tbuckley/cabot-search huggingface dataset:
A New Series of Small Molecular Weight Compounds Induce Read Through of All Three Types of Nonsense Mutations in the ATM Gene
Authors: Liutao Du, Michael E Jung, Robert Damoiseaux, Gladys Completo, Francesca Fike, Jin-Mo Ku, Shareef Nahas, Cijing Piao, Hailiang Hu, Richard A Gatti
Journal: Molecular Therapy (2013)

Chemical-induced read through of premature stop codons might be exploited as a potential treatment strategy for genetic disorders caused by nonsense mutations. Despite the promise of this approach, only a few read-through compounds (RTCs) have been discovered to date. These include aminoglycosides (e.g., gentamicin and G418) and nonaminoglycosides (e.g., PTC124 and RTC13). The therapeutic benefits of these RTCs remain to be determined. In an effort to find new RTCs, we screened an additional ~36,000 small molecular weight compounds using a high-throughput screening (HTS) assay that we had previously developed and identified two novel RTCs, GJ071, and GJ072. The activity of these two compounds was confirmed in cells derived from ataxia telangiectasia (A-T) patients with three different types of nonsense mutation in the ATM gene. Both compounds showed activity comparable to stop codons (TGA, TAG, and TAA) PTC124 and RTC13. Early structure-activity relationship studies generated eight active analogs of GJ072. Most of those analogs were effective on all three stop codons. GJ071 and GJ072, and some of the GJ072 analogs, appeared to be well tolerated by A-T cells. We also identified another two active RTCs in the primary screen, RTC204 and RTC219, which share a key structural feature with GJ072 and its analogs.
A Rib Belt for Shoulder Immobilization
Authors: Heinrich Lamm
Journal: JAMA (1965)

<h3>To the Editor:—</h3> Often one has to immobilize a patient's shoulder joint in adduction after reduction of dislocation, in certain fractures near the head of the humerus, after certain operations on or near the shoulder joint, and occasionally for a few days after radical mastectomy. Conventional methods of immobilization have drawbacks. Bandages and swathes do not stay in place well. In order to apply circular bandages or tapes on an anesthetized patient, one has to pull half his trunk off the table and support his chest. This is difficult for everyone, especially if the patient vomits. Adhesive may irritate the skin, and its removal hurts. Of late I have fastened the humerus to the chest by a nonelastic rib belt, as shown in the Figure. This rib belt is readily available. It fixes the arm well. If one puts it under the patient's chest before operation or reduction, one can
Seronegative spondarthritis associated with Takayasu's arteritis.
Authors: M Magaro', L Altomonte, L Mirone, A Zoli, G Corvino
Journal: Annals of the Rheumatic Diseases (1988)

A young woman presented with an aortic arch syndrome a few years after the onset of ankylosing spondylitis. Tissue typing showed HLA-B27. The possibility of an association between ankylosing spondylitis and Takayasu9s arteritis is suggested.
Lack of association between PADI4 and functional severity in Japanese rheumatoid arthritis patients
Authors: K Nishimoto, K Ikari, T Mochizuki, T Tomatsu, Y Toyama, M Hara, H Yamanaka, N Kamatani, S Momohara
Journal: Annals of the Rheumatic Diseases (2007)

Clinical presentation of rheumatoid arthritis (RA) varies from mild deformity of small joints to mutilating severe arthritis causing remarkable functional disorder and restriction of daily life activities. Prediction of disease outcome may allow better targeting of aggressive treatment. Recently, anti-cyclic citrullinated peptide antibody (anti-CCP) has been reported to be associated with disease outcomes.1–5 Peptidylarginine deiminase type 4 ( PADI4 ), encoding citrullinating enzyme, was identified as one of the RA susceptibility genes and was also reported to be associated with the level of anti-CCP in RA patients.6 These findings suggest the hypothesis that PADI4 determines disease severity of RA as well as its susceptibility. Our aim was to investigate the association between …
The potential of mannosylated chitosan microspheres to target macrophage mannose receptors in an adjuvant-delivery system for intranasal immunization
Authors: Hu-Lin Jiang, Mi Lan Kang, Ji-Shan Quan, Sang Gyun Kang, Toshihiro Akaike, Han Sang Yoo, Chong-Su Cho
Journal: Biomaterials (2008)
Significance of Pulmonary Elastic and Viscous Resistance in Orthopnea
Authors: R. M. CHERNIACK, T. E. CUDDY, J. B. ARMSTRONG
Journal: Circulation (1957)

The mechanical properties of the lungs were measured in the sitting and supine positions in 5 normal subjects and in 5 patients with orthopnea due to congestive heart failure. The patients had higher elastic and viscous resistances in the sitting position. Recumbency increased both resistances in both groups but there was a disproportionate increase in the viscous resistance of the patients. This increase was most marked in late expiration and early inspiration. The significance of these findings to orthopnea is discussed.
Microalbuminuria in chronic obstructive lung disease. Consider coexistent disease.
Authors: R C Horton
Journal: BMJ (1993)

<h3>Background</h3> Kidney tubular secretion is an essential mechanism for clearing many common antihypertensive drugs and other metabolites and toxins. It is unknown whether novel measures of tubular secretion are associated with adverse events (AEs) during hypertension treatment. <h3>Methods</h3> Among 2089 SPRINT (Systolic Blood Pressure Intervention Trial) participants with baseline eGFR &lt;60 ml/min per 1.73 m<sup>2</sup>, we created a summary secretion score by averaging across the standardized spot urine-to-plasma ratios of ten novel endogenous tubular secretion measures, with lower urine-to-plasma ratios reflecting worse tubular secretion. Multivariable Cox proportional hazards models were used to evaluate associations between the secretion score and risk of a composite of prespecified serious AEs (hypotension, syncope, bradycardia, AKI, electrolyte abnormalities, and injurious falls). The follow-up protocol for SPRINT routinely assessed two laboratory monitoring AEs (hyperkalemia and hypokalemia). <h3>Results</h3> Overall, 30% of participants experienced at least one AE during a median follow-up of 3.0 years. In multivariable models adjusted for eGFR and albuminuria, lower (worse) secretion scores at baseline were associated with greater risk of the composite AE outcome (hazard ratio per 1-SD lower secretion score, 1.16; 95% confidence interval, 1.04 to 1.27). In analyses of the individual AEs, lower secretion score was associated with significantly greater risk of AKI, serious electrolyte abnormalities, and ambulatory hyperkalemia. Associations were similar across randomized treatment assignment groups. <h3>Conclusion</h3> Among SPRINT participants with CKD, worse tubular secretion was associated with greater risk of AEs, independent of eGFR and albuminuria.
Vibrio vulnificus and Pulmonary Infection
Authors: Ramesh Sabapathi
Journal: Annals of Internal Medicine (1988)

Letters and Corrections15 December 1988Vibrio vulnificus and Pulmonary InfectionRamesh Sabapathi, MDRamesh Sabapathi, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-12-988_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:I read with interest the article by Klontz and colleagues (1) on syndromes ofVibrio vulnificusinfections. In August 1986, a 60-year-old man with a history of alcoholism fell into the waters of the Inner Harbor in Baltimore after having a cardiopulmonary arrest. He was successfully revived and admitted to a community hospital. On his second day of hospitalization, he had a fever of 40 °C. The leukocyte count was 16 000 mm3, with a profound left shift (69 band forms). A chest roentgenogram showed infiltrates in his right lower lobe and left upper lobe. He also...Reference1. KlontzLiebSchreiberJanowskiBaldyGunn KSMHLR. Syndromes of Vibrio vulnificus infections: clinical and epidemiologic features in Florida cases, 1981-1987. Ann Intern Med. 1988;109:318-23. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Columbia, MD 21044 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNew Atypical Manifestations and Prognostic Factors of Vibrio vulnificus Infection: a 10-Year Retrospective StudyThe human pathogenic vibrios – A public health update with environmental perspectives 15 December 1988Volume 109, Issue 12Page: 988-989KeywordsAlcoholismFeversHeartHospitalizationsPulmonary diseasesThoraxVibrio Issue Published: 15 December 1988 PDF DownloadLoading ...
Reliance of 111 on non-clinical staff has increased pressure on emergency departments, MPs say
Authors: G. Iacobucci
Journal: BMJ (2013)

The 111 urgent care telephone hotline has failed to relieve the pressure on accident and emergency departments in England since its introduction in April and needs to be remodelled to give greater priority to early clinical assessment, MPs have concluded.

In its report on urgent and emergency care services, published this week,1 the House of Commons health select committee said that the reliance on non-clinically trained staff to triage 111 calls had led to some patients attending emergency departments unnecessarily.

The inquiry has been prompted by growing fears about the strain being placed on emergency departments and comes after the College of Emergency Medicine warned that problems with the new urgent care hotline had contributed to the “severe pressure” on emergency departments.2 3

MPs concluded that NHS 111 was introduced “without a sufficiently …
Influence of surgically induced varicocele on testicular blood flow, temperature, and histology in adult rats and dogs.
Authors: D C Saypol, S S Howards, T T Turner, E D Miller
Journal: Journal of Clinical Investigation (1981)

Varicocele had been repeatedly implicated as a cause of infertility in selected men, although neither a causal relationship nor a mechanism has been documented. The purpose of this investigation was to create a varicocele model in animals and to study the subsequent alterations in testicular physiology. Secondary dilatation of the left internal spermatic vein was achieved either by partial ligation of the left renal vein in rats and dogs or by surgical destruction of the valve of the left testicular vein in a second group of dogs. 1 mo after partial ligation in the rats and 3 mo after partial ligation or valve destruction in the dogs, testicular blood flow was measured using Strontium 85 (SR-85)-labeled microspheres (15 +/- 1.1 micrometer). Intratesticular temperature was measured with a Bailey needle probe thermometer and biopsies were obtained for histologic sections. Mean testicular blood flow in milliliters per minute per 100 g was significantly greater in the partially ligated rats; right testis control 26 +/- 2, left testis control 24 +/- 2 compared to right testis experimental 35 +/- 3, left testis experimental 35 +/- 4 (p less than 0.02). Dogs undergoing either partial vein ligation or valve destruction showed similar increases in mean testicular blood flow; right testis control 8 +/- 1, left testis control 8 +/- 1 vs. right testis experimental 16 +/- 3, left testis experimental 18 +/- 4 (p less than 0.01). The mean difference between intratesticular and intraperitoneal temperature in control rats was significantly higher (4.02 +/- 0.25 degrees C right testis, 3.77 +/- 0.14 degrees C left testis), than rats who underwent partial vein ligation (right testis 2.14 +/- 0.09 degrees C, left testis 2.34 +/- 0.12 degrees C) (p less than 0.001). Control dogs also had a significantly higher mean difference between intratesticular and rectal temperatures; (right testis control 3.61 +/- 0.42 degrees C, left testis control 3.60 +/- 0.40 degrees C) than the partially ligated or valve destruction dogs (right testis 2.31 +/- 0.17 degrees C, left testis 2.67 +/- 0.32 degrees C) (p less than 0.05). In addition, histologic evaluation revealed abnormalities in spermatogenesis in some of the animals. Thus, venous dilatation secondary to partial vein ligation or testicular vein valve obliteration is followed by large bilateral increases in testicular blood flow in these two species. A consequence of this increased flow is an elevation in bilateral testicular temperature, which it is postulated, leads to impaired spermatogenesis in some of the animals. In selected men varicocele may impair spermatogenesis by a similar physiologic mechanism.
Renin: A Risk Factor for Cardiovascular Disease?
Authors: A. RICHARD CHRISTLIEB
Journal: Annals of Internal Medicine (1974)

Sixty-seven of 80 patients with essential hypertension were prospectively studied for a mean 5 years. The prevalence of well-known risk factors had no apparent association with renin levels in these patients. But the incidence of cardiovascular events in patients with low plasma renin activity, measured in the supine or upright posture, was significantly lower than that in the normal- and high-renin groups combined. No cardiovascular events occurred in the low renin group; however, the data showed that patients with cardiovascular events had a higher prevalence of risk factors than those without. It is not clear whether renin activity itself is a risk factor or whether elevated renin activity is a "marker" for or consequence of other well-established risk factors. Low-renin hypertensive patients may be good risks, but, with our limited data, it seems inadvisable to withold hypertensive therapy from them.
Das festgeklemmte Gastroskop bei der Inversionsgastroskopie
Authors: P. Semler
Journal: Endoscopy (1973)

Fallbericht über einen Zwischenfall während des Inversionsmaneuvers bei der Gastroskopie, wobei das Instrument in maximaler Abwinkelung im Ösophagus steckenblieb. Das Instrument konnte in dieser Position unter Buscopan i. v. extrahiert werden.
Men and Medicine
Authors: T. M. Taylor
Journal: BMJ (1949)

ACUTE DYSPEPSIA IRCONALThe patient should avoid undue fatigue, chilling, and work which involves constant bending; but it is seldom advisable to change the patient's occupation, for this often causes more problems than are solved.Regular hours are highly desirable, and limitation of overtime duties is necessary.Dietary restriction is probably of value indefinitely, but the most important aspect of feeding is maintaining regular meals without long intervals between them.The patient is well advised to avoid fried foods of all kinds, pastries and suet, pickles and spices, curry, pepper, onions, reheated dishes, coffee, strong tea, and anything which he finds indigestible.Priority milk should be continued, and has proved to be of great value for many patients with a ready tendency to relapse.Alcohol is best omitted for six months and then allowed in strict moderation.Smoking should be restricted, or preferably stopped, but it is legitimate to allow a few cigarettes after meals, unless the patient relapses.Continued medication with antacids or atropine is not desirable, but the patient should have a supply of phenobarbitone.He should be strongly advised to rest completely at the onset of a relapse and return to the strict ulcer regime, for early treatment may abort an otherwise long and tiresome recurrence.
Beyond the negative: Political attitudes and ideologies strategically manage opportunities, too
Authors: Andrew Edward White, Steven L. Neuberg
Journal: Behavioral and Brain Sciences (2014)

Abstract Hibbing et al. use evolutionarily derived logic to suggest that political attitudes are related to responses to negative features of the environment. We suggest that the authors focus too narrowly on the negative and contend, instead, that a more comprehensive evolutionary approach focusing on people's responses to threats and opportunities will better account for variation in political attitudes.
Effects of pethidine on the newborn.
Authors: R S Brown
Journal: BMJ (1976)

Pyloric stenosis and sustained-release iron tablets SIR,-The case reported below gives an interesting and salutary warning about the possible effects of giving long-acting iron tablets to patients with a history of peptic ulceration or long-standing dyspepsia.The patient, an arthritic spinster of 74 who was known to live on a diet of cake and Maltesers, was started on treatment with Ferrogradumet C for a
A Critical Review of the Results of Lung Resection for Pulmonary Tuberculosis
Authors: B. J. Bickford, F. R. Edwards, J. R. Esplen, J. H. Gifford, O. F. Thomas, J. K. B. Waddington
Journal: Thorax (1957)

1,575 patients have had pulmonary resection performed in the treatment of tuberculosis at Aintree and Broad- green Hospitals, Liverpool.During this period, although a certain number of cases of active bi- lateral disease have been treated by thoracoplasty, resection of the affected area has been the method of choice for the surgical treatment of all types of the disease.In two previous communications (Bickford, Edwards, Esplen, Gifford, Mair, and Thomas, 1951; Bickford, Edwards, Esplen, Gifford, and Thomas, 1952) we laid down our principles for undertaking resection, and these have remained basically unchanged to date, except that our views in relation to compensatory space reduction of the thoracic cavity have crystallized in favour of corrective thoracoplasty.It is probable that during the years our indica- tions for resection have widened somewhat, as it became clear that with sufficient chemotherapeutic control, areas of lung could be removed, leaving active disease behind which might be expected to heal without severe lung damage.The changing face of tuberculosis has resulted in a considerable number of very chronic carriers being submitted to surgery, and many of these cases fall into the above group.The surgery of the caseous nodule has changed in later years with the development of long-term therapy, and a more conservative approach to these is now being taken.We still believe that a caseous nodule of over 2.5 cm. in diameter should be excised, however much chemotherapy has been given or is proposed in the future.The use of chemotherapy has so altered the scheme of treatment that surgery must be con- * Based on a paper given by one of us (F.
The Bioethicist as Public Intellectual
Authors: Kayhan P. Parsi, Karen E. Geraghty
Journal: The American Journal of Bioethics (2004)

Public intellectuals have long played a role in American culture, filling the gap between the academic elite and the educated public. According to some commentators, the role of the public intellectual has undergone a steady decline for the past several decades, being replaced by the academic expert. The most notable cause of this decline has been both the growth of the academy in the twentieth century,which has served to concentrate intellectual activity within its confines, and the changing nature of the media, which has framed the way in which information is conveyed to the public. We argue that although bioethics has developed primarily within the academic tradition and utilized the role of expert when dealing with the public, bioethicists are well suited to don the mantle of the public intellectual. Indeed, because they address issues in medicine and science of great relevance for the general public, bioethicists have a duty to revitalize the tradition of public intellectuals as a necessary complement to the important, but narrower role of the expert.
Abstract 4778: Dissecting the gender disparity of hepatocellular carcinoma: roles of HBV X protein and androgen receptor.
Authors: Yung Tuen Chiu, Irene Oi Lin Ng
Journal: Cancer Research (2013)

Abstract Hepatocellular carcinoma (HCC) is a leading cancer worldwide and especially prevalent in Southeast Asia, due to prevalent hepatitis B virus (HBV) infection. HBV-associated HCC has a male predominance, with a male-to-female ratio of about 4-5:1. HBV is a partially double-stranded DNA virus containing four overlapping open reading frames. Among them, X gene is most frequently integrated into host genome naturally and plays an important role in hepatocarcinogenesis. In male HBV carriers, the risk of HCC development is significantly increased in those with higher serum androgen and androgen receptor (AR) activity. HBV infection may, therefore, particularly cooperate with male-specific AR signalling to accelerate hepatocarcinogenesis. In this study, we hypothesized that HBx cooperated with male-specific AR signalling to enhance hepatocarcinogenesis, and natural HBx truncated mutants exerted different effects on this AR signalling. Firstly, we demonstrated that the expression of androgen receptor was significantly higher in the HCC cells when compared to the immortalized non-tumorigenic normal liver cell lines (LO2 and MIHA). Moreover, the HCC cell lines with higher metastatic potential (MHCC-97L, MHCC-97M and LM3) had a higher AR protein expression level, suggesting a role of AR in HCC development and progression. In human HBV-associated HCC tissues, we found that the natural COOH-terminal truncated HBx was more frequently detectable in HCC tumors from male than female patients (43% and 11%, respectively). Here, we also showed that the natural COOH-terminal HBx truncated mutants HBx ΔC3 (1-95 a.a) and HBx ΔC4 (1-89a.a) physically interacted with AR, indicating the possibility of HBx ΔC3 and HBx ΔC4 in regulating AR activity and the binding of HBx with AR at its N-terminal part. Furthermore, we demonstrated that HBx truncated mutants localized in the nuclear fraction, unlike the full-length HBx protein which localized in the cytoplasm. The capability of the nuclear translocation may suggest a role of the HBx truncated mutants in regulating AR transcriptional activity. In addition, androgen induced the expression of GADD45, a DNA damage-inducible gene, in HCC cells. The androgen-induced GADD45 expression was even higher with the co-expression of full-lengthen HBx protein, demonstrating a synergistic effect between HBx and AR in inducing DNA damage and genetic instability in HCC cells. Taken altogether, these findings may provide a linkage between HBx, AR signaling, genomic instability and HCC carcinogenesis Citation Format: Yung Tuen Chiu, Irene Oi Lin Ng. Dissecting the gender disparity of hepatocellular carcinoma: roles of HBV X protein and androgen receptor. [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 4778. doi:10.1158/1538-7445.AM2013-4778
324 TLR-2 ACTIVATION WITH HCV CORE AND NS3 ENHANCES PROANGIOGENIC DIFFERENTIATION OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS
Authors: F. Wolter, H.D. Nischalke, C. Luda, M. Eisenhardt, A. Glassner, B. Kramer, P. Kokordelis, T. Sauerbruch, J. Nattermann, U. Spengler
Journal: Journal of Hepatology (2012)
The Workmen's Compensation Act and the Testing of Workmen's Eyesight
Authors: Huge. E. Jones
Journal: BMJ (1901)

IN this paper I propose to deal with one side only of the sub- ject, namely, the difficulty of obtaining evidence regarding the eyesight of men previous to an accident, and the importance of such evidence in the settlement of claims.I exclude such questions as the greater liability to injury of defective eyes over sound eyes.
Successful treatment of eruptive pyoderma gangrenosum with intravenous vancomycin and mezlocillin
Authors: S. KANG, J.S. DOVER
Journal: British Journal of Dermatology (1990)

A marked exacerbation of pyoderma gangrenosum in a patient with Crohn's disease was treated with intravenous vancomycin and mezlociUin and an excellent response was observed without any notable side‐effects.
Connective tissue nevi in children: Institutional experience and review
Authors: Catherine C. McCuaig, Caridad Vera, Victor Kokta, Danielle Marcoux, Afshin Hatami, Thusanth Thuraisingam, Dominique Marton, Geneviève Fortier-Riberdy, Julie Powell
Journal: Journal of the American Academy of Dermatology (2012)