tbuckley/cabot-search huggingface dataset:
Incidence of Cervical Squamous Intraepithelial Lesions Associated With HIV Serostatus, CD4 Cell Counts, and Human Papillomavirus Test Results
Authors: Tiffany G. Harris
Journal: JAMA (2005)

Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA.To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results.Participants were HIV-seropositive (n = 855; mean age, 36 years) and HIV-seronegative (n = 343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women's Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years.The cumulative incidence of any SIL and high-grade SIL or cancer (HSIL+) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count.Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/microL, 9% (95% CI, 1%-18%); with CD4 counts between 200/muL and 500/microL, 9% (95% CI, 4%-13%); and with CD4 counts greater than 500/microL, 4% (95% CI, 1%-7%). The CIs for these estimates overlapped with those for HIV-seronegative women with normal baseline cytology who were HPV-negative (3%; 95% CI, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSIL+ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIV-seropositive women with CD4 counts greater than 500/microL (hazard ratio [HR], 1.2; 95% CI, 0.5-3.0), but not those with CD4 counts less than or equal to 500/microL (HR, 2.9; 95% CI, 1.2-7.1), was similar to that in HIV-seronegative women.The similar low cumulative incidence of any SIL among HIV-seronegative and HIV-seropositive women with CD4 counts greater than 500/microL and who had normal cervical cytology and HPV-negative test results suggests that similar cervical cancer screening practices may be applicable to both groups, although this strategy warrants evaluation in an appropriate clinical trial.
CHEMICAL STUDIES ON BACTERIAL AGGLUTINATION
Authors: Hattie E. Alexander, Michael Heidelberger
Journal: The Journal of Experimental Medicine (1940)

1. The quantitative, absolute methods of agglutinin and precipitin analysis previously developed for antipneumococcus sera have been shown to be applicable to horse and rabbit anti-influenza type B sera and plasmas. 2. With the aid of these methods and improved immunization schedules the antibody content of the rabbit sera has been increased five to ten times. 3. The method recommended for the purification of rabbit antipneumococcus antibody has also been found applicable to rabbit anti-influenza type B sera.
Molecular targets for tumour progression in gastrointestinal stromal tumours
Authors: N Koon
Journal: Gut (2004)

<b>Background and aims:</b> The distinction between benign and malignant gastrointestinal stromal tumours (GISTs) is often unclear at the clinical and histopathology levels. GISTs are believed to arise from the stem cells of Cajal. In order to define genetic biomarkers and identify target genes related to GIST progression, we analysed and compared benign and malignant GISTs with verified follow up data using cDNA expression arrays. <b>Methods:</b> Eight genes were frequently overexpressed in malignant GISTs and their overexpression was confirmed using quantitative real time reverse transcription-polymerase chain reaction. These genes included ezrin (villin 2 (VIL2)), collagen 8 alpha 1 subunit (COL8A1), G2/mitotic specific cyclin B1 (CCNB1), high mobility group protein (HMG2), TSG101 tumour susceptibility protein, CENP-F kinetochore protein, protein tyrosine kinase 2 (FAK), and protein kinase DYRK2. To test these genes in a clinical setting, we obtained diagnostic samples of 16 additional GISTs that were classified at diagnosis as benign, malignant, and uncertain malignant potential (UMP). <b>Results:</b> There was remarkable gene overexpression in all malignant GISTs. Statistical analyses revealed significant correlations between overexpression of several gene pairs in malignant GISTs. We found the strongest correlations (ρ&gt;0.70) among the significant correlations (p&lt;0.01) between CCNB1-CENP-F (ρ = 0.87) and CCNB1-FAK (ρ = 0.73). Gene expression of the UMP GISTs suggested two different groups. Three UMP GISTs had gene expression consistent with malignant tumours and their follow up data revealed that indeed these patients had recurrences later on. On the other hand, UMP GISTs that had low gene expression levels continued free of disease for several years. <b>Conclusions:</b> These results provide insight into the oncogenesis of GISTs and suggest that testing the expression profile of a number of genes may segregate GISTs into groups of different tumour behaviour.
in left human atrium: a potential contributor to atrial ectopy
Authors: K ZORNPAULY, P SCHAFFER, B PELZMANN, P LANG, H MACHLER, B RIGLER, B KOIDL
Journal: Cardiovascular Research (2004)

Objective: The left human atrium plays an important role in initiation of atrial fibrillation (AF) and the hyperpolarization activated cation current (If) is a candidate for contributing to abnormal automaticity. However, electrophysiological data concerning If are not available in this cardiac region and we therefore investigated If in human left atrial tissue.
INFLAMMATION AND PROTEIN METABOLISM STUDIES OF CARBON-14-LABELED PROTEINS IN DOGS WITH STERILE ABSCESSES
Authors: C. L. Yuile, F. V. Lucas, C. K. Jones, S. J. Chapin, G. H. Whipple
Journal: The Journal of Experimental Medicine (1953)

Carbon-14-labeled plasma proteins given by mouth to dogs with sterile abscesses undergo decreased absorption, presumably owing to impaired digestion of protein. The turnover of plasma albumin is greatly accelerated but the globulins, excluding fibrinogen, show little change during the acute stage of the sterile inflammation. Fibrinogen shows very rapid production and utilization during acute inflammation. Large amounts of C(14) are incorporated in fibrinogen within a few hours after ingestion of the labeled material. The labeled fibrinogen largely disappears within 2 to 4 days after its production. The appearance of C(14) in new red cells from labeled protein or amino acid sources is reduced by inflammation-evidence of impaired synthesis. The pus of the sterile abscess contains a good deal of C(14) activity which at times is as much as that found in the liver. Pus cell C(14) activity per milliliter is similar after injection of labeled plasma and ingestion of labeled plasma or lysine. However, the pus cell fraction contains 3 to 4 times more C(14) activity per milliliter than does the supernatant fluid when the isotope is fed. In the supernatant fluid the activity is all within precipitable protein, much of which is probably derived from the blood plasma. In spite of increased loss of C(14) as CO(2) in the expired air and in the pus, there is evidence of conservation of protein-building materials for maintenance of new plasma proteins and tissue proteins in the more active organs (e.g. liver)-a shift of protein C(14) from the less active tissues (muscle and skin).
Enhanced Survival and Cure of F98 Glioma–Bearing Rats following Intracerebral Delivery of Carboplatin in Combination with Photon Irradiation
Authors: Julia Rousseau, Caroline Boudou, Rolf F. Barth, Jacques Balosso, François Estève, Hélène Elleaume
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The goal of the present study was to evaluate the efficacy of intracerebral (i.c.) administration of carboplatin by means of convection-enhanced delivery (CED) in combination with fractionated, external beam photon irradiation for the treatment of F98 glioma–bearing rats. Experimental Design: Carboplatin (20 μg/20 μL) was administrated i.c. by CED to F98 glioma–bearing rats, 13 days after stereotactic implantation of 103 tumor cells. One day following initiation of CED, a 24-Gy X-ray dose was administered in three daily fractions of 8 Gy each. Photon irradiation was carried out using either a conventional (6 MV) linear accelerator or a monochromatic synchrotron source (80 keV) at the European Synchrotron Radiation Facility. The primary end point of this study was overall survival. Results: The median survival times were 79 and 60 days and the corresponding percent increase in life spans were 182% and 114%, respectively, for the combination of carboplatin chemotherapy and irradiation with either 6-MV or 80-keV photons. A subset of long-term survivors (&amp;gt;200 days) were observed in both chemoradiotherapy groups: 16.6% and 8.3% for 6 MV and 80 keV, respectively. In contrast, the median survival times for 6-MV or 80-keV irradiated controls, chemotherapy alone, and untreated controls were 42, 51, 45, and 28 days, respectively. Conclusions: Our results convincingly show the therapeutic efficacy of i.c. administration of carboplatin by means of CED in combination with either 6-MV or 80-keV photons. Further studies are warranted to optimize this combination of chemoradiotherapy for malignant gliomas.
Studies on platelet membrane glycoproteins and platelet function during hemodialysis.
Authors: J A Sloand, E M Sloand
Journal: Journal of the American Society of Nephrology (1997)

Hemodialysis only partially corrects the defects in platelet function associated with uremia. Platelet contact with the artificial surfaces of the dialysis filter during hemodialysis can itself cause platelet activation, degranulation, and loss of platelet membrane glycoproteins. Although the transient platelet dysfunction that occurs after platelet contact with foreign surfaces during cardiopulmonary bypass has been well characterized, there has been no such investigation of hemodialysis. In this study of hemodialysis patients, bleeding times (BT) and the response of their platelets to thrombin, ristocetin, and collagen were measured before, immediately after, and in some patients, the day after hemodialysis. In addition, membrane glycoproteins in platelets obtained at these time intervals were studied using fluorescein isothiocyanate (FITC) conjugated monoclonal antibodies (mAb) CD42b (anti-GPIb), CD41a (anti-GPIIb/IIIa), and CD62 (anti-P-selectin), with flow cytometry. BT was significantly prolonged, and response to thrombin and ristocetin was significantly decreased immediately after hemodialysis (P < 0.01). Binding of CD42b mAb to the platelet membrane was decreased in platelets obtained immediately after hemodialysis. Most patients had shortened BT and demonstrated increased response of their platelets to thrombin and increased CD42b binding to their platelets the day after hemodialysis. These findings suggest that in uremic patients, hemodialysis is associated with transient platelet dysfunction and decreased membrane expression of GPIb.
Bioactivation of Drugs: Risk and Drug Design
Authors: John S. Walsh, Gerald T. Miwa
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Bioactivation through drug metabolism is frequently suspected as an initiating event in many drug toxicities. The CYP450 and peroxidase enzyme systems are generally considered the most important groups of enzymes involved in bioactivation, producing either electrophilic or radical metabolites. Drug design efforts routinely consider these factors, and a number of structural alerts for bioactivation have been identified. Among the most frequently encountered structural alerts are aromatic systems with electron-donating substituents and some five-membered heterocycles. Metabolism of these groups can lead to chemically reactive electrophiles. Strategies that have been used to minimize the associated risk involve replacing the structural-alert moiety, blocking or making metabolism less favorable, and incorporating metabolic soft spots to facilitate metabolism away from the structural-alert substituent. The metabolism of drugs to radicals usually leads to cellular oxidative stress. The formation of radical metabolites can be minimized through the use of similar approaches but remains an area less frequently considered in drug design.
Budget crises, health, and social welfare programmes
Authors: D. Stuckler, S. Basu, M. McKee
Journal: BMJ (2010)

Governments may feel they are protecting health by safeguarding healthcare budgets, yet <b>David Stuckler, Sanjay Basu</b>, and <b>Martin McKee</b> argue that social welfare spending is as important, if not more so, for population health
Extracranial-Intracranial Bypass Surgery for Stroke Prevention in Hemodynamic Cerebral Ischemia
Authors: William J. Powers, William R. Clarke, Robert L. Grubb, Tom O. Videen, Harold P. Adams, Colin P. Derdeyn, for the COSS Investigators
Journal: JAMA (2011)

Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically.To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia.Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010.Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers.Patients with arteriographically confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Of 195 patients who were randomized, 97 were randomized to receive surgery and 98 to no surgery. Follow-up for the primary end point until occurrence, 2 years, or termination of trial was 99% complete. No participant withdrew because of adverse events.Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Antithrombotic therapy and risk factor intervention were recommended for all participants.For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days after surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery, the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within 2 years of randomization.The trial was terminated early for futility. Two-year rates for the primary end point were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (P = .78, Z test), a difference of 1.7% (95% CI, -10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.4% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group, a difference of 12.4% (95% CI, 4.9% to 19.9%).Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared with medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years.clinicaltrials.gov Identifier: NCT00029146.
Sickness Response Symptoms among Healthy Volunteers after Controlled Exposures to Diesel Exhaust and Psychological Stress
Authors: Robert J. Laumbach, Howard M. Kipen, Kathie Kelly-McNeil, Junfeng Zhang, Lin Zhang, Paul J. Lioy, Pamela Ohman-Strickland, Jing Gong, Alexander Kusnecov, Nancy Fiedler
Journal: Environmental Health Perspectives (2011)

Interactions between acute exposures to environmental chemical contaminants and psychological stress may be important in situations where they are likely to co-occur, ranging in intensity from daily urban living to participation in war. Modification of symptomatic responses by stress may play a role in medically unexplained symptoms attributed to low-level chemical exposures.We hypothesized that the combination of exposure to diesel exhaust (DE) and acute psychological stress would cause sickness responses in healthy volunteers. Moreover, these responses would be greater in individuals with self-reported prior chemical odor intolerance.One hundred adult subjects underwent 1-hr exposures to diluted DE and clean air control. Half of the subjects performed a public-speaking stressor task during the exposures. Subjects completed questionnaires to determine their Chemical Odor Intolerance Index score. Plasma cortisol, end-tidal carbon dioxide, and the severity of 35 symptoms were measured at time points before and after the exposures.Subjects exposed to DE demonstrated small but statistically significant increases in severity for several symptom categories, including sickness response and upper respiratory, central nervous system, and total symptoms. The psychological stressor did not increase symptom severity independently or via interaction with DE. Subjects with prior self-reported chemical intolerance had more severe sickness response symptoms from DE.These results suggest that exposure to DE can cause acute sickness response symptoms and that these symptoms are also associated with increased levels of self-reported chemical intolerance. The results did not confirm our hypothesis that an acute stressor would increase sickness response symptom severity during the exposure.
Role of Axillary Clearance After a Tumor-Positive Sentinel Node in the Administration of Adjuvant Therapy in Early Breast Cancer
Authors: Marieke E. Straver, Philip Meijnen, Geertjan van Tienhoven, Cornelis J.H. van de Velde, Robert E. Mansel, Jan Bogaerts, Gaston Demonty, Nicole Duez, Luigi Cataliotti, Jean Klinkenbijl, Helen A. Westenberg, Huub van der Mijle, Coen Hurkmans, Emiel J.T. Rutgers
Journal: Journal of Clinical Oncology (2009)

Purpose The After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) phase III study compares axillary lymph node dissection (ALND) and axillary radiation therapy (ART) in early breast cancer patients with tumor-positive sentinel nodes. In the ART arm, the extent of nodal involvement remains unknown, which could have implications on the administration of adjuvant therapy. In this preliminary analysis, we studied the influence of random assignment to ALND or ART on the choice for adjuvant treatment. Patients and Methods In the first 2,000 patients enrolled in the AMAROS trial, we analyzed the administration of adjuvant systemic therapy. Multivariate analysis was used to assess variables affecting the administration of adjuvant chemotherapy. Adjuvant therapy was applied according to institutional guidelines. Results Of 2,000 patients, 566 patients had a positive sentinel node and were treated per random assignment. There was no significant difference in the administration of adjuvant systemic therapy. In the ALND and ART arms, 58% (175 of 300) and 61% (162 of 266) of the patients, respectively, received chemotherapy. Endocrine therapy was administered in 78% (235 of 300) of the patients in the ALND arm and in 76% (203 of 266) of the patients in the ART arm. Treatment arm was not a significant factor in the decision, and no interactions between treatment arm and other factors were observed. Multivariate analysis showed that age, tumor grade, multifocality, and size of the sentinel node metastasis significantly affected the administration of chemotherapy. Within the ALND arm, the extent of nodal involvement remained not significant in a sensitivity multivariate analysis. Conclusion Absence of knowledge regarding the extent of nodal involvement in the ART arm appears to have no major impact on the administration of adjuvant therapy.
Thiol suppression of human immunodeficiency virus type 1 replication in primary cord blood monocyte-derived macrophages in vitro.
Authors: J Lioy, W Z Ho, J R Cutilli, R A Polin, S D Douglas
Journal: Journal of Clinical Investigation (1993)

We investigated the effects of glutathione (GSH), the major naturally occurring thiol, and a pharmacologic thiol precursor of GSH, N-acetyl cysteine (NAC), on the expression of human immunodeficiency type 1 (HIV-1) in primary cord blood and adult donor monocyte-derived macrophages (MDM). HIV-1 infection of cord blood and adult MDM was accomplished after incubating 10-15-d-old cultures for 4 h with a monocyte-tropic strain of HIV-1 (Bal). After 1 wk in culture cell supernatants were tested for reverse transcriptase (RT) activity. MDM were exposed to 5, 10 and 20 mM concentrations of both GSH and NAC before infection, during infection, and after infection was established. GSH and NAC suppressed the replication of HIV-1 in both primary cord blood and adult donor MDM in a concentration dependent fashion. These suppressive effects were more pronounced in cord-derived cells than in adult-derived cells. In cells treated with GSH or NAC before infection, there was no significant rise in RT activity as compared with controls. Similarly, when cells were treated with GSH and NAC and simultaneously infected, there was also no significant rise in RT activity after 1 wk in culture. In cells treated after infection was established, RT values were suppressed 80-90% that of untreated controls. This effect persisted for 1-2 wk after exposure to GSH and NAC. Untreated controls demonstrated syncytium formation and lost characteristics of spreading and elongation 2 wk after HIV-1 infection, whereas most of the treated cells remained free of syncytium and retained cytoplasmic spreading, adherence, and elongation. These data are consistent with other studies of thiol suppression of HIV-1 replication and demonstrate a similar observation for primary cultured cord MDM. These results may offer new approaches toward cellular protection after infection with HIV-1.
Global analyses of mRNA translational control during early Drosophila embryogenesis
Authors: Xiaoli Qin, Soyeon Ahn, Terence P Speed, Gerald M Rubin
Journal: Genome biology (2007)

Abstract Background In many animals, the first few hours of life proceed with little or no transcription, and developmental regulation at these early stages is dependent on maternal cytoplasm rather than the zygotic nucleus. Translational control is critical for early Drosophila embryogenesis and is exerted mainly at the gene level. To understand post-transcriptional regulation during Drosophila early embryonic development, we used sucrose polysomal gradient analyses and GeneChip analysis to illustrate the translation profile of individual mRNAs. Results We determined ribosomal density and ribosomal occupancy of over 10,000 transcripts during the first ten hours after egg laying. Conclusion We report the extent and general nature of gene regulation at the translational level during early Drosophila embryogenesis on a genome-wide basis. The diversity of the translation profiles indicates multiple mechanisms modulating transcript-specific translation. Cluster analyses suggest that the genes involved in some biological processes are co-regulated at the translational level at certain developmental stages.