tbuckley/cabot-search huggingface dataset:
Effects of the 65-mph Speed Limit on Rural Interstate Fatalities in New Mexico
Authors: Margaret M. Gallaher
Journal: JAMA (1989)

As a result of federal legislation passed in April 1987, New Mexico was the first state to resume a 65-mph speed limit on rural Interstate highways. We compared the rates of fatal crashes before and after the speed limit change. The rate of fatal crashes in the 1 year after the speed limit was increased was 2.9 per 100 million vehicle-miles traveled, compared with a predicted rate of 1.5 per 100 million vehicle-miles based on the trend of the 5 previous years. When fatal crashes that occurred after the speed limit change were compared with fatal crashes in the 5 previous years, there was no difference in the mean age and sex of the at-fault drivers, mean age and sex of the victims, seat belt use by the victims, or alcohol involvement of the crashes. The increase in fatal crashes can be attributed to an increase in fatal single-vehicle crashes. Vehicles on rural Interstates are traveling at greater rates of speed and a larger proportion of vehicles are exceeding the 65-mph speed limit. The benefits associated with the 65-mph speed limit should be weighed against the increased loss of lives.
Carriers of Loss-of-Function Mutations in <i>ABCA1</i> Display Pancreatic β-Cell Dysfunction
Authors: Menno Vergeer, Liam R. Brunham, Joris Koetsveld, Janine K. Kruit, C. Bruce Verchere, John J.P. Kastelein, Michael R. Hayden, Erik S.G. Stroes
Journal: Diabetes Care (2010)

OBJECTIVE Abnormal cellular cholesterol handling in islets may contribute to β-cell dysfunction in type 2 diabetes. β-Cell deficiency for the ATP binding cassette transporter A1 (ABCA1), which mediates the efflux of cellular cholesterol, leads to altered intracellular cholesterol homeostasis and impaired insulin secretion in mice. We aimed to assess the impact of ABCA1 dysfunction on glucose homeostasis in humans. RESEARCH DESIGN AND METHODS In heterozygous carriers of disruptive mutations in ABCA1 and family-based noncarriers of similar age, sex, and BMI, we performed oral glucose tolerance tests (OGTTs) (n = 15 vs. 14) and hyperglycemic clamps (n = 8 vs. 8). RESULTS HDL cholesterol levels in carriers were less than half those in noncarriers, but LDL cholesterol levels did not differ. Although fasting plasma glucose was similar between groups, glucose curves after an OGTT were mildly higher in carriers than in noncarriers. During hyperglycemic clamps, carriers demonstrated lower first-phase insulin secretion than noncarriers but no difference in insulin sensitivity. The disposition index (a measure of β-cell function adjusted for insulin sensitivity) of the carriers was significantly reduced in ABCA1 heterozygotes. CONCLUSIONS Carriers of loss-of-function mutations in ABCA1 show impaired insulin secretion without insulin resistance. Our data provide evidence that ABCA1 is important for normal β-cell function in humans.
Asthma: surfactant eliminates the early allergen-induced response
Authors: B.A. Hills
Journal: European Respiratory Journal (2003)

The thyroid is a rare site for metastasis, occurring in 0.1% of colorectal cases. A 46-year-old man with rectal adenocarcinoma developed an enlarging anterior neck mass and increasing carcinoembryonic antigen 2 years after curative intent treatment. Imaging showed aggressive features with invasion of the larynx, trachea and oesophagus, suspicious for anaplastic thyroid carcinoma. The patient underwent tumour debulking with neck dissection and tracheostomy. Final histopathological review revealed metastatic adenocarcinoma from a colorectal primary. Despite chemotherapy, the patient eventually succumbed to disease progression and complications of his illness. This case demonstrates that recognising rare sites of metastasis may help clinicians effectively institute earlier intervention.
Phase I and pharmacodynamic study of an orally administered novel inhibitor of histone deacetylases, SB939, in patients with refractory solid malignancies
Authors: W.P. Yong, B.C. Goh, R.A. Soo, H.C. Toh, K. Ethirajulu, J. Wood, V. Novotny-Diermayr, S.C. Lee, W.L. Yeo, D. Chan, D. Lim, E. Seah, R. Lim, J. Zhu
Journal: Annals of Oncology (2011)
Impaired Renal Sensory Responses after Renal Ischemia in the Rat
Authors: Ming-Chieh Ma, Ho-Shiang Huang, Ming-Shiou Wu, Chiang-Ting Chien, Chau-Fong Chen
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Renal sensory responses and reflex function were examined in rats 24 h after 45 min of ischemic injury caused by unilateral renal arterial occlusion (RAO). The integrity of renal pelvic mechanoreceptor (MRu)-mediated renorenal reflex was examined. An increase in ipsilateral afferent renal nerve activity (ARNA) and a reflex decrease in efferent renal nerve activity (ERNA) and contralateral diuresis and natriuresis produced by increasing the intrapelvic pressure were seen in sham-operated (Sham) rats, but it was largely attenuated in RAO rats. Using single-fiber recordings of the renal MRu discharge, graded increases in intrapelvic pressure or renal pelvic administration of substance P (SP) resulted in pressure- or concentration-dependent increases in ARNA in the control kidney of Sham rats, whereas attenuated responses were seen in the postischemic kidney of RAO rats. The unresponsiveness of renal MRus in RAO rats was accompanied by an insufficient release of SP. However, the baseline SP release is higher in RAO kidneys due to a reduced neutral endopeptidase (NEP) activity in the renal pelvis of the postischemic kidney. No changes in NK-1 receptor mRNA levels were demonstrated; however, the expression of NK-1 receptors in the plasma membrane of RAO pelvis were decreased, possibly resulting from the internalization of the receptors associated with β-arrestin trafficking. Renal excretory responses after saline loading were significantly lower in the postischemic kidney of RAO rats than in Sham rats. Responses of ARNA and ERNA were also lower. It is concluded that the defective activation of renal sensory mechanoreceptors in the postischemic kidney results from an inadequate release of SP after mechanostimulation and the reduced functional NK-1 receptors.
Nuclear magnetic resonance spectroscopy in patients with anion-gap acidosis.
Authors: D Malhotra, J I Shapiro, L Chan
Journal: Journal of the American Society of Nephrology (1991)

Proton nuclear magnetic resonance spectroscopy was performed on blood or urine from five patients with an anion-gap metabolic acidosis. In all of these cases, this methodology allowed the rapid and specific diagnosis of the nature of the metabolic acidosis. In several of these patients, spectroscopic evidence for intoxication with toxic alcohols was obtained. On the basis of these preliminary data, proton nuclear magnetic resonance spectroscopy may be a useful technique in the evaluation of patients with anion-gap acidosis.
PCP Gene Family in Symbiodinium from Hippopus hippopus: Low Levels of Concerted Evolution, Isoform Diversity, and Spectral Tuning of Chromophores
Authors: J. R. Reichman
Journal: Molecular Biology and Evolution (2003)

Photosynthetic dinoflagellates have evolved unique water-soluble light harvesting complexes known as peridinin-chlorophyll a–binding proteins (PCPs). Most species of dinoflagellates express either 14 to 17 kDa or 32 to 35 kDa mature PCP apoproteins and do so in stable combinations of isoforms that differ in isoelectric point (pI). The source (posttranslational modification, protein degradation, or genetic) and functional significance of PCP isoform variation have remained unclear. PCPs are encoded by multigene families. However, previous reports conflict over the diversity of PCP genes within gene arrays. We present the first genomic characterization of the PCP gene family from a symbiotic dinoflagellate. Symbiodinium from the Pacific bivalve Hippopus hippopus (203) contains genes for 33 kDa PCP apoproteins that are organized in tandem arrays like those of free-living dinoflagellates Amphidinium carterae, Lingulodinium (Gonyaulax) polyedra, and Heterocapsa pygmaea. The Symbiodinium 203 PCP cassette consists of 1,098-bp coding regions separated by approximately 900-bp spacers. The spacers contain a conserved upstream sequence similar to the promoter in L. polyedra. Surprisingly, sequences of cloned coding regions are not identical, and can differ at up to 2.2% of the nucleotide sites. Sequence variation is found at both silent and nonsilent sites, and analysis of cDNA clones indicate that the variation is present in the mRNA pool. We propose that this variation represents nucleotide diversity among PCP gene copies that are evolving under low-level concerted evolution. Interestingly, the predicted proteins have pIs that are within the range of those published for other species of Symbiodinium. Thus, posttranslational modifications are not necessary to explain the multiple PCP isoforms. We have also identified several polymorphic sites that may influence spectral absorption tuning of chromophores.
PPARα Inhibits TGF-β–Induced β <sub>5</sub> Integrin Transcription in Vascular Smooth Muscle Cells by Interacting With Smad4
Authors: Ulrich Kintscher, Christopher Lyon, Shu Wakino, Dennis Bruemmer, Xu Feng, Stephan Goetze, Kristof Graf, Aristidis Moustakas, Bart Staels, Eckart Fleck, Willa A. Hsueh, Ronald E. Law
Journal: Circulation Research (2002)

Integrins play an important role in vascular smooth muscle cell (VSMC) migration, a crucial event in the development of restenosis and atherosclerosis. Transforming growth factor-β (TGF-β) is highly expressed in restenotic and atherosclerotic lesions, and known to induce integrin expression. Peroxisome proliferator-activated receptor α (PPARα), a member of the nuclear receptor superfamily, regulates gene expression in a variety of vascular cells. We investigated the effects of PPARα ligands on TGF-β–induced β 3 and β 5 integrin expression and potential interaction between PPARα and TGF-β signaling. PPARα ligands WY-14643 (100 μmol/L) and 5,8,11,14-eicosatetranoic acid (ETYA, 50 μmol/L) inhibited TGF-β–induced β 5 integrin protein expression by 72±6.8% and 73±7.1%, respectively (both P &lt;0.05). TGF-β–stimulated β 3 integrin expression was not affected by PPARα ligands. Both PPARα ligands also suppressed TGF-β–induced β 5 integrin mRNA levels. PPARα ligands inhibited TGF-β–inducible transcription of β 5 integrin by an interaction with a TGF-β response element between nucleotides −63 and −44, which contains a Sp1/Sp3 transcription factor binding site. Nuclear complexes binding to the TGF-β response region contained Sp1/Sp3 and TGF-β–regulated Smad 2, 3, and 4 transcription factors. TGF-β–stimulated Sp1/Smad4 nuclear complex formation was inhibited by WY-14643 and ETYA with a parallel induction of PPARα/Smad4 interactions. However, in vitro pull-down experiments failed to demonstrate direct binding between PPARα/Smad4. Both PPARα ligands blocked PDGF-directed migration of TGF-β–pretreated VSMCs, a process mediated, in part, by β 5 integrins. The present study demonstrates that PPARα activators inhibit TGF-β–induced β 5 integrin transcription in VSMCs through a novel indirect interaction between ligand-activated PPARα and the TGF-β–regulated Smad4 transcription factors. The full text of this article is available at http://www.circresaha.org.
Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice
Authors: Mary A Hoelscher, Sanjay Garg, Dinesh S Bangari, Jessica A Belser, Xiuhua Lu, Iain Stephenson, Rick A Bright, Jacqueline M Katz, Suresh K Mittal, Suryaprakash Sambhara
Journal: The Lancet (2006)
PART II.--PATHOLOGICAL
Authors: R. A. Q. O'Meara
Journal: BMJ (1930)

Dr. Geraghty revealed small bilateral basal pleural effusions.Thlere was achlorliydilia anid a mild secondary aniaemnia.The palienit was oni a low protein dict for about a monitlh previous to admission.Fun ction Tests a7nd Blood Chflcm istry.The total proteini, albtrnlinl, anid globulini determinations were performed on plasmza, by the combinied methods of Howe,9 Wtu,"' anid Kock and McMeekiii,1 as described by Hawke and Bergeim2; blood cholesterol was estimated as described bly M3yers and Wardell,13 blood plhosplhorus by the method of Benedict anid
Dengue virus-specific human T cell clones. Serotype crossreactive proliferation, interferon gamma production, and cytotoxic activity.
Authors: I Kurane, A Meager, F A Ennis
Journal: The Journal of Experimental Medicine (1989)

The severe complications of dengue virus infections, hemorrhagic manifestation and shock, are much more commonly observed during secondary infections caused by a different serotype of dengue virus than that which caused the primary infections. It has been speculated, therefore, that dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are caused by serotype crossreactive immunopathological mechanisms. We analyzed clones of dengue serotype crossreactive T lymphocytes derived from the PBMC of a donor who had been infected with dengue 3 virus. These PBMC responded best to dengue 3 antigen, but also responded to dengue 1, 2, and 4 antigens, in bulk culture proliferation assays. 12 dengue antigen-specific clones were established using a limiting dilution technique. All of the clones had CD3+ CD4+ CD8 phenotypes. Eight clones responded to dengue 1, 2, 3, and 4 antigens and are crossreactive, while four other clones responded predominantly to dengue 3 antigen. These results indicate that the serotype crossreactive dengue-specific T lymphocyte proliferation observed in bulk cultures reflects the crossreactive responses detected at the clonal level. Serotype crossreactive clones produced high titers of IFN-gamma after stimulation with dengue 3 antigens, and also produced IFN-gamma to lower levels after stimulation with dengue 1, 2, and 4 antigens. The crossreactive clones lysed autologous lymphoblastoid cell line (LCL) pulsed with dengue antigens, and the crossreactivity of CTL lysis by T cell clones was consistent with the crossreactivity observed in proliferation assays. Epidemiological studies have shown that secondary infections with dengue 2 virus cause DHF/DSS at a higher rate than the other serotypes. We hypothesized that the lysis of dengue virus-infected cells by CTL may lead to DHF/DSS; therefore, the clones were examined for cytotoxic activity against dengue 2 virus-infected LCL. All but one of the serotype crossreactive clones lysed dengue 2 virus-infected autologous LCL, and they did not lyse uninfected autologous LCL. The lysis of dengue antigen-pulsed or virus-infected LCL by the crossreactive CTL clones that we have examined is restricted by HLA DP or DQ antigens. These results indicate that primary dengue virus infections induce predominantly crossreactive memory CD4+ T lymphocytes. These crossreactive T lymphocytes proliferate and produce IFN-gamma after stimulation with a virus strain of another serotype, and demonstrate crossreactive cyotoxic activity against autologous cells infected with heterologous dengue viruses.(ABSTRACT TRUNCATED AT 400 WORDS)
Factors Affecting Blister Formation
Authors: R. D. G. Peachey
Journal: British Journal of Dermatology (1971)

Journal Article Factors Affecting Blister Formation Get access R. D. G. Peachey R. D. G. Peachey St John's Hospital for Diseases of the Skin Lisle Street, Leicester Square London, WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 5, 1 November 1971, Page 497, https://doi.org/10.1111/j.1365-2133.1971.tb14067.x Published: 01 November 1971
Syngeneic monoclonal antiidiotype can induce cellular immunity to reovirus.
Authors: A H Sharpe, G N Gaulton, K K McDade, B N Fields, M I Greene
Journal: The Journal of Experimental Medicine (1984)

A syngeneic monoclonal antiidiotypic antibody was generated in BALB/c mice after repeated immunization with a BALB/c monoclonal anti-reovirus hemagglutinin (HA) antibody. The resultant syngeneic monoclonal antiidiotypic antibody, in the absence of adjuvant, was found to be capable of priming both BALB/c (H-2d, Igh-1a) and C3H/Hej (H-2k, Igh-1j) mice for Lyt-1+- and Lyt-2+-dependent responses against the mammalian reovirus. By the use of intertypic reassortants and variant virus analysis, the specificity of the response was finely mapped to the neutralization domain of the viral hemagglutinin (HA). Using purified monoclonal antiidiotype, we were able to compare the potency of antiidiotype to virus in terms of induction of immunity. 8 X 10(8) protein molecules were able to prime for cellular responses to reovirus. These studies indicate that in the reovirus system, T cells and B cells share idiotypic configurations, and that antiidiotypic antibodies of the type described herein may be useful in the development of vaccines against certain viral infections.
Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines
Authors: G. Curigliano, D. Cardinale, T. Suter, G. Plataniotis, E. de Azambuja, M.T. Sandri, C. Criscitiello, A. Goldhirsch, C. Cipolla, F. Roila
Journal: Annals of Oncology (2012)
Clinical Evaluation of BR96 sFv-PE40 Immunotoxin Therapy in Canine Models of Spontaneously Occurring Invasive Carcinoma
Authors: Carolyn J. Henry, Michael S. Buss, Ingegerd Hellström, Karl Erik Hellström, William G. Brewer, Jeffrey N. Bryan, Clay B. Siegall
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The immunotoxin BR96 sFv-PE40 is an effective antitumor agent against human breast and lung carcinoma xenografts in rodents. This study was designed to (a) determine the frequency with which canine carcinoma cells express Lewisy (Ley) antigen, thereby identifying canine carcinoma types suitable for the clinical evaluation of BR96 sFv-PE40, and (b) determine the safety and efficacy of BR96 sFv-PE40 in a canine model of spontaneously occurring cancers for investigation of targeted therapy. Experimental Design: Carcinoma tissue samples were obtained from client-owned dogs presented for medical care. The tissues were assessed for Ley antigen expression using immunohistochemical methods. Dogs with tumors expressing Ley antigen were offered enrollment in a clinical trial to receive twice-weekly infusions of 4 to 12 mg/m2 BR96 sFv-PE40. Clinical toxicity and response data were assessed at each treatment. Results: Twenty-two of 61 carcinomas evaluated were positive for Ley expression, including mammary, prostate, lung, and rectal carcinomas, and 12 dogs were enrolled in the clinical trial. The primary side effect was transient emesis. Partial responses or disease stabilization were noted in dogs with inflammatory mammary, bronchogenic, rectal, and tonsillar carcinoma. At least nine of the dogs developed antibodies to the immunotoxin after two to five infusions. Conclusions: Although development of anti-BR96 sFv-PE40 antibodies limited the long-term effectiveness of this immunotoxin in dogs, rapid clinical responses in several aggressive canine carcinomas suggest the immunotoxin has utility for treatment of certain naturally occurring tumors and that its clinical evaluation for treatment of similar human carcinomas is warranted.
Double-Blind, Placebo-Controlled, Multicenter Trial of Selegiline Augmentation of Antipsychotic Medication to Treat Negative Symptoms in Outpatients With Schizophrenia
Authors: J. Alexander Bodkin, Samuel G. Siris, Paul C. Bermanzohn, John Hennen, Jonathan O. Cole
Journal: American Journal of Psychiatry (2005)

The authors' goal was to test the efficacy of selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who had negative symptoms of moderate or greater severity.A 12-week, double-blind, placebo-controlled, multicenter trial of oral selegiline augmentation of antipsychotic medication was carried out. Outpatients were chosen who did not manifest severe positive symptoms at baseline, who did not meet criteria for coexisting major depression, and who had been maintained on a stable regimen of antipsychotic medication.Negative symptoms were found to be significantly more improved in the patients who received selegiline, and global improvement scores reinforced the impression that selegiline augmentation was beneficial.These findings support further investigation of low-dose selegiline augmentation of antipsychotic medication in outpatients with schizophrenia who have at least a moderate burden of negative symptoms.
Identifying college athletes at risk for pathogenic eating
Authors: M T DePalma, W M Koszewski, W Romani, J G Case, N J Zuiderhof, P M McCoy
Journal: British Journal of Sports Medicine (2002)

Objectives: To evaluate the effectiveness of a discriminant function that predicts risk of pathogenic eating in comparison with a standard self report measure (EAT) and a clinical interview. In addition, to determine the effectiveness of this discriminant function using a variety of collegiate athletes. Methods: A total of 319 participants were asked to complete a series of self report measures that assessed dietary practices. In addition, anthropometric measures were obtained, and a random sample of 15% participated in a structured clinical interview. Results: Correlational analyses indicated that the discriminant function categorisation of risk was significantly related to both the clinical interview and EAT (p≤0.05). The discriminant function was accurate in predicting risk category in this diverse group of athletes, particularly with respect to those at low risk (83.1%) and those at high risk (72.7%). Conclusion: This information may be helpful in the development of a simple, accessible tool to identify athletes at risk of engaging in pathogenic eating behaviours.
“Petrified” Right Ventricle in Long-Standing Naxos Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Cristina Basso, Adalena Tsatsopoulou, Gaetano Thiene, Aris Anastasakis, Marialuisa Valente, Nikos Protonotarios
Journal: Circulation (2001)

A 19-year-old asymptomatic man was evaluated be- cause of his sister's sudden death due to Naxos disease, a recessive form of arrhythmogenic right ventricular (RV) cardiomyopathy associated with palmoplantar keratoderma and woolly hair.It is caused by a plakoglobin mutation.Twelve-lead ECG showed inverted T waves in V1 through V6, incomplete right bundle branch block, and epsilon waves (Figure 1).Frequent ventricular extrasystoles were recorded on a 24-hour ECG.On echocardiography and angiography, the right ventricle was dilated and diffusely hypokinetic, but the left ventricle appeared normal.During 14 years of follow-up, he had 2 episodes of well-tolerated sustained ventricular tachycardia followed by biventricular progression leading to heart failure (New York Heart Association class III to IV) without arrhythmias.The patient died at 33 years of age while waiting for heart transplantation.
ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults
Authors: William O. Cooper, Laurel A. Habel, Colin M. Sox, K. Arnold Chan, Patrick G. Arbogast, T. Craig Cheetham, Katherine T. Murray, Virginia P. Quinn, C. Michael Stein, S. Todd Callahan, Bruce H. Fireman, Frank A. Fish, Howard S. Kirshner, Anne O'Duffy, Frederick A. Connell, Wayne A. Ray
Journal: New England Journal of Medicine (2011)

Adverse-event reports from North America have raised concern that the use of drugs for attention deficit–hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events.