tbuckley/cabot-search huggingface dataset:
Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells
Authors: T. Osanai, H. Tomita, M. Kushibiki, M. Yamada, M. Tanaka, T. Ashitate, T. Echizen, C. Katoh, K. Magota, K. Okumura
Journal: Cardiovascular Research (2008)

Coupling factor 6 (CF6) induces hypertension by attenuating the endothelial generation of prostacyclin. However, intracellular signalling of CF6 in the resistance arteriole vascular smooth muscle cells (VSMCs) that are directly related to vasoconstriction has not been determined. Here we investigated the direct effect of exogenous CF6 on Ca2+ signalling in cultured VSMCs and the in vivo role of endogenous CF6 in the genesis of hypertension using CF6 transgenic (TG) mice. CF6 induced a monophasic increase in the intracellular free Ca2+ concentration ([Ca2+]i) through nifedipine-sensitive Ca2+ channels in A7r5 cells, a cell line of VSMCs, and enhanced the angiotensin II-induced spike phase of [Ca2+]i to a greater degree in VSMCs derived from spontaneously hypertensive rats (SHRs). In the mesenteric arterioles obtained from CF6-TG mice that manifested hypertension, angiotensin II-induced vasoconstriction was enhanced, compared with wild-type mice, and its enhancement was abolished by an anti-CF6 antibody. Pre-treatment with PP1, a tyrosine kinase c-Src inhibitor, blocked CF6-induced increase in Ca2+ signalling in VSMCs and vasoconstriction in TG mice. The receptor of CF6 was F1 motor of adenosine triphosphate (ATP) synthase with a higher affinity in SHRs. CF6 decreased intracellular pH via activation of ATPase activity and led to c-Src activation to a greater degree in SHR-derived VSMCs. CF6 causes hypertension by directly enhancing Ca2+ signalling in VSMCs and vasoconstriction in the mesenteric arteriolar network via c-Src activation.
Targeting the Insulin-like Growth Factor Axis for the Development of Novel Therapeutics in Oncology
Authors: Jin Gao, Yong S. Chang, Bahija Jallal, Jaye Viner
Journal: Cancer Research (2012)

Abstract Insulin-like growth factors (IGF) are polypeptide hormones with potent anabolic and mitogenic effects that regulate cell growth and differentiation. Dysregulation of the IGF axis has been well documented in the development and progression of multiple types of cancer. As a result, compounds targeting the IGF axis have become an area of intense preclinical and clinical research for cancer therapeutics. The IGF axis is intimately involved with the insulin-signaling pathway because of their close homologies. This homology may explain hurdles encountered in the clinical development of IGF-targeted therapies, such as less-than-expected antitumor efficacy that may arise from compensatory increases in the activity of insulin receptor isoform A (IR-A), in response to IGF-I receptor (IGF-IR) inhibition and perturbations in glucose homeostasis, arising from the inhibition of insulin receptor isoform B (IR-B) activity. In this brief review, we compare differentiating factors that characterize the 3 major classes of IGF-targeting compounds: therapeutic antibodies that target IGF-IR, small molecule tyrosine kinase inhibitors that inhibit kinase activities of IGF-IR and IR, and antibodies that target IGF ligands. Cancer Res; 72(1); 3–12. ©2012 AACR.
Aspirin and Hormone Therapy for Prostate Cancer
Authors: Anthony V. D'Amico, Philip W. Kantoff, Ming-Hui Chen
Journal: New England Journal of Medicine (2007)

These results are from a multivariable Cox regression analysis 5 of data for the 206 men in the study cohort.AJCC denotes the American Joint Committee on Cancer.† Possible scores on the 27-item Adult Comorbidity Evaluation (ACE-27) are 0 (no comorbidity), 1 (minimal comorbidity), 2 (moderate comorbidity), and 3 (severe comorbidity).‡ Relative risk for prostate-specific antigen (PSA) is given for each unit increase in nanograms per milliliter.§ The Gleason score can range from 2 to 10, with higher scores indicating more aggressive disease.¶ Relative risk for age is given for each unit increase in years.
Insulin Secretion in Normal Glucose-Tolerant Relatives of Type 2 Diabetic Subjects: Assessments using hyperglycemic glucose clamps and oral glucose tolerance tests
Authors: Timon W van Haeften, Suzanne Dubbeldam, Maria L Zonderland, D Willem Erkelens
Journal: Diabetes Care (1998)

OBJECTIVE To assess insulin secretion in normal glucose-tolerant Caucasian first-degree relatives of type 2 diabetes subjects and in matched normal glucose-tolerant control subjects and to compare insulin secretion as assessed using a hyperglycemic glucose clamp with insulin secretion as assessed using an oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS Twenty-one first-degree relatives of type 2 diabetic subjects and 21 control subjects without a family history of type 2 diabetes, who were matched for sex, age, BM1, waist-to-hip ratio, and aerobic capacity, underwent a hyperglycemic glucose clamp (10 mmol/1, 180 min). An OGTT (75 g glucose in 300 ml water) was also performed. RESULTS First-phase insulin release (plasma insulin, 0–10 min) was not different (multiple analysis of variance [MANOVA]: F = 2.63, P = 0.11). Second-phase insulin release was lower (MANOVA: F = 4.18, P = 0.047). Separate analyses of variance showed decreased plasma insulin levels from 120 min onward (all P &amp;lt; 0.05), decreasing to geometric mean (95% CI) levels of 330 (270–402) and 462 (366–582) pmol/1 at 180 min in relatives and control subjects, respectively. The insulin sensitivity index (ISI) as assessed using a hyperglycemic clamp was not different between the two groups. Mean ± SE ISI during the 3rd hour was 27.5 ± 2.2 and 30.5 ± 3.0 μg · kg−1 · min−1 · pmol−1 · l−1 in relatives and control subjects, respectively (P &amp;gt; 0.20). At 90 min after the OGTT, log plasma insulin levels correlated significantly with secondphase insulin release as assessed using the hyperglycemic glucose clamp. CONCLUSIONS Normal glucose-tolerant first-degree relatives of type 2 diabetic subjects have a decreased second-phase insulin release, compared with matched control subjects. After an OGTT, 90-min values of log plasma insulin and 90-min values of the ratio of log plasma insulin to blood glucose may be good indicators of insulin secretory properties in normal glucose-tolerant family members of type 2 diabetic subjects.
Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence.
Authors: R L Jilka, R S Weinstein, K Takahashi, A M Parfitt, S C Manolagas
Journal: Journal of Clinical Investigation (1996)

Bone marrow is the principal site for osteoclastogenesis and osteoblastogenesis; and an increase in the former has been linked with bone loss caused by acute loss of gonadal steroids. We have now used an established murine model of accelerated senescence and osteopenia (SAMP6) to test the hypothesis that reduced osteoblastogenesis is linked with decreased bone mass. At 1 mo of age, the number of osteoblast progenitors in SAMP6 marrow was indistinguishable from controls; however a threefold decrease was found at 3-4 mo of age. Impaired osteoblast formation was temporally associated with decreased bone formation and decreased bone mineral density, as determined by histomorphometric analysis of tetracycline-labeled cancellous bone and dual-energy x-ray absorptiometry, respectively. Osteoclastogenesis determined in ex vivo bone marrow cultures was also decreased in these mice, as was the number of osteoclasts in histologic sections. Moreover, unlike controls, senescence-accelerated mice failed to increase osteoclast development after gonadectomy. The osteoclastogenesis defeat was secondary to impaired osteoblast formation as evidenced by the fact that osteoclastogenesis could be restored by addition of osteoblastic cells from normal mice. These findings provide the first demonstration of a link between low bone mineral density and decreased osteoblastogenesis in the bone marrow and validate the senescence-accelerated mouse as a model of involutional osteopenia.
A Physician's Dilemma
Authors: James Svenson
Journal: JAMA (1988)

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
Evidence-Based Standards for Cancer Pain Management
Authors: Sydney M. Dy, Steven M. Asch, Arash Naeim, Homayoon Sanati, Anne Walling, Karl A. Lorenz
Journal: Journal of Clinical Oncology (2008)

High-quality management of cancer pain depends on evidence-based standards for screening, assessment, treatment, and follow-up for general cancer pain and specific pain syndromes. We developed a set of standards through an iterative process of structured literature review and development and refinement of topic areas and standards and subjected recommendations to rating by a multidisciplinary expert panel. Providers should routinely screen for the presence or absence and intensity of pain and should perform descriptive pain assessment for patients with a positive screen, including assessment for likely etiology and functional impairment. For treatment, providers should provide pain education, offer breakthrough opioids in patients receiving long-acting formulations, offer bowel regimens in patients receiving opioids chronically, and ensure continuity of opioid doses across health care settings. Providers should also follow up on patients after treatment for pain. For metastatic bone pain, providers should offer single-fraction radiotherapy as an option when offering radiation, unless there is a contraindication. When spinal cord compression is suspected, providers should treat with corticosteroids and evaluate with whole-spine magnetic resonance imaging scan or myelography as soon as possible but within 24 hours. Providers should initiate definitive treatment (radiotherapy or surgical decompression) within 24 hours for diagnosed cord compression and should follow up on patients after treatment. These standards provide an initial framework for high-quality evidence-based management of general cancer pain and pain syndromes.
Chlorthalidone-Induced Hyperosmolar Hyperglycemic Nonketotic Coma
Authors: John Curtis
Journal: JAMA (1972)

Hyperosmolar hyperglycemic nonketotic coma developed in a patient with diabetes mellitus. Essential hypertension followed the addition of chlorthalidone to his usual medication. Profound hyponatremia, sustained insulin-resistant hyperglycemia, and hyperuricemia were atypical findings attributed to the pharmacologic properties of chlorthalidone.
Trade agreement may restrict supply of essential drugs in Central America, experts say
Authors: John Zarocostas
Journal: BMJ (2005)

Health and development advocacy groups fear that stringent intellectual property provisions imposed by the United States in a new free trade pact will trigger higher prices of drugs and will restrict access to cheap essential generic drugs, including antiretrovirals, in poor Central American nations.

The Central American free trade agreement between and the US and Costa Rica, the Dominican Republic, El Salvador, Guatemala, Honduras, and Nicaragua was approved by the US House of Representatives on 27 July by a vote of 217 to 215.

The pact has many aspects that are problematic and will raise drug prices and strengthen the …
Getting help for sick doctors
Authors: J. Oxley, S. Brandon
Journal: BMJ (1997)

Doctors are a scarce and expensive resource and there are not enough of them to meet identified demands. Concerted action to prevent stress and ill health in doctors and consequent harm to patients and unnecessary loss of doctors should be a priority. The statements and conclusions in this article are based on the experience of the NCSSD since its inception in 1985 together with a review of some of the published literature. Doctors have high standardised mortality rates in respect of cirrhosis, accident and suicide.1,2 Surveys have shown high levels of stress and related disorders among hospital consultants,3,4 general practitioners,5 and doctors in training.6

Qualification in medicine brings automatic social status with expectations of good health, good income, an assured and satisfying job, and identification with a respected profession. At the same time membership demands an acceptance of the ethos in medicine which carries an expectation of dedication, hard work, and long hours. Commitment to the individual patient and to the service makes it difficult for the physician to abandon this obligation because of personal ill health. The structure of the NHS is such that if an individual doctor is unexpectedly absent because of illness there is often no one to provide alternative cover at the same level.

For a variety of complex reasons many doctors are reluctant to seek help in the normal way when they become stressed or ill. From the experience of the NCSSD there seems to be a deeply ingrained fear that admission of vulnerability or illness will result in loss of respect from colleagues and impaired future employment prospects. Any service connected with management, including occupational health, is often viewed with suspicion. Misunderstanding of the role of both NHS management and of the General Medical Council (GMC) is common.

These concerns are compounded by the …
Factitious meningitis. Diagnostic error due to nonviable bacteria in commercial lumbar puncture trays
Authors: R. A. Weinstein
Journal: JAMA (1975)

A cluster of five false-positive cerebrospinal fluid (CSF) Gram stains led to an investigation of possible causes of specimen or smear contamination. Specimen tubes supplied in commercial lumbar puncture trays from the lot being used in the involved hospital were shown to contain nonviable bacteria. When filled with a test solution and processed in a manner similar to that used for processing CSF specimens, 10 of 12 tubes evaluated yielded Gram stains containing either Gram-negative rods, diplococci, or coccobacilli. Before this problem was recognized, the patient from whom the first false-positive smear was obtained was treated for bacterial meningitis. It is important to realize that microbial contamination of commercial CSF specimen tubes can result in findings simulating those of early bacterial meningitis. (<i>JAMA</i>233:878-879, 1975)
Release of oxytocin and prolactin in response to suckling
Authors: J. Raeburn
Journal: BMJ (1983)

far the greatest cause of perinatal loss in Britain is asphyxia but this is fatal only if relief, and particularly delivery, is delayed too long.Mastery of asphyxia calls for elimination of causes of delay in delivery, and artificial suckling provides a potentially life saving weapon for combating asphyxia.It is simple to perform, usually rapidly effective, apparently harmless, and costs nothing.
Statistics Notes: Logarithms
Authors: J M. Bland, D. G Altman
Journal: BMJ (1996)

Logarithms (or logs for short) are much used in statistics. We often analyse the logs of measurements rather than the measurements themselves, and some widely used methods of analysis, such as logistic and Cox regression, produce coefficients on a logarithmic scale. Here we shall give a brief summary of the properties of logarithms which make them so useful.

We shall start with logarithms to base 10. These are the common logarithms formerly widely used to do calculations for which we now use calculators and computers. The log to base 10 of a number …
Secondary Breast Cancer of Prostatic Origin
Authors: James H. Campbell
Journal: JAMA (1962)

CARCINOMA of the prostate is noted for its widespread metastases and has been reported to invade practically every organ and tissue of the body. However, it is unusual for carcinoma of the prostate, or any other type of cancer, to metastasize to the breast. Campbell and Cummins reviewed the literature and reported a case of cancer of the prostate simulating primary breast cancer. Their case was that of a 69-year-old man with prostatic cancer that developed metastasis to the breasts, skin, lymph nodes, liver, lungs, adrenals, epididymis, heart, and bones. The acid-phosphatase stains of the prostate and breasts were strongly positive. This paper reports of another case of metastatic cancer to the breast from the prostate.  Report of a Case  A 78-year-old man was admitted to Confederate Memorial Medical Center, on July 27, 1959, with the chief complaint of acute urinary retention and enlarged breasts. He gave a 5½-year history
Rugby union should ban contested scrums: Engage, don't ban
Authors: John J Macfarlane
Journal: BMJ (2006)

EDITOR—With reference to Bourke's personal view,1 I caution relying on personal experience rather than systematic study of the risk from contested scrums in rugby. In my six years in rehabilitation medicine, I have encountered six people with spinal cord injuries from playing rugby, one of whom was rugby league, and only one was injured in a …
Contact Dermatitis from "Scotchgard," A Stain Repellent for Fabrics
Authors: Y. D. Eskelson, Louis S. Goodman
Journal: JAMA (1963)

ONE OF US (L.S.G.) recently sustained a severe contact dermatitis from the wearing of slacks treated with "Scotchgard,"* a fluorocarbon-containing formulation designed to impart stain and water repellency to cloth used for garments, furniture covers, and similar items. We are unaware of any report in the medical literature concerning untoward dermatological effects from this product, and the manufacturer has informed us that, to date, they have not received complaints of this nature.<sup>1</sup>Since Scotchgard-treated fabrics are now widely sold, it was thought important to call the attention of the medical profession to the possibility that contact with such fabrics can cause dermatitis. In the present case, Scotchgard was proved to be the offending agent, and the cloth itself and the dye were eliminated as causal factors. The patient wore a new pair of Scotchgardtreated slacks for 4 days. About 4 days later, the dorsal surfaces of the hands began
Abstract 2235: Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1.
Authors: Darya V. Urusova, Jung-Hyun Shim, Dong Joon Kim, Sung Keun Jung, Tatyana Zykova, Andria Carper, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2013)

Abstract The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 Å resolution. Notably, the structure revealed the presence of EGCG in both the WW and PP1ase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PP1ase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of TPA-induced AP-1 or NFκB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor promoting effect of Pin1. Citation Format: Darya V. Urusova, Jung-Hyun Shim, Dong Joon Kim, Sung Keun Jung, Tatyana Zykova, Andria Carper, Ann M. Bode, Zigang Dong. Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2235. doi:10.1158/1538-7445.AM2013-2235
Liver-specific loss of β-catenin results in delayed hepatocyte proliferation after partial hepatectomy
Authors: Shigeki Sekine, Pedro J. A. Gutiérrez, Billy Yu-Ang Lan, Sandy Feng, Matthias Hebrok
Journal: Hepatology (2007)

Recent studies have suggested that β-catenin is involved in the regulation of hepatocyte proliferation in multiple contexts, including organ development and tumorigenesis. We explored the role of β-catenin during liver regeneration using T cell factor/lymphoid enhancer factor (TCF/LEF)-reporter mice (TOPGal mice) and liver-specific β-catenin knockout mice. Liver-specific β-catenin knockout mice showed a delayed onset of DNA synthesis after hepatectomy, whereas recovery of liver mass was not affected. Among putative β-catenin target genes examined, the induction of Ccnd1 expression was reduced, whereas the expression of Myc and Egfr was unaffected. Furthermore, cyclin D1 protein levels were not induced, and the expression of cyclins A, E, and proliferating cell nuclear antigen was delayed. Intriguingly, the analysis of TOPGal mice showed that hepatocytes with active TCF/LEF transcription are confined to the pericentral zone and are not increased in number during regeneration, indicating an uncoupling between β-catenin/TCF signaling activity and hepatocyte proliferation. Conclusion: Our results indicate that β-catenin is critical for the proper regulation of hepatocyte proliferation during liver regeneration; however, the activity of β-catenin/TCF signaling does not correlate with hepatocyte proliferation, suggesting that this regulation might be indirect/secondary.
Drug Evaluation and Practical Psychiatric Therapeutics
Authors: Sidney Merlis
Journal: JAMA (1961)

The evaluation of psychotropic drugs presents special problems to the pharmacologist and clinician. In such evaluation, the severity of the patient's anxiety is a useful parameter, but it is not the only one that needs to be considered. The best therapy may be to learn more about the circumstances of the patient and to resolve difficulties when possible. Drugs are prescribed only when this fails. Some properties of 25 drugs now used to relieve anxiety are given. In severe anxiety, potent drugs are used initially despite their inherent dangers. If an office patient drives a car, takes care of a home, cooks, watches children, or competes in business, parameters other than anxiety are obviously important. The problems of psychopharmacology are therefore complex, but the principles here outlined provide orientation.
Intravascular Ultrasonic Imaging of Vulnerable Plaque in a Bare Metal Stent 10 Years After Implantation
Authors: Kanae Hasegawa, Masahiro Ito, Masato Oda, Satoru Hirono, Takuya Ozawa, Komei Tanaka, Hiroaki Obata, Makoto Kodama, Yoshifusa Aizawa
Journal: Circulation (2010)
Cigarette Smoking Cessation and Extracranial Carotid Atherosclerosis
Authors: Grethe S. Tell
Journal: JAMA (1989)

Using B-mode ultrasonography, cigarette smoking was found to be a strong, independent risk factor for extracranial carotid atherosclerosis in 1692 black and white men and women admitted for diagnostic evaluation of the carotid arteries. We found that the difference in mean plaque thickness was smaller between past smokers and nonsmokers than between current smokers and nonsmokers, suggesting that the rate of progression of carotid atherosclerosis may be slower in people who quit smoking compared with people who continue to smoke. (<i>JAMA</i>1989;261:1178-1180)