tbuckley/cabot-search huggingface dataset:
1066. Optimisation of the Tet-On System for In Vivo Electro Gene Transfer to Muscle Tissue in Mice
Authors: Pernille H. Moller, Jens Eriksen, Lluis M. Mir, Julie Gehl
Journal: Molecular Therapy (2005)

Top of pageAbstract
Aim: In vivo electric pulses delivery to muscle for gene transfer (electro gene transfer) can yield long term high levels of gene expression. The method holds great promise for safe and simple gene delivery for gene therapy. A system to regulate the expression of transferred genes is the Tet-On system, which modulates gene expression by administration of doxycycline. The transactivator rtTA induces gene expression in the presence of doxycycline while the repressor tTS inhibits gene expression in the non-induced state. We have optimised the rtTA/tTS system in vivo to minimise DNA use and improve silencing in the non-induced state.

Methods: Control of gene expression was investigated by in vivo delivery of three plasmids, one encoding the transactivator (pTet-On), one encoding the repressor (pTet-tTS), and one encoding the green fluorescent protein (GFP) under a Tet-On transactivator (rtTA) responsive promoter (ptetO-GFP). Different amounts of plasmids were co-injected in the tibialis cranialis muscle and followed by transfer into the muscle fibres by electro gene transfer.

Results & Conclusion: It was found that 1) the total amount of the injected DNA could be significantly reduced whilst maintaining local expression, 2) the non-induced basal expression of GFP could be significantly reduced by increasing the repressor/activator ratio. When using a mixture of 5 |[mu]|g of ptetO-GFP, 5 |[mu]|g of pTet-On, and 5 |[mu]|g of pTet-tTS transferred into the tibialis cranialis muscle in mice, it was possible both to limit the toxicity related to exposure of high concentrations of DNA in the muscle, improve the control of gene expression as well as reduce the consumption of DNA for experiments. Indeed the use of less DNA may lead to fewer physiological changes happening in the muscle, a particular advantage for physiological studies of the organ.
Diuretic Response to Furosemide in the Presence of Renal Insufficiency
Authors: Robert G. Muth
Journal: JAMA (1966)

DURING THE COURSE of renal insufficiency, edema frequently develops. The management of this edema offers a therapeutic challenge of somewhat greater magnitude than that met in cardiac decompensation and hepatic cirrhosis. The edema of uncomplicated cardiac failure usually responds well to the saluretic agents currently available including the organic mercurials, the carbonic anhydrase inhibitors, the benzothiadiazines, and the aldosterone antagonists. The response in hepatic cirrhosis is not quite so predictable, but is usually good. The response in renal insufficiency, however, is almost predictably poor.1  Recently, furosemide, a newly synthesized monosulfamoylanthranilic acid derivative, has been shown to be a potent diuretic agent, superior to the thiazides.2-5  We have studied the diuretic action of furosemide in a wide category of disease entities where the edema was usually resistant to prior diuretic therapy. This report concerns 22 courses of furosemide therapy in 14 patients who had renal insufficiency and in whom
ON THE ANTIGENIC PROPERTIES OF HEMOGLOBIN
Authors: M. Heidelberger, K. Landsteiner
Journal: The Journal of Experimental Medicine (1923)

Sera produced by immunization with crystalline oxyhemoglobin react species-specifically with hemoglobin solutions. Evidence is presented that in this reaction the hemoglobin itself is the active substance. Conversion of oxyhemoglobin into methemoglobin, carbon-monoxy hemoglobin, or cyanhemoglobin does not alter the response to the precipitating immune serum. Not only the hemoglobin of homologous species, but also that of other species causes inhibition in greater or less degree of the precipitin reaction.
Retained Penrose Drain Following Cholecystectomy
Authors: Bill S. McCullough
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Most authorities on biliary surgery recommend drainage following cholecystectomy, soft rubber Penrose drains preferred. These are advanced at intervals postoperatively until completely removed, usually between 7 and 14 days. Meanwhile, care is taken to prevent drain retraction back into the peritoneal cavity, and to avoid breaking the drains as they are advanced. Fortunately the retained Penrose drain following cholecystectomy is a rare complication. <h3>Report of a Case.—</h3> A 40-year-old obese multiparous woman underwent cholecystectomy, bilateral partial salpingectomy, and umbilical hernioplasty. Prior to wound closure, two small (1.27 cm) Penrose drains were placed adjacent to the bed of gallbladder and foramen of Winslow, respectively, and then drawn through a lateral stab incision, just below the 12th rib. On the second postoperative day during the first attempt to advance the drains they broke, leaving most of the drain intraperitoneally (Figure). An immediate, but unsuccessful attempt failed to retrieve the
High levels of human anti-human antibodies to adalimumab in a patient not responding to adalimumab treatment
Authors: G M Bartelds, G J Wolbink, S Stapel, L Aarden, W F Lems, B A C Dijkmans, M T Nurmohamed
Journal: Annals of the Rheumatic Diseases (2006)

Adalimumab is an effective treatment for rheumatoid arthritis. However, a substantial proportion of patients with rheumatoid arthritis either do not respond or lose their initial response.1 We report a patient who initially responded to adalimumab treatment, but in whom disease activity increased as treatment continued. We believe that this lack of response to adalimumab is probably caused by the formation of human anti-human antibodies (HAHAs).

A 69-year-old woman with rheumatoid arthritis (diagnosed in 1991) and progressive joint destruction had active disease despite treatment with methotrexate 10 mg weekly and prednisone 7.5 mg/day. Therefore, treatment with adalimumab, 40 mg every other week, was started, in combination …
Homoeopathy and the star that fell
Authors: Wendy Moore
Journal: BMJ (2007)

Some are born great, some achieve greatness, and some tragically squander greatness in a hopelessly misguided obsession, launching centuries of self delusion.

Take Samuel Hahnemann. Born in Meissen in 1755, he displayed early brilliance in languages before opting to study medicine, graduating in 1779 with a promising medical career before him. Rapidly disillusioned by the barbaric medical practices of the day, Hahnemann condemned his peers' ignorant reliance on copious bloodletting, toxic purges, and caustic enemas. By contrast Hahnemann advocated the healing effects of a sensible diet, fresh air, plentiful exercise, and routine hygiene as “the preliminary conditions of wellbeing.” His proposals for …
Pseudobullseye Sign of the Testicle
Authors: JAMES W. MELTON, CHARLES J. CHUNG, LEONIE GORDON
Journal: Clinical Nuclear Medicine (1991)

Although the finding of a central photopenic area with a rim of increased uptake of radiopharmaceutical in the scrotum has been described as the “bullseye” sign for testicular torsion, thesame finding can be seen with other lesions. When the processus vaginalis remains patent, the scrotum can serve as a “window” to pathologies of the intraperitoneal cavity. This report briefly demonstrates two scintigraphic studies that presented as “pseudobullseye” of the scrotum.
Frequency of Pregnancy-Related Venous Thromboembolism in Anticoagulant Factor-Deficient Women: Implications for Prophylaxis
Authors: Philip W. Friederich
Journal: Annals of Internal Medicine (1996)

Background: It has been reported that women with an inherited deficiency of antithrombin, protein C, or protein S have an increased risk for developing venous thromboembolic disease during pregnancy and the postpartum period. However, because the available data on risk are flawed, it is difficult to define a rational, efficacious, and safe policy about prophylaxis for venous thromboembolism in these women. Objective: To determine the frequency of venous thromboembolism during pregnancy and the postpartum period in women with heritable deficiencies of anticoagulant factors. Design: Retrospective cohort study. Setting: University outpatient clinics in the Netherlands and Italy. Participants: 129 otherwise asymptomatic female family members of patients with a history of venous thromboembolism and an established deficiency of antithrombin, protein C, or protein S. Measurements: Medical history, with specific attention to episodes of venous thromboembolism and obstetric history, was taken. The anticoagulant factor status of the study participants was determined. If a patient had an episode of venous thromboembolism, subsequent pregnancies in that patient were not analyzed. Results: Of the 129 women who participated in the study, 60 had anticoagulant factor deficiency and 69 did not. In the nondeficient group, 198 pregnancies occurred; 1 of these (0.5%) was complicated by an episode of venous thromboembolism during the postpartum period. In the deficient group, 169 pregnancies occurred; 7 of these (4.1%) were complicated by an episode of venous thromboembolism during the third trimester of pregnancy (2 pregnancies [1.2%]) and the postpartum period (5 pregnancies [3.0%]). The risk for venous thromboembolism was increased eightfold in deficient women compared with nondeficient women (hazard ratio, 8.0 [95% CI, 1.2 to 184]). Conclusions: Anticoagulant factor-deficient women have an increased risk for venous thromboembolism during pregnancy and the postpartum period. Although data from an appropriate randomized clinical trial are lacking, the frequency of venous thromboembolism seen in deficient women might justify the use of anticoagulative prophylaxis during the third trimester of pregnancy and the postpartum period.
NHS consults on new strategy to reduce carbon emissions
Authors: M. Limb
Journal: BMJ (2013)

NHS leaders in England are seeking a fresh “mandate” to speed up the greening of healthcare, warning that targets on reducing greenhouse gas emissions will not be met by current means.

Experts launching a consultation on a new sustainable development strategy for 2014-20 said that a new strategy needed to be far broader in scope and more radical than its predecessor, the NHS carbon reduction strategy of 2009.

Although reducing carbon emissions should remain a core objective, the new strategy should seek “transformational change” and foster genuinely sustainable models of care, they said.

David Nicholson, chief executive of the NHS Commissioning Board, launched the document on 29 January alongside Duncan Selbie, chief executive of Public Health England, and other senior figures.

Nicholson said, “This is an ideal moment for everyone in the NHS to come together to create a far …
TREPHINING FOR BRAIN TUMORS; REPORT OF TWO SUCCESSFUL CASES—ONE OF NINE YEARS.
Authors: JOSEPH RANSOHOFF
Journal: JAMA (1902)

Operable brain tumors are rare. Only 6 per cent. of all cases are suitable for operation. In a recent compilation by Haas<sup>1</sup>122 were tabulated. Permanent successes after operation are rare, even in the experience of such masters in this special field as Horsley, McEwen, Bergman and Keen. Therefore, every case carried to a successful issue is worthy of record. While I have trephined eight times for a supposed neoplasm, I was but twice rewarded by success. In a third case, a syphilitic thickening of the dura equivalent to a tumor formation was found. As a success from a diagnostic standpoint it is equivalent to a successful trephining for tumor. In each of these cases the tumor was in the psycho-motor area, thus again emphasizing the fact that only when in this limited field can brain tumors be recognized with any degree of certainty. My first case was operated
Qualitative assessment of coronary lesions treated with sirolimus-eluting stents: Serial intravascular ultrasound analysis from the SIRIUS trial
Authors: Shinjo Sonoda, Toru Kataoka, Yoshihiro Morino, Junya Ako, Ali Hassan, Emerson C. Perin, Robert L. Wilensky, Lowell Satler, Yasuhiro Honda, Paul G. Yock, Martin B. Leon, Jeffrey W. Moses, Peter J. Fitzgerald
Journal: Journal of the American College of Cardiology (2003)
The Treatment of Clostridium difficile Colitis
Authors: Gregory M. Caputo, Michael R. Weitekamp
Journal: JAMA (1993)

<h3>To the Editor.</h3> —We applaud the recent Editorial by Drs Spera and Farber,<sup>1</sup>which should increase awareness of the growing problem of multiply-resistant<i>Enterococcus faecium</i>. We agree that limitation of the use of antimicrobial agents that select for growth of these strains should be a major element of infection control practice. However, one of their specific recommendations deserves further comment. They state that "oral metronidazole should become the treatment of choice for colitis due to<i>Clostridium difficile</i>since it has efficacy equal to that of oral vancomycin and is much more cost-effective." We believe that metronidazole has an important role in the treatment of mildly to moderately ill patients with<i>C difficile</i>colitis. The largest prospective, randomized trial to date of metronidazole vs vancomycin for<i>C difficile</i>—associated diarrhea did show the drugs equally effective in such patients.<sup>2</sup>However, only 30% of the patients treated in that study
Resolution of obstructive sleep apnoea with growth in the Robin sequence
Authors: JL Kiely, PC Deegan, WT McNicholas
Journal: European Respiratory Journal (1998)

A 12 year old female with the Robin sequence presented with a one year history of snoring, witnessed apnoeas and daytime sleepiness. Surgery in early childhood had consisted of cleft palate repair, tonsillectomy and adenoidectomy and, later, revision palatoplasty. Overnight polysomnography (PSG) demonstrated severe obstructive sleep apnoea syndrome with an apnoea/hypopnoea index (AHI) of 49 events x h(-1), and repetitive oxygen desaturations below 50%. Nasal continuous positive airway pressure (nCPAP) effectively controlled her sleep abnormalities. After 3 yrs of nCPAP therapy, she requested discontinuation and was fully reassessed. PSG without nCPAP revealed an AHI &lt;5 events x h(-1) with no desaturations below 90% and normal sleep quality. A repeat lateral cephalometrogram showed increased mandibular length and posterior airway space and reduced soft palate length. The patient remains asymptomatic 9 months following nCPAP discontinuation. This case indicates that nasal continuous positive airway pressure is an effective nonsurgical therapy in children with obstructive sleep apnoea syndrome and the Robin sequence. It is likely that mandibular growth, increase in mandibular length and enlargement of the posterior airway space was responsible for the resolution of obstructive sleep apnoea syndrome in this case.
Reiter's Disease
Authors: P. Wood
Journal: BMJ (1946)

Background: Head and neck squamous cell carcinoma (HNSCC) has a 50% relapse rate. The tumor microenvironment has been linked to resistance of cancer cells to chemotherapy. We hypothesized that the tumor matrix proteins collagen and fibronectin play protective roles in HNSCC. Materials and Methods: We investigated the effects of collagen I, collagen IV and fibronectin on growth, 2-D and 3-D clonogenic potential, resistance to paclitaxel, apoptosis and activation of phosphoinositol-3 kinase (PI3K) in MD-1483 HNSCC cells. Results: Collagen I, collagen IV and fibronectin specifically increased the efficiency of 2-D colony formation through binding integrins α2β1 and α5β1, respectively, and provided resistance to paclitaxel-induced colony elimination and apoptosis. Collagen I, but not fibronectin, increased the efficiency of 3-D colony formation and induced resistance to paclitaxel. Activation of protein kinase-B by collagen I was necessary for the protective effect. Conclusion: These data support the potential contribution of fibronectin and collagen to chemotherapy resistance in HNSCC, with effects of collagen mediated by PI3K.
Expression and localization of the small and large delta antigens during the replication cycle of hepatitis D virus
Authors: Jaw-Ching Wu, Chih-Li Chen, Shou-Dong Lee, I-Jane Sheen, Ling-Pai Ting
Journal: Hepatology (1992)

To study the expression and localization of delta antigen during the replication cycle of hepatitis D virus, we cotransfected HuH-7 hepatoma cells with a hepatitis B virus expression plasmid and plasmids expressing the small or large delta antigen or the entire HDV genome. The transfected cells and culture medium were analyzed on double immunofluorescence staining for delta antigen and HBsAg, on Western blotting and on Northern-blot hybridization from 4 hr to 9 days after transfection. In cells transfected with the expression plasmid carrying the small delta antigen open reading frame, only the small delta antigen was expressed; it was localized in the nucleolus and was not released into the medium during the culture period. In cells transfected with the large delta antigen expression plasmid, the large delta antigen expressed was localized in the nucleolus at the initial stage; this was followed by relocalization in nucleoplasm. Finally, large delta antigen was released in HBsAg-enveloped particles within 1 day of transfection. In cells cotransfected with hepatitis B virus and hepatitis D virus expression plasmids, the small delta antigen was expressed 4 hr after transfection, whereas the large form was expressed 3 days after transfection. Expression of the large delta antigen coincided with the localization changes from nucleolar to mixed stage and, finally, to nucleoplasm and release of the hepatitis D virus particles. The large delta antigen appears to play a key role in relocalization of the delta antigen and packaging of the hepatitis D virus virions.(ABSTRACT TRUNCATED AT 250 WORDS)
Comprehensive and quantitative proteome profiling of the mouse liver and plasma
Authors: Keane K. Y. Lai, Deepak Kolippakkam, Laura Beretta
Journal: Hepatology (2008)

We report a comprehensive and quantitative analysis of the mouse liver and plasma proteomes. The method used is based on extensive fractionation of intact proteins, further separation of proteins based on their abundance and size, and high-accuracy mass spectrometry. This analysis reached a depth in proteomic profiling not reported to date for a mammalian tissue or a biological fluid, with 7099 and 4727 proteins identified with high confidence in the liver and in the corresponding plasma, respectively. This method allowed for the identification in both compartments of low-abundance proteins such as cytokines, chemokines, and receptors and for the detection in plasma of proteins in the pg/mL concentration range. This method also allowed for semiquantitation of all identified proteins. The calculated abundance scores correlated with the abundance of the corresponding transcripts for the large majority of the proteins identified in the liver. Finally, comparison of the liver and plasma datasets demonstrated that a significant number of proteins identified in the liver can be detected in plasma. These included proteins involved in complement and coagulation, in fatty acid, purine and pyruvate metabolism, in gluconeogenesis and glycolysis, in protein ubiquitination, and in insulin, interleukin-4, epidermal growth factor, and platelet-derived growth factor signaling. Conclusion: This in-depth analysis of the mouse liver and corresponding plasma proteomes provides a strong basis for investigations of liver pathobiology and biology that employ mouse models of hepatic diseases in an effort to better understand, diagnose, treat, and prevent human hepatic diseases.
Diagnostic value of scratch‐chamber test, skin prick test, histamine release and specific IgE in birch‐allergic patients with oral allergy syndrome to apple
Authors: M. Osterballe, R. Scheller, P. Stahl Skov, K. E. Andersen, C. Bindslev‐Jensen
Journal: Allergy (2003)

Background: The aim of the study was to examine the diagnostic value of skin prick test (SPT), scratch‐chamber test (SCT), histamine release (HR) and specific immunoglobulin E (IgE) in birch‐allergic patients with oral allergy syndrome to apple. Methods: Ten birch‐allergic patients with oral allergy syndrome to apple and 10 control subjects were included. All were tested with SPT, SCT, HR and specific IgE [CAP, Pharmacia, Sweden and Magic Lite (ML), ALK‐ABELLÓ, Denmark]. Results: The SPT with apple, acetone extract of apple (A72) and commercial apple extract showed sensitivities of 0.80, 0.90 and 0.10, respectively. The SCT with the same extracts showed sensitivities of 0.30, 0.50 and 0.20, respectively. The sensitivity of specific IgE to apple were 0.90 (CAP) and 0.10 (ML). The sensitivity of the HR test was 90% (A72), and 25% using the commercial extract. Conclusion: The SPT and HR test with apple and A72 showed a good diagnostic value with a sensitivity of more than 70% and a specificity of 100%. The SCT showed a poor sensitivity to apple, A72 and commercial apple extract. The ML test was not suitable in detecting specific IgE to apple compared with the CAP test. In daily practice a detailed case history about symptoms of oral allergy syndrome combined with a SPT with fresh apple peel or A72 will be useful.
Cardiorespiratory effects of D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin in the third ventricle, and in anterior hypothalamic and paraventricular areas of the rat brain
Authors: S. W RABKIN
Journal: Cardiovascular Research (1989)

Journal Article Cardiorespiratory effects of D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin in the third ventricle, and in anterior hypothalamic and paraventricular areas of the rat brain Get access SIMON W RABKIN SIMON W RABKIN From the Cardiovascular Research Laboratories, Department of Medicine, University of British Columbia, Vancouver, Canada Address for correspondence and reprints: Dr S Rabkin, Faculty of Medicine, 4500 Oak Street, Vancouver, British Columbia, Canada V6H 3N1. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 10, October 1989, Pages 904–912, https://doi.org/10.1093/cvr/23.10.904 Published: 01 October 1989 Article history Accepted: 04 May 1989 Published: 01 October 1989
Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis
Authors: X Puechal, C Miceli-Richard, O Mejjad, P Lafforgue, C Marcelli, E Solau-Gervais, S Steinfeld, C Villoutreix, R Treves, X Mariette, L Guillevin
Journal: Annals of the Rheumatic Diseases (2007)

To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV).1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids.We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other.This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.
1090-213 The sinus nodal tissue arrangement into the musculature of the terminal crest: Implications in ablation of inappropriate sinus node tachycardia?
Authors: José Angel Cabrera, Damian Sanchez-Quintana, Siew Y Ho, Vicente Climent, Jose M Rubio, Fernando Cabestrero, Robert H Anderson, Jeronimo Farre
Journal: Journal of the American College of Cardiology (2004)