tbuckley/cabot-search huggingface dataset:
Upping the Ante: Recent Advances in Direct Reprogramming
Authors: Lars UW Müller, George Q Daley, David A Williams
Journal: Molecular Therapy (2009)

The concept of reversing the characteristics of differentiated tissues to pluripotency through reprogramming was introduced over 50 years ago in the first somatic cell nuclear transfer (SCNT) experiments. More recently, direct reprogramming of differentiated somatic cells by gene transfer of a small number of defined transcription factors has been shown to yield cells that are indistinguishable from inner cell mass–derived embryonic stem (ES) cells. These cells, termed induced pluripotent stem (iPS) cells, offer exciting possibilities for studying mechanism of pluripotency, establishing models for disease-specific investigations, and enabling future applications in regenerative medicine. In this review, we discuss the basic foundation of reestablishing pluripotency and recent progress toward enhancing the efficiency and safety of the process through optimization of the reprogramming factor combination, identification of small molecules that augment efficiency, and assessment of distinct target cells in reprogramming efficiency. We also highlight recent advances that eliminate stable genetic modification from the reprogramming process, and summarize preclinical models that provide proof-of-concept for ES/iPS cell-based regenerative medicine. The concept of reversing the characteristics of differentiated tissues to pluripotency through reprogramming was introduced over 50 years ago in the first somatic cell nuclear transfer (SCNT) experiments. More recently, direct reprogramming of differentiated somatic cells by gene transfer of a small number of defined transcription factors has been shown to yield cells that are indistinguishable from inner cell mass–derived embryonic stem (ES) cells. These cells, termed induced pluripotent stem (iPS) cells, offer exciting possibilities for studying mechanism of pluripotency, establishing models for disease-specific investigations, and enabling future applications in regenerative medicine. In this review, we discuss the basic foundation of reestablishing pluripotency and recent progress toward enhancing the efficiency and safety of the process through optimization of the reprogramming factor combination, identification of small molecules that augment efficiency, and assessment of distinct target cells in reprogramming efficiency. We also highlight recent advances that eliminate stable genetic modification from the reprogramming process, and summarize preclinical models that provide proof-of-concept for ES/iPS cell-based regenerative medicine.
A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells
Authors: Sheng Zhou, Disha Mody, Suk See DeRavin, Julia Hauer, Taihe Lu, Zhijun Ma, Salima Hacein-Bey Abina, John T. Gray, Michael R. Greene, Marina Cavazzana-Calvo, Harry L. Malech, Brian P. Sorrentino
Journal: Blood (2010)
Hypertrophy and dilation: a TOTally new story?
Authors: S Baudet
Journal: Cardiovascular Research (2000)

See article by Sussman et al. [15] (pages 90–101) in this issue. 

Myocardial hypertrophy is either a primary disease of the heart as found for genetic cardiomyopathies (hypertrophic or dilated), or an adaptative response secondary to, for instance, hemodynamic disturbances (pressure or volume overload) or endocrine dysfunction (hyperthyroidism, diabetes mellitus) [1,2]. Reactive concentric hypertrophy is fundamentally a compensatory response as the enlargement of the ventricular wall maintains normal hemodynamics and therefore allows physiological tissue perfusion. However, hypertrophy does not proceed indefinitely: the maintenance of the initial stress that induced the compensatory response overwhelms, after a variable delay, the hypertrophic capacity of the heart. From a functional standpoint, systolic dysfunction, metabolic exhaustion and insufficient tissue perfusion, i.e. major signs of heart failure, occur and in absence of adequate treatment, lead to premature death. Cardiac hypertrophy is clearly a double-edged sword: on one hand, it is beneficial as it preserves tissue perfusion while, on the other, it is a deleterious process as it predisposes the heart to pump failure [3].

Until now, the biochemical and molecular mechanisms leading to cardiac dilation have been much less studied than those responsible for cardiac hypertrophy [3]. For the latter process, it is becoming clear that the signaling pathways are numerous, complex and interactive. In particular, the hypertrophic role of the protein kinases C, the mitogen-activated protein and Janus kinases family, and the tyrosine kinases has been stressed [4–8]. Their activation has been shown to induce fetal gene reprogramming, to upregulate natriuretic peptide genes and to downregulate the expression of certain genes such as the one encoding the calcium pump of the sarcoplasmic reticulum [3]. More recently, the involvement of phosphatases in the hypertrophic process has been demonstrated, not only as ‘turn-off’ effectors of the kinases action [9,10] but also, more … 

* Corresponding author. Tel.: +33-241-22-8269; fax: +33-241-22-8251 stephane.baudet{at}intervet.akzonobel.nl
My lousy doctor
Authors: M. E Gatt
Journal: BMJ (2004)

My senior attending physician recently told me, “A physician who treats himself, has got a lousy doctor.” This he said while being hospitalised just a few days after having a myocardial infarction. Feeling an uncontrolled severe reflux for two days, he had finally recorded an electrocardiogram “just in case.” Seeing the inferior wall Q waves and remnant ST segment elevations, he still waited to show the electrocardiogram to a cardiologist, who eventually made him go to the emergency room.

Shortly after, on an unforgettable evening, I suddenly felt the worst abdominal pain I have ever had in my life. I knew, palpating my lower abdomen, that severe tenderness, rebound, and guarding are …
Is 81-mg Aspirin Associated With Age-Related Macular Degeneration Risk?—Reply
Authors: Jie Jin Wang, Gerald Liew, Paul Mitchell
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome
Authors: Jean Y. Tang, Julian M. Mackay-Wiggan, Michelle Aszterbaum, Robert L. Yauch, Joselyn Lindgren, Kris Chang, Carol Coppola, Anita M. Chanana, Jackleen Marji, David R. Bickers, Ervin H. Epstein
Journal: New England Journal of Medicine (2012)

Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas.We tested the anti-basal-cell carcinoma efficacy of vismodegib in a randomized, double-blind, placebo-controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011. The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection (surgically eligible) with vismodegib versus placebo after 3 months; secondary end points included reduction in the size of existing basal-cell carcinomas.In 41 patients followed for a mean of 8 months (range, 1 to 15) after enrollment, the per-patient rate of new surgically eligible basal-cell carcinomas was lower with vismodegib than with placebo (2 vs. 29 cases per group per year, P<0.001), as was the size (percent change from baseline in the sum of the longest diameter) of existing clinically significant basal-cell carcinomas (-65% vs. -11%, P=0.003). In some patients, all basal-cell carcinomas clinically regressed. No tumors progressed during treatment with vismodegib. Patients receiving vismodegib routinely had grade 1 or 2 adverse events of loss of taste, muscle cramps, hair loss, and weight loss. Overall, 54% of patients (14 of 26) receiving vismodegib discontinued drug treatment owing to adverse events. At 1 month, vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90% (P<0.001) and diminished tumor-cell proliferation, but apoptosis was not affected. No residual basal-cell carcinoma was detectable in 83% of biopsy samples taken from sites of clinically regressed basal-cell carcinomas.Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of new basal-cell carcinomas in patients with the basal-cell nevus syndrome. The adverse events associated with treatment led to discontinuation in over half of treated patients. (Funded by Genentech and others; ClinicalTrials.gov number, NCT00957229.).
Spike bursts increase amyloid-β 40/42 ratio by inducing a presenilin-1 conformational change
Authors: Iftach Dolev, Hilla Fogel, Hila Milshtein, Yevgeny Berdichevsky, Noa Lipstein, Nils Brose, Neta Gazit, Inna Slutsky
Journal: Nature Neuroscience (2013)
Koop Convenes Tobacco Policy Advisory Group
Authors: Andrew A. Skolnick
Journal: JAMA (1997)

TO INSURE that the voices of public health advocates will be heard if Congress enacts legislation to settle the rising tide of lawsuits against the tobacco industry, former US Surgeon General C. Everett Koop, MD, has convened an Advisory Committee on Tobacco Policy and Public Health. In addition to co-chairs Koop and former US Food and Drug Administration commissioner David Kessler, MD, JD, the panel includes: John Banzhaf, Action on Smoking and Health; Mike Pertschuk, Advocacy Institute; Robert Graham, MD, American Academy of Family Physicians; George Comerci, MD, American Academy of Pediatrics; John Seffrin, American Cancer Society; D. Robert McCaffree, MD, American College of Chest Physicians; George Anderson, MD, American College of Preventive Medicine; Dudley Hafner, American Heart Association; John Garrison, American Lung Association; Randolph Smoak, MD, American Medical Association; Thomas Houston, MD, Smokeless States National Program; Barbara Levine, American Public Health Association; Anne Marie O'Keefe, Americans for Non-Smokers Rights;
Effects of Regitine (C-7337) in Patients, Particularly Those with Peripheral Arterial Vascular Disease
Authors: HAROLD D. GREEN, WILLIAM T. GRIMSLEY
Journal: Circulation (1953)

This is a study of the clinical effects of Regitine, a new antiadrenergic drug, the pharmacologic properties of which are similar to those of Priscoline. Thirty-four patients, whose diagnoses fall into the peripheral vascular disease group and into a miscellaneous group were first given thedrug intravenously and the responses were studied with skin temperature recordings in an attempt to predict the response to therapeutic administration of Regitine. The drug was then given orally for varying periods of time, with subjective and objective evidences of response, as well as side effects being noted. The results of these observations are set forth in the paper.
AGREEMENT BETWEEN THE HISTORY OF YELLOW FEVER AND ITS TRANSMISSION BY THE CULEX MOSQUITO (STEGOMYIA OF THEOBALD).
Authors: CHARLES FINLAY
Journal: JAMA (1902)

from the Sanitary Map, size 8x9 feet, which was made and compiled at the time.It is an accurate map of the city and shows the location of every house, hut, outhouse and insanitary place in the city ; separate sanitary cards were made also for each premise, containing not only a complete record of sanitary information but a plan of the same.The total population of Manila, exclusive of officers and men of the army and navy, was found to be 244,732, and the number of buildings 19,463, divided as follows :
The Photography of Retinal Impressions
Authors: G. M. Keevil
Journal: BMJ (1896)

<h3>Background</h3> Alarm symptom presentations are predictive of cancer diagnosis but may also be associated with cancer survival. <h3>Aim</h3> To evaluate diagnostic time intervals, and consultation patterns after presentation with alarm symptoms, and their association with cancer diagnosis and survival. <h3>Design and setting</h3> Cohort study using the Clinical Practice Research Database, with linked Cancer Registry data, in 158 general practices. <h3>Method</h3> Participants included those with haematuria, haemoptysis, dysphagia, and rectal bleeding or urinary tract cancer, lung cancer, gastro-oesophageal cancer, and colorectal cancer. <h3>Results</h3> The median (interquartile range) interval in days from first symptom presentation to the corresponding cancer diagnosis was: haematuria and urinary tract cancer, 59 (28–109); haemoptysis and lung cancer, 35 (18–89); dysphagia and gastro-oesophageal cancer, 25 (12–48); rectal bleeding and colorectal cancer, 49 (20–157). Three or more alarm symptom consultations were associated with increased odds of diagnosis of urinary tract cancer (odds ratio [OR] 1.84, 95% CI = 1.50 to 2.27), lung cancer (OR = 1.76, 95% CI = 1.07 to 2.90) and gastro-oesophageal cancer (OR = 2.17, 95% CI = 1.48 to 3.19). Longer diagnostic intervals were associated with increased mortality only for urinary tract cancer (hazard ratio 2.23, 95% CI = 1.35 to 3.69). Patients with no preceding alarm symptom had shorter survival from diagnosis of urinary tract, lung or colorectal cancer than those presenting with a relevant alarm symptom. <h3>Conclusion</h3> After alarm symptom presentation, repeat consultations are associated with cancer diagnoses. Longer diagnostic intervals appeared to be associated with a worse prognosis for urinary tract cancer only. Mortality is higher when cancer is diagnosed in the absence of alarm symptoms.
Book Review Self and Process: Brain states and the conscious present By Jason W. Brown. 201 pp. New York, Springer-Verlag, 1991. $42.50. ISBN 0–387–97514–4 . Information in the Brain: A molecular perspective By Ira B. Black. 225 pp., illustrated. Cambridge, Mass., MIT Press, 1991. $30. ISBN 0–262–02321–0 .
Authors: Neil W. Kowall
Journal: New England Journal of Medicine (1992)
"Relieving" Therapy For Antigen Exposure
Authors: Robert Collier
Journal: JAMA (1971)

<h3>To the Editor.—</h3> This concerns a double-blind study of the neutralizing dose as used in the provocative testing technique. The technique of testing for abnormal reactivity or allergy by deliberate trial of suspected allergens is often the only practical way to identify offenders. In the last eight or nine years, an attempt has been made to systematize this study by using injections of various dilutions of antigens to provoke a mild systemic response after which it is claimed that often another dose of antigen can be found which relieves the induced symptoms within minutes (Rinkle or Lee provocative testing method). This "relieving dose" is administered repeatedly for therapy when continued exposure to the antigen is anticipated as in coseasonal treatment for pollenosis or to offset intolerance to common food offenders. This study did not investigate the possible long-term benefit of such therapy, but was concerned with whether immediate effectiveness of
Multiple daily self-glucose monitoring: its essential role in long-term glucose control in insulin-dependent diabetic patients treated with pump and multiple subcutaneous injections
Authors: A. Schiffrin, M. Belmonte
Journal: Diabetes Care (1982)

Twenty-one insulin-dependent diabetic patients, previously treated with continuous subcutaneous insulin infusion (CSII), multiple subcutaneous insulin injections (MSI), and a combination of CSII and MSI (combined CSII-MSI) all supported by frequent capillary self-blood glucose (CBG) determinations (5-7 times daily) participated in a program to assess the importance of frequent CBG monitoring. We used a crossover design where diabetic control as measured by mean blood glucose and glycosylated hemoglobin were compared during periods of frequent and infrequent capillary blood glucose monitoring. Diabetic control was significantly better during periods of frequent self-glucose monitoring. We conclude that in compliant, motivated young adults with insulin-dependent diabetes, frequent self-glucose monitoring is critical for the long-term maintenance of glycemic control.
Further Reduction in Hospital Infection of Wounds
Authors: V. Logue, W. McKissock
Journal: BMJ (1945)

<h3>Abstract</h3> Vagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and rapidly expanding set of neurologic conditions. Classically used to treat epilepsy and depression, VNS has recently received FDA approval for stroke rehabilitation and is under preclinical and clinical investigation for other neurologic indications. Despite benefits across a diverse range of neurological disorders, the mechanism through which VNS influences central nervous system circuitry is not well described, limiting therapeutic optimization. A deeper understanding of the influence of VNS on neural circuits and activity is needed to maximize the use of VNS therapy across a broad range of neurologic conditions. To investigate how VNS can influence the neurons and circuits that underlie behavior, we paired VNS with upper limb movement in mice learning a skilled motor task. We leveraged genetic tools to perform optogenetic circuit dissection, as well as longitudinal <i>in vivo</i> imaging of calcium activity in cortical neurons to understand the effect of VNS on neural function. We found that VNS robustly enhanced motor learning when temporally paired with successful movement outcome, while randomly applied VNS impaired learning. This suggests that temporally-precise VNS may act through augmenting outcome cues, such as reinforcement signals. Within motor cortex, VNS paired with movement outcome selectively modulates the neural population that represents outcome, but not other movement-related neurons, across both acute and behaviorally-relevant timescales. Phasic cholinergic signaling from basal forebrain is required both for VNS-driven improvements in motor learning and the effects on neural activity in M1. These results indicate that VNS enhances motor learning through precisely-timed phasic cholinergic signaling to reinforce outcome, resulting in the recruitment of specific, behaviorally-relevant cortical circuits. A deeper understanding of the mechanisms of VNS on neurons, circuits and behavior provides new opportunities to optimize VNS to treat neurologic conditions.
Guanethidine in Hyperthyroidism
Authors: Sheldon S. Waldstein, George H. West, Winfred Y. Lee, David Bronsky
Journal: JAMA (1964)

Guanethidine sulfate has been administered to 90 patients with overt hyperthyroidism. By virtue of its potent and unique sympatholytic effects it ameliorates promptly and effectively those signs and symptoms of thyrotoxicosis due to sympathetic hyperactivity without affecting the function of the thyroid gland. It does not produce mental depression as will effective doses of reserpine in this disease. It is tolerated in large doses by the hyperthyroid patient but not by the euthyroid subject. Therefore, it is recommended for use only in patients with moderately severe to severely thyrotoxic conditions. Guanethidine is a potent drug for adjunctive therapy of the more severe forms of hyperthyroidism to be used on a short-term basis, before or concomitantly with specific antithyroid treatment.
THE ACCUMULATION OF IRON IN TUBERCULOUS AREAS
Authors: Valy Menkin
Journal: The Journal of Experimental Medicine (1932)

Repeated intravenous injections of ferric chloride are followed by an increase in the survival time of tuberculous rabbits. In the particular series of experiments reported this increase amounts to about 78 per cent over the average survival time of control rabbits. Tuberculous animals repeatedly injected with ferric chloride increase in weight during part of the period of these injections. The level reached in the series studied markedly exceeds that attained by control rabbits. Both control and experimental animals die of generalized tuberculosis. There is no indication at the time of death of any differences in the degree of pathological involvement between the two groups of animals.
Clinical Usefulness of the I131 Triiodothyronine Erythrocyte Uptake Test
Authors: D. Bruce Sodee
Journal: JAMA (1963)

In a series of 1,033 patients seen over a period of 25 months, 1,223 determinations of the in vitro I131triiodothyronine uptake of red blood cells (T3 RBC uptake rate) were completed. The results of routine protein-bound iodine and radioiodine thyroid uptake tests and the final clinical impression were correlated with the results of this test. Of the euthyroid patients 667 (85%) had normal T3 RBC uptake values, while 115 (14.7%) had unexplained elevations of the rate of T3 RBC uptake; of 121 hyperthyroid patients, 98% had supportive results to the T3 RBC uptake studies, and, of 33 hypothyroid patients, 27 had correlative results. The various disease states and technical artifacts that influence this test are mentioned. The T3 RBC uptake determination is established as a supportive test in the evaluation of thyroid status.
Impaired Absorption of Insulin Aspart From Lipohypertrophic Injection Sites
Authors: Unn-Britt Johansson, Susanne Amsberg, Lena Hannerz, Regina Wredling, Ulf Adamson, Hans J. Arnqvist, Per-Eric Lins
Journal: Diabetes Care (2005)

Lipohypertrophy is a common side effect of subcutaneous insulin therapy, occurring in up to 50% of patients with type 1 diabetes (1–3). It is generally held that absorption of insulin from such palpably abnormal sites is erratic, although the consequence thereof on glucose control has been considered controversial (1,4,5). Notably, a recent study using the continuous glucose monitoring system to monitor swings of blood glucose documented a significant correlation between the mean of daily differences of glucose and the severity of injection site lipohypertrophy (6). Few studies have investigated insulin uptake from lipohypertrophic tissue. Absorption of isophane (NPH) insulin, as determined by plasma free insulin, was found to be markedly defective at abnormal injection sites (7), and absorption of regular insulin (Actrapid) was delayed as determined by the clearance of 125I-insulin (8). It was concluded from these studies that the differences were of sufficient magnitude to be of clinical importance. Currently, both of these insulin preparations give way to insulin analogs. Therefore, the present study was conducted to investigate whether the absorption of a single subcutaneous dose of insulin aspart is impaired when administered to lipohypertrophic tissue in patients with type 1 diabetes.

Nine male patients (51.6 ± 5.4 years of age [means ± SE; range 22–69], HbA1c 7.3 ± 0.4% [ref. <5.2%], BMI 24.3 ± 1.0 kg/m2, and duration of diabetes 34.9 ± 5.1 years) were recruited from the …
The use of polyion complex micelles to enhance the oral delivery of salmon calcitonin and transport mechanism across the intestinal epithelial barrier
Authors: Na Li, Xin-Ru Li, Yan-Xia Zhou, Wen-Jing Li, Yong Zhao, Shu-Jin Ma, Jin-Wen Li, Ya-Jie Gao, Yan Liu, Xing-Lin Wang, Dong-Dong Yin
Journal: Biomaterials (2012)