tbuckley/cabot-search huggingface dataset:
Creation of an In vivo cytosensor using engineered mesangial cells. Automatic sensing of glomerular inflammation controls transgene activity.
Authors: M Kitamura, H Kawachi
Journal: Journal of Clinical Investigation (1997)

Automatic control over exogenous gene expression in response to the activity of disease is a crucial hurdle for gene transfer-based therapies. Towards achieving this goal, we created a "cytosensor" that perceives local inflammatory states and subsequently regulates foreign gene expression. alpha-Smooth muscle actin is known to be expressed in glomerular mesangial cells exclusively in pathologic situations. CArG box element, the crucial regulatory sequence of the alpha-smooth muscle actin promoter, was used as a sensor for glomerular inflammation. Rat mesangial cells were stably transfected with an expression plasmid that introduces a beta-galactosidase gene under the control of CArG box elements. In vitro, the established cells expressed beta-galactosidase exclusively after stimulation with serum. To examine whether the cells are able to automatically control transgene activity in vivo, serum-stimulated or unstimulated cells were transferred into normal rat glomeruli or glomeruli subjected to anti-Thy 1 glomerulonephritis. When stimulated cells were transferred into the normal glomeruli, beta-galactosidase expression was switched off in vivo within 3 d. In contrast, when unstimulated cells were transferred into the nephritic glomeruli, transgene expression was substantially induced. These data indicate the feasibility of using the CArG box element as a molecular sensor for glomerular injury. In the context of advanced forms of gene therapy, this approach provides a novel concept for automatic regulation of local transgene expression where the transgene is required to be activated during inflammation and deactivated when the inflammation has subsided.
The National Practitioner Data Bank: Why Not Hospitals?
Authors: Douglas J. Segan
Journal: JAMA (1991)

<h3>To the Editor.—</h3> I read with interest the article by Johnson<sup>1</sup>on the National Practitioner Data Bank. Hospitals will now have access to records containing certain unpleasant events in the professional lives of American physicians. A physician who has a "record" in the Practitioner Data Bank, especially if hospital based, will be at a distinct disadvantage when negotiating with a hospital concerning salary and privileges. There is something fundamentally unfair in allowing a hospital to be aware of a physician's dirty laundry without allowing the physician access to information about the hospital. Ideally, both the hospital and the physician would make a full and fair disclosure of their histories to the other party. The present National Practitioner Data Bank ensures only that the physician be honest. In the interest of having a level playing field, the medical community should call on Congress to establish a National Hospital Data Bank.
Pattern of Gastric Emptying after Vagotomy and Pyloroplasty
Authors: M. R. Colmer, G. M. Owen, R. Shields
Journal: BMJ (1973)

The pattern and rate of gastric emptying have been studied in 16 patients before and after vagotomy and pyloroplasty. The rate of emptying, expressed as half life in minutes, was not greatly changed by operation. After operation, however, there was a rapid initial phase of emptying, particularly marked in patients who had post-vagotomy diarrhoea.
Role of endogenous prostacyclin in myocardial blood flow regulation distal to a severe coronary stenosis
Authors: N. A RUOCCO, A. S MOST, H. SASKEN, M. STEINER, H. GEWIRTZ
Journal: Cardiovascular Research (1988)

To test the hypothesis that endogenous prostacyclin is required to maintain reduced arteriolar tone distal to a severe coronary arterial stenosis under basal conditions and during challenge with a vasoconstrictor eicosanoid such as thromboxane A2 10 closed chest, domestic swine were prepared with an artificial stenosis, which reduced the luminal diameter of the left anterior descending coronary artery by 80%. Haemodynamic variables, regional myocardial blood flow (microsphere method), and lactate metabolism were measured at control (1); after infusion of U46619 (thromboxane A2 mimetic) distal to the stenosis at 1 μg·min−1 for 10 min and 5 μg·min−1 for 10 min; at control (2); after indomethacin infusion distal to the stenosis; and after repeat infusion of U46619. At the end of the study the animal hearts were removed and their coronary vessels harvested for in vitro determination of prostacyclin (PGI2) production. Regional myocardial blood flow in all layers of the heart distal to the stenosis did not change compared with control during the initial 1 μg·min−1 dose of U46619 but was reduced significantly after the 5 μg·min−1 dose (≈20% vs control). Distal zone flow (all layers) returned to baseline at control (2) and remained unchanged after indomethacin infusion. Although distal zone flows were reduced significantly in response to the second 5 μg·min−1 dose, the reduction in each layer after indomethacin was comparable to that observed with the 5 μg·min−1 dose before indomethacin infusion. Finally, the in vitro production of PGI2 by coronary vessels was considerably impaired by indomethacin infusion. Accordingly, the results of the study indicate that endogenous prostacyclin is not required to maintain reduced arteriolar tone distal to a severe coronary arterial stenosis either at rest or in response to challenge with a vasoconstrictor substance such as thromboxane A2.
Spontaneous Rupture of Spleen Infiltrated by Secondary Carcinoma
Authors: R. Chapman
Journal: BMJ (1962)

COMMENTVaccinia in a child of this age and of such extent and severity carries with it a very unfavourable prog- nosis, and until the drug was administered this child appeared to be no exception.The failure of the natural defences and of the hyperimmune gamma-globulin to control the condition and the rapid and dramatic improvement three days after starting therapy with N- methylisatin 8-thiosemicarbazone (Compound 33T57) suggest that the drug was responsible for the resolution of the lesions.The diarrhoea may have been a complica- tion of treatment with this drug, but as at the time there were other patients in the ward suffering from a severe form of gastroenteritis, cross-infection from one of these cannot be excluded.
All care commissioners should have someone responsible for marginalised groups
Authors: Z. Kmietowicz
Journal: BMJ (2014)

New minimum standards to guide the planning, commissioning, and provision of healthcare for excluded groups say that all NHS trusts and clinical commissioning groups (CCGs) should have someone with specific responsibility for “inclusion health,” to liaise between the trust, CCGs, and the local authority, including with the public health department.

The report says that there is a growing …
TETRAHYDROBIOPTERIN RESTORES CARDIOPROTECTION BY ISCHEMIC PRECONDITIONING DURING HYPERGLYCEMIA THROUGH PROTEIN S-NITROSYLATION
Authors: Hajime Otani, Toru Okazaki, Takayuki Shimazu, Kei Yoshioka, Masanori Fujita, Toshiji Iwasaka
Journal: Journal of the American College of Cardiology (2011)
France bans reproductive and therapeutic cloning
Authors: Brad Spurgeon
Journal: BMJ (2004)

France has banned reproductive human cloning, labelling it a “crime against the human species.” It will be punishable by 30 years in prison and a fine of €7.5m (£5m; $9.3m), drawing to an end a two and a half year parliamentary debate to modernise France's 1994 bioethics laws.

France has also banned therapeutic cloning—the creation of stem cells to replace damaged organs and tissue—making it a misdemeanour punishable by seven years in prison and fine of €100 000.

But in a controversial about-face it suspended for five years a ban on stem cell research on human embryos (produced by in-vitro …
An image analysis algorithm based on the hue saturation density transformation, an important tool for melanoma immunotherapy research
Authors: Jeffrey A Dzubay, Alan Jerusalmi, Rajiv Jesudason, Johannes Zimmermann, Martin Baatz, Zipei Feng, Sachin Puri, Tarsem Moudgil, Carlo Bifulco, Bernard Fox
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Melanoma is the most serious form of skin cancer, resulting in nearly 10,000 deaths per year in the US alone. Approximately 76,000 people are diagnosed with melanoma each year, and that number has been growing steadily over the last 30 years. Tragically, melanoma affects younger
How to Improve Coordination of Care
Authors: Edward J. Volpintesta
Journal: Annals of Internal Medicine (2008)

Letters15 April 2008How to Improve Coordination of CareEdward J. Volpintesta, MDEdward J. Volpintesta, MDFrom Bethel, CT 06810.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-8-200804150-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As discussed in Farber and colleagues' article (1) and its accompanying editorial (2), all primary care physicians would certainly enjoy getting reimbursed for the time and energy they spend on coordinating care.But there is a serious drawback that should be considered: The “coordinating care” function may degenerate into a dumping ground for all those time-consuming tasks that are shunned by every other care provider. It would become analogous to, but much more onerous than, the scut work that first-year medical residents do. If it does, then the coordinating care function will become so burdensome that it ...References1. Farber J, Siu A, Bloom P. How much time do physicians spend providing care outside of office visits? Ann Intern Med. 2007;147:693-8. [PMID: 18025445] LinkGoogle Scholar2. Bodenheimer T. Coordinating care: a major (unreimbursed) task of primary care [Editorial]. Ann Intern Med. 2007;147:730-1. [PMID: 18025448] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Edward J. Volpintesta, MDAffiliations: From Bethel, CT 06810.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHow Much Time Do Physicians Spend Providing Care Outside of Office Visits? Jeffrey Farber , Albert Siu , and Patricia Bloom Coordinating Care: A Major (Unreimbursed) Task of Primary Care Thomas Bodenheimer Metrics Cited byPrimary and community care of diabetes in older people 15 April 2008Volume 148, Issue 8Page: 628KeywordsConflicts of interestFallsNursing homesPatients ePublished: 15 April 2008 Issue Published: 15 April 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The B Cell — Old Player, New Position on the Team
Authors: Henry F. McFarland
Journal: New England Journal of Medicine (2008)

A phase 2 clinical trial of rituximab in the treatment of multiple sclerosis reported by Hauser et al. in this issue of the Journal (pages 676–688) provides important insights into the biology of the disease. The study showed that rituximab reduces disease activity in patients with relapsing–remitting multiple sclerosis; patients treated with rituximab had a substantial reduction in the number of clinical relapses and the number of contrast-enhancing lesions detected on magnetic resonance imaging (MRI).It is generally accepted that the MRI equivalent of an acute relapse is the disruption of the blood–brain barrier evidenced by increased signal after the . . .
Book: Snake Oil and Other Preoccupations
Authors: A. Ferriman
Journal: BMJ (2001)

John Diamond Vintage UK, £7.99, pp 285 ISBN 0 099 42833 4 Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Every doctor in the country should mourn the passing of columnist John Diamond, who died of oral cancer in March. Not only was he the scourge of the charlatans in the alternative medicine industry, but he was also the champion of today's embattled medical practitioners, who cannot open a newspaper without reading of yet another heinous crime or error perpetrated by one of their colleagues. “We used to like doctors,” he says in this book published posthumously last month. “But that was in the days when there was some communal respect for people who … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Body surface distributions of repolarization potentials after acute myocardial infarction. II. Relationship between isopotential mapping and ST-segment potential summation methods.
Authors: D M Mirvis
Journal: Circulation (1981)

Isopotential body surface distribution derived from 14 subjects with acute anterior and 14 patients with acute inferior myocardial infarction were studied to examine three possible difficulties with ST-segment summation methods as used for evaluation of infarction severity. First, recorded sums of potentials recorded from 150 electrodes placed on anterior and posterior thoracic surfaces and from five subsets of 42 electrodes located only on the left anterior precordium were compared. Lead subsets detected only one-half of total thoracic positivity in acute anterior infarction and the sums of potentials in these sets were significantly altered by small (approximately 1-1.5-inch) deviations in grid location. Second, differing isopotential distributions could yield nearly identical sums of potentials in left precordial electrode grids. Third, the effects of the wide variations in the normal ST-segment isopotential distribution were evaluated by studying 45 normal subjects and application of difference map and departure map and departure map techniques. The results illustrate the significant variation in potentials considered to be generated by the ischemic lesion caused by differences in control patterns. Thus, the recording of potential sums over limited torso areas, the attention to potential magnitudes rather than to distributions and the assumption that the normal ST segment is isoelectric represent significant problems in applying ECG methods to the quantitative evaluation of myocardial infarction.
Statin Prevents Tissue Factor Expression in Human Endothelial Cells
Authors: Masato Eto, Toshiyuki Kozai, Francesco Cosentino, Hana Joch, Thomas F. Lüscher
Journal: Circulation (2002)

Background — Tissue factor plays a pivotal role in thrombus formation in acute coronary syndromes. However, the regulatory mechanisms underlying tissue factor expression are poorly understood. Statins are effective in patients with acute coronary syndromes. Hence, the aim of this study was to clarify in human endothelial cells the signaling pathways of thrombin-induced tissue factor expression and potential inhibitory effects of statins. Methods and Results — In human aortic endothelial cells, simvastatin prevented tissue factor induction by thrombin (4 U/mL) in a concentration-dependent manner. The increase in tissue factor activity on the cell surface was also blocked by simvastatin. Simvastatin also prevented the upregulation of tissue factor expression and activity in human aortic smooth muscle cells. Mevalonate (100 μmol/L) reversed the inhibitory effect of simvastatin on tissue factor expression. Thrombin induced rapid activation of Rho A and p38 MAP kinase. The Rho-kinase inhibitor Y-27632 and the p38 MAP kinase inhibitor SB203580 prevented tissue factor induction. Akt was dephosphorylated by thrombin; the phosphoinositol 3-kinase inhibitor wortmannin enhanced its dephosphorylation as well as thrombin-induced tissue factor expression. Simvastatin prevented thrombin-induced Rho A activation but not p38 MAP kinase activation. Akt dephosphorylation by thrombin was blocked by both simvastatin and Y-27632. Conclusions — Endothelial tissue factor induction by thrombin is regulated by Rho/Rho-kinase, Akt, and p38 MAP kinase. Simvastatin prevents its induction through inhibition of Rho/Rho-kinase and activation of Akt. These findings provide new insights into the action of statins in acute coronary syndromes.
P455 BACTERIAL ENDOCARDITIS IN PATIENTS WITH CIRRHOSIS: A MULTICENTER RETROSPECTIVE STUDY OF 78 CASES
Authors: J.-F.D. Cadranel, M. Allaire, H. Blasco-Perrin, T. Thevenot, C. Chagneau-Derrode, E.-A. Pariente, A. Garioud, H. Lison, X. Causse, X. Adhoute, J.B. Nousbaum, I. Rosa-Hezode, V. Jouannaud, T. Antonini, J. Denis, E. Sarlon, K. Dupont, G. Le Folgoc, I. Ollivier-Hourmand, J.M. Peron, V. Di Martino, C. Silvain, R. Arotcarena, M. Bakkar, M. Bourliere, A. Viennot, J.D. Grange, H. Hagege, B. Lesgourgues, D. Samuel, C. Bureau, T. Dao
Journal: Journal of Hepatology (2014)
Biosynthetic origin of serum cholesterol in the squirrel monkey: evidence for a contribution by the intestinal wall
Authors: Jean D. Wilson
Journal: Journal of Clinical Investigation (1968)

The possibility that the intestinal wall serves as a biosynthetic site for serum cholesterol has been examined in two types of studies in the squirrel monkey. First, animals were fed cholesterol in order to inhibit cholesterol synthesis in the liver, and the intestinal lymph ducts were cannulated. After the administration of acetate-2-(14)C it was possible to demonstrate that cholesterol synthesized by the intestinal wall enters intestinal lymph and thereby in the intact animal enters the circulating pool. Second, an attempt to quantitate the significance of this intestinal contribution has been made in animals fed cholesterol-3-(3)H and injected with cholesterol-4-(14)C for long periods. By an application of the technique of analysis utilizing the isotopic steady state we estimated as a minimal value that in the squirrel monkey 1.5-2.0 mg of cholesterol synthesized in the intestinal wall reaches the circulation each day.
Causes of Death After Kidney Transplantation
Authors: Graeme F. Washer
Journal: JAMA (1983)

During the five-year period September 1974 through August 1979, two hundred nine consecutive patients received their first kidney transplant in Denver. During 2.5 to 7.5 years of follow-up, 54 patients (26%) died. Infection was the leading cause of death during all intervals and was responsible for 22 (41%) of the 54 deaths. Pneumonia was primarily responsible for 14 of the 22 deaths from infection. The other causes of death were cardiovascular problems in 11 patients (20%), suicide in eight patients (15%), gastrointestinal (GI) tract problems in seven patients (13%), malignant neoplasms in two patients (4%), and miscellaneous problems in four patients (7%). Twenty-six (48%) of the 54 deaths occurred more than one year after primary transplantation; 12 of these 26 patients had already returned to chronic hemodialysis. To minimize mortality after transplantation, patients and their physicians must remain alert to the ongoing risks to which these patients are exposed, including the risks of sudden death from infection, myocardial infarction, pulmonary embolus, suicide, or GI tract perforation. (<i>JAMA</i>1983;250:49-54)
Abnormal Patterns of Insulin Secretion in Non-Insulin-Dependent Diabetes Mellitus
Authors: Kenneth S. Polonsky, Bruce D. Given, Laurence J. Hirsch, Hartmut Tillil, E. Timothy Shapiro, Christine Beebe, Bruce H. Frank, John A. Galloway, Eve Van Cauter
Journal: New England Journal of Medicine (1988)

To determine whether non-insulin-dependent diabetes is associated with specific alterations in the pattern of insulin secretion, we studied 16 patients with untreated diabetes and 14 matched controls. The rates of insulin secretion were calculated from measurements of peripheral C-peptide in blood samples taken at 15- to 20-minute intervals during a 24-hour period in which the subjects ate three mixed meals. Incremental responses of insulin secretion to meals were significantly lower in the diabetic patients (P less than 0.005), and the increases and decreases in insulin secretion after meals were more sluggish. These disruptions in secretory response were more marked after dinner than after breakfast, and a clear secretory response to dinner often could not be identified. Both the control and diabetic subjects secreted insulin in a series of discrete pulses. In the controls, a total of seven to eight pulses were identified in the period from 9 a.m. to 11 p.m., including the three post-meal periods (an average frequency of one pulse per 105 to 120 minutes), and two to four pulses were identified in the remaining 10 hours. The number of pulses in the patients and controls did not differ significantly. However, in the patients, the pulses after meals had a smaller amplitude (P less than 0.03) and were less frequently concomitant with a glucose pulse (54.7 +/- 4.9 vs. 82.2 +/- 5.0, P less than 0.001). Pulses also appeared less regularly in the patients. During glucose clamping to produce hyperglycemia (glucose level, 16.7 mmol per liter [300 mg per deciliter]), the diabetic subjects secreted, on the average, 70 percent less insulin than matched controls (P less than 0.001). These data suggest that profound alterations in the amount and temporal organization of stimulated insulin secretion may be important in the pathophysiology of beta-cell dysfunction in diabetes.
Smoking and the Emphysema Patient
Authors: Alvin Barach
Journal: JAMA (1963)

"Suppose that an indvidual does not inhale, and that little or no smoke enters the lungs. What then is the harm of cigaret smoking to patients with pulmonary emphysema and other diseases that have been ascribed to absorption of nicotine, carbon monoxide, and tars?" So asked Dr. Alvin Barach of New York in a disgression from his subject of pulmonary emphysema therapy, during a talk before the American College of Chest Physicians in Atlantic City. "It seems to me," he added, "that methods of nonirritant smoking deserve study." Barach explained his nonirritant technique thus: The patient draws a puff of smoke into the mouth, closes the lips, inhales deeply through the nose, and finally expels the smoke retained in the mouth, along with the air previously inhaled, from the mouth. The technique, he said, "provides considerable satisfaction and is more esthetic in appearance than the "usual" method of drawing the
Age-Associated Aortic Stenosis in Apolipoprotein E-Deficient Mice
Authors: Kimie Tanaka, Masataka Sata, Daiju Fukuda, Yoshihiro Suematsu, Noboru Motomura, Shinichi Takamoto, Yasunobu Hirata, Ryozo Nagai
Journal: Journal of the American College of Cardiology (2005)
Prophylactic Use of Oxytetracycline for Exacerbations of Chronic Bronchitis
Authors: P. C. Elmes, C. M. Fletcher, A. A. C. Dutton
Journal: BMJ (1957)

The mortality of sea-snake bite appears to be low, but fear of them is universal and a potent source of worry.Effective treatment, including a polyspecific antivenene, would be a great boon to Asian fishing folk.We wish to thank the State Surgeon,
Nutrient-toxicant interactions: susceptible populations.
Authors: K R Mahaffey, J E Vanderveen
Journal: Environmental Health Perspectives (1979)

Nutritional status can substantially modify the toxicity of environmental pollutants. Investigations with experimental animals and epidemiological observations on humans have established the role of nutrition in altering susceptibility to a variety of pollutants including pesticides and heavy metals. The degree of nutritional deficiency that alters susceptibility need not be severe. Frequently only biochemical indications of nutritional deficiency can be associated with changes in the dose-response of an animal or person to a toxic compound.