tbuckley/cabot-search huggingface dataset:
Pharmacological Regulation of Protein Expression from Adeno-Associated Viral Vectors in the Eye
Authors: Alberto Auricchio, Victor M Rivera, Tim Clackson, Erin E O'Connor, Albert M Maguire, Michael J Tolentino, Jean Bennett, James M Wilson
Journal: Molecular Therapy (2002)

The control, over time and space, of the levels of therapeutic proteins is crucial for successful retinal gene therapy. We tested the ability of adeno-associated viral vectors (AAV) delivered intraocularly to release a secreted protein (erythropoietin (Epo) used as a marker) in the eye, either constitutively or in a pharmacologically regulated manner using the dimerizer-inducible transcriptional regulatory system. Following delivery of a constitutively expressing vector to the intravitreal or subretinal space of nude rats, Epo protein was detected in both the anterior chamber and vitreous fluids. A dual-vector system inducible by the dimerizer rapamycin and expressing Epo was administered into the subretinal space in an attempt to achieve pharmacologic control of trangene expression in the eye. Before induction with rapamycin, the intraocular Epo level was negligible. However, following a systemic administration of rapamycin, Epo was detected in the anterior chamber, peaking on day 3 and returning to baseline 2–3 weeks after withdrawal of the drug. Peak-induced Epo in the anterior chamber was proportional to the dose of rapamycin and was not detected in serum. Similar results were obtained following subretinal administration of the vectors in one nonhuman primate. The rapamycin inducible system promises to be useful for developing gene therapies for inherited retinal degeneration and ocular neovascularization. The control, over time and space, of the levels of therapeutic proteins is crucial for successful retinal gene therapy. We tested the ability of adeno-associated viral vectors (AAV) delivered intraocularly to release a secreted protein (erythropoietin (Epo) used as a marker) in the eye, either constitutively or in a pharmacologically regulated manner using the dimerizer-inducible transcriptional regulatory system. Following delivery of a constitutively expressing vector to the intravitreal or subretinal space of nude rats, Epo protein was detected in both the anterior chamber and vitreous fluids. A dual-vector system inducible by the dimerizer rapamycin and expressing Epo was administered into the subretinal space in an attempt to achieve pharmacologic control of trangene expression in the eye. Before induction with rapamycin, the intraocular Epo level was negligible. However, following a systemic administration of rapamycin, Epo was detected in the anterior chamber, peaking on day 3 and returning to baseline 2–3 weeks after withdrawal of the drug. Peak-induced Epo in the anterior chamber was proportional to the dose of rapamycin and was not detected in serum. Similar results were obtained following subretinal administration of the vectors in one nonhuman primate. The rapamycin inducible system promises to be useful for developing gene therapies for inherited retinal degeneration and ocular neovascularization.
SOME OBSERVATIONS ON THE PRINCIPLES INVOLVED IN PROPHYLAXIS OR PREVENTION OF DISEASES IN GENERAL, AND OF PULMONARY TUBERCULOSIS IN PARTICULAR.
Authors: N. S. DAVIS
Journal: JAMA (1897)

Prophylaxis or preventive medicine is founded on the supposition that a large proportion of the important diseases that afflict the human race are preventable by judicious measures adopted for the purpose. Such measures must be directed toward the accomplishment of one or more of the following objects: 1. To prevent the development of the specific causes capable of inducing disease. 2. To destroy or neutralize such causes after they are developed and before they had excited active symptoms of disease. 3. To so increase the natural vital resistence of the living body that it successfully resists the action of the supposed causes of any form of disease; and 4, to interrupt contact or communication of the sick with the well. To be successful in the accomplishment of these important objects we must have reliable knowledge of the causes that produce disease, or at least the conditions and laws under which
Reversal by naloxone of the antihypertensive action of clonidine: involvement of the sympathetic nervous system.
Authors: C Farsang, J Kapocsi, L Vajda, K Varga, Z Malisak, M Fekete, G Kunos
Journal: Circulation (1984)

The effects of clonidine, naloxone, and their combination on arterial blood pressure (BP), heart rate (HR), and hemodynamic and biochemical parameters were examined in 29 patients with essential hypertension. Treatment for 3 days with 0.3 mg/day clonidine reduced BP and HR, and these effects were quickly reversed by a single injection of 0.4 mg iv naloxone in 17 of the patients (responders), but not in the remaining 12 (nonresponders). Responders had higher control values for cardiac output, stroke index, plasma renin activity (PRA), and plasma epinephrine levels than did nonresponders. Basal BP was similar in the two groups, but clonidine decreased BP, PRA, and plasma epinephrine more in responders than in nonresponders. Naloxone given during placebo treatment had no significant effects. During clonidine treatment naloxone increased BP, HR, total peripheral resistance, PRA, and plasma epinephrine and norepinephrine, and decreased stroke volume in responders, whereas in nonresponders its only effect was a small increase in HR. It is concluded that in a subset of hyperadrenergic, hypertensive patients the antihypertensive effect of clonidine involves a naloxone-reversible inhibition of central sympathetic outflow, probably mediated by the release of an endogenous opioid.
Complications des corps étrangers oesophagiens chez l'enfant
Authors: F Benhassine, ML Benhassine, L Smati, NK Benhalla, M Baghriche
Journal: Endoscopy (2009)

But: Le but de cette étude est d'évaluer la gravité des corps étrangers (CE) bloqués au niveau de l'œsophage chez l'enfant.
The Public and the Controversy Over Abortion
Authors: Robert J. Blendon
Journal: JAMA (1993)

THE ARRIVAL of a new presidential administration in Washington, DC, has been marked by vigorous debate about two major health policy issues—national health reform and abortion. While the national health reform debate will be centered on the passage of a single piece of legislation, the abortion controversy encompasses a number of distinct judicial, legislative, and administrative policy decisions. In each of these areas, the Clinton administration seeks to reverse the trend established in the Reagan-Bush years of increased restrictions on access to abortion and other reproductive services. Within the American medical community and among the general public, few issues are as controversial as abortion. Concern has deepened recently as violent protests and personal attacks on physicians have escalated in the wake of Clinton's decision to remove the gag rule on abortion counseling in family planning centers, and as he and Congress take up several policy initiatives: passing a freedom of
Onset of obesity in a 36 year birth cohort study.
Authors: F E Braddon, B Rodgers, M E Wadsworth, J M Davies
Journal: BMJ (1986)

A large national cohort of children studied from birth to 36 years was used to test the predictive value of childhood obesity for obesity in adult life. Only 21% (39) of obese 36 year olds had been obese at age 11 years, and even when associated social factors were taken into account the correctly predicted percentage was much lower than the prediction rate achieved using body mass data from age 26 years. The comparatively poor predictive value of childhood obesity and the association of adult obesity with educational achievements and socioeconomic circumstances of family of origin emphasise the need for encouraging good nutritional and exercise habits rather than placing undue emphasis on the control of childhood obesity.
Tumor-associated T cell receptor repertoires in low- and high-grade gliomas
Authors: Jennifer S Sims, Boris Grinshpun, Benjamin I Amendolara, Yufeng Shen, Peter D Canoll, Peter A Sims, Jeffrey N Bruce
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Glioblastoma (GBM) remains prognostically dismal, with care centered on resection, motivating research into novel therapies. Although inducing anti-tumor immunity remains an attractive target for therapeutic and preventative intervention, the interplay between evolving
Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects
Authors: Timothy E. Graham, Qin Yang, Matthias Blüher, Ann Hammarstedt, Theodore P. Ciaraldi, Robert R. Henry, Christopher J. Wason, Andreas Oberbach, Per-Anders Jansson, Ulf Smith, Barbara B. Kahn
Journal: New England Journal of Medicine (2006)

Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin resistance and change after an intervention that improves insulin sensitivity. We also determined whether elevated serum RBP4 levels are associated with reduced expression of glucose transporter 4 (GLUT4) in adipocytes, an early pathological feature of insulin resistance.We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes.Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated.RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels.
INCIDENCE, PREDICTORS AND CLINICAL OUTCOME OF LEFT VENTRICULAR THROMBUS AND SPONTANEOUS ECHO CONTRAST IN PATIENTS WITH ACUTE ANTERIOR WALL MYOCARDIAL INFARCTION
Authors: Sun Hwa Lee, Ji Young Yoon, Soo Kyeong Song, Yisik Kim, Lae Young Jung, Sang Rok Lee, Kyoung Suk Rhee, Jeikeon Chae, Wonho Kim, Jaeki Ko
Journal: Journal of the American College of Cardiology (2015)
STUDIES ON THE EFFECT OF TRITON (WR-1339) ON GUINEA PIG TISSUES
Authors: Robert A. Patnode, Paul C. Hudgins, Bernard W. Janicki
Journal: The Journal of Experimental Medicine (1958)

Guinea pigs given three subcutaneous injections of triton WR-1339, 300 mg./kg., at 3 day intervals develop an intense lipemia as evidenced by marked increases in serum phospholipide, free cholesterol, ester cholesterol, neutral fat, and total fatty acids. The total fatty acid content of the lung, liver, and spleen, however, remains unchanged. No qualitative change in the fatty acids of the lung and liver from treated animals could be detected by the methods used. The injection of triton was found to diminish slightly the cholesterol content of the adrenal glands. The implications of these findings are discussed in relation to an understanding of the mechanism involved in the therapeutic action of triton in experimental tuberculosis.
Anemia, Dialysis, and Dollars
Authors: Saulo Klahr
Journal: New England Journal of Medicine (1996)

The association of anemia with renal failure was noted by Richard Bright 160 years ago.1 Anemia develops early in the course of renal failure, becomes prominent as the disease progresses, and contributes substantially to disability. Patients with renal failure have lower plasma levels of erythropoietin and less erythropoiesis than other patients with similar degrees of anemia, implicating inadequate production of erythropoietin by the diseased kidney as the primary mechanism of the anemia of renal failure. Other factors may also contribute, including “uremic toxins” that inhibit erythropoiesis, occult blood loss, hemolysis, and deficiencies in folate, iron, or both.Recombinant human erythropoietin . . .
75 deaths in asthmatics prescribed home nebulisers.
Authors: M R Sears, H H Rea, J Fenwick, A J Gillies, P E Holst, T V O'Donnell, R P Rothwell
Journal: BMJ (1987)

The circumstances surrounding the deaths of 75 asthmatic patients who had been prescribed a domiciliary nebuliser driven by an air compressor pump for administration of high dose beta sympathomimetic drugs were investigated as part of the New Zealand national asthma mortality study. Death was judged unavoidable in 19 patients who seemed to have precipitous attacks despite apparently good long term management. Delays in seeking medical help because of overreliance on beta agonist delivered by nebuliser were evident in 12 cases and possible in a further 11, but these represented only 8% of the 271 verified deaths from asthma in New Zealanders aged under 70 during the period. Evidence for direct toxicity of high dose beta agonist was not found. Nevertheless, the absence of serum potassium and theophylline concentrations and of electrocardiographic monitoring in the period immediately preceding death precluded firm conclusions whether arrhythmias might have occurred due to these factors rather than to hypoxia alone. In most patients prescribed domiciliary nebulisers death was associated with deficiencies in long term and short term care similar to those seen in patients without nebulisers. Discretion in prescribing home nebulisers, greater use of other appropriate drugs, including adequate corticosteroids, and careful supervision and instruction of patients taking beta agonist by nebuliser should help to reduce the mortality from asthma.
Carcinoma of the oesophagus in Transkei: treatment by intubation.
Authors: M H Cotton, A M Sammon
Journal: Thorax (1989)

The management of carcinoma of the oesophagus poses formidable logistic problems in countries such as Transkei where the condition is common and resources are limited. Most patients present late, often with complications, and are reluctant to undergo major surgery. Two hundred and fifty consecutive patients who presented over nine months in Transkei were studied. The incidence increased with age until 70 years and the disease occurred equally in men and women. The neoplasm was predominantly squamous cell (243 patients, 97%) and was found most often in the middle third of the oesophagus (118, 47%). On admission only eight of the 250 patients could take a semi-solid diet and only 21 a fluid diet. The policy where feasible was to introduce a Proctor Livingstone tube endoscopically through the dilated oesophageal stricture by a pulsion technique under light general anaesthesia. When abdominal perforation of the oesophagus seemed likely, retrograde intubation via a gastrotomy was performed. Sixty patients were not intubated, because the stricture was too proximal (47) or could not be dilated adequately (6), the lesion was suitable for resection (6), or the patient refused (1). Fifty one (27%) patients died in hospital, 29 deaths being due to oesophageal perforation (including six of the 10 who were intubated retrogradely). The mean hospital stay was 4.7 days. On discharge 64% of the intubated patients were able to take semi-solid food and a further 6% a fluid diet. Palliation by intubation was performed rapidly and the tube was well tolerated by patients. The overall mortality was high, but this can be reduced by experience. Intubation is an acceptable, cost effective solution where large numbers of patients present with advanced oesophageal carcinoma in circumstances where resources are severely limited.
Physical activity in COPD patients: patterns and bouts
Authors: David Donaire-Gonzalez, Elena Gimeno-Santos, Eva Balcells, Diego A. Rodríguez, Eva Farrero, Jordi de Batlle, Marta Benet, Antoni Ferrer, Joan A. Barberà, Joaquim Gea, Robert Rodriguez-Roisin, Josep M. Antó, Judith Garcia-Aymerich
Journal: European Respiratory Journal (2012)

The present study aims to describe the pattern of physical activity and the frequency, duration and intensity of physical activity bouts in patients with chronic obstructive pulmonary disease (COPD), to assess how these patterns differ according to COPD severity, and to explore whether these patients meet the general guidelines for physical activity for older adults. 177 patients (94% male, mean±sd age 71±8 years and forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro2 Armband accelerometer for eight consecutive days. Physical activity bouts were defined as periods of ≥10 min above 1.5 metabolic equivalent tasks and classified according to their median intensity. Patients engaged in activity a median of 153 min·day(-1) and 57% of that time was spent in bouts. Median frequencies of bouts per day were four and three for all and moderate-to-vigorous intensities, respectively. With increasing COPD severity, time in physical activity, proportion of time in bouts and frequency of bouts decreased. 61% of patients fulfilled the recommended physical activity guidelines. In conclusion, COPD patients of all spirometric severity stages engage in physical activity bouts of moderate-to-vigorous intensities. Patients with severe and very severe COPD perform their daily activities in fewer and shorter bouts than those in mild and moderate stages.
Spotlight on Antimicrobial Agents—1973
Authors: Benjamin M. Kagan
Journal: JAMA (1973)

This is one of several articles sponsored by the American Society for Clinical Pharmacology and Therapeutics. The goals are as follows: (1) maximally effective drug therapy, (2) reduction of the incidence of serious adverse drug reactions, and (3) maximum effectiveness and safety at the lowest cost for the patient. To accomplish the goals set forth with antimicrobial agents, it is necesssary that the physician have a basic understanding of the constantly changing relationships between microbes, the human host, and antimicrobial agents.<sup>1</sup> Both microbes and humans are in a constant state of change. The growth rates of microbes and their degrees of susceptibility to antimicrobial agents may change via a number of different mechanisms. For instance, during a single course of therapy a microbe may become resistant to the antimicrobial agent by (1) emergence of genotypic drug resistance or (2) transfer of resistant factor (R) or (3) alterations in microbe
Low MCL-1 mRNA expression correlates with prolonged survival in B-cell chronic lymphocytic leukemia
Authors: L Véronèse, O Tournilhac, P Verrelle, F Davi, G Dighiero, E Chautard, R Veyrat-Masson, F Kwiatkowski, C Goumy, P Vago, P Travade, A Tchirkov
Journal: Leukemia (2007)
ELECTRON MICROSCOPIC LOCALIZATION OF THE NEPHROTOXIC ANTIBODY IN THE GLOMERULI OF THE RAT AFTER INTRAVENOUS APPLICATION OF PURIFIED NEPHRITOGENIC ANTIBODY-FERRITIN CONJUGATES
Authors: Arnold Vogt, Hermann Bockhorn, Keniti Kozima, Masamichi Sasaki
Journal: The Journal of Experimental Medicine (1968)

Nephritis in rats was induced by intravenous injection of purified ferritin-conjugated rabbit and duck nephrotoxic globulin. Using the fluorescent antibody technique, the same capillary pattern was found as that in glomeruli of rats receiving uncoupled nephrotoxic globulin. Electron microscopy revealed a heavy accumulation of the basement membrane-fixed antibody almost exclusively at the endothelial side. A higher concentration of ferritin was demonstrable in the peripheral basement membrane. The once-fixed antibody remained at the site of reaction though decreasing with time. The half-disappearance time seemed to be shorter than that of the uncoupled nephrotoxic globulin. No difference in localization was observed between rabbit and duck antibody. At least 40 basement membrane-fixed antibody molecules from the rabbit per 3000 mmicro(2) of filtration surface were needed to cause immediate nephritis. To induce nephritis using duck antibody, a greater number of basement membrane-fixed antibody seemed to be necessary. No evidence of specific reaction with constituents of glomerular cells was obtained.
Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study.
Authors: M Luengo, C Picado, L Del Rio, N Guanabens, J M Montserrat, J Setoain
Journal: Thorax (1991)

BACKGROUND: Reduced bone mass predisposes patients to the development of vertebral fractures. Measurement of bone mass by non-invasive methods is used to detect patients with involutional osteoporosis at risk from fractures. These methods have not been assessed in patients with steroid dependent osteoporosis. The objective of this study was to assess the value of a predictive fracture threshold value of bone density in patients with steroid dependent asthma. METHODS: Three groups of patients were studied. Group 1 (67 patients) had steroid dependent asthma (mean daily dose of prednisone 11.7 mg) and no vertebral fractures, group 2 (32 patients) had steroid dependent asthma (mean daily dose of prednisone 12 mg) and vertebral fractures, and group 3 (55 patients) were not taking steroids but had involutional osteoporosis and a recent non-traumatic vertebral fracture. Bone mineral density was measured by dual photon absorptiometry and vertebral fractures by radiography of the lumbar spine. A fracture threshold was determined in the two groups with fractures as the 90th percentile of the mean bone mineral density measured in the lumbar spine. RESULTS: Bone mineral density was significantly higher in the steroid dependent group with fractures (group 2) than in group 3 patients, who had involutional osteoporosis and fractures (0.946 (0.18) g/cm2 v 0.830 (0.16) g/cm2). The fracture threshold value was therefore higher for patients with steroid related vertebral fractures (group 2, 1.173 g/cm2) than for those with involutional osteoporosis (group 3, 0.979 g/cm2). Vertebral fractures were more likely to occur in steroid dependent asthmatic patients with bone density above the fracture threshold value (obtained from subjects with involutional osteoporosis) than in subjects in group 3 (34% v 9%). CONCLUSION: Vertebral fractures occur in patients treated with steroids in the presence of higher bone mineral density than is the case with patients with involutional osteoporosis. The findings suggests that the assessment of the efficacy of preventive treatment requires measurement of bone mineral density and radiology.
An evaluation of sunscreens in patients with broad action-spectrum photosensitivity
Authors: B.L. DIFFEY, P.M. FARR
Journal: British Journal of Dermatology (1985)

The photoprotection afforded by three sunscreens available by prescription in the U.K. has been studied in patients with severe broad action-spectrum photosensitivity. All products investigated exhibited high protection against UV-B radiation in accordance with the protection factors quoted by the respective manufacturers. On the other hand, the protection against UV-A ranged only from fair to poor. The need for a sunscreen which has good protection against UV-A is shown to be important for the satisfactory management of patients with severe broad action spectrum photosensitivity.