nanochannels via a co-assembly of two rationally designed glycolipids.
Experimental models of heart failure
Authors: H. J SMITH, A. NUTTALL
Journal: Cardiovascular Research (1985)

Experimental models of heart failure can be used to address specific questions not easily answered in patients, but no single model can reproduce exactly any of the clinical syndromes of heart failure since these are dominated by fatigue and breathlessness. Heart failure may be induced experimentally by pressure loading, volume loading, myocardial infarction, or by the creation of other disease states within the myocardium. Pressure loading may be especially useful in the study of ventricular hypertrophy, cellular derangements and vascular changes. Volume loading may be useful when examining the pathogenesis of hormone and electrolyte disturbances. Models of myocardial infarction or destruction are likely to be the most suitable for assessing novel therapy provided that peripheral reflexes are maintained. Experimental cardiomyopathy can provide an important means of identifying pathological subcellular mechanisms. They may be of use in the evaluation of vasodilator drugs but caution should be exercised in the study of inotropic agents. Any one model may be useful if it permits study of a single factor or variable in isolation or at a time when information is not obtainable from patients. For greatest clinical relevance, studies should be made in conscious animals with intact reflexes.
Activated Protein C Ameliorates Renal Ischemia-Reperfusion Injury by Restricting Y-Box Binding Protein-1 Ubiquitination
Authors: Wei Dong, Hongjie Wang, Khurrum Shahzad, Fabian Bock, Moh'd Mohanad Al-Dabet, Satish Ranjan, Juliane Wolter, Shrey Kohli, Juliane Hoffmann, Vishnu Mukund Dhople, Cheng Zhu, Jonathan A. Lindquist, Charles T. Esmon, Elisabeth Gröne, Herman-Josef Gröne, Thati Madhusudhan, Peter R. Mertens, Dirk Schlüter, Berend Isermann
Journal: Journal of the American Society of Nephrology (2015)

Ischemia-reperfusion injury (IRI) is the leading cause of ARF. A pathophysiologic role of the coagulation system in renal IRI has been established, but the functional relevance of thrombomodulin (TM)-dependent activated protein C (aPC) generation and the intracellular targets of aPC remain undefined. Here, we investigated the role of TM-dependent aPC generation and therapeutic aPC application in a murine renal IRI model and in an in vitro hypoxia and reoxygenation (HR) model using proximal tubular cells. In renal IRI, endogenous aPC levels were reduced. Genetic or therapeutic reconstitution of aPC efficiently ameliorated renal IRI independently of its anticoagulant properties. In tubular cells, cytoprotective aPC signaling was mediated through protease activated receptor-1- and endothelial protein C receptor-dependent regulation of the cold-shock protein Y-box binding protein-1 (YB-1). The mature 50 kD form of YB-1 was required for the nephro- and cytoprotective effects of aPC in vivo and in vitro, respectively. Reduction of mature YB-1 and K48-linked ubiquitination of YB-1 was prevented by aPC after renal IRI or tubular HR injury. aPC preserved the interaction of YB-1 with the deubiquitinating enzyme otubain-1 and maintained expression of otubain-1, which was required to reduce K48-linked YB-1 ubiquitination and to stabilize the 50 kD form of YB-1 after renal IRI and tubular HR injury. These data link the cyto- and nephroprotective effects of aPC with the ubiquitin-proteasome system and identify YB-1 as a novel intracellular target of aPC. These insights may provide new impetus for translational efforts aiming to restrict renal IRI.
Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD
Authors: Jessica Bazick, Michele Donithan, Brent A. Neuschwander-Tetri, David Kleiner, Elizabeth M. Brunt, Laura Wilson, Ed Doo, Joel Lavine, James Tonascia, Rohit Loomba
Journal: Diabetes Care (2015)

OBJECTIVE Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75–0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with an AUROC of 0.80 (95% CI 0.76–0.85, P &amp;lt; 0.001). The specificity, sensitivity, NPV, and PPV were 90.0%, 57%, 75.1%, and 80.2%, respectively, and the model correctly classified 76.6% of patients as having advanced fibrosis. Results remained consistent for both models in the validation cohort. The proposed model performed better than the NAFLD fibrosis score in detecting advanced fibrosis. CONCLUSIONS Routinely available clinical variables can be used to quantify the likelihood of NASH or advanced fibrosis in adult diabetic patients with NAFLD. The clinical models presented can be used to guide clinical decision making about referrals of patients with diabetes and NAFLD to hepatologists.
Ischemic preconditioning reduces Na+ accumulation and cell killing in isolated rat hepatocytes exposed to hypoxia
Authors: Rita Carini, Maria Grazia De Cesaris, Roberta Splendore, Marco Bagnati, Emanuele Albano
Journal: Hepatology (2000)

Short periods of ischemia followed up by reperfusion are known to protect the heart against injury caused by a subsequent sustained ischemia. This phenomenon, known as ischemic preconditioning, has also been recently shown to reduce ischemic liver damage, but the mechanisms involved are still unknown. By using isolated hepatocytes as an in vitro model of liver preconditioning, we have investigated the possible effect of preconditioning on intracellular pH and Na(+) homeostasis. Freshly isolated rat hepatocytes were preconditioned by 10 minutes of incubation under hypoxic conditions followed up by 10 minutes of reoxygenation and subsequently exposed to 90 minutes of hypoxia. Although preconditioning did not ameliorate adenosine triphosphate (ATP) depletion, preconditioned hepatocytes exhibited an increased resistance to cell killing during hypoxic incubation. Intracellular acidosis and Na(+) accumulation developing during hypoxia were appreciably reduced in preconditioned cells. The effects of preconditioning on intracellular pH, Na(+) homeostasis, and cytotoxicity were mimicked by stimulating protein kinase C (PKC) with 4beta-phorbol-12-myristate-13-acetate (PMA) or 1,2 dioctanoyl-glycerol (1,2 DOG). Conversely, inhibiting PKC with chelerythrine or blocking vacuolar proton ATPase (V-ATPase) with bafilomycin A(1) abolished the protection given by preconditioning or by PMA treatment on hypoxic acidosis, Na(+) overload, and hepatocyte killing. Similarly, the addition of Na(+) ionophore monensin also reverted the cytoprotection exerted by preconditioning. This indicated that ischemic preconditioning of isolated hepatocytes decreased cell killing during hypoxia by preventing intracellular Na(+) accumulation. We propose that, after preconditioning, the stimulation of PKC might activate proton extrusion through V-ATPase, thus, limiting intracellular acidosis and Na(+) overload promoted by Na(+)-dependent acid buffering systems.
Papular-purpuric “gloves and socks” syndrome: Polymerase chain reaction demonstration of parvovirus B19 DNA in cutaneous lesions and sera
Authors: R. Grilli, M.J. Izquierdo, M.C. Fariña, H. Kutzner, I. Gadea, L. Martin, L. Requena
Journal: Journal of the American Academy of Dermatology (1999)
The enzymatic mechanisms for deoxythymidine synthesis in human leukocytes
Authors: Robert C. Gallo, Seymour Perry
Journal: Journal of Clinical Investigation (1969)

(1) Synthesis of deoxythymidine by either direct transfer of deoxyribosyl to thymine (pyrimidine deoxyribosyltransferase) or by a coupled deoxynucleoside phosphorylase mechanism is approximately twofold greater with normal leukocyte extracts (55 to 88% granulocytes) than with extracts prepared from leukocytes obtained from patients with chronic myelogenous leukemia. Activities in lymphocytes (normal or leukemic) are one-fifth the activity of normal granulocytes.(2) The lower activity in chronic myelogenous leukemia remains at 50% of normal even when patients are in hematologic remission with a normal per cent mature granulocytes in the peripheral blood.(3) The leukemic enzyme could not be distinguished from the normal by pH optima, thermal stability, or kinetic properties. The Km's for the deoxyribosyl acceptor and deoxyribosyl donors were identical for both enzymes. Both are subject to substrate inhibition by thymine and to inhibition by purine bases with similar Ki's. In addition, the transferase component of both the leukemic and the normal cell enzyme is activated by phosphate and arsenate. It appears, therefore, that there is no qualitative difference between the enzyme obtained from leukocytes of patients with chronic myelogenous leukemia and the enzyme obtained from normal leukocytes, suggesting that the difference in total cell activity is due to an actual decrease in amount of enzyme in chronic myelogenous leukemia or to a mixed cell population, one with a normal quantity of enzyme and the other with little or no active enzyme.(4) In both the normal cell and the leukemic cell extracts, transferase and phosphorylase activities could not be separated. The ratio of the two activities remained constant over a 140- and a 230-fold purification in normal and leukemic cell extracts, respectively. These and other observations indicate that transferase and phosphorylase activities are associated with the same protein.(5) The metabolism of pyrimidine and purine deoxynucleosides is similar for normal and leukemic cells. Catabolism of all deoxynucleosides tested was by direct phosphorolysis, except for deoxyadenosine which required initial deamination to deoxyinosine before phosphorolysis. In contrast to the greater rates of pyrimidine deoxynucleoside synthesis and cleavage with normal leukocyte extracts, the rates of purine deoxynucleoside synthesis and cleavage were approximately twofold greater with extracts prepared from cells of patients with chronic myelogenous leukemia. There was no significant difference in the rate of phosphorolytic cleavage of pyrimidine nucleosides (uridine) between the CML and normal leukocyte extracts.