tbuckley/cabot-search huggingface dataset:
767. Role of the Cytoskeleton in Intracellular Plasmid Movement
Authors: Erin E. Vaughan, David A. Dean
Journal: Molecular Therapy (2005)

Top of pageAbstract
Little is known about how naked DNA moves through the cytoplasm to the nucleus. It has been suggested that the dense latticework of the cytoskeleton impedes free diffusion of DNA, implying that plasmids would be unable to reach the nucleus. However, transfections do work, and thus there must be mechanisms by which DNA circumvents cytoplasmic obstacles. One possibility is that plasmids become cargo on cytoskeltal motors, much like viruses do, and move to the nucleus in a directed fashion. In order to assess what occurs once DNA enters the cytoplasm, adherent, confluent A549 cells were electroporated with a plasmid expressing luciferase driven by a CMV promoter. Since electroporation results in endocytosis-independent, direct entry of DNA across the plasma membrane into the cytoplasm, we could use a variety of cytoskeletal drugs known to affect endocytosis without these effects confounding our studies. This provides a model for DNA movement not only applicable to electroporation but also to any type of gene therapy where the DNA becomes free in the cytoplasm (e.g. after endosomal escape). Once the DNA is inside the cell, we found that perturbation of the actin cytoskeleton by either stabilization with jasplakinolide or breakdown with latrunculin B did not affect the ability of exogenous DNA to be expressed. This suggests that the actin network is not involved in the directed movement of DNA through the cytoplasm. In contrast, stabilization of the microtubule network with taxol increased reporter gene expression approximately five-fold in cultured cells, two hours after electroporation. This suggests that microtubules are involved in transporting the DNA through the cytoplasm to the nucleus. Since the reporter plasmid used has NFkB binding sites in its CMV promoter, if any of the drugs increased nuclear translocation of NFkB they could affect the transcription of the plasmid and skew the results. To test this, a series of control experiments were preformed. First, cells were electroporated with the DNA and allowed to rest for 24 hours (by which point the DNA would have entered the nucleus) prior to the addition of drugs. It was found that none of the drugs used significantly increased expression from the plasmid. Second, to look at the response of NFkB more directly, an NFkB reporter plasmid was used. Again, the cells were electroporated and 24 hours later they were treated with drug and harvested two hours afterwards to measure NFkB responsive and luciferase expression. Again, no significant changes in expression were observed. Taken together, these results suggest that the microtubule network somehow facilitates transfer of naked DNA to the nucleus and not transcription, per se. Elucidating the pathways by which DNA reaches the nucleus is imperative and will lead to improvements in nonviral gene delivery.
Abstract 4405: RNases: Approaching RNA as a target for cancer therapy.
Authors: Laura E. Strong, John Kink, Baigen Mei, Mark Shahan, Ronald T. Raines
Journal: Cancer Research (2013)

Abstract Ribonucleases (RNases) are a unique class of anti-cancer drugs that target the RNA in cancer cells without the complications of delivering RNA. Efficacious RNases have diminished binding to the naturally occurring RNase inhibitor protein in the cytosol of cells. Since human RNase I binds tightly to the inhibitor, changes to the amino acid residues in the contact region were made and resulted in the lead candidate referred to as QBI-139. This variant maintains 95% sequence identity with the wild type human RNase 1. Broad efficacy and a strong therapeutic window were seen across multiple tumor types in xenograft models and QBI-139 was advanced to an ongoing Phase I clinical trial. For the Investigational New Drug application package, rat and dog toxicology studies were used to aid in selection of the starting dose for humans. Exposure levels (pharmacokinetics, PK) are an important factor in evaluating whether toxicity and efficacy will be comparable across the species. A complicating issue in the evaluation of the results is the range of routes of administration across species, specifically intraperitoneal injection (mice), intravenous injection (rat and dog) and intravenous infusion (human). One parameter that is consistent is rapid clearance, which is likely due to the small size of QBI-139 (15 kiloDaltons). With preliminary results from the early stage clinical trial, the exposure levels across the experiments will be compared. The results demonstrate that the exposure profiles in the clinic where the route of administration is intravenous infusion, is most similar to that in the mouse efficacy models, which is intraperitoneal injection. A human RNase variant, called QBI-139 provides an innovative drug development approach to targeting RNA. In model systems, QBI-139 has shown broad in vivo anti-tumor activity alone and in combination with standard of care therapies and a strong tolerability profile. The knowledge gained about the impact of PK on therapeutic effect will be valuable as the method of administration is selected and confirmed in the next stage of clinical trials. Citation Format: Laura E. Strong, John Kink, Baigen Mei, Mark Shahan, Ronald T. Raines. RNases: Approaching RNA as a target for cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4405. doi:10.1158/1538-7445.AM2013-4405
Improvement of magnetic resonance spectroscopic abnormalities but not pallidal hyperintensity followed amelioration of hepatic encephalopathy after occlusion of a large spleno–renal shunt
Authors: Juan Córdoba, Gemma Olivé, Juli Alonso, Alex Rovira, Antonio Segarra, Mercedes Pérez, Carlos Jacas, VÍctor Vargas
Journal: Journal of Hepatology (2001)
SCHOOL CHILDREN'S EYES—A PLEA FOR THE EXAMINATION OF EVERY CHILD'S EYES, WHEN COMMENCING TO ATTEND SCHOOL.Read in the Section on Ophthalmology, at the Forty-fifth Annual Meeting of the American Medical Association, held "at San Francisco, June 5-8, 1894.
Authors: W. F. SOUTHARD
Journal: JAMA (1894)

Looking over the annual report of the public schools of the city of San Francisco for the year 1893, I find that there was an average daily attendance of 31,002 pupils between the ages of 5 and 17. Of this number 69 and sixty-three-hundredths percent. were in the primary grades. This includes all children between 5 and 10 years of age. Twenty-six and six-hundredths per cent. were pupils in the grammar grades, while but 4 and thirty-one-hundredths per cent. were high school pupils. These pupils between say, the ages of 10 and 17 were divided between the grammar grade and the high school. I wish to emphasize the point that, though this does not state the total enrollment of pupils, it does very correctly give the daily attendance throughout the year. An analysis of these figures will give us some very important results. In the first place, you will observe
THE TREATMENT OF CANCER OF THE JAW WITH THE ACTUAL CAUTERY
Authors: A. J. OCHSNER
Journal: JAMA (1923)

During a period of nearly forty years I have had an opportunity of observing and treating a very large number of cases of cancer of the jaw, first as chief assistant of Prof. Charles T. Parkes for three years, and later for four years in the same position with Prof. Nicholas Senn in the enormous surgical clinic these men conducted from 1888 to 1895 at Rush Medical College and the Presbyterian Hospital in this city. Since 1888, I have acted as surgeon-in-chief of Augustana Hospital, and since 1895, of St. Mary's Hospital, and in each of these services many of these cases have come under my observation and treatment—126 operative cases during the period of twenty years from 1901 to 1921.  In 1888, I became greatly interested in the treatment of cancer of the uterus by means of the actual cautery, introduced by Dr. John Byrne of Brooklyn, which Professor
Recombinant human stem cell factor, a <i>c‐kit</i> ligand, stimulates granulopoiesis in severe congenital neutropenia
Authors: Hiroko Ijima, Toshiji Shitara, Shin‐Ichiroh Yugami, Manabu Sotomatu, Takayoshi Kuroume
Journal: American Journal of Hematology (1993)
Postmarketing surveillance of the safety of cimetidine: mortality during second, third, and fourth years of follow up.
Authors: D G Colin-Jones, M J Langman, D H Lawson, M P Vessey
Journal: BMJ (1985)

A previous report analysed the pattern of mortality during the first year of follow up among 9928 patients taking cimetidine who were recruited to a postmarketing drug surveillance study in Glasgow, Nottingham, Oxford, and Portsmouth. A further analysis has now been conducted extending the period of follow up to four years. The 12 month report noted that cimetidine was being given, knowingly or unknowingly, in the late stages of many diseases and also to counter the adverse gastric effects of other drugs used in the treatment of serious disorders. This finding was underlined by a steady fall in the excess death rate among cimetidine users with increasing length of follow up, such that by the fourth year the pattern of observed deaths was not much different from that expected on the basis of national rates. Some excess of observed over expected deaths from gastric cancer, lung cancer, and urinary disorders was still apparent after four years of follow up, but there was no evidence that cimetidine was responsible. Indeed, no fatal disorder emerged as being associated with cimetidine during the follow up period. Deaths from the complications of disease related to gastric acid occurred in only 38 of the 9928 subjects over the four years. These findings provide further evidence of the safety of cimetidine.
Mechanical and histological evaluation of a PMMA-based bone cement modified with γ-methacryloxypropyltrimethoxysilane and calcium acetate
Authors: Tadashi Tsukeoka, Masahiko Suzuki, Chikara Ohtsuki, Atsushi Sugino, Yoshikazu Tsuneizumi, Jin Miyagi, Kouichi Kuramoto, Hideshige Moriya
Journal: Biomaterials (2006)
A low molecular weight fraction of polyethylenimine (PEI) displays increased transfection efficiency of DNA and siRNA in fresh or lyophilized complexes
Authors: Stephanie Werth, Beata Urban-Klein, Lige Dai, Sabrina Höbel, Marius Grzelinski, Udo Bakowsky, Frank Czubayko, Achim Aigner
Journal: Journal of Controlled Release (2006)
NEUROLOGIC COMPLICATIONS FOLLOWING ADMINISTRATION OF PERTUSSIS VACCINE
Authors: Matthew Brody
Journal: JAMA (1949)

<h3>To the Editor:—</h3> Prompted by the disturbing report of Byers and Moll on the "Encephalopathies Following Prophylactic Pertussis Vaccine" which appeared in<i>Pediatrics</i>(<b>1</b>:437 [April] 1948), Toomey conducted a survey based on a questionnaire, the results of which were published inThe Journal, February 12, page 448. He rejects the possibility that these reactions are due to an antigen antibody response because the children were not previously immunized. Although this is a plausible deduction based on the information Toomey had at his disposal, my reports on this problem which appeared in<i>The Brooklyn Hospital Journal</i>(<b>2</b>: 107 [April] 1947), and with Sorley in the<i>New York State Journal of Medicine</i>(<b>47</b>: 1016 [May 1] 1947) were apparently not available to him. In them is a description of a clinical experiment which offers conclusive evidence to the contrary. I take this opportunity to abstract the cases reported (for a detailed
Stress Fracture of the First Metatarsal in a Fencer
Authors: Montse Minoves, Ana Ponce, Ramon Balius, Luis Til
Journal: Clinical Nuclear Medicine (2011)

Stress fractures in the feet of athletes seldom involve the first metatarsal, with few documented case reports. We report a case of stress fracture in the base of the first metatarsal in a professional fencer with the typical scintigraphic appearance of a fracture line clearly demonstrated by selective pinhole imaging.
A DNA Variant at the Angiotensin-Converting Enzyme Gene Locus Associates With Coronary Artery Disease in the Caerphilly Heart Study
Authors: Raj K. Mattu, Edward W. A. Needham, David J. Galton, Evanthia Frangos, Adrian J. L. Clark, Mark Caulfield
Journal: Circulation (1995)

Background We analyzed an insertion/deletion (I/D) polymorphism of the angiotensin I–converting enzyme (ACE) gene in 1226 subjects from the Caerphilly Prospective Heart Disease Study. Amplification of genomic DNA using the polymerase chain reaction yielded the genotypes II, ID, and DD. Distribution of the polymorphism was analyzed among the whole group and within subgroups (specified following multiple risk factor analysis) for coronary artery disease (CAD) and against multiple risk factors. Methods and Results Allele frequencies were I=0.413 and D=0.587. No association was observed between the polymorphism and CAD in the whole group. Among subjects defined at lower risk of CAD by total cholesterol/HDL cholesterol (TC/HDL) ratios, we found significant associations of the DD genotype with CAD ( P &lt;.0053, n=586 for TC/HDL &lt;5.654 [median] and P &lt;.009, n=385 for TC/HDL &lt;5.0 [clinical threshold]). On further exclusion of subjects with blood pressures ≥140/90 or on hypotensive medications, the DD genotype still associated with CAD ( P &lt;.07, n=210, TC/HDL &lt;5.654 and P &lt;.016, n=135, TC/HDL &lt;5.0). Further stratification of risk incorporating other risk factors, except body mass index, did not alter or enhance this association. Although similar association was observed when risk was specified by using HDL and apo B levels instead of TC/HDL, this association was lost when body mass index was included in the low-risk stratification. Conclusions The DD genotype is a linkage marker for an etiologic mutation at or near the ACE gene that may confer risk of CAD detectable in subjects previously unidentifiable with “classic” risk factors. However, this risk may be quantitatively small among the general male population.
Computerized Blood Bank Control
Authors: David Singman
Journal: JAMA (1965)

An advanced inventory control system which uses a remotely located computer is now in its eighth month of operation. The Blood Bank Control System resulted from a joint effort by a blood bank and an aerospace company to resolve blood bank operational problems through proved information-processing techniques. The system links the blood bank to the computer for automated record keeping, inventory analysis, performance audit, and management report preparation. By means of exception reporting, the system enables the bank to do the following: monitor release of cross-matched blood within preset periods; encourage more effective use of inventory by member hospitals; plan more closely the procurement, stock level, and distribution of whole-blood inventory; reduce losses from outdating and lower the age of transfused blood.
Reye's Syndrome and Aspirin
Authors: Paul F. Pinsky
Journal: JAMA (1988)

Data collected from the Public Health Service Main Study of Reye's Syndrome and Medications were analyzed to assess the relationship between the development of Reye's syndrome and the dose of aspirin received during the antecedent respiratory or chickenpox illness. Among those exposed to aspirin, case-patients were found to have received greater average daily and maximum daily doses of aspirin and greater doses of aspirin on the first four days of the antecedent illness (median, 25.1 mg/kg; 33.0 mg/kg; and 65.4 mg/kg; respectively) than did controls (median, 14.5 mg/kg; 19.0 mg/kg; and 27.0 mg/kg; respectively). The excess risk associated with increasing aspirin doses was due primarily to intermediate levels of dose (eg, 15 to 27 mg/kg per day) rather than higher levels (greater than 27 mg/kg per day). The dose difference between exposed case-patients and controls was greatest on days 3 and 4 of the antecedent illness.
Lipids in Silicone Rubber Valve Prostheses After Human Implantation
Authors: H. P. CHIN, EARL C. HARRISON, DAVID H. BLANKENHORN, JOVAN MOACANIN
Journal: Circulation (1971)

Fourteen prosthetic valves were obtained from human recipients at autopsy or valve replacement surgery. The silicone rubber poppets were extracted with lipid solvent and examined by thin-layer chromatography, infrared absorption spectroscopy, and phosphorus analysis. The significant findings were: (1) No phospholipid was present in any of the valves; neither was there any protein. (2) The relative content of cholesterol, cholesteryl ester, fatty acid, and triglyceride varied widely. (3) Residual uncured silicone polymers were found in all valves; in one patient these appeared to combine with lipid and form a component with unusual chromatographic behavior.
Advances in Heart Disease
Authors: Raymond Harris
Journal: JAMA (1978)

Many clinical cardiologists and others concerned with cardiovascular research encounter difficulty and even frustration attempting to keep abreast of developments while engaged in a busy practice or specialized research.<i>Advances in Heart Disease</i>, presenting a balanced, comprehensive analysis of the most recent advances in patient care, practice, research, and theory, is, therefore, a welcome addition to the avalanche of cardiovascular books that pour from the presses. It emphasizes relevant concepts and principles pertinent to the practice of modern cardiology and can assist the clinical cardiologist in reassessing his own brand of cardiology. Although this book is a by-product of a symposium on clinical cardiology, it is usually well edited and organized. The chapters, carefully integrated and built sequentially on a crucial body of information, afford a balanced overview of each subject and enable the reader to use this material in practice and to acquire greater familiarity with these advances. The
External and internal validity in clinical trials
Authors: P. Sedgwick
Journal: BMJ (2012)

<h3>Background and objectives</h3> Bioelectrical impedance analysis (BIA) devices can help assess volume overload in patients receiving maintenance peritoneal dialysis. However, the effects of BIA on the short-term hard end points of peritoneal dialysis lack consistency. This study aimed to test whether BIA-guided fluid management could improve short-term outcomes in patients on peritoneal dialysis. <h3>Design, setting, participants, &amp; measurements</h3> A single-center, open-labeled, randomized, controlled trial was conducted. Patients on prevalent peritoneal dialysis with volume overload were recruited from July 1, 2013 to March 30, 2014 and followed for 1 year in the initial protocol. All participants with volume overload were 1:1 randomized to the BIA-guided arm (BIA and traditional clinical methods) and control arm (only traditional clinical methods). The primary end point was all-cause mortality and secondary end points were cardiovascular disease mortality and technique survival. <h3>Results</h3> A total of 240 patients (mean age, 49 years; men, 51%; diabetic, 21%, 120 per group) were enrolled. After 1-year follow-up, 11(5%) patients died (three in BIA versus eight in control) and 21 patients were permanently transferred to hemodialysis (eight in BIA versus 13 in control). The rate of extracellular water/total body water decline in the BIA group was significantly higher than that in the control group. The 1-year patient survival rates were 96% and 92% in BIA and control groups, respectively. No significant statistical differences were found between patients randomized to the BIA-guided or control arm in terms of patient survival, cardiovascular disease mortality, and technique survival (<i>P</i>&gt;0.05). <h3>Conclusions</h3> Although BIA-guided fluid management improved the fluid overload status better than the traditional clinical method, no significant effect was found on 1-year patient survival and technique survival in patients on peritoneal dialysis.
Poly(2-methacryloyloxyethyl phosphorylcholine) grafting and vitamin E blending for high wear resistance and oxidative stability of orthopedic bearings
Authors: Masayuki Kyomoto, Toru Moro, Shihori Yamane, Kenichi Watanabe, Masami Hashimoto, Yoshio Takatori, Sakae Tanaka, Kazuhiko Ishihara
Journal: Biomaterials (2014)
The effects of smoking on the health and sleep of sportswomen.
Authors: P. Bale, M. White
Journal: British Journal of Sports Medicine (1982)

This survey studied the health and sleeping patterns of 92 physical education and sports science students highly involved in sport. A strong correlation was found between smoking and various complaints of ill health as well as between smoking and sleep duration and quality of sleep. The results suggest that there is a strong relationship between the constituents of tobacco smoke and poor sleeping habits.
Segmental Colitis Associated with Diverticula: A 7-Year Follow-Up Study
Authors: G. Imperiali, M. Terpin, G. Meucci, A. Ferrara, G. Minoli
Journal: Endoscopy (2006)

Background and Study Aims: We performed a long-term follow-up study of patients with segmental colitis associated with diverticula, in order to clarify the natural history of this disease. Patients and Methods: We identified 15 patients who were diagnosed as having segmental colitis associated with diverticula during 1997. We assessed these patients by means of periodic follow-up visits from 1997 to 2004. Results: Eight of the 15 patients had no clinical recurrence during follow-up. Five patients had sporadic recurrences that were clinically mild (on average, one in 5 years), which responded to topical therapy and often to self-medication. Only two patients were diagnosed during the follow-up period as having Crohn's disease; notably, these were the only patients who did not have hematochezia as the main symptom at onset. Conclusion: The course of this disease appears to be substantially benign.
MUM1 expression does not differentiate primary cutaneous anaplastic large-cell lymphoma and lymphomatoid papulosis
Authors: B. Hernandez-Machin, R.F. de Misa, T. Montenegro, J.C. Rivero, J. Bastida, C. Febles, E. Pique
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Sir, We read with interest the article entitled ‘MUM1 expression in cutaneous CD30+ lymphoproliferative disorders: a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large‐cell lymphoma’ recently published in the British Journal of Dermatology.1 We have been reviewing and studying the cutaneous CD30+ lymphoproliferative disorders of the Canarian Primary Cutaneous Lymphoma Network. Clinical, demographic, morphological and immunohistochemical data were obtained from 21 selected cases. Futhermore, we examined the expression of MUM1 in these disorders to assess its value as a diagnostic marker, because of the two papers published recently with conflicting results.1, 2 Twenty‐one cases: 13 lymphomatoid papulosis (LyP), seven cutaneous anaplastic large‐cell lymphoma (C‐ALCL) and one secondary cutaneous anaplastic large‐cell lymphoma (S‐ALCL) were selected from the database of the Canarian Primary Cutaneous Lymphoma Network. All of them met diagnostic criteria according to the WHO–EORTC classification for cutaneous lymphomas.3 Clinical, demographic, morphological and immunohistochemical data were reviewed and studied. Formalin‐fixed, paraffin‐embedded specimens were analysed by immunohistochemistry with a monoclonal antibody against MUM1 (Dako, Glostrup, Denmark).