tbuckley/cabot-search huggingface dataset:
Abstract 1292: Identification of BRCA1 and BRCA2 founder mutations in population isolates from Colombia
Authors: Anna Marie D. Tuazon, Carolina Ramírez, Mabel Bohorquez, Rodrigo Prieto, Jorge Castro, Gilbert Mateus, Alejandro Velez, Magdalena Echeverry, Luis G. Carvajal-Carmona
Journal: Cancer Research (2014)

Abstract Breast cancer (BC) is the most common malignancy in women. Germline mutations in breast cancer risk genes, such as BRCA1 and BRCA2, account for a large portion of hereditary breast cancer families. The contribution of mutations in breast cancer susceptibility genes has been poorly investigated in minority populations, such as in Hispanics from South America. While mutations in BRCA1 and BRCA2 display a heterogeneous mutation spectrum, specific mutations often occur in population isolates. Using the KASP genotyping technology, we screened 476 unselected Colombian breast cancer patients for three common BRCA1 and one BRCA2 founder mutations in the Hispanic population. The BRCA2 c.2806_2809delAAAC founder mutation was identified in 3 of the 476 BC cases (0.6%). Strikingly, 24 out of 476 cases (5.0%) harbored the BRCA1 founder mutation c.3331_3334delCAAG, which has also been reported in Southern European populations, including Spain and Portugal. The clinical data and family history of these patients have highlighted a distinct geographic region from where these cases originate. This finding potentially represents one of the most remarkable founder effects reported in human populations. To date the arrival of the BRCA1 c.3331_3334delCAAG mutation to Colombia, we are completing haplotype analysis of the patients and their families, along with BC cases from Spain and Portugal that harbor the same mutation. Interestingly, haplotype analyses of our BC cases have revealed a haplotype larger than 3.5 cM. In the future, we aim to perform haplotype analysis of family members of the mutation carriers and BC cases from Portugal and Spain to further study the haplotype around this BRCA1 mutation, which will allow us to date the origin of the mutation. By understanding the prevalence of mutations in known breast cancer risk genes in minority populations, cancer disparities can be better addressed and breast cancer screening can be improved. Furthermore, the ability to identify such strong founder effects highlights an advantage of using this Colombian population isolate in facilitating the identification of novel BC risk genes. Citation Format: Anna Marie D. Tuazon, Carolina Ramírez, Mabel Bohorquez, Rodrigo Prieto, Jorge Castro, Gilbert Mateus, Alejandro Velez, Magdalena Echeverry, Luis G. Carvajal-Carmona. Identification of BRCA1 and BRCA2 founder mutations in population isolates from Colombia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1292. doi:10.1158/1538-7445.AM2014-1292
Reducing the Long-term Effects of Chemotherapy in Young Women With Early-Stage Breast Cancer
Authors: Hope S. Rugo, Mitchell P. Rosen
Journal: JAMA (2011)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
CATHETER CLOSURE OF ATRIAL SEPTAL DEFECT IN GERIATRIC POPULATION (&gt; 70 YEARS OLD)
Authors: Koji Nakagawa, Teiji Akagi, Yasufumi Kijima, Manabu Taniguchi, Kengo Kusano, Hiroshi Itoh, Shunji Sano
Journal: Journal of the American College of Cardiology (2010)
Atrial Natriuretic Peptide Has Different Effects on Contractility and Intracellular pH in Normal and Hypertrophied Myocytes From Pressure-Overloaded Hearts
Authors: Minori Tajima, Jozef Bartunek, Ellen O. Weinberg, Nobuhiko Ito, Beverly H. Lorell
Journal: Circulation (1998)

Background —Atrial natriuretic peptide (ANP) depresses contractility in left ventricular myocytes. Its expression is upregulated in pressure-overloaded hypertrophied hearts; however, the effects of ANP on contractility in hypertrophied myocytes are not known. Our aims were (1) to examine the cellular mechanisms of this depression in contractility in normal myocytes and (2) to test the hypothesis that the effects of ANP on contractility differ in hypertrophied myocytes from rats with ascending aortic stenosis. Methods and Results —We measured the myocyte shortening as an index of contractility, [Ca 2+ ] i with fluo 3, and pH i with seminaphthorhodafluor-1 (SNARF-1). In normal control myocytes (n=26), ANP caused a concentration-dependent depression of contractility and reduction in pH i . In the presence of 10 −6 mol/L ANP, fractional cell shortening was 78±5% of baseline ( P &lt;0.05) and pH i was reduced by 0.16±0.04 U from baseline ( P &lt;0.01) without changes in [Ca 2+ ] i . The magnitude of the depression of contraction caused by ANP was similar to that caused by intracellular acidification induced by an NH 4 Cl pulse. The effects of ANP on contractility and pH i were prevented in the presence of 5-( N -ethyl- N -isopropyl)-amiloride (EIPA), which inhibits the Na + /H + exchanger. In hypertrophied myocytes (n=23), ANP did not depress either myocyte contractility or pH i at concentrations of either 10 −8 , 10 −7 , or 10 −6 mol/L. ANP caused no change in pH i or the [Ca 2+ ] i transient in hypertrophied myocytes. The cGMP level was increased and Na + /H + exchanger mRNA levels were normal in left ventricles from aortic stenosis rats compared with controls. Conclusions —ANP directly depresses contractility in normal myocytes via intracellular acidification, which decreases myofilament [Ca 2+ ] i sensitivity. In contrast, ANP causes no effects on contractility and pH i in hypertrophied myocytes, suggesting a suppression in the coupling of the ANP-cGMP intracellular signaling pathway to the Na + /H + exchanger.
FDA Approves Generic Enoxaparin
Authors: Rebecca Voelker
Journal: JAMA (2010)

But the FDA does not become involved in such oversight until a sponsor submits an Investigational New Drug Application. This creates a loophole in oversight because such applications may not be submitted for certain ongoing or early-phase trials— trials in which participants may be particularly exposed to safety risks, the OIG said. While these concerns apply equally to domestic and foreign studies, the fact that the FDA inspects foreign trials at only 37% of the rate seen domestically makes individuals outside the United States statistically more vulnerable to possible substandard safety. Also, the OIG found that the FDA was unable to provide detailed clinical trial data for 29 of the 129 applications reviewed in the report, and that the agency inspected trial sites in only 20 of 72 countries the OIG identified in those applications. How often the FDA inspects foreign trial sites is not the key issue, as the agency still plays a major role in ensuring that drug research is conducted in an appropriate manner, said Ken Johnson, senior vice president, Pharmaceutical Research and Manufacturers of America. “Regardless of the location, however, companies seeking US approval must maintain the FDA’s high standards for conducting the trial,” Johnson said in a statement. “For instance, any related trials conducted outside the US must comply with FDA requirements covering good clinical practices, in addition to meeting the requirements mandated in these important emerging markets.” To improve oversight of foreign trials, the OIG suggested that the FDA continue to develop inspection agreements with foreign regulatory bodies, inspect in more countries, and look to new models of oversight. A spokesperson for the FDA said the agency is already tackling the problems: “The agency already has several initiatives under way to improve FDA’s oversight of clinical trials conducted internationally, including sharing inspection information with foreign regulatory authorities, engaging in broader outreach with other countries around the world, and developing an analysis tool for efficiently identifying foreign and domestic sites for inspection.” Sidney Wolfe, MD, director of Public Citizens Health Research Group, expressed skepticism that the FDA will follow through on its initiatives. He pointed to its poor track record in inspecting pharmaceutical manufacturing plants in foreign countries and its apparent lack of effort to seek more funding to improve its factory inspections. “That showed a lackadaisical attitude on the part of the FDA,” Wolfe said. “The FDA . . . has not been assertive in seeking funding to improve such inspections.”
The Pulmonary Circulation and Interstitial Space
Authors: Louis J. Kettel
Journal: JAMA (1969)

An important advantage of attending a scientific meeting is the interchange between presenters and floor discussants. In recent years, scientific programs have often lacked adequate time for this interchange. Such was not a deficit at the Satellite Conference on the  Circulation held in Chicago as part of the XXIVth International Congress of Physical Sciences in 1968. This meeting brought together a large number of scientists and specifically called for the free exchange of ideas among peers after each presentation. With the editorial guidance of Drs. Fishman and Hecht, this book is the outgrowth of the symposium. The result is a superb compilation of ideas, a written record for those who attended the meeting, and an important reference source for those who were unable to attend.  The text is divided into four sections with the following titles: Pulmonary Alveolar-Capillary Interface and Interstitium, Vasomotion and Electrophysiology of Smooth Muscle, Regulation of
Prevalence of Haarlem I and Beijing types of Mycobacterium tuberculosis strains in Iranian and Afghan MDR-TB patients
Authors: Parissa Farnia, Mohamad Reza Masjedi, Mehdi Mirsaeidi, Foroozan Mohammadi, None Jallaledin-Ghanavi, Veronique Vincent, Moslem Bahadori, Ali Akbar Velayati
Journal: Journal of Infection (2006)
Regional left ventricular epicardial deformation in the passive dog heart.
Authors: A D McCulloch, B H Smaill, P J Hunter
Journal: Circulation Research (1989)

Epicardial wall motion was measured on the left ventricular free wall in six isolated potassium-arrested dog hearts using a biplane video technique. Significant regional variations in epicardial deformations were recorded during static ventricular filling. Epicardial stretches varied linearly with cavity volume, sometimes exceeding 20% at physiological left ventricular end-diastolic pressures. The maximum component of epicardial stretch and the derived wall thinning increased substantially from the base to the apex on both the anterior and the posterior free walls of the left ventricle. In five hearts, the direction of greatest epicardial stretch at moderate and high filling pressures coincided closely with the local epicardial fiber direction, suggesting that the left-handed epicardial fiber helices stretch preferentially during passive filling to maximize end-diastolic fiber lengths. Epicardial rotation was always counterclockwise, consistent with a reduction in the pitch of the fiber helix during filling. These results suggest that, on the epicardial surface, the passive myocardium is anisotropic with respect to the local fiber direction. We suggest that the resulting torsional shear acts to minimize transmural gradients of fiber stretch.
PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR
Authors: Douglas A. MacFadyen
Journal: The Journal of Experimental Medicine (1934)

1. Aqueous extracts of Chicken Tumor I cause a disintegration of yeast nucleic acid. 2. Two enzyme activities, a polynucleotidase and a phosphatase, are demonstrated. 3. These activities are distinguished by different reactions to an environment of hydrogen, different optima of hydrogen ion concentration, and different rates of activity. 4. Adsorption with aluminum hydroxide Type C removes substances inhibiting the polynucleotidase activity. 5. There is a rough proportionality between the polynucleotidase activity and the tumor-inducing power of different fractions of extracts of Chicken Tumor I. 6. There is a rough proportionality between the inhibition of polynucleotidase activity and the inhibition of the tumor agent. 7. The polynucleotidase activity of Chicken Tumor I is as great as that of spleen, slightly less than that of kidney and liver, but much greater than that of muscle. There are also qualitative differences.
Crunch time for doctors' hours
Authors: F. Godlee
Journal: BMJ (2009)

Concern about the European Working Time Directive continues to run high, and its effects on patient care and specialist training remain hotly disputed. Fewer hours a week and fewer years in training presage a cohort of less experienced new consultants. A shortage of doctors in the UK means juniors doing unpaid or additional locum work to fill rotas and having to lie about their hours (http://careers.bmj.com/careers/advice/view-article.html?id=20000485). Shift systems, loss of the team structure, and poor handover are also reported to be damaging morale.

The strongest protests come from the surgeons, who are especially vulnerable to the effects of reduced hands-on experience. …
Depression of Myocardial Contractility with Low Doses of Ethanol in Normal Man
Authors: S. SULTAN AHMED, GILBERT E. LEVINSON, TIMOTHY J. REGAN
Journal: Circulation (1973)

Depression of myocardial contractility after ethanol ingestion in man has previously been shown only in patients with heart disease. In the present study, normal subjects, aged 23-30 years, ingested six ounces of 43% alcohol over a two hour period (Group I, 6 subjects) or a one hour period (Group II, 5 subjects). Systolic time intervals were measured every 15 min from simultaneous ECG, phonocardiogram and carotid pulse tracings. Heart rate, total electromechanical systole and left ventricular ejection time (LVET) were not changed at any time from pre-alcohol values and, except for a small (5 mm Hg) and transient change in diastolic pressure in Group II, aortic pressures also were unchanged. However, in Group I, after 60 min, at a blood ethanol of 74 ± 3 mg%, left ventricular depression was manifested by increased pre-ejection period (PEP) from 90 ± 2 to 96 ± 3.1 msec, isovolumic time (IVT) from 44 ± 3.5 to 52 ± 4 ( P &lt; .01), and PEP/LVET ratio from 0.299 ± 0.009 to 0.323 ± 0.01 ( P &lt; .05). Further depression occurred at two hours with blood ethanol at 111 ± 6 mg%. Doubling ingestion rate (Group II) produced reduction of left ventricular performance at 30 min at a blood level of 50 ± 3 mg%. Feeding of isocaloric sucrose in 5 subjects (Group III) as a control produced a decrease in PEP, IVT, and PEP/LVET. Thus, alcohol in nonintoxicating doses elicits a depression of cardiovascular function in normal unhabituated subjects.
The Next Decade: Expectations From the Biological Sciences
Authors: George Tarjan
Journal: JAMA (1965)

Theference collected substantial knowledge on mental retardation. It focused on the aspects which have major relevance to the daily practice of the primary physician. Lest we gain the impression that most problems concerning mental retardation have been resolved, we turn our attention now to the unresolved issues. Dr. Gardner has presented the psychosocial and educational aspects. My focus is on those topics which have a stronger biomedical component. I have selected five subject areas which I expect will gain in importance during the next decades.  A Problem in Epidemiology  It is often stated, on the basis of reasonably hard data, that 3% of the newborn will develop as mentally retarded individuals. It is estimated that (1) once in 1,000 a child is born whose IQ will not exceed 20; (2) the birth frequency of children with IQs between 20 to 50 is four times higher; and (3) 25 of 1,000
Treatment of Spasticity in Multiple Sclerosis With Dantrolene
Authors: Eduardo S. Tolosa
Journal: JAMA (1975)

<h3>To the Editor.—</h3> The review article on dantrolene sodium (231:862, 1975) was read with great interest. We have conducted a double-blind, placebo-controlled, trial of this drug in a group of patients with multiple sclerosis, on an outpatient basis. Since the results of our study appeared to be different from those of the article inThe Journal, we wish to report them here. Twenty-three patients took part in the study. Spasticity in the lower extremities was prominent in all patients; 11 suffered from severe disability, and were confined to a wheelchair. After an initial base-line evaluation, the patients were randomly allocated to the drug (12 patients) and the placebo (11 patients) groups. Treatment with dantrolene sodium or appropriate placebo was then started at 25 mg four times a day, and increased at weekly increments of 100 mg, if tolerated, up to a maximum daily dose of 800 mg. Evaluations were made again
RADICAL CURE OF UMBILICAL HERNIA.
Authors: WILLIAM J. MAYO
Journal: JAMA (1907)

The older methods of operation for the radical cure of large umbilical hernias were so unpromising that few surgeons cared to attack them unless forced to do so by acute conditions. Not only was the prospect of relief uncertain, but there was considerable danger attending the operation itself because of increased intraabdominal tension, as the recognized procedure was to dissect out the recti muscles and transplant them to the median line. These patients are usually obese with thinned-out recti muscles widely separated, so that when brought in apposition they have but little retentive power, even if the tension which is necessarily put on them is sufficient to maintain them in position. The hernial opening lies above the attachments of the urachus and remnants of the hypogastric arteries in the umbilical scar. That these three structures exercise some influence is evidenced by the fossa which they normally outline in the peritoneal
Hooked on Hormones-Reply
Authors: Kenneth B. Kashkin
Journal: JAMA (1990)

<h3>In Reply. —</h3> We thank Drs Rosse and Deutsch for presenting their evidence for the interaction of sex steroids with benzodiazepine/γ-aminobutyric acidA receptors. There is other evidence for such interactions.<sup>1</sup>Based on such data and the clinical similarity of acute alcohol and steroid withdrawal syndromes, agents used in the treatment of alcohol withdrawal (benzodiazepines, α<sub>2</sub>-adrenergic agonists, and β-adrenergic antagonists) should be investigated for effectiveness in reducing hyperadrenergic symptoms precipitated by anabolic steroid withdrawal. Alcohol withdrawal-type seizures have not been reported in anabolic steroid users, although this may be related to the long half-life of elimination of the steroids ingested or injected. Interestingly, anabolic steroids may be more like alcohol than like the rapidly addicting stimulants, such as cocaine, in their potential to produce a substance dependence disorder. Drs Rosse and Deutsch's data highlight the complex biochemical, if not clinical, relationships of steroid, alcohol, sedative/hypnotic, opioid, and stimulant
Hepatitis B virus X protein modulates oncogene yes-associated protein by CREB to promote growth of hepatoma cells
Authors: Tao Zhang, Junping Zhang, Xiaona You, Qian Liu, Yumei Du, Yuen Gao, Changliang Shan, Guangyao Kong, Youliang Wang, Xiao Yang, Lihong Ye, Xiaodong Zhang
Journal: Hepatology (2012)

Hepatitis B virus X protein (HBx) plays critical roles in the development of hepatocellular carcinogenesis (HCC). Yes-associated protein (YAP), a downstream effector of the Hippo-signaling pathway, is an important human oncogene. In the present article, we report that YAP is involved in the hepatocarcinogenesis mediated by HBx. We demonstrated that the expression of YAP was dramatically elevated in clinical HCC samples, hepatitis B virus (HBV)-infected hepatoma HepG2.2.15 cell line, and liver cancer tissues of HBx-transgenic mice. Meanwhile, we found that overexpression of HBx resulted in the up-regulation of YAP in stably HBx-transfected HepG2/H7402 hepatoma cell lines, whereas HBx RNA interference reduced YAP expression in a dose-dependent manner in the above-mentioned cell lines, suggesting that HBx up-regulates YAP. Then, we investigated the mechanism underlying the up-regulation of YAP by HBx. Luciferase reporter gene assays revealed that the promoter region of YAP regulated by HBx was located at nt −232/+115 containing cyclic adenosine monophosphate response element-binding protein (CREB) element. Chromatin immunoprecipitation (ChIP) demonstrated that HBx was able to bind to the promoter of YAP, whereas it failed to work when CREB was silenced. Moreover, we confirmed that HBx activated the YAP promoter through CREB by electrophoretic mobility shift assay and luciferase reporter gene assays. Surprisingly, we found that YAP short interfering RNA was able to remarkably block the HBx-enhanced growth of hepatoma cells in vivo and in vitro. Conclusion: YAP is a key driver gene in HBx-induced hepatocarcinogenesis in a CREB-dependent manner. YAP may serve as a novel target in HBV-associated HCC therapy. (HEPATOLOGY 2012;56:2051–2059)
Clinical and Angiographic Follow-Up After Primary Stenting in Acute Myocardial Infarction
Authors: Gregg W. Stone, Bruce R. Brodie, John J. Griffin, Costantino Costantini, Marie Claude Morice, Frederick G. St. Goar, Paul A. Overlie, Jeffrey J. Popma, JoAnn McDonnell, Denise Jones, William W. O’Neill, Cindy L. Grines
Journal: Circulation (1999)

Background —Restenosis has been reported in as many as 50% of patients within 6 months after PTCA in acute myocardial infarction (AMI), which necessitates repeat target-vessel revascularization (TVR) in ≈20% of patients during this time period. Routine (primary) stent implantation after PTCA has the potential to further improve late outcomes. Methods and Results —Primary stenting was performed as part of a prospective study in 236 consecutive patients without contraindications who presented with AMI of &lt;12 hours’ duration at 9 international centers. A mean of 1.4±0.7 stents were implanted per patient (97% Palmaz-Schatz) at 17.3±2.4 atm. During a clinical follow-up period of 7.4±2.6 months, death occurred in 4 patients (1.7%), reinfarction occurred in 5 patients (2.1%), and TVR was required in 26 patients (11.1%). By Cox regression analysis, small reference-vessel diameter and the number of stents implanted were the strongest determinants of TVR. Angiographic restenosis occurred in 27.5% of lesions. By multiple logistic regression analysis, the number of stents implanted and the absence of thrombus on the baseline angiogram were independent determinants of binary restenosis. Conclusions —A strategy of routine stent implantation during mechanical reperfusion of AMI is safe and is associated with favorable event-free survival and low rates of restenosis compared with primary PTCA alone.