tbuckley/cabot-search huggingface dataset:
The Capsid of the T4 Phage Superfamily: The Evolution, Diversity, and Structure of Some of the Most Prevalent Proteins in the Biosphere
Authors: A. M. Comeau, H. M. Krisch
Journal: Molecular Biology and Evolution (2008)

The Escherichia coli bacteriophage T4 has served as a classic system in phage biology for more than 60 years. Only recently have phylogenetic analyses and genomic comparisons demonstrated the existence of a large, diverse, and widespread superfamily of T4-like phages in the environment. We report here on the T4-like major capsid protein (MCP) sequences that were obtained by targeted polymerase chain reaction (PCR) of marine environmental samples. This analysis was then expanded to include 1,000s of new sequences of T4-like capsid genes from the metagenomic data obtained during the Sorcerer II Global Ocean Sampling (GOS) expedition. This data compilation reveals that the diversity of the major and minor capsid proteins from the GOS metagenome follows the same general patterns as the sequences from cultured phage genomes. Interestingly, the new MCP sequences obtained by PCR targeted to MCP sequences in environmental samples are more divergent (deeper branching) than the vast majority of the MCP sequences coming from the other sources. The marine T4-like phage population appears to be largely dominated by the T4-like cyanophages. Using ∼1,400 T4-like MCP sequences from various sources, we mapped the degree of sequence conservation on a structural model of the T4-like MCP. The results indicate that within the T4 superfamily there are some clear phylogenetic groups with regard to the more conserved and more variable domains of the MCP. Such differences can be correlated with variations in capsid morphology, the arrangement of the MCP lattice, and the presence of different capsid accessory proteins between the subgroups of the T4 superfamily.
Subcutaneous interstitial pressure and volume characteristics in renal impairment associated with edema
Authors: Leonard M. Ebah, Helge Wiig, Idalia Dawidowska, Charlotte O'Toole, Angela Summers, Milind Nikam, Anuradha Jayanti, Beatrice Coupes, Paul Brenchley, Sandip Mitra
Journal: Kidney International (2013)
Myeloid-Derived Suppressor Cells Promote Cross-Tolerance in B-Cell Lymphoma by Expanding Regulatory T Cells
Authors: Paolo Serafini, Stephanie Mgebroff, Kimberly Noonan, Ivan Borrello
Journal: Cancer Research (2008)

Abstract Tumor-induced T-cell tolerance is a major mechanism that facilitates tumor progression and limits the efficacy of immune therapeutic interventions. Regulatory T cells (Treg) play a central role in the induction of tolerance to tumor antigens, yet the precise mechanisms regulating its induction in vivo remain to be elucidated. Using the A20 B-cell lymphoma model, here we identify myeloid-derived suppressor cells (MDSC) as the tolerogenic antigen presenting cells capable of antigen uptake and presentation to tumor-specific Tregs. MDSC-mediated Treg induction requires arginase but is transforming growth factor-β independent. In vitro and in vivo inhibition of MDSC function, respectively, with NOHA or sildenafil abrogates Treg proliferation and tumor-induced tolerance in antigen-specific T cells. These findings establish a role for MDSCs in antigen-specific tolerance induction through preferential antigen uptake mediating the recruitment and expansion of Tregs. Furthermore, therapeutic interventions, such as in vivo phosphodiesterase 5–inhibition, which effectively abrogate the immunosuppressive role of MDSCs and reduce Treg numbers, may play a critical role in delaying and/or reversing tolerance induction. [Cancer Res 2008;68(13):5439–49]
Re-excisions of scar in primary cutaneous melanoma: a histopathological study
Authors: MARY E. FALLOWFIELD, M. G. COOK
Journal: British Journal of Dermatology (1992)

In many centres the wide excision and split-skin grafting remains the standard therapy for primary cutaneous melanoma. One-hundred and thirty-seven primary cutaneous melanomas were seen in our department during a 3-year period; 25 patients were subsequently subjected to re-excision of scar following the initial excision biopsy. Lymphatic permeation, field change in the epidermal melanocytes and micrometastases were sought in the re-excision specimens in order to examine the pathological basis for this therapy. Two of the 25 primary melanomas included in this study were known to have been incompletely excised at the time of initial biopsy and both re-excision specimens included a few nests of atypical melanocytes adjacent to one edge of the biopsy wound. Examination of the re-excision specimens failed to demonstrate evidence of direct lymphatic permeation by melanoma, or of a field change in the epidermal melanocytes adjacent to the melanomas, although five specimens from sun-exposed sites showed slight melanocyte atypia. One re-excision specimen did include a single small group of melanocytes, less than 120 microns in size, in the dermis within 2 mm of the initial excision biopsy site of a melanoma 8.4 mm in thickness. These results support the view that more extensive local therapy than complete excision of primary cutaneous melanoma with a narrow margin of adjacent normal skin, is unlikely to benefit the patient.
Permanent Epicardial Pacing in Pediatric Patients
Authors: Mitchell I. Cohen, David M. Bush, Victoria L. Vetter, Ronn E. Tanel, Tammy S. Wieand, J. William Gaynor, Larry A. Rhodes
Journal: Circulation (2001)

The purpose of this study was to evaluate the long-term outcome of all pediatric epicardial pacing leads.All epicardial leads and 1239 outpatient visits between January 1, 1983, and June 30, 2000, were retrospectively reviewed. Pacing and sensing thresholds were reviewed at implant, at 1 month, and at subsequent 6-month intervals. Lead failure was defined as the need for replacement or abandonment due to pacing or sensing problems, lead fracture, or phrenic/muscle stimulation. A total of 123 patients underwent 207 epicardial lead (60 atrial/147 ventricular, 40% steroid) implantations (median age at implant was 4.1 years [range 1 day to 21 years]). Congenital heart disease was present in 103 (84%) of the patients. Epicardial leads were followed for 29 months (range 1 to 207 months). The 1-, 2-, and 5-year lead survival was 96%, 90%, and 74%, respectively. Compared with conventional epicardial leads, both atrial and ventricular steroid leads had better stimulation thresholds 1 month after implantation; however, only ventricular steroid leads had improved chronic pacing thresholds (at 2 years: for steroid leads, 1.9 muJ [from 0.26 to 16 mu]; for nonsteroid leads, 4.7 muJ [from 0.6 to 25 muJ]; P<0.01). Ventricular sensing was significantly better in steroid leads 1 month after lead implantation (at 2 years: for steroid leads, 8 mV [from 4 to 31 mV]; for nonsteroid leads, 4 mV [from 0.7 to 10 mV]; P<0.01). Neither congenital heart disease, lead implantation with a concomitant cardiac operation, age or weight at implantation, nor the chamber paced was predictive of lead failure.Steroid epicardial leads demonstrated relatively stable acute and chronic pacing and sensing thresholds. In this evaluation of >200 epicardial leads, lead survival was good, with steroid-eluting leads demonstrating results similar to those found with historical conventional endocardial leads.
Influence of glucose, insulin, and potassium on vulnerability to ventricular fibrillation in the canine heart.
Authors: A I Obeid, R L Verrier, B Lown
Journal: Circulation Research (1978)

We studied the influence of glucose (G), insulin (I) and potassium (K + ) on vulnerability to ventricular fibrillation (VF) of the nonischemic canine myocardium.Vulnerability was assessed by determining VF and repetitive extrasystole (RE) thresholds with a single stimulus applied to the right ventricular endocardium during the vulnerable period.Electrical testing of the heart was performed before and after 1 and 2 hours of infusing G (10 mg/kg per min) and I (0.025 U/kg per min) with and without K + .Infusion of glucose, insulin, and potassium (GIK) in 11 dogs significantly increased both VF (22%) and RE (33%) thresholds within the 1st hour and only the VF threshold (64%) in the 2nd hour.No significant changes in serum K + concentration occurred.Spontaneous termination of VF was observed in six dogs during GIK infusion.Glucose and insulin infusion increased both VF and RE thresholds within the 1st (17% and 19%) and 2nd hours (43% and 43%).This occurred despite substantial reductions in serum K + concentration.Lowering serum K + by hemodialysis in six dogs decreased both VF and RE thresholds within the 1st (33% and 32%) and 2nd hours (35% and 14%).Restoration of the serum K + concentration by KC1 infusion while maintaining dialysis returned the thresholds to control values.In six dogs, insulin infusion during low K + dialysis increased the VF and RE thresholds despite a further reduction in serum K + concentration.We concluded that insulin exerts a protective effect against vulnerability to VF in the normal canine heart.This salutary action is most marked when the drug's hypokalemic effect is prevented by concomitant K + infusion.
Drug Evaluation Programs of the AMA 1905-1966
Authors: Jeffrey Bishop
Journal: JAMA (1966)

Sixty-one years ago, the Council on Pharmacy and Chemistry was created as a standing committee of the Board of Trustees of the American Medical Association. Its declared purpose to serve the medical profession by providing accurate information on the status of agents used in the treatment of disease has remained constant. In its early years, the efforts of the Council were directed to the suppression of advertisements for quack medicines and nostrums, the analysis of secret remedies, and the publication of their formulae. The principle of absolute impartiality to all manufacturers and all products was enunciated and rigidly adhered to. Certain rules and standards concerning the origin, composition, and availability of tests for the identification of proprietary drugs were established with the object of protecting the medical profession and the public against fraud, undesirable secrecy, and objectionable advertising. To aid the Council, the AMA established a chemical laboratory to determine
Fulminating Hyperpyrexia during Anaesthesia in a Member of a Myopathic Family
Authors: A. J. W. Steers, J. A. Tallack, D. E. A. Thompson
Journal: BMJ (1970)

Changes in body weight and haemoglobin concentration, showing specific response to parenteral folate.She was readmitted on 17 July with severe anaemia, weakness, and pyrexia.The mouth and tongue had numerous aphthous ulcers, the tongue being red and atrophic, and there was a small boil on the face.The motions were bulky and semiformed, two or three times daily, and contained 9 g. of fat a day.The xylose absorption test was again abnormal (five-hour excretion 19 %).Oral folic acid and iron were continued under supervision in hos- pital, in spite of which the haemoglobin fell from 5-1 to 4.8 g., with an M.C.H.C. of 330%, reticulocytes 1°o, W.B.C. 3,500, and a partly macrocytic film as before.Bone marrow aspiration on 23 July showed frank megaloblastosis.Serum vitamin B12 was 150 pg./ml., folic acid 0-8 ng./ml., and iron 188 ug./100 ml.(400%O saturation).On 19 July she was given a single :ntravenous infusion of 35 ml. of chelated iron (Imferon).There was no reticulocyte response and no rise in haemoglobin.On 24 July the daily intramuscular injection of 15 mg. of folic acid was started.There was a maximal reticulocyte response of 36% and the haemoglobin rose rapidly (see Chart).A dramatic immediate improvement in her well-being occurred, her appetite improved, and a week after starting the injections she began to gain weight.At the same time the continuous mild pyrexia settled to normal, abdominal discomfort disappeared, and the bowels became regular.Further recovery was uninterrupted.The patient was discharged in mid-August, twice-weekly injections of folic acid being con- ment of the London Hospital for their assistance in the diagnosis of Barnes's myopathy.
A study of the permeability barrier in epidermis and oral epithelium using horseradish peroxidase as a tracer in vitro
Authors: C.A. SQUIER, ROSAMUND M. HOPPS
Journal: British Journal of Dermatology (1976)

Small biopsies of skin, and of keratinized and non-keratinized oral mucosa were incubated with horseradish peroxidase, fixed and reacted to demonstrate peroxidase activity at the light and electron microscope level. In all tissues peroxidase extended through the intercellular spaces of the epithelium up to, but not into, the stratum corneum of keratinized, or the superficial layer of non-keratinized, tissue. This distribution corresponds to that seen in studies using the tracer in vivo where the presence of an intercellular permeability barrier has been demonstrated in the upper cell layers. It is suggested that the method is a useful way of investigating the permeability of normal and pathological human epithelial tissues.
Loss of histone deacetylases 1 and 2 in hepatocytes impairs murine liver regeneration through Ki67 depletion
Authors: Jie Xia, Yongjie Zhou, Hongjie Ji, Yujia Wang, Qiong Wu, Ji Bao, Feng Ye, Yujun Shi, Hong Bu
Journal: Hepatology (2013)

Histone deacetylases 1 and 2 (HDAC1 and HDAC2) are ubiquitously expressed in tissues, including the liver, and play critical roles in numerous physiopathological processes. Little is known regarding the role of HDAC1 and HDAC2 in liver regeneration. In this study we generated mice in which Hdac1, Hdac2 or both genes were selectively knocked out in hepatocytes to investigate the role of these genes in liver regeneration following hepatic injury induced by partial hepatectomy or carbon tetrachloride administration. The loss of HDAC1 and/or HDAC2 (HDAC1/2) protein resulted in impaired liver regeneration. HDAC1/2 inactivation did not decrease hepatocytic 5-bromo-2-deoxyuridine uptake or the expression of proliferating cell nuclear antigen, cyclins, or cyclin-dependent kinases. However, the levels of Ki67, a mitotic marker that is expressed from the mid-G1 phase to the end of mitosis and is closely involved in the regulation of mitotic progression, were greatly decreased, and abnormal mitosis lacking Ki67 expression was frequently observed in HDAC1/2-deficient livers. The down-regulation of either HDAC1/2 or Ki67 in the mouse liver cancer cell line Hepa1-6 resulted in similar mitotic defects. Finally, both HDAC1 and HDAC2 proteins were associated with the Ki67 gene mediated by CCAAT/enhancer-binding protein β.Both HDAC1 and HDAC2 play crucial roles in the regulation of liver regeneration. The loss of HDAC1/2 inhibits Ki67 expression and results in defective hepatocyte mitosis and impaired liver regeneration.
Catatonia in Alzheimer's disease: The role of the amygdalo-hippocampal circuits
Authors: Andrei C. Miu, Adrian I. Olteanu
Journal: Behavioral and Brain Sciences (2002)

The intrinsic merit of Northoff's model lies primarily in the fact that it integrates data concerned with different levels of organization of the brain. This approach implicitly argues against reductionism, although, apparently, its rather simplistic assumption gives too many degrees of freedom. In considering that a symptom from two different syndromes indicates a common neural alteration, we grossly disregard neural plasticity.
Quantitative Measures of Electrocardiographic Left Ventricular Mass, Conduction, and Repolarization, and Long-Term Survival After Coronary Artery Bypass Grafting
Authors: Michael S. Lauer, Derlis Martino, Hemant Ishwaran, Eugene H. Blackstone
Journal: Circulation (2007)

Quantitative ECG measures of left ventricular mass and repolarization predict outcome in population-based cohorts and patients with hypertension. We assessed the prognostic value of preoperative quantitative electrocardiography in patients who underwent isolated coronary artery bypass grafting.For 6 years we followed 8166 patients who underwent primary isolated coronary artery bypass grafting between 1990 and 2003, all of whom had routine preoperative ECGs. With use of specialized digital software, quantitative measures were recorded on ventricular rate, P duration, PR interval, QRS duration, QT interval, QRS axis, Sokolow-Lyon and Cornell voltages, and ST-segment depression and slope. There were 1516 deaths. After adjustment for age, gender, clinical characteristics, left ventricular ejection fraction, and other confounders, death was independently predicted by ventricular rate (adjusted hazard ratio [AHR] for 90 versus 60 beats per minute, 1.34; 95% confidence interval [CI], 1.21 to 1.50; P<.0001), PR interval (AHR for 200 versus 150 ms, 1.05; 95% CI, 1.00 to 1.10; P<.0001), QRS duration (AHR for 120 versus 80 ms, 1.24; 95% CI, 1.07 to 1.44; P<.0001), Sokolow-Lyon voltage (AHR for 3.5 versus 1.5 mV, 1.18; 95% CI, 1.05 to 1.31; P<.0001), and ST-segment slope (AHR for -0.1 versus 0 mV, 1.16; 95% CI, 1.02 to 1.31; P<.0001). We derived a quantitative ECG score and demonstrated that, with the exception of age, it was the most powerful predictor of long-term death.Quantitative ECG measures of left ventricular rate, mass, and repolarization are predictive of mortality among patients who underwent isolated coronary artery bypass grafting. These findings suggest that quantitative electrocardiography may be valuable for risk stratification in patients with severe coronary artery disease.
Intraoperative transesophageal Doppler color flow imaging used to guide patient selection and operative treatment of ischemic mitral regurgitation.
Authors: K H Sheikh, J R Bengtson, J S Rankin, N P de Bruijn, J Kisslo
Journal: Circulation (1991)

BACKGROUND Intraoperative transesophageal Doppler color flow imaging (TDCF) affords the opportunity to assess mitral valve competency immediately before and after cardiopulmonary bypass (CPB). The purpose of this study was to assess the utility of TDCF to assist in the selection and operative treatment of ischemic mitral regurgitation (MR). METHODS AND RESULTS Two hundred forty-six patients undergoing surgery for ischemic heart disease were prospectively studied. All had preoperative cardiac catheterization. Catheterization and pre-CPB TDCF were discordant in their estimation of MR in 112 patients (46%). Compared with patients in whom both techniques agreed in estimation of MR, patients with discordance in MR were more likely to have had unstable clinical syndromes at the time of catheterization (79% versus 40%, p less than 0.05) or to have received thrombolytics (16% versus 8%, p less than 0.05). Pre-CPB TDCF resulted in a change in the operative plan with respect to the mitral valve in 27 patients (11%). Because less MR was found by TDCF than catheterization, 22 patients had only coronary bypass grafting when combined coronary bypass and mitral valve surgery had been planned. Because more MR was found by TDCF than catheterization, five patients had combined coronary bypass and mitral valve surgery when coronary bypass alone had been planned. Unsatisfactory results noted by TDCF following mitral valve surgery in five patients resulted in immediate corrective surgery. Cox regression analysis identified residual MR at the completion of surgery to be an important predictor of survival (chi 2 = 21.4) after surgery--more important than patient age (chi 2 = 8.3) or left ventricular ejection fraction (chi 2 = 5.3). CONCLUSIONS These results indicate that TDCF is useful in guiding patient selection and operative treatment of ischemic MR and that in such patients, intraoperative TDCF should be performed routinely.
Identification of Genes Required for Protection from Doxorubicin by a Genome-Wide Screen in <i>Saccharomyces cerevisiae</i>
Authors: Ling Xia, Lahcen Jaafar, Anil Cashikar, Hernan Flores-Rozas
Journal: Cancer Research (2007)

Abstract Anthracyclines are chemotherapeutic agents commonly used to treat a broad range of malignancies. Although effective, these drugs present serious complications, most notably cardiotoxicity. To determine the mechanisms that mediate cytoprotection from doxorubicin, we have screened the collection of Saccharomyces cerevisiae haploid gene deletion mutants. We have identified 71 deletion strains that display varying degrees of hypersensitivity to doxorubicin at a concentration that does not significantly reduce the viability of wild-type cells. Complementation of the doxorubicin-sensitive phenotype of the deletion strains with the wild-type genes proves that the sensitivity of the strain to doxorubicin is due to the gene deletion. The genes that mediate cytoprotection from doxorubicin belong to multiple pathways including DNA repair, RNA metabolism, chromatin remodeling, amino acid metabolism, and heat shock response. In addition, proteins with mitochondrial, osmosensing, vacuolar, and ribosomal functions are also required for protection from doxorubicin. We tested the sensitivity of the deletion strains to other cytotoxic agents, which resulted in different drug-specific sensitive groups. Most of the identified genes have mammalian homologues that participate in conserved pathways. Our data may prove useful to develop strategies aimed at sensitizing tumor cells to doxorubicin as well as protecting cardiac cells from its cytotoxic effects. [Cancer Res 2007;67(23):11411–8]
Principles of Exercise Testing and Interpretation
Authors: Peter Bale
Journal: British Journal of Sports Medicine (1987)

This is a well presented, compact colour atlas detailing the majority of rheumatological conditions which are amenable to photography.Each chapter begins with a resume of the condition under discussion followed by a mixture of clinical and X-ray pictures, each accompanied by an appropriate legend.The longest chapter deals with rheumatoid arthritis and emphasises the multi-system nature of this disease.The following chapter on juvenile chronic arthritis was the only disappointment, in that it utilised the term Still's disease more frequently than one would in clinical practice today.After dealing with inflammatory condition the author covers degenerative arthopathies, crystal arthopathies and connective tissues diseases.A picture of an LE cell is perhaps unnecessary since this test would now be obsolete in most laboratories but suppose may turn up in an examination situation.Rarer arthopathies and miscellaneous conditions are then covered.Generally the quality of the photographs is good, although a few of the X-rays have not been well reproduced.This book is recommended to fit in the pocket of any clinician, whatever their specialty or stage of career, and has the value of providing a spectrum of rheumatology that can be covered in a matter of minutes.
Stalking the elusive mental image screen
Authors: Zenon W. Pylyshyn
Journal: Behavioral and Brain Sciences (2002)

After thirty years of the current “imagery debate,” it appears far from resolved, even though there seems to be a growing acceptance that a cortical display cannot be identified directly with the experienced mental image, nor can it account for the experimental findings on imagery, at least not without additional ad hoc assumptions. The commentaries on the target article range from the annoyed to the supportive, with a surprising number of the latter. In this response I attempt to correct some misreadings of the target article and discuss some of the ideas and evidence introduced by the commentators – much of which I found helpful, even though they do not alter my basic thesis. I also further develop the idea that the spatial character of images may come from the way they are connected to our immediate or immediately-recalled environment (by attention or by visual indexes) and towards which we may orient while we are imaging, thus leaving the alleged spatial properties of images outside the head and freeing image-representations from having to be displayed on any surface.