tbuckley/cabot-search huggingface dataset:
Abstract 1224: Repression of cancer cell senescence by PKCι
Authors: Ian J. Restall, Judith A. Paget, Manijeh Daneshmand, Md. Shahrier Amin, Shahidul Islam, Ian A.J. Lorimer
Journal: Cancer Research (2011)

Abstract Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase C iota (PKCι) is a member of the atypical protein kinase C family and an important downstream mediator in the phosphoinositide pathway. PKCι expression was found to be upregulated in a subset of breast cancers and breast cancer cell lines. Introduction of mutant, oncogenic PIK3CA, but not wild-type PIK3CA, into breast mammary epithelial cells increased both the expression and activation of PKCι. In breast cancer cell lines overexpressing PKCι, depletion of PKCι increased the number of senescent cells, as assessed by senescence-associated β-galactosidase, morphology and bromodeoxyuridine incorporation. This phenomenon was not restricted to breast cancer cells, as it was also seen in glioblastoma cells. Senescence induction did not require p53, p16 or Arf and was not associated with activation of the DNA damage response. Depletion of PKCι had no effect on senescence in normal mammary epithelial cell lines. We conclude that PKCι is overexpressed in a subset of cancers where it functions to suppress premature senescence. This function appears to be restricted to cancer cells and inhibition of PKCι may therefore be an effective way to selectively activate premature senescence in cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1224. doi:10.1158/1538-7445.AM2011-1224
INSULIN THERAPY IN UNDERNOURISHED PSYCHOTIC PATIENTS: PRELIMINARY REPORT
Authors: Clifford B. Farr
Journal: JAMA (1928)

A considerable foreign literature has appeared on the use of insulin in undernutrition. Critical undernutrition is a frequent problem in the treatment of psychotic patients. The following is a brief report on thirty-three cases treated with insulin in our hospital. The majority of these were patients who had failed to gain on the usual fattening regimen. The accompanying table, showing the technic employed, is self-explanatory. The upper limit of insulin dosage was determined by the individual appetite and tolerance. Mild symptoms of hypoglycemia, such as increased appetite and very slight uneasiness, were permitted to occur. Symptoms such as weakness, sweating, vertigo, increased pulse rate, and palpitation led us to reduce the dosage or in a few cases to discontinue the treatment. Frequent blood sugar determinations were made as a check on such clinical symptoms.<sup>1</sup>Notwithstanding careful checking of the blood sugars at different times of the day, three cases
Side Effects of Minoxidil
Authors: Michael T. Savino
Journal: JAMA (1976)

<h3>To the Editor.—</h3> If the editors who put together the July 21, 1975, issue of<i>JAMA</i>had appreciated the article on page 280, "The Quality of Survival in Response to Treatment," I do not see how they could have published the article on page 249, in its present form, depicting side-effects as "relatively mild" considering the changed quality of life experienced by the patient who looks 20 years older after treatments. While the value of the therapeutic technique is demonstrated, it would also be in order to demonstrate some sensitivity to the total human needs of the patient.
IMMUNOCHEMICAL IDENTIFICATION OF PARATHYROID HORMONE IN NON-PARATHYROID NEOPLASMS ASSOCIATED WITH HYPERCALCEMIA
Authors: Armen H. Tashjian, Lawrence Levine, Paul L. Munson
Journal: The Journal of Experimental Medicine (1964)

1. Immunochemical cross-reactivity, but not identity, has been demonstrated between bovine parathyroid hormone and an antigen in biologically active extracts of human parathyroid tissue by quantitative C' fixation and C' fixation inhibition. 2. An antigen that fixes C' with rabbit antibody to bovine parathyroid hormone has been found in urea extracts of six human non-parathyroid neoplasms associated with a hypercalcemic syndrome mimicking primary hyperparathyroidism. Comparable extracts of control tissues and other tumors were serologically negative. 3. It is concluded that the tumor antigen is parathyroid hormone or a very closely related protein, and that its production by these neoplasms was the cause of the hypercalcemic syndrome in these six patients.
Review: Quality improvement strategies reduce HbA<sub>1c</sub>, LDL cholesterol, and BP in diabetes
Authors: Sean F. Dinneen, Máire O’Donnell
Journal: Annals of Internal Medicine (2012)

Source Citation Tricco AC, Ivers NM, Grimshaw JM, et al. Effectiveness of quality improvement strategies on the management of diabetes: a systematic review and meta-analysis. Lancet. 2012;379:2252-61. 22683130
CARDIAC RESYNCHRONIZATION THERAPY IS ASSOCIATED WITH REDUCTIONS IN LEFT ATRIAL VOLUME AND INAPPROPRIATE ICD THERAPY IN MADIT-CRT
Authors: Tyler Slyngstad, Anne-Christine Ruwald, Valentina Kutyifa, Scott McNitt, Bronislava Polonsky, Scott Solomon, Elyse Foster, Ilan Goldenberg, Paul Wang, Helmut Klein, Wojciech Zareba, Arthur Moss
Journal: Journal of the American College of Cardiology (2014)
Comment on Zhang et al. Second-Line Agents for Glycemic Control for Type 2 Diabetes: Are Newer Agents Better? Diabetes Care 2014;37:1338–1345
Authors: Andrea Messori, Alfonso Bellia
Journal: Diabetes Care (2014)

Given the increasing burden of diabetic disease worldwide and the high number of available medications, the objective of the research by Zhang et al. (1) is praiseworthy. The study design is straightforward and, in our opinion, there are no particular points of concern from a clinical perspective. However, we do believe the study suffers from a number of inconsistencies that might reflect methodological errors or require further elucidation to reinforce the scientific value of the results.

It is well known that pharmacoeconomic analyses using quality-adjusted life-years (QALYs) should have an incremental design. In 2012, Stein (2) observed that “the absolute cost-effectiveness ratio (cost divided …
Managing the Patient-Focused Laboratory
Authors: Ellis S. Benson
Journal: JAMA (1977)

The key word in the title is "managing." This book is basically a management guide for the modern hospital laboratory and especially for the laboratory director. While there are eleven contributors, most of the book was written by Dr Lundberg, and he brings to the task his experience of many years in directing the laboratory services of one of the largest county hospitals in the country. This experience is rich in providing efficient, high quality laboratory services and, in this sense, it is "patient-focused." Patients are undoubtedly much better served by efficient, well-managed, high quality laboratories than by poorly managed, inefficient ones. Among the topics included are organization of laboratory services, laws and regulations in the laboratory field, liability, labor relations, work load reporting and productivity, laboratory design, administrative techniques, and safety, personnel, and space and equipment management. Two chapters deal with the education of laboratory personnel and that of
Growth, Development, and Behavior in Early Childhood Following Prenatal Cocaine Exposure
Authors: Deborah A. Frank, Marilyn Augustyn, Wanda Grant Knight, Tripler Pell, Barry Zuckerman
Journal: JAMA (2001)

ContextDespite recent studies that failed to show catastrophic effects of prenatal cocaine exposure, popular attitudes and public policies still reflect the belief that cocaine is a uniquely dangerous teratogen.ObjectiveTo critically review outcomes in early childhood after prenatal cocaine exposure in 5 domains: physical growth; cognition; language skills; motor skills; and behavior, attention, affect, and neurophysiology.Data SourcesSearch of MEDLINE and Psychological Abstracts from 1984 to October 2000.Study SelectionStudies selected for detailed review (1) were published in a peer-reviewed English-language journal; (2) included a comparison group; (3) recruited samples prospectively in the perinatal period; (4) used masked assessment; and (5) did not include a substantial proportion of subjects exposed in utero to opiates, amphetamines, phencyclidine, or maternal human immunodeficiency virus infection.Data ExtractionThirty-six of 74 articles met criteria and were reviewed by 3 authors. Disagreements were resolved by consensus.Data SynthesisAfter controlling for confounders, there was no consistent negative association between prenatal cocaine exposure and physical growth, developmental test scores, or receptive or expressive language. Less optimal motor scores have been found up to age 7 months but not thereafter, and may reflect heavy tobacco exposure. No independent cocaine effects have been shown on standardized parent and teacher reports of child behavior scored by accepted criteria. Experimental paradigms and novel statistical manipulations of standard instruments suggest an association between prenatal cocaine exposure and decreased attentiveness and emotional expressivity, as well as differences on neurophysiologic and attentional/affective findings.ConclusionsAmong children aged 6 years or younger, there is no convincing evidence that prenatal cocaine exposure is associated with developmental toxic effects that are different in severity, scope, or kind from the sequelae of multiple other risk factors. Many findings once thought to be specific effects of in utero cocaine exposure are correlated with other factors, including prenatal exposure to tobacco, marijuana, or alcohol, and the quality of the child's environment. Further replication is required of preliminary neurologic findings.
A family with Dowling Degos disease showing features of Kitamura's reticulate acropigmentation
Authors: J. BERTH-JONES, R.A.C. GRAHAM-BROWN
Journal: British Journal of Dermatology (1989)

We report a family showing a combination of features described in the two, rare genodermatoses, Dowling Degos disease and Kitamura's acropigmentatio reticularis.
The Regulation of Valvular and Vascular Sclerosis by Osteogenic Morphogens
Authors: Kristina I. Boström, Nalini M. Rajamannan, Dwight A. Towler
Journal: Circulation Research (2011)

Vascular calcification increasingly afflicts our aging, dysmetabolic population. Once considered only a passive process of dead and dying cells, vascular calcification has now emerged as a highly regulated form of biomineralization organized by collagenous and elastin extracellular matrices. During skeletal bone formation, paracrine epithelial-mesenchymal and endothelial-mesenchymal interactions control osteochondrocytic differentiation of multipotent mesenchymal progenitor cells. These paracrine osteogenic signals, mediated by potent morphogens of the bone morphogenetic protein and wingless-type MMTV integration site family member (Wnt) superfamilies, are also active in the programming of arterial osteoprogenitor cells during vascular and valve calcification. Inflammatory cytokines, reactive oxygen species, and oxylipids—increased in the clinical settings of atherosclerosis, diabetes, and uremia that promote arteriosclerotic calcification—elicit the ectopic vascular activation of osteogenic morphogens. Specific extracellular and intracellular inhibitors of bone morphogenetic protein–Wnt signaling have been identified as contributing to the regulation of osteogenic mineralization during development and disease. These inhibitory pathways and their regulators afford the development of novel therapeutic strategies to prevent and treat valve and vascular sclerosis.
A 55-Year-Old Man With Attention-Deficit/Hyperactivity Disorder
Authors: Joseph Biederman
Journal: JAMA (1998)

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
In vivo activity and in vitro specificity of CD4+ Th1 and Th2 cells derived from the spleens of diabetic NOD mice.
Authors: D Healey, P Ozegbe, S Arden, P Chandler, J Hutton, A Cooke
Journal: Journal of Clinical Investigation (1995)

CD4+ T cell lines were generated from the spleens of diabetic NOD mice against crude membrane preparations derived from a rat insulinoma. Adoptive transfer of these lines into neonatal mice confirms that overt diabetes is induced by gamma-IFN-secreting Th1 cells, whereas transfer of IL-4-secreting Th2 cells resulted in a nondestructive peri-islet insulitis. Analysis of the antigens recognized by individual T cell clones from the Th1 line included reactivity against an insulinoma membrane fraction enriched in proteins of approximately 38 kD. Immune responses to the same antigen preparation have been associated with T cell clones derived from human insulin-dependent diabetes mellitus. The specificity of Th2 cells includes reactivity to a fraction enriched in proteins of 30 kD. The data suggest that in insulin-dependent diabetes mellitus the balance between beta cell destruction, associated with intra-islet infiltration, and nondestructive (potential protective) peri-islet insulitis may depend on both the antigens recognized, and the prevailing cytokine environment.
Points: Undergraduate medical education
Authors: R M Harden
Journal: BMJ (1988)

cyclizine hydrochloride, which could have slowed his intestinal transit rate.Systemic toxicity is an alterna- tive possibility.In view of the animal studies small bowel perforation is not an unexpected side effect, especially in association with the high dose of diclo- fenac sodium that this man was taking.Non-steroidal anti-inflammatory drugs are often prescribed for pain that is unremitting and difficult to control, but their therapeutic window is small.With high dose slow release preparations it is easy to reach harmful concentrations by taking relatively few tablets.Patients taking slow release preparations of non-steroidal anti-inflammatory drugs should be warned specifically of the dangers of increasing the dose beyond that recommended.The risk of localised toxicity may be increased when non-steroidal anti- inflammatory preparations are taken in conjunction with opiates or their derivatives, which decrease intestinal motility.I Day TK.Intestinal perforation associated with osmotic slow release indomethacin capsules.
Enrichment of Nur77 mediated by retinoic acid receptor β leads to apoptosis of human hepatocellular carcinoma cells induced by fenretinide and histone deacetylase inhibitors
Authors: Hui Yang, Qi Zhan, Yu-Jui Yvonne Wan
Journal: Hepatology (2010)

Abstract The synthetic retinoid fenretinide is one of the most promising clinically tested retinoids. Previously, we have shown that fenretinide induces apoptosis of Huh7 cells, but HepG2 cells are relatively resistant to fenretinide-induced apoptosis. This study examines the interactive role of fenretinide and histone deacetylase inhibitors (HDACi) in inducing apoptosis of human hepatocellular carcinoma (HCC) cells and the underlying mechanism. Trichostatin A and scriptaid can either enhance fenretinide-induced apoptosis in the fenretinide sensitive HCC cells (Huh7 and Hep3B) or sensitize the fenretinide resistant cells (HepG2) to become sensitive to the apoptotic effect of fenretinide in a cancer cell–specific manner. The sensitivity of cells to fenretinide-induced apoptosis was not associated with reactive oxygen species production nor with antioxidant gene expression. However, the level of retinoic acid receptor β (RARβ) and Nur77 (NR4A1) was important for inducing apoptosis. Upon fenretinide and HDACi treatment, the expression of RARβ and Nur77 were induced and colocalized in the cytosol. The induction of Nur77 protein level, but not the messenger RNA level, was RARβ-dependent. In addition, RARβ interacted with Nur77. Nur77 was essential for fenretinide-induced and HDACi-induced apoptosis of Huh7 cells. Induction of the expression, the interaction, and the nuclear export of RARβ and Nur77 mediate fenretinide-induced and HDACi-induced apoptosis. Conclusion: Our findings suggest that targeting Nur77 and RARβ simultaneously provides an effective way to induce HCC cell death. (Hepatology 2011)
Choreoathetosis in Alcoholism
Authors: J. M. Kellett
Journal: BMJ (1970)

There is supporting evidence that bradyarrhythmias and ventricular fibrillation are the cause of most of the early deaths following infarction.In order to reduce this very high prehospital mortality, it is suggested that the general practitioner should visit the patient as soon as possible, cutting down the admission delay, and that he should try to treat not only pain and dysrhythmias, but also left ventricular failure with digoxin and frusemide if it is severe, or with frusemide alone if it is mild.The accompanying letter should contain information about the medical history of the patient, and the treatment given to the patient at home, with drugs, dosage, route of administration, and the exact time given.
763. Multimodality Imaging of Genetically Modified Lymphocytes In Vivo
Authors: Konstantin Dobrenkov, Malgorzata Dabrowska, Larissa Shenker, Elena Vider, Gertrude Gunset, Michel Sadelain, Vladimir Ponomarev
Journal: Molecular Therapy (2006)

Background: the lack of specific trafficking of genetically engineered T cells to tumor sites is one of the major limitations in adoptive immunotherapy. Multimodality imaging represents a powerful tool for repetitive non-invasive assessment of migration, activation and survival of immune effectors in living subjects in pre-clinical models and in patients. Methods: to establish a cancer model for adoptive immunotherapy we challenged immunodeficient mice with RM1 murine prostate carcinoma cells transduced with human prostate-specific membrane antigen (PSMA). The tumor cells were also co-transduced with dual fusion (red fluorescent protein and Renilla lusiferase) reporter gene for imaging of tumor progression. Human peripheral blood T-lymphocytes were transduced with chimeric receptors specific either for PSMA or CEA (control) and with reporter vector bearing HSV1-thymidine kinase (HSV1-tk), green fluorescent protein (GFP) and Click Beetle luciferase (CBR). GFP was used for assessment of transduction efficiency of T-lymphocytes and T-cell tumor infiltration. After ex vivo expansion genetically modified PSMA-specific or CEA-specific (control) lymphocytes were adoptively transferred into tumor bearing mice. Metastatic lung tumors were detected using in vivo bioluminescent imaging in all animals on the day of lymphocyte injection and thereafter. All mice underwent biolumincescent and microPET imaging with [18F]FEAU. Results: on day 1 after T-cell injection distinct luciferase and PET signals were detected in both PSMA-specific and CEA-specific (control) lymphocyte groups. On day 3 clear signal was obtained only in PSMA-specific lymphocyte group. PET signal was not detected on day 6 in either group. The %ID/g differed significantly on day 3 between two groups (Table 1). The bioluminescence data corroborated PET data. Tumor growth delay was observed using bioluminescent signal dynamic in the group, injected with PSMA-specific lymphocytes. Statistically significant survival advantage (p=0.01) was also observed in the same group. The presence of human genetically modified lymphocytes as well as PSMA antigen in lung tumor was confirmed by immunofluorescence and immunohistochemistry. Conclusion: multimodality imaging strategy is feasible and can be applied for longitudinal visualization of genetically modified immune cells and prediction of adoptive immunotherapy outcome.
Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.
Authors: T Wang, G Malnic, G Giebisch, Y L Chan
Journal: Journal of Clinical Investigation (1993)

Bicarbonate transport was studied in vivo by separate microperfusion experiments of early and late distal tubules. Total CO2 was measured by microcalorimetry and fluid absorption by 3H-inulin. Significant bicarbonate absorption was observed in all experimental conditions. Bicarbonate transport was load-dependent upon increasing the luminal bicarbonate concentration from 15 to 50 mM in both early and late distal tubule segments and remained constant at higher concentrations at a maximum rate of 100-110 pmol/min per mm. At low lumen bicarbonate concentrations (15 mM), higher rates of bicarbonate absorption were observed in early (32.9 +/- 4.57 pmol/min per mm) as compared to late distal tubules (10.7 +/- 3.1 pmol/min per mm). Amiloride and ethyl-isopropylamiloride both inhibited early but not late distal tubule bicarbonate absorption whereas acetazolamide blocked bicarbonate transport in both tubule segments. Fluid absorption was significantly reduced in both tubule segments by amiloride but only in early distal tubules by ethyl-isopropylamiloride. Substitution of lumen chloride by gluconate increased bicarbonate absorption in late but not in early distal tubules. Bafilomycin A1, an inhibitor of H-ATPase, inhibited late and also early distal tubule bicarbonate absorption, the latter at higher concentration. After 8 d on a low K diet, bicarbonate absorption increased significantly in both early and late distal tubules. Schering compound 28080, a potent H-K ATPase inhibitor, completely blocked this increment of bicarbonate absorption in late but not in early distal tubule. The data suggest bicarbonate absorption via Na(+)-H+ exchange and H-ATPase in early, but only by amiloride-insensitive H+ secretion (H-ATPase) in late distal tubules. The study also provides evidence for activation of K(+)-H+ exchange in late distal tubules of K depleted rats. Indirect evidence implies a component of chloride-dependent bicarbonate secretion in late distal tubules and suggests that net bicarbonate transport at this site results from bidirectional bicarbonate movement.
Generation of human T cells directed against an agonist epitope of Brachyury, a transcription factor involved in human tumor cell epithelial to mesenchymal transition (EMT)
Authors: Benjamin Boyerinas, Jo A Tucker, Diane J Poole, Caroline Jochéms, Claudia Palena, Jeffrey Schlom, Kwong Y Tsang
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The T-box family transcription factor Brachyury is overexpressed in a variety of human carcinomas, including lung, breast, colon, ovarian and prostate. Brachyury has been shown to promote epithelial to mesenchymal transition (EMT) in tumor cells, a critical step in the path to