tbuckley/cabot-search huggingface dataset:
Safety of Minibikes
Authors: John Amidon
Journal: JAMA (1975)

<h3>To the Editor.—</h3> Contrary to the impression cast by the articles in the April 7, 1975 issue of<i>JAMA</i>, "About the Cover...," "Minibike and Motorcycle Accidents in Adolescents: A New Epidemic," and "Defusing the Two-Wheeled Menace" (232:15, 55, 58, 1975), minibike riding has a high social value, and minibike use should be encouraged. The<i>American Illustrated Medical Dictionary</i>(ed 22) defines "epidemic" as "attacking many people in any region at the same time; widely diffused and rapidly spreading." Given this definition, the authors fail to support their claims that minibike injuries are epidemic. Twenty-one cases taken from a one-state area is a totally unrepresentative sample to be used as a basis for extrapolation to the country as a whole. In real numbers, 21 cases over three years, more than one third of which involved minor injuries, constitute an outstanding safety record. The figures cited from the New Jersey Department of
Snoring and its treatment.
Authors: S Jennett
Journal: BMJ (1984)

Snoring and its treatment "Snore events" are defined in a recent study as inspiratory, raspy, snortlike sounds, and nine habitual snorers each emitted 500 to 1300 such noises nightly.'No one who has slept beside a snorer needs any definition for their recog- nition, or any convincing that a remedy would be welcome.And one is on offer: continuous positive airway pressure applied through the nose-nasal CPAP.Snoring occurs when an excessive inspiratory effort is overcoming obstruction of the upper airway.The walls of the oropharynx tend to collapse with the generalised muscular relaxation which is particvilarly profound in rapid eve novement sleep.Altered drives to breathing result in a
Prevention of Diabetes-Induced Microangiopathy by Human Tissue Kallikrein Gene Transfer
Authors: Costanza Emanueli, Maria B. Salis, Alessandra Pinna, Tiziana Stacca, Anna F. Milia, Alessandra Spano, Julie Chao, Lee Chao, Luigi Sciola, Paolo Madeddu
Journal: Circulation (2002)

Background— Microvascular insufficiency represents a major cause of end-organ failure among diabetics. Methods and Results— In streptozotocin-induced diabetic mice, we evaluated the potential of human tissue kallikrein (hTK) gene as a sole therapy against peripheral microangiopathy. Local delivery of hTK gene halted the progression of microvascular rarefaction in hindlimb skeletal muscle by inhibiting apoptosis, thus ensuring an improved hemodynamic recovery in case of supervening vascular occlusion. The curative action of hTK did not necessitate insulin supplementation. Application of gene therapy at a stage of established microangiopathy stimulated vascular regeneration. Conclusions— Our studies indicate that hTK may represent a useful tool for the treatment of microvascular complications in diabetics.
Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly
Authors: K YAMAMOTO, K TAKESHITA, T KOJIMA, J TAKAMATSU, H SAITO
Journal: Cardiovascular Research (2004)

Thrombotic cardiovascular diseases increase in incidence in the elderly, a tendency dependent on the age-related changes in vascular and hemostatic systems that include platelets, coagulation, and fibrinolytic factors as well as in the endothelium. The hypercoagulability of and advanced sclerotic changes in the vascular wall may contribute to the increased incidence of thrombosis in the elderly. One of the important key genes for aging-associated thrombosis is plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis. The expression of PAI-1 is not only elevated in the elderly but also significantly induced in a variety of pathologies associated with the process of aging. These conditions include obesity, insulin resistance, emotional stress, immune responses, and vascular sclerosis/remodeling. Several cytokines and hormones, including tumor necrosis factor-alpha, transforming growth factor-beta, angiotensin II, and insulin, positively regulate the gene expression of PAI-1. The recent epidemic in obesity with aging in the industrialized society may heighten the risk for thrombotic cardiovascular disease because adipose tissue is a primary source of PAI-1 and cytokines. Emotional or psychosocial stress and inflammation also cause the elevated expression of PAI-1 in an age-specific pattern. Thus, PAI-1 could play a key role in the progression of cardiovascular aging by promoting thrombosis and vascular (athero)sclerosis. Further studies on the genetic mechanism of aging-associated PAI-1 induction will be necessary to define the basis for cardiovascular aging in relation to thrombosis.
Kidney failure: aims for the next 10 years and barriers to success
Authors: Giuseppe Remuzzi, Ariela Benigni, Fredric O Finkelstein, Jean-Pierre Grunfeld, Dominique Joly, Ivor Katz, Zhi-Hong Liu, Toshio Miyata, Norberto Perico, Bernardo Rodriguez-Iturbe, Luca Antiga, Franz Schaefer, Arrigo Schieppati, Robert W Schrier, Marcello Tonelli
Journal: The Lancet (2013)
Quantitative Three-Dimensional Analysis of the Intracellular Trafficking of Plasmid DNA Transfected by a Nonviral Gene Delivery System Using Confocal Laser Scanning Microscopy
Authors: H Akita, R Ito, I.A Khalil, S Futaki, H Harashima
Journal: Molecular Therapy (2004)

Since endosomal escape and the nuclear delivery of plasmid DNA (pDNA) constitute major barriers for transgene expression, a quantitative evaluation of intracellular trafficking of pDNA would be highly desirable in terms of optimizing a nonviral gene delivery system. In the present study, a novel strategy is proposed for the quantification of rhodamine-labeled pDNA in endosomes/lysosomes, cytosol, and nucleus. Endosomes/lysosomes and nucleus were stained with LysoSensor DND-189 and Hoechst 33258, respectively, to distinguish them from the cytosol. The pixel areas of the clusters derived from the rhodamine were used as an index for the amount of pDNA. This approach was applied to the analysis of the intracellular trafficking of pDNA transfected by LipofectAMINE PLUS, stearylated octaarginine (STR-R8), and octaarginine (R8). In the case of R8, most of the pDNA was trapped by endosomes/lysosomes. STR-R8 exhibited endosomal escape followed by nuclear translocation in a time-dependent manner. LipofectAMINE PLUS was the most effective in rapidly delivering pDNA to the nucleus as well as the cytosol. These differences in the intracellular trafficking of pDNA correlated well with the transgene expression. Therefore, this method enables the quantitative analysis of the intracellular pharmacokinetics of pDNA and promises to provide useful information for optimizing nonviral gene delivery systems.
Providing intensive care
Authors: D W Ryan
Journal: BMJ (1996)

The recent deaths of two severely ill patients being transferred from one hospital to another in search of specialised intensive care have caused public alarm in Britain and have raised questions about the resourcing and organisation of adult and paediatric intensive care.

The British Paediatric Association has repeatedly pointed to the apparent shortfall in paediatric intensive care beds,1 2 but to seemingly little effect. The fact that major paediatric centres often have to refuse admission negates the association's recommendation that sick children be provided with specialist nursing and medical care. Shann points out that twice as many children per head of population are admitted to intensive care in Australia and the United …
Association between the TaqIB polymorphism in the cholesteryl ester transfer protein gene locus and plasma lipoprotein levels in familial hypercholesterolemia
Authors: Rafael Carmena-Ram[oacute]n, Juan F. Ascaso, Jos[eacute] T. Real, Gloria N[aacute]jera, Jos[eacute] M. Ordov[aacute]s, Rafael Carmena
Journal: Metabolism (2001)
Idiopathic Cellulitis of Facial Soft Tissue
Authors: Joel M. Salon
Journal: JAMA (1988)

To the Editor.—  In the March 11 issue of JAMA , Dr Deutsch 1 addressed a question to the QUESTIONS AND ANSWERS section. His letter described a 25-yearold woman who had a history of pain and swelling of the right side of her face. In addition, this patient had moderate trismus that prevented complete opening of her mouth. The described clinical workup was appropriate but not complete.  The response by Dr Klein 1 addressed several possible reasons for this patient's condition. However, these are not the most likely causes for this patient's symptoms and clinical findings.  This patient may have an internal derangement of the temporomandibular joint meniscus or even a perforation of the meniscus. Appropriate workup of this condition would include a complete examination of the temporomandibular joint, noting specific muscle pain and measurement of limitation of mandibular opening. Based on the results of the clinical examination, appropriate radiographic studies might
Structure and potential mutagenicity of new hydantoin products from guanosine and 8-oxo-7,8-dihydroguanine oxidation by transition metals.
Authors: Cynthia J Burrows, James G Muller, Olga Kornyushyna, Wenchen Luo, Victor Duarte, Michael D Leipold, Sheila S David
Journal: Environmental Health Perspectives (2002)

In vitro work in this laboratory has identified new DNA lesions resulting from further oxidation of a common biomarker of oxidative damage, 8-oxo-7,8-dihydroguanine (OG). The major product of oxidation of OG in a nucleoside, nucleotide, or single-stranded oligodeoxynucleotide using metal ions that act as one-electron oxidants is the new nucleoside derivative spiroiminodihydantoin (Sp). In duplex DNA an equilibrating mixture of two isomeric products, guanidinohydantoin (Gh) and iminoallantoin (Ia), is produced. These products are also formed by the overall four-electron oxidation of guanosine by photochemical processes involving O(2). DNA template strands containing either Sp or Gh/Ia generally acted as a block to DNA synthesis with the Klenow exo(-) fragment of pol I. However, when nucleotide insertion did occur opposite the lesions, only 2'-deoxyadenosine 5-triphosphate and 2'-deoxyguanine 5-triphosphate were used for primer extension. The Escherichia coli DNA repair enzyme Fpg was able to remove the Sp and Gh/Ia lesions from duplex DNA substrates, although the efficiency was depended on the base opposite the lesion.
Conscientious Objection to Abortion
Authors: M. Wilkinson
Journal: BMJ (1972)

pressed and took from the bathroom cupboard 80 500-mg paracetamol tablets which had been bought by a relative for toothache.Immediately after taking the tablets she greatly regretted her action and had no wish to die.For 24 hours her clinical condition was excellent and she repeatedly asked to go home.On the second day in hospital acute hepatic failure developed together with a severe oliguria with the characteristics of acute tubular necrosis.She died shortly afterwards and gross hepatic and renal damage were found at necropsy.This tragic case emphasizes some of the dangers of self-poisoning with paracetamol.There is no recognized effective treatment for the toxic effects of paracetamol once the drug is absorbed.2-4The very minimal initial symptoms ensure that medical advice is not sought at a stage when gastric lavage might prevent further absorption.There is a general misconception that paracetamol is a safe drug and for this reason may be chosen in preference to aspirin in attempted suicide.It would therefore seem reasonable to suggest that paracetamol should become a prescription drug instead of being freely available in large quantities to those who wish only to make a suicidal gesture.-Weare, etc.,
Role of protein kinase C- or RhoA-induced Ca2+ sensitization in stretch-induced myogenic tone
Authors: D Yeon
Journal: Cardiovascular Research (2002)

Objective: It has been suggested that Ca2+ sensitization mechanisms might contribute to myogenic tone. However, specific mechanisms have yet to be fully identified. Therefore, we investigated the role of protein kinase C (PKC)- or RhoA-induced Ca2+ sensitization in myogenic tone of the rabbit basilar vessel. Methods: Myogenic tone was developed by stretch of rabbit basilar artery. Fura-2 Ca2+ signals, contractile responses, PKC immunoblots, translocation of PKC and RhoA, and phosphorylation of myosin light chains were measured. Results: Stretch of the resting vessel evoked a myogenic contraction and an increase in the intracellular Ca2+ concentration ([Ca2+]i) only in the presence of extracellular Ca2+. Stretch evoked greater contraction than high K+ at a given [Ca2+]i. The stretch-induced increase in [Ca2+]i and contractile force were inhibited by treatment of the tissue with nifedipine, a blocker of voltage-dependent Ca2+ channel, but not with gadolinium, a blocker of stretch-activated cation channels. The PKC inhibitors, H-7 and calphostin C, and a RhoA-activated protein kinase (ROK) inhibitor, Y-27632, inhibited the stretch-induced myogenic tone without changing [Ca2+]i. Immunoblotting using isoform-specific antibodies showed the presence of PKCα and PKCε in the rabbit basilar artery. PKCα, but not PKCε, and RhoA were translocated from the cytosol to the cell membrane by stretch. Phosphorylation of the myosin light chains was increased by stretch and the increased phosphorylation was blocked by treatment of the tissue with H-7 and Y-27632, respectively. Conclusions: Our results are consistent with important roles for PKC and RhoA in the generation of myogenic tone. Furthermore, enhanced phosphorylation of the myosin light chains by activation of PKCα and/or RhoA may be key mechanisms for the Ca2+ sensitization associated myogenic tone in basilar vessels.
The Normal QRS Loop Observed Three Dimensionally Obtained with the Frank Precordial System
Authors: GEORGE E. SEIDEN
Journal: Circulation (1957)

By means of a relatively orthogonal lead system combined with the use of an electronic resolver, 3-dimensional QRS loops of normal individuals have been seen broadside in 2 dimensions after proper rotation. QRS loops so visualized have been studied by certain quantitative measurements which it is hoped may be of assistance in distinguishing normal from abnormal loops.
Abstract PR4: Regulation of the Fanconi anemia pathway by a SUMO-like delivery network
Authors: Kailin Yang, George-Lucian Moldovan, Patrizia Vinciguerra, Junko Murai, Shunichi Takeda, Alan D. D'Andrea
Journal: Cancer Research (2011)

Abstract Objective: The USP1/UAF1 complex is a critical regulator of the FA pathway. The USP1/UAF1 complex deubiquitinates the Fanconi Anemia proteins, FANCD2/FANCI, and promotes homologous recombination and DNA crosslink repair. USP1/UAF1 also deubiquitinates PCNA-Ub, a key player in translesion DNA synthesis. This step requires the PCNA interacting protein, hELG1. The goal of our study is to identify the molecular mechanism of USP1/UAF1 complex targeting to the FANCD2-Ub/FANCI-Ub heterodimer and tothePCNA-Ub/hELG1 complex. Methods: Using bioinformatics, we identified a tandem repeat of SUMO-like domains (SLD) in the C-terminus of UAF1 (SLD1 and SLD2). A SLD sequence is a domain of approximately 100 amino acids with significant sequence identity and homology to the small ubiquitin-like modifier (SUMO). We tested the function of a mutant form of UAF1 lacking the SLD2 domain. Interestingly, this mutant UAF1 protein bound and stimulated the deubiquitinating activity of USP1 but failed to complement UAF1 knockout DT40 cells. We then discovered a SUMO-like-domain interacting motif (SIM) on both FANCI and hELG1. We therefore investigated the functional importance of the SLD-SIM interaction in regulating the Fanconi anemia pathway. Results: The SLD2 domain of UAF1 is dispensable for activating USP1 in vitro. However, complementation analyses using UAF1 knockout DT40 cells showed that the SLD2 is critical for the deubiquitination of USP1 substrates in vivo and for homologous recombination. We demonstrated that the SLD2 domain of UAF1 binds directly to the SIM sequence on FANCI and hELG1, and thereby regulates the deubiquitination of FANCD2-Ub and PCNA-Ub respectively. Disruption of these SLD-SIM interactions blocked the deubiquitination of FANCD2-Ub and/or PCNA-Ub, rendering cells DNA repair deficient. We also modeled the 3-D structure of SLD2 and identified critical residues involved in SLD-SIM interaction. Conclusions: Our study demonstrates that unique SLD-SIM interactions mediate the targeting of the USP1/UAF1 deubiquitinating complex to its monoubiquitinated substrates, FANCD2/FANCI and hELG1/PCNA, and thereby coordinate homologous recombination. This is a novel mechanism of DNA repair regulation, and it may have relevance to other DNA repair pathways. The SLD-SIM interaction sites are potential drug target sites for agonists or antagonists of the FA pathway. They may be useful in screening drugs for the treatment of FA patients and cancer patients from the general (non-FA) population. This abstract is also presented as Poster B38. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR4.
Doctors and patients don't agree: cross sectional study of patients' and doctors' perceptions and assessments of disability in multiple sclerosis
Authors: P M Rothwell, Z McDowell, C K Wong, P J Dorman
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To compare the judgments of clinicians on which domains of health in the short form questionnaire (SF-36) would be most important to patients with multiple sclerosis with the opinions of patients themselves; to compare assessment of physical disability in multiple sclerosis by a clinician using Kurtzke9s expanded disability status scale and a non-clinically qualified assistant using the Office of Population Census and Surveys9 (OPCS) disability scale with self assessment of disability and other domains of health related quality of life by patients using the SF-36 and the EuroQol questionnaire; and to compare the scores of patients for each domain of the SF-36 with control data matched for age and sex. <b>Design:</b> Cross sectional study. <b>Setting:</b> Clinical department of neurology, Edinburgh. <b>Subjects:</b> 42 consecutive patients with multiple sclerosis attending a neurology outpatient clinic for review or a neurology ward for rehabilitation. <b>Main outcome measures:</b> Scores on the SF-36; EuroQol; Kurtzke9s expanded disability status scale; the OPCS disability scale. <b>Results:</b> Patients and clinicians disagreed on which domains of health status were most important (χ<sup>2</sup>=21, df=7, P=0.003). Patients9 assessment of their physical disability using the physical functioning domain of the SF-36 was highly correlated with the clinicians9 assessment (<i>r</i>=-0.87, P&lt;0.001) and the non-clinical assessment (<i>r</i>=-0.90, P&lt;0.001). However, none of the measures of physical disability correlated with overall health related quality of life measured with EuroQol. Quality of life correlated with vitality, general health, and mental health in the SF-36, each of which patients rated as more important than clinicians and for each of which patients scored lower than the controls. <b>Conclusions:</b> Patients with multiple sclerosis, and possibly those with other chronic diseases, are less concerned than their clinicians about physical disability in their illness. Clinical trials in multiple sclerosis should assess the effect of treatment on the other elements of health status that patients consider important, which are also affected by the disease process, are more closely related to overall health related quality of life, and may well be adversely affected by side effects of treatment. <h3>Key messages</h3> Patients can accurately assess their own physical disability Physical disability may not always be the main determinant of overall health related quality of life Patients and clinicians differ in their assessments of the relative importance of different elements of health related quality of life The opinions of patients should be taken into account in the selection of outcome measures for clinical trials
P2-128: Sequence dependant antiproliferative effect of cytotoxic drugs and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer cell lines (NCI-H1975).
Authors: Kyu-Sik Kim, Ju-Yeon Jeong, Mi-Ran Kim, Jung-Hwan Lim, Dong-Ryeol Chae, Gye-Jung Cho, Jin-Young Ju, In-Jae Oh, Yu-Il Kim, Sung-Chul Lim, Young-Chul Kim, Kyung-Ok Park
Journal: Journal of Thoracic Oncology (2007)
Environmental Lead Exposure and Progression of Chronic Renal Diseases in Patients without Diabetes
Authors: Ja-Liang Lin, Dan-Tzu Lin-Tan, Kuang-Hung Hsu, Chun-Chen Yu
Journal: New England Journal of Medicine (2003)

Previous research suggests that environmental lead exposure correlates with age-related decreases in renal function.Two hundred two patients with chronic renal insufficiency (indicated by a serum creatinine level between 1.5 mg per deciliter and 3.9 mg per deciliter) who had a normal total-body lead burden and no history of exposure to lead were observed for 24 months. After the observation period, 64 subjects with an elevated body lead burden were randomly assigned to the chelation control groups. For three months, the patients in the chelation group received lead-chelation therapy with calcium disodium EDTA, and the control group received placebo. During the ensuing 24 months, repeated chelation therapy was administered weekly to 32 patients with high-normal body lead burdens (at least 80 microg but less than 600 microg) unless on repeated testing the body lead burden fell below 60 microg; the other 32 patients served as controls and received weekly placebo infusions for 5 weeks every 6 months. The primary end point was an increase in the serum creatinine level to 1.5 times the base-line value during the observation period. A secondary end point was the change in renal function during the intervention period.The primary end point occurred in 24 patients during the observation period; the serum creatinine levels and body lead burden at base line were the most important risk factors. The glomerular filtration rate improved significantly by the end of the 27-month intervention period in patients receiving chelation therapy: the mean (+/-SD) change in the glomerular filtration rate in the patients in the chelation group was 2.1+/-5.7 ml per minute per 1.73 m2 of body-surface area, as compared with -6.0+/-5.8 ml per minute per 1.73 m2 of body-surface area in the controls (P<0.001). The rate of decline in the glomerular filtration rate in the chelation group was also lower than that in the controls during the 24-month period of repeated chelation therapy or placebo.Low-level environmental lead exposure may accelerate progressive renal insufficiency in patients without diabetes who have chronic renal disease. Repeated chelation therapy may improve renal function and slow the progression of renal insufficiency.
Health-Services Research and Innovations in Health-Care Delivery
Authors: Charles E. Lewis
Journal: New England Journal of Medicine (1977)

Members of the Institute of Medicine were asked to list the most important innovations in the health-care system for the past quarter century, and to identify health-services researchers who might be recognized by some prize or award. There was considerable difficulty in identifying such innovations. A large number of investigators were named as health-services researchers deserving commendation, but only a few received more than two or three votes. There was little evidence of linkage between the innovations described and the work for which investigators were nominated for recognition. There is little reason to expect such research to produce major alterations in the system, since these alterations are linked to changes in the values and expectations of society. However, the research may of some value in documenting the effects (or lack thereof) of proposed changes and also promote if not create change.