tbuckley/cabot-search huggingface dataset:
Abstract 5497: An inhibitor of phosphatase PP2A enhances in vivo anticancer activity of a phospho (ADP-ribosyl) polymerase inhibitor (PARPi) combined with temozolomide (TMZ)
Authors: Jie Lu, Barbara Ikejiri, Chunzhang Yang, Eli Thompson, Harry Mushlin, John S. Kovach, Russell Lonser, Zhengping Zhuang
Journal: Cancer Research (2011)

Abstract We previously showed that a novel inhibitor of PP2A enhances the in vivo activity of TMZ against human glioblastoma xenografts (Lu et al, PNAS 2009;104:11697-11702). Several mechanisms underlie this effect of PP2A inhibition and include an increased rate of cancer cell entry into DNA synthesis, inhibition of cell cycle arrest at G1 and G2/M, and a marked reduction in p53. Because inhibitors of PARP1 have been shown to enhance the activity of cytotoxic cancer drugs by inhibiting repair of single-strand breaks in cells with impaired mechanisms for double-stranded DNA repair (BrCa mutants, triple negative breast cancer cells), we reasoned that blocking other types of DNA-damage defense mechanisms by PP2A inhibition might further enhance the activity of a PARPi combined with TMZ in cancers, not necessarily already deficient in DNA repair. We treated mice bearing xenografts of human melanoma, line A2058, with single agent LB-100, a novel water soluble PP2A inhibitor (Lixte Biotechnology Holdings, Inc., East Setauket, NY; Lu et al, J Neurosurg 2010; 113: 225-233) at 1.5mg/kg by continuous intraperitoneal (i.p.) infusion for 21 days and TMZ at 80mg/kg i.p. days 3,6,9,12,15,18. LB-100 and TMZ were given alone and in combination with each other and in 2-drug combinations with the PARPi, ABT-888 (Sigma), at 6.25 mg/kg i.p. on days 3,6,9,12,15,18, and all three drugs were given together at the same doses and schedules as when used alone or in 2-drug combinations. (ABT-888 was inactive as a single agent and was not used alone). The combination of LB-100 + TMZ was more inhibitory to the xenografts at 21 days than ABT-888 + TMZ, but the 3-drug regimen was most effective and no more toxic than any of the 2-drug regimens. Histologic analysis of xenografts 24 hours after treatment of animals with each of the single agents, each 2-drug regimen, and the 3-drug regimen showed increased apoptosis and necrosis by the 3-drug combination compared to the two-drug regimens, which in turn were more effective that the single agents. Similar results were found in vitro by flow cytometric analysis of A2058 cells 24 hours after exposure to the single agent and 2- and 3-drug regimens. Inclusion of a PP2A inhibitor may increase and extend the effectiveness of cytotoxic regimens containing a PARPi to cancers without acquired mutations in DNA repair. 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 5497. doi:10.1158/1538-7445.AM2011-5497
Complication of proximal gastric vagotomy.
Authors: H Burge
Journal: BMJ (1974)

hepatitis and hepatitis-B antigen was shown to be present by both haenmalutination and electrophoresis.This case cannot, of course, be claimed to provide proof of a causal association between acupuncture and serum hepatitis.The possibility of transfer of infection by an inadequately sterilized needle should, however, be borne in mind.-Iam, etc.,
Heterogeneity of endothelium-dependent and endothelium-independent responses to aggregating platelets in porcine pulmonary arteries.
Authors: T M Zellers, H Shimokawa, J Yunginger, P M Vanhoutte
Journal: Circulation Research (1991)

Experiments were designed to determine the endothelium-dependent and endothelium-independent responses to aggregating platelets in porcine pulmonary arteries. Isolated rings with and without endothelium from large (5-7-mm-diameter) and small (2-3-mm-diameter) pulmonary arteries were suspended in modified Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2 in the presence of indomethacin. Aggregating platelets caused relaxations in rings with endothelium but contractions in rings without endothelium, both of which were significantly larger in small versus large pulmonary artery rings. Serotonin and ADP caused concentration-dependent endothelium-augmented relaxations that were unaffected by ketanserin. Methiothepin, but not apyrase, significantly decreased the platelet-induced endothelium-dependent relaxations; the residual relaxation was abolished when rings were incubated with methiothepin, apyrase, and theophylline but was unaffected if apyrase was absent, indicating that ADP is responsible for the residual relaxation caused by aggregating platelets. Quiescent rings, with and without endothelium, contracted in a dose-dependent manner to norepinephrine and histamine but not to serotonin or vasopressin. The contraction to aggregating platelets was blocked by methiothepin, pyrilamine, and diphenhydramine but was unaffected by phentolamine, ketanserin, or incubation of the platelets with dazoxiben. These data indicate that, in large and small porcine pulmonary arteries, serotonin and ADP are the major contributors to the endothelium-dependent relaxation caused by aggregating platelets, while histamine appears to be responsible for the contraction that platelets cause in rings without endothelium.
A Prospective, Randomised Trial Comparing Plasmakinetic Enucleation to Standard Transurethral Resection of the Prostate for Symptomatic Benign Prostatic Hyperplasia: Three-year Follow-up Results
Authors: Zhigang Zhao, Guohua Zeng, Wen Zhong, Zanlin Mai, Shaohua Zeng, Xueting Tao
Journal: European Urology (2010)
A CONTRIBUTION TO THE EPIDEMIOLOGY OF LOBAR PNEUMONIA
Authors: Ernest G. Stillman
Journal: The Journal of Experimental Medicine (1916)

1. Pneumococci of Type I and Type II are responsible for the majority of the cases of lobar pneumonia. 2. Among the pneumococci found in the mouths of healthy individuals, Type IV predominates, Type III is fairly frequent, and atypical organisms of Type II are occasionally encountered. Organisms of these types give rise to a minority of cases of lobar pneumonia. 3. Healthy persons intimately associated with cases of lobar pneumonia may harbor in their mouth secretions the highly parasitic pneumococci of Types I and II. 4. Occasionally a carrier of Type I or Type II pneumococcus is encountered in whom it is impossible to trace any contact with an infected patient. 5. Convalescents from lobar pneumonia may carry for a considerable period of time the type of pneumococcus with which they were infected.
Textbook of International Health: Global Health in a Dynamic World
Authors: Thomas A. Faunce
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Involving community may be way forward post-Shipman
Authors: A. P Morton
Journal: BMJ (2003)

EDITOR—Baker et al monitored mortality in general practice after Shipman.1 A statistical monitoring process with high enough sensitivity to detect murder would almost certainly give many false positive signals. This could cause severe damage both to practitioners and to their relationships with their patients.

A statistical monitoring process with high enough specificity to avoid false positive signals may …
The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential
Authors: Hiroki Fujita, Tsukasa Morii, Hiromi Fujishima, Takehiro Sato, Tatsunori Shimizu, Mihoko Hosoba, Katsushi Tsukiyama, Takuma Narita, Takamune Takahashi, Daniel J. Drucker, Yutaka Seino, Yuichiro Yamada
Journal: Kidney International (2013)
How should airways resistance be measured in young children: mask or mouthpiece?
Authors: F. Child, S. Clayton, S. Davies, A.A. Fryer, P.W. Jones, W. Lenney
Journal: European Respiratory Journal (2001)

The reproducibility and acceptability of airways resistance measurements using the interrupter technique (Micro R int ) obtained using a mouthpiece were compared with those using a face mask. Fifty children aged 4–7 yrs performed four sets of six R int measurements; two using a mouthpiece and two using a face mask with integral mouthpiece. Complete data were obtained from 45 (90%) children using the mouthpiece and 43 (86%) children using the mask. The two methods were equally repeatable with comparable intraclass correlation coefficients (ICC) and coefficients of variation. Mean R int values obtained using the mouthpiece were significantly lower than those using the face mask ((mean±sd) mouthpiece=0.81±0.18 kPa·L −1 ·s, mask=0.88±0.24 kPa·L −1 ·s p=0.0002). Although the mean paired differences between the two methods were small (0.07 kPa·L −1 ·s), the ICC and limits of agreement confirmed that the two methods could not be used interchangeably. Sixty-seven per cent of children preferred the face mask but this was more time-consuming (p=0.03). Children did not produce more repeatable results using their preferred method, nor did they improve with practice. Repeatable airway resistance measurements using the interrupter technique can be obtained from young children using either a mouthpiece or a face mask, but there are significant clinical and statistical differences between the results obtained.
p300 Regulates Androgen Receptor–Independent Expression of Prostate-Specific Antigen in Prostate Cancer Cells Treated Chronically with Interleukin-6
Authors: Jose D. Debes, Barbara Comuzzi, Lucy J. Schmidt, Scott M. Dehm, Zoran Culig, Donald J. Tindall
Journal: Cancer Research (2005)

Abstract Prostate cancer is the most frequent non–skin cancer in men. Although the mechanisms involved in the progression of prostate cancer are not entirely understood, androgen receptor has been shown to play an important role. Androgen receptor is expressed in both early and late-stage prostate cancer. Also, androgen-regulated pathways are thought to be active as evidenced by elevated levels of prostate-specific antigen (PSA). In addition, several androgen receptor coactivators and cytokines are involved in prostate cancer progression. In this regard, we have shown previously that the coactivator p300 plays a major role in the androgen-independent activation of PSA by interleukin 6 (IL-6), a cytokine involved in late-stage prostate cancer. In this study, we investigated the role of p300 and its homologue CREB-binding protein in prostate cancer cells treated chronically with IL-6. We found that p300 but not CREB-binding protein induced activation of PSA in these cells and that the histone acetyltransferase activity of p300 was critical. This effect was independent of the presence of androgens or antiandrogens. Moreover, we found markedly reduced levels of androgen receptor in these cells and p300 transfection did not affect those levels, suggesting that the p300 effect on PSA could be bypassing the androgen receptor. Transfection with exogenous androgen receptor showed minimal response of PSA to androgens but higher response to p300. We found similar effects of p300 on the androgen response element III, which mediates the androgen receptor–dependent activation of PSA. Finally, we showed that p300 alone regulates expression of the endogenous PSA gene in the IL-6–treated cells. These findings reveal a new insight in the progression of prostate cancer, suggesting that coactivators, such as p300, play more important roles in late-stage prostate cancer, and could regulate androgen-dependent genes in the absence or with very low levels of androgen receptor.
Psychiatric studies of Borstal lads
Authors: Marjorie C. Meehan
Journal: JAMA (1963)

It is disappointing that this book adds little to our understanding of lawbreakers. The author has investigated the psychological and social characteristics of 200 London youths, aged 17 to 21, who were sentenced to Borstal institutions (reformatories for long-term rehabilitation of persistent offenders). Most of the subjects had had several previous convictions. Psychotics and mental defectives were not included. The investigation included relatively brief psychiatric interviews, psychological and personality tests, home visits by a social worker, and records of official documents. One hundred and thirty-two boys were re-examined about a year later while still in the institution, and records were later obtained of reconvictions in the five years after discharge. There are detailed case reports (averaging about 1,000 words) of 18 boys, with follow-up studies of 12. A five-page appendix summarizes the follow-up findings of the entire group. Otherwise, the book includes only material from the initial examination, together with
Targeting the Cell Cycle: A New Approach to Cancer Therapy
Authors: Gary K. Schwartz, Manish A. Shah
Journal: Journal of Clinical Oncology (2005)

The cell cycle represents a series of tightly integrated events that allow the cell to grow and proliferate. Critical parts of the cell cycle machinery are the cyclin-dependent kinases (CDKs), which, when activated, provide a means for the cell to move from one phase of the cell cycle to the next. The CDKs are regulated positively by cyclins and regulated negatively by naturally occurring CDK inhibitors (CDKIs). Cancer represents a dysregulation of the cell cycle such that cells that overexpress cyclins or do not express the CDKIs continue to undergo unregulated cell growth. The cell cycle also serves to protect the cell from DNA damage. Thus, cell cycle arrest, in fact, represents a survival mechanism that provides the tumor cell the opportunity to repair its own damaged DNA. Thus, abrogation of cell cycle checkpoints, before DNA repair is complete, can activate the apoptotic cascade, leading to cell death. Now in clinical trials are a series of targeted agents that directly inhibit the CDKs, inhibit unrestricted cell growth, and induce growth arrest. Recent attention has also focused on these drugs as inhibitors of transcription. In addition, there are now agents that abrogate the cell cycle checkpoints at critical time points that make the tumor cell susceptible to apoptosis. An understanding of the cell cycle is critical to understanding how best to clinically develop these agents, both as single agents and in combination with chemotherapy.
Hypoxia-induced increases in pulmonary transvascular protein escape in rats. Modulation by glucocorticoids.
Authors: T J Stelzner, R F O'Brien, K Sato, J V Weil
Journal: Journal of Clinical Investigation (1988)

Pulmonary edema after ascent to altitude is well recognized but its pathogenesis is poorly understood. To determine whether altitude exposure increases lung vascular permeability, we exposed rats to a simulated altitude of approximately 14,500 feet (barometric pressure [Pb] 450 Torr) and measured the pulmonary transvascular escape of radiolabeled 125I-albumin corrected for lung blood content with 51Cr-tagged red blood cells (protein leak index = PLI). Exposures of 24 and 48 h caused significant increases in PLI (2.30 +/- 0.08 and 2.40 +/- 0.06) compared with normoxic controls (1.76 +/- 0.06), but brief hypoxic exposures of 1-13 h produced no increase in PLI, despite comparable increases in pulmonary artery pressure. There were associated increases in gravimetric estimates of lung water in the altitude-exposed groups and perivascular edema cuffs on histologic examination. Normobaric hypoxia (48 h; fractional inspired oxygen concentration [FIO2] = 15%) also increased lung transvascular protein escape and lung water. Dexamethasone has been used to prevent and treat altitude-induced illnesses, but its mechanism of action is unclear. Dexamethasone (0.5 or 0.05 mg/kg per 12 h) started 12 h before and continued during 48 h of altitude exposure prevented the hypoxia-induced increases in transvascular protein escape and lung water. Hemodynamic measurements (mean pulmonary artery pressure and cardiac output) were unaffected by dexamethasone, suggesting that its effect was not due to a reduction in pulmonary artery pressure or flow. The role of endogenous glucocorticoid activity was assessed in adrenalectomized rats that showed augmented hypoxia-induced increases in transvascular protein escape, which were prevented by exogenous glucocorticoid replacement. In summary, subacute hypoxic exposures increased pulmonary transvascular protein escape and lung water in rats. Dexamethasone prevented these changes independent of reductions of mean pulmonary artery pressure or flow, whereas adrenalectomy increased pulmonary vascular permeability and edema at altitude. Increases in vascular permeability in hypoxia could contribute to the development of high-altitude pulmonary edema and endogenous glucocorticoids may have an important influence on pulmonary vascular permeability in hypoxia.
The Mechanism of Inhibition of Hepatitis B Virus Replication by the Carbocyclic Analog of 2′–Deoxyguanosine
Authors: Peter M. Price, Ranjit Banerjee, Alan M. Jeffrey, George Acs
Journal: Hepatology (1992)

The carbocyclic analog of deoxyguanosine inhibits hepatitis B virus replication by greater than 95% in the hepatitis B virus-producing cell line (2.2.15) as monitored by decreases of secreted hepatitis B virus DNA, hepatitis B virus polymerase activity and intracellular episomal hepatitis B virus DNA. Transcription of hepatitis B virus RNA from chromosomally integrated hepatitis B virus DNA was unaffected. Radioactive carbocyclic 2'-deoxyguanosine was directly phosphorylated within the 2.2.15 cells and was incorporated exclusively into DNA. In contrast, radioactive deoxyguanosine was presumably metabolized through the "salvage" pathway in which the guanine was primarily incorporated into cellular RNAs. The rate of incorporation of carbocyclic 2'-deoxyguanosine in 2.2.15 cells was similar to that in the parental cell line (HepG2), which does not contain hepatitis B virus sequences. Greater than 90% of the analog was present at internal sites within the DNA, indicating that the analog did not function as a DNA chain terminator. Kinetic analysis of the Km and Ki of dGTP and carbocyclic 2'-deoxyguanosine 5'-triphosphate, respectively, using both hepatitis B virus polymerase and DNA polymerase delta indicated that the analog is a competitive inhibitor for dGTP. Although both polymerases had similar Km's for dGTP, the Ki for carbocyclic 2'-deoxyguanosine 5'-triphosphate was about 6 times lower using the hepatitis B virus polymerase. This would indicate that, at low concentrations of intracellular carbocyclic 2'-deoxyguanosine 5'-triphosphate, the hepatitis B virus polymerase would be preferentially inhibited. We propose this to be the mechanism acting to inhibit preferentially hepatitis B virus replication in the tissue culture cells.
Assessment of Maternal Attributions of Infant's Hostile Intent and Its Use in Child Maltreatment Prevention/Intervention Efforts
Authors: Joel S. Milner, Julie L. Crouch
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Lack of correlation between fulminant form of viral hepatitis and retrovirus infection associated with the acquired immune deficiency syndrome (AIDS) in drug addicts.
Authors: P Amoroso, G Lettieri, A Giorgio, P Fico, P Pierri, G Giraldo, E Beth-Giraldo
Journal: BMJ (1986)

Chez les toxicomanes, les retrovirus lies au SIDA sont trouves avec la meme frequence dans l'hepatite virale non compliquee et dans l'hepatite virale fulminante. Ces retrovirus ne peuvent pas etre responsables de la forme fulminante de l'hepatite
Distribution, Morphology, and Neurochemistry of Endocardial and Epicardial Nerve Terminal Arborizations in the Human Heart
Authors: K. Marron, J. Wharton, M.N. Sheppard, D. Fagan, D. Royston, D.M. Kuhn, M.R. de Leval, B.F. Whitehead, R.H. Anderson, J.M. Polak
Journal: Circulation (1995)

Background The heart contains a variety of morphologically distinct nerve terminals known to influence cardiac function. Little is known about the distribution, morphology, and neurochemistry of these terminals in the human heart. Methods and Results We examined the entire endocardial and epicardial surfaces of infant and adult hearts obtained postmortem and at transplantation using immunohistochemical and histochemical staining of whole-mount preparations in conjunction with confocal and fluorescence microscopy. Terminals arising from nerve fibers (diameter, 6 to 10 μm) immunoreactive for myelin basic protein were identified in the atrial endocardium, epicardium, and coronary sinus, and four types were distinguished by differences in immunostained nerve area (range, 358 to 797 μm 2 ) and dispersion (range, 620 to 4684 μm 2 ). These terminals displayed immunoreactivity for tyrosine hydroxylase, neuropeptide Y, and the general neural marker protein gene product 9.5. Acetylcholinesterase (AChE) activity was detected in &lt;5% of endocardial terminals and in no epicardial terminals arising from myelinated fibers. The latter were observed in close proximity to mesothelial cells, and nerve fibers supplying these terminals were found to be associated with local ganglia. A distinct population of terminals (mean stained area, 35 μm 2 ; 18 to 53 μm 2 , 95% CI; and mean dispersion, 59 μm 2 ; 38 to 80 μm 2 , 95% CI) was demonstrated to arise from nonmyelinated fibers (mean diameter, 2.5 μm; 2.2 to 2.8 μm, 95% CI) in the endocardial plexus of the atria and left ventricle and were predominantly AChE-positive. Conclusions Specialized nerve terminals are distributed more widely in the human heart than has been described in experimental animals. These terminals express either AChE activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity, suggesting that acetylcholine, catecholamines, and neuropeptide Y may be present in sensory and autonomic nerves in the human heart.