tbuckley/cabot-search huggingface dataset:
Is Cancer Adaptation Gone Awry?
Authors: Beverly Merz
Journal: JAMA (1989)

GENES ARE NOT THE MASTERS but the servants of the cell.  That was the heretical word from Emmanuel Farber, MD, one of a handful of speakers at the recent 80th annual meeting of the American Association for Cancer Research (AACR) in San Francisco, Calif. It emanated from a symposium entitled   of Cancer, sandwiched among scores of presentations on the molecular genetics of cancer.  For a better part of the decade, the prevailing wisdom of the AACR, whose membership is heavily weighted with basic investigators, has been that cancer is a genetic disease, which can be traced to a succession of DNA mutations and the influences of the resultant gene products. The epigeneticists are challenging this notion, declaring that genetic alterations alone are not sufficient to cause cancer; they need to occur in hostile extracellular environments. Their declarations have fallen on deaf ears. Epigenetics is the stepchild of cancer
Two Different Scenarios of Squamous Cell Carcinoma Within Advanced Basal Cell Carcinomas
Authors: Gefei A. Zhu, Uma Sundram, Anne Lynn S. Chang
Journal: JAMA Dermatology (2014)

Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment.The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected.These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.
Relation of phasic coronary flow velocity profile to clinical and hemodynamic characteristics of patients with aortic valve disease.
Authors: M Hongo, T Goto, N Watanabe, T Nakatsuka, M Tanaka, O Kinoshita, H Yamada, S Okubo, M Sekiguchi
Journal: Circulation (1993)

BACKGROUND Our objective was to assess phasic coronary blood flow and velocity characteristics of the proximal portion of the left anterior descending artery and to evaluate their relation to the clinical and hemodynamic manifestations in patients with aortic valve disease. METHODS AND RESULTS We examined 26 patients with chronic aortic regurgitation (AR), 12 patients with predominant aortic stenosis (AS), and 11 control subjects using an intravascular Doppler catheter with spectral analysis. Angiographic assessment of AR identified 10 patients with mild regurgitation and 16 with severe regurgitation. The resting systolic coronary flow velocity-time integral (VTI) was significantly higher and the diastolic VTI was slightly but significantly higher in patients with severe regurgitation than in those with mild regurgitation (11.8 +/- 4.2 vs 4.1 +/- 1.1 cm, P &lt; .001; 18.5 +/- 5.8 vs 13.2 +/- 3.2 cm, P &lt; .05) and control subjects (4.0 +/- 1.0 cm, P &lt; .001 and 13.3 +/- 3.6 cm, P &lt; .05), respectively. Patients with AS had a slightly lower resting systolic VTI (3.8 +/- 1.4 cm) and a higher diastolic VTI (14.6 +/- 3.7 cm) than control subjects. Resting coronary blood flow was greater in patients with aortic valve disease than in control subjects. There was a significant correlation between the ratio of the resting systolic to diastolic VTI (S/D ratio) and the ratio of the aortic systolic to diastolic pressure (r = .75, P &lt; .001) in patients with AR. The S/D ratio was inversely correlated with left ventricular systolic pressure (r = -.92, P &lt; .001) and positively correlated with the ratio of the aortic systolic to diastolic pressure (r = .68, P &lt; .05) in patients with AS. CONCLUSIONS Our results indicate that hemodynamic changes related to aortic valve disease contribute to alterations in the resting phasic coronary blood flow and velocity profiles observed in these patients.
Promoting Primary Care: Where to Start?-Reply
Authors: Barry Stimmel
Journal: JAMA (1993)

<h3>In Reply.</h3> —The decreasing number of graduates from US medical schools entering primary care fields is of increasing public concern. At the onset of the article, two points were made. Primary care included family practice, general internal medicine, and general pediatrics, recognizing that a community might best be served by any one or more of these specialties. No value judgment was placed on any field over any other. Second, regardless of how primary care is defined, "all schools should have clerkships in primary care, as this is an essential part of an undergraduate medical education," with "attractive role models and effective curricula." Diversity among schools in producing family practitioners or general internists and pediatricians is a strength not a weakness. As an example, with respect to Dr Naumburg's comments concerning graduates of the Mount Sinai School of Medicine, in the class of 1992, although only 4% entered family practice residencies,
Hepatic granulomata in AIDS
Authors: Richard J. Stenger
Journal: Hepatology (1986)

During a one month period liver biopsy was carried out on eight patients with established acquired immune deficiency syndrome (AIDS) and two suspected of having AIDS to evaluate raised liver enzymes or unexplained fever and weight loss. Each of the 10 patients was found to have hepatic granulomas. Appropriate staining techniques showed acid-fast bacilli in seven of the liver specimens. One specimen contained numerous Cryptococcal organisms. Two biopsies showed granulomas but no organisms. Liver biopsy was found to be a high yield and rapid diagnostic procedure in patients with AIDS. Our results suggest that hepatic mycobacterial infection may be more common in the syndrome than previously recognized and that liver biopsy specimens should be examined routinely for the presence of acid-fast bacilli.
Distribution and Supervision of Oral Contraceptives
Authors: M. Smith
Journal: BMJ (1974)

The distribution and supervision of oral contraceptives is discussed.  Previously there were reasons to restrict the use of these drugs solely to prescription by doctors for the effects of them were unknown fewer patients were involved and the doses were greater.  It is recommended at this point however that the range of those empowered to dispense oral contraceptives be widened to include state registered n urses midwives and health visitors who have had some additional traini ng in contraceptive  practice.  The doctor would continue to supervise the service.  It is suggested that any woman who wishes to see a doctor when starting oral contraceptives or during their use should continue to do so.
"ANOMALY OF THE APPENDIX"
Authors: J. F. Baldwin
Journal: JAMA (1923)

To the Editor:  —In the Cincinnati Lancet-Clinic , Dec. 23, 1911, I reported the case of an appendix similar to the one reported by Dr. Willour inThe Journal, July 21, and in addition referred to another case taken from the Australasian Medical Gazette , July 20, 1911, as abstracted inThe Journal, Sept. 16, 1911. In my own case, in addition to the appendix communicating with the bowel at both ends, the intervening loop of bowel had been caught under the appendix so as to produce partial obstruction.  A good many years ago I reported a case in which the appendix extended directly upward from the cecum, and attached itself to the gallbladder, and then perforated so that bile could pass directly from the gallbladder to the cecum. The bile ducts were normal and there was no way of determining how much bile passed through the new opening.  While on the
The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy
Authors: Adam M. Jacques, Natalia Briceno, Andrew E. Messer, Clare E. Gallon, Shapour Jalilzadeh, Edwin Garcia, Gaelle Kikonda-Kanda, Jennifer Goddard, Sian E. Harding, Hugh Watkins, M. Tomé Esteban, Victor T. Tsang, William J. McKenna, Steven B. Marston
Journal: Cardiovascular Research (2008)

The aim of the study was to compare the functional and structural properties of the motor protein, myosin, and isolated myocyte contractility in heart muscle excised from hypertrophic cardiomyopathy patients by surgical myectomy with explanted failing heart and non-failing donor heart muscle.Myosin was isolated and studied using an in vitro motility assay. The distribution of myosin light chain-1 isoforms was measured by two-dimensional electrophoresis. Myosin light chain-2 phosphorylation was measured by sodium dodecyl sulphate-polyacrylamide gel electrophoresis using Pro-Q Diamond phosphoprotein stain.The fraction of actin filaments moving when powered by myectomy myosin was 21% less than with donor myosin (P = 0.006), whereas the sliding speed was not different (0.310 +/- 0.034 for myectomy myosin vs. 0.305 +/- 0.019 microm/s for donor myosin in six paired experiments). Failing heart myosin showed 18% reduced motility. One myectomy myosin sample produced a consistently higher sliding speed than donor heart myosin and was identified with a disease-causing heavy chain mutation (V606M). In myectomy myosin, the level of atrial light chain-1 relative to ventricular light chain-1 was 20 +/- 5% compared with 11 +/- 5% in donor heart myosin and the level of myosin light chain-2 phosphorylation was decreased by 30-45%. Isolated cardiomyocytes showed reduced contraction amplitude (1.61 +/- 0.25 vs. 3.58 +/- 0.40%) and reduced relaxation rates compared with donor myocytes (TT(50%) = 0.32 +/- 0.09 vs. 0.17 +/- 0.02 s).Contractility in myectomy samples resembles the hypocontractile phenotype found in end-stage failing heart muscle irrespective of the primary stimulus, and this phenotype is not a direct effect of the hypertrophy-inducing mutation. The presence of a myosin heavy chain mutation causing hypertrophic cardiomyopathy can be predicted from a simple functional assay.
Abstract 2776: Inhibition of Nek2 by novel small molecules affects proteasome activity
Authors: Lingyao Meng, Steven L. Warner, Alexis Mollard, Hariprasad Vankayalapati, Sunil Sharma, David J. Bearss
Journal: Cancer Research (2012)

Abstract Nek2 is a serine/threonine kinase that has been associated with centrosome function and cell cycle progression. Nek2 overexpression has been reported in several tumor types including breast and lung cancers. We have previously shown that elevated expression of Nek2 in clinical samples of multiple myeloma (MM) correlates with bortezomib resistance. Furthermore, the overexpression of Nek2 in MM cell lines decreases sensitivity to bortezomib and knockdown with RNAi sensitizes bortezomib resistant cells. Due to the proteaseome inhibitory activity of bortezomib, we hypothesized that Nek2 overexpression may increase proteasome activity. 26S proteasomes were isolated by ultracentrifugation from stably transfected Hela cells (+Nek2 or +GFP) and Nek2 was shown to be involved in the 26S proteasome complex by western blot. Proteasome activity assays were performed both biochemically and in cell culture demonstrating that proteasome activity in Hela+Nek2 is significantly higher than in Hela+GFP. Furthermore, the isolated 26S proteasomes were incubated with novel Nek2 inhibitors (HCI-2184 and HCI-2389) resulting in a significant reduction in proteasome function when used as single agents or in combination with bortezomib. HCI-2184, a reversible inhibitor of Nek2, demonstrated an IC50 value in the range of 13-38 nM, and HCI-2389, an irreversible inhibitor of Nek2, showed an IC50 value between 8-26 nM. Similarly, both compounds significantly increased the efficacy of bortezomib in inhibiting the proteasome activity. These results were confirmed in multiple cancer cell lines, including ARP1 (human MM cell line), H299 (human lung cancer cell line) and K28 (mouse Leydig tumor cell line). The effect of inhibiting Nek2 on cell cycle was also investigated. The expression levels of cyclinB1 and cdc2, proteins degraded by the proteasome for cells to exit mitosis, were increased in HCI-2389 treated Hela+Nek2 and to a lesser extent Hela+GFP treated cells. While Nek2 overexpression leads to the down-regulation of cyclinB1 and cdc2, HCI-2389 treatment successfully rescued this effect. Flow cytometry data showed that both treatments of HCI-2184 and HCI-2389 significantly arrested Hela+Nek2 and Hela+GFP in G2/M phase after 24 hours at concentration as low as 10nM. In conclusion, we have discovered a novel biological function of Nek2 related to elevated proteasome activity. We also demonstrated that our novel Nek2 inhibitors efficiently inhibit Nek2 function, resulting in reduced proteasome activity. These Nek2 inhibitors have the potential to be applied clinically for treatment of the MM patients resistant to bortezomib. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2776. doi:1538-7445.AM2012-2776
Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair
Authors: Christopher B. Little, Clare T. Meeker, Suzanne B. Golub, Kate E. Lawlor, Pamela J. Farmer, Susan M. Smith, Amanda J. Fosang
Journal: Journal of Clinical Investigation (2007)

Aggrecan loss from cartilage in arthritis is mediated by aggrecanases. Aggrecanases cleave aggrecan preferentially in the chondroitin sulfate-2 (CS-2) domain and secondarily at the E(373) downward arrow(374)A bond in the interglobular domain (IGD). However, IGD cleavage may be more deleterious for cartilage biomechanics because it releases the entire CS-containing portion of aggrecan. Recent studies identifying aggrecanase-2 (ADAMTS-5) as the predominant aggrecanase in mouse cartilage have not distinguished aggrecanolysis in the IGD from aggrecanolysis in the CS-2 domain. We generated aggrecan knockin mice with a mutation that rendered only the IGD resistant to aggrecanases in order to assess the contribution of this specific cleavage to cartilage pathology. The knockin mice were viable and fertile. Aggrecanase cleavage in the aggrecan IGD was not detected in knockin mouse cartilage in situ nor following digestion with ADAMTS-5 or treatment of cartilage explant cultures with IL-1 alpha. Blocking cleavage in the IGD not only diminished aggrecan loss and cartilage erosion in surgically induced osteoarthritis and a model of inflammatory arthritis, but appeared to stimulate cartilage repair following acute inflammation. We conclude that blocking aggrecanolysis in the aggrecan IGD alone protects against cartilage erosion and may potentiate cartilage repair.
Persistent Earnings Inequities for Female Physicians
Authors: Molly Cooke
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
Comparison in Man of Adrenergic Blockade Produced by Dibenzyline, Ilidar, Priscoline, and Regitine
Authors: HAROLD D. GREEN
Journal: Circulation (1957)

A method is presented for analyzing the probable effectiveness of blocking drugs in relieving vasospasm in the extremities, and comparison is given of the relative potency and side effects of 4 adrenergic blocking drugs and of their effects on heart rate, arterial pressure, and cardiac output, as estimated from a "circulatory index." Data are also given on the use of these drugs in evaluation of the circulation in patients.
Alcohol Interventions in Trauma Centers-Reply
Authors: Larry M. Gentilello
Journal: JAMA (1996)

In Reply.  —There are a number of pre-event interventions that may be used to reduce the rate of alcohol-related motor vehicle crashes. These include education, enforcement, and engineering modifications such as an ignition interlock device. However, these additional strategies were not the focus of our article. We would like to thank Ms Miller for providing updated data on the New York State Health Care Intervention Services program. We applaud their efforts and agree that we need more programs of this type, not only in primary care settings, but in trauma centers throughout the country.  We congratulate Dr Rostenberg and the Center for Substance Abuse Treatment for the development of the TIP. There is growing recognition that alcohol-related trauma is a public health problem of enormous dimensions. Interventions exist that have been demonstrated to be useful and cost-effective in a variety of settings, and their acceptance by trauma centers is long
Abstract SY20-03: Nuclear-mitochondrial cross-talk: A key determinant of cancer metastasis
Authors: Danny R. Welch, Wen Liu, Kyle P. Feeley, Scott W. Ballinger
Journal: Cancer Research (2014)

Abstract Despite the well known energy requirements and stresses of metastasis, the relationships between metabolism, mitochondrial genetics and metastasis are still underdeveloped. Two lines of investigation point to more intimate involvement of mtDNA than is widely appreciated. First, recent data demonstrate that the metastasis suppressor KISS1 essentially reverses the so-called Warburg Effect by regulating mitochondrial biogenesis. KISS1 re-expression results in higher pH[Ex] due to reduced lactate secretion concomitant with reduced glycolysis and a shift toward oxidative phosphorylation. KISS1-expressing cells have 30-50% more mitochondrial mass, which appears to be due to higher expression of PPARγ co-activator 1α (PGC1α), a master regulator of mitochondrial biogenesis. shRNA-mediated knockdown of KISS1 and PGC1α establish a pathway between these molecules, mitochondrial biogenesis and metastatic potential. Second, genetic crosses with a newly described MNX (mitochondrial-nuclear exchange) mice suggest that mitochondrial polymorphisms (haplotypes) may control susceptibility to metastasis. Transgenic FVB/N-tg:MMTV-PyMT which spontaneously develop mammary tumors and lung metastasis with high penetrance were crossed with female MNX mice having the same nuclear background (FVB - wild-type) but with C57BL/6 and BALB/c mitochondrial backgrounds. Using this strategy, the mtDNA contributions to metastasis can be discriminated. Results demonstrate that tumor and metastasis incidence do not appear to be significantly different. However, metastasis size is greatly affected. Taken together, these data strongly support the concept that mitochondrial-nuclear cross-talk is a more significant determinant of metastasis than generally appreciated. SUPPORT: NCI-CA134981; Natl Fndn Cancer Res, Susan G. Komen SAC11037, Hall Family Fndn, KS Bioscience Auth. Citation Format: Danny R. Welch, Wen Liu, Kyle P. Feeley, Scott W. Ballinger. Nuclear-mitochondrial cross-talk: A key determinant of cancer metastasis. [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 SY20-03. doi:10.1158/1538-7445.AM2014-SY20-03
Multiple Hepatic Adenomas
Authors: SEOK TAE LIM, MYUNG-HEE SOHN, JAE-YONG KWAK, CHANG-YEOL YIM
Journal: Clinical Nuclear Medicine (2002)

A 24-year-old man with multiple hepatic masses incidentally detected by ultrasonography underwent Tc-99m RBC liver SPECT. SPECT images showed increased blood pooling mimicking hemangiomas in two of four masses or activity similar to normal liver in the others. The patient had a 3-year history of steroid therapy for rheumatoid arthritis. Computed tomography and magnetic resonance imaging showed multiple liver lesions. Angiography revealed three hypervascular and one hypovascular mass. Microscopic examination of the enucleated specimens disclosed hepatic adenomas with many dilated sinusoids in the masses showing blood pooling and fatty change, and adenomas without dilated sinusoids in the masses not showing blood pooling. This case report shows that the appearance of hepatic adenomas can vary on Tc-99m RBC liver SPECT, depending on whether dilated sinusoid and hepatic adenomas show blood pooling. This is one of the few examples of false-positive findings that can be mistaken for hemangioma.
Antibodies to E1 and E2/Protein X components of pyruvate dehydrogenase complex in sera of patients with primary biliary cirrhosis
Authors: Masahito Kuroda, Takao Morito, Tohru Takagi, Hiromasa Ohira, Masae Kokubun, Tosihiko Kojima, Kazuo Ono, Hideo Kochi, Reiji Kasukawa
Journal: Journal of Hepatology (1996)
Cystic Fibrosis Diagnosed after Age 13
Authors: ROBERT C. STERN
Journal: Annals of Internal Medicine (1977)

Cystic fibrosis was diagnosed after age 13 in 25 patients. All had an elevated sweat chloride and either a sibling with cystic fibrosis or typical pulmonary infection or digestive symptoms caused by exocrine pancreatic deficiency. Fourteen had long-standing pulmonary or digestive symptoms. In contrast, four of eight patients whose symptoms began after age 13 presented with biliary cirrhosis. Three male patients were asymptomatic at diagnosis. Opacification of all paranasal sinuses was found in all patients examined radiologically. At diagnosis, pulmonary-function testing showed obstructive changes in 19 patients and sputum cultures showed Pseudomonas aeruginosa in 15 patients. Delayed menarche in five of seven female patients and infertility in the asymptomatic male patients (two of whom were found to have aspermia) could have led to earlier diagnosis. Teenagers and young adults with long-standing pulmonary or digestive symptoms, unexplained cirrhosis, aspermia, or a sibling with cystic fibrosis should be sweat-tested by pilocarpine iontophoresis.