tbuckley/cabot-search huggingface dataset:
Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity
Authors: Rodger E. Tiedemann, Xinliang Mao, Chang-Xin Shi, Yuan Xiao Zhu, Stephen E. Palmer, Michael Sebag, Ron Marler, Marta Chesi, Rafael Fonseca, P. Leif Bergsagel, Aaron D. Schimmer, A. Keith Stewart
Journal: Journal of Clinical Investigation (2008)

Knockout and transgenic studies in mice demonstrate that normal somatic tissues redundantly express 3 cyclin D proteins, whereas tumor cells seem dependent on a single overexpressed cyclin D. Thus, selective suppression of the individual cyclin D deregulated in a tumor represents a biologically valid approach to targeted cancer therapy. In multiple myeloma, overexpression of 1 of the cyclin D proteins is a ubiquitous feature, unifying at least 7 different initiating genetic events. We demonstrate here that RNAi of genes encoding cyclin D1 and cyclin D2 (CCND1 and CCND2, respectively) inhibits proliferation and is progressively cytotoxic in human myeloma cells. By screening a chemical library using a cell-based assay for inhibition of CCND2 trans-activation, we identified the plant cytokinin kinetin riboside as an inhibitor of CCND2 trans-activation. Kinetin riboside induced marked suppression of CCND2 transcription and rapidly suppressed cyclin D1 and D2 protein expression in primary myeloma cells and tumor lines, causing cell-cycle arrest, tumor cell–selective apoptosis, and inhibition of myeloma growth in xenografted mice. Mechanistically, kinetin riboside upregulated expression of transcription repressor isoforms of cAMP-response element modulator (CREM) and blocked both trans-activation of CCND2 by various myeloma oncogenes and cis-activation of translocated CCND1, suggesting induction of an overriding repressor activity that blocks multiple oncogenic pathways targeting cyclin D genes. These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies.
CH5424802, a Selective ALK Inhibitor Capable of Blocking the Resistant Gatekeeper Mutant
Authors: Hiroshi Sakamoto, Toshiyuki Tsukaguchi, Sayuri Hiroshima, Tatsushi Kodama, Takamitsu Kobayashi, Takaaki A. Fukami, Nobuhiro Oikawa, Takuo Tsukuda, Nobuya Ishii, Yuko Aoki
Journal: Cancer Cell (2011)
Abstract 3069: Importance of zinc-binding domain of <i>matrix metalloproteinase 19</i> (<i>MMP19</i>) in tumor suppression and anti-angiogenesis of nasopharyngeal carcinoma
Authors: Chan King Chi, Josephine M.Y. Ko, Hong Lok Lung, Radislav Sedlacek, Maria Li Lung
Journal: Cancer Research (2010)

Abstract Background and aims: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases consisting of more than 20 enzymes. MMP19 shares the typical MMP structural domains. It degrades various ECM components including collagen type IV, nidogen-1, fibronectin, tenascin-C isoform, aggrecan, and laminin-5-gamma-2-chain. In our previous studies, MMP19 was identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC). It was down-regulated in NPC cell lines and NPC biopsies, when compared to an immortalized normal nasopharyngeal epithelial cell line and corresponding non-tumor nasopharyngeal tissues. Transfection of wild-type (WT) MMP19 into the HONE1-2 NPC cell line significantly suppressed tumor formation in the nude mouse tumorigenicity assay and decreased the tube-forming ability of both human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1). In this study, we aimed to validate the importance of the zinc-binding domain of MMP19 in NPC. Methods: We transfected the mutant MMP19, which contained a mutation at the zinc-binding domain, into HONE1-2 to study the effect of mutant MMP19 in tumor suppression and anti-angiogenesis compared to WT MMP19. Results: Mutant MMP19 was not tumor-suppressive, as is the WT MMP19, and aggressive tumors appeared with the same growth kinetics as the vector-alone control. The anti-angiogenesis effect was also not observed in endothelial cells incubated with conditioned medium from mutant MMP19 clones compared to WT MMP19 clones. Conclusions: Previous studies showed mutation of the zinc-binding domain in MMP19 leads to loss of MMP19 function in cell proliferation, migration, and protein degradation in a human keratinocyte cell model. This study demonstrates loss of tumor suppressive and anti-angiogenesis function of mutant MMP19 in NPC and indicates the importance of the zinc-binding motif for WT MMP19 in suppression of tumor formation and in inhibition of tube-forming ability of endothelial cells in NPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3069.
Clinical Factors Associated With Resistance to Microvascular Complications in Diabetic Patients of Extreme Disease Duration
Authors: Hillary A. Keenan, Tina Costacou, Jennifer K. Sun, Alessandro Doria, Jerry Cavellerano, Joseph Coney, Trevor J. Orchard, Lloyd Paul Aiello, George L. King
Journal: Diabetes Care (2007)

Duration of diabetes and degree of hyperglycemia have consistently been identified as predictors of retinopathy and nephropathy (1–6). Multiple studies have concluded that nearly all individuals with type 1 diabetes will develop some level of retinopathy within 20 years of diagnosis (2,4,5,7,8). However, the study by Bain et al. (9) described the Golden Years study group of type 1 diabetic patients with ≥50 years of diabetes duration who appeared to be protected against nephropathy and large vessel disease but not against retinopathy. However, the associations of glycemic control, duration of disease, and vascular complications were not evaluated (9). This report characterizes the prevalence of complications and associated risk factors in a large number of individuals who have been insulin dependent for ≥50 years.

The 50-Year Medal Program of the Joslin Diabetes Center (JDC) was initiated to recognize JDC or non-JDC patients who survived ≥50 years with type 1 diabetes. This was documented by either medical record or family report. This was a survey-based cross-sectional study of subjects living in the U.S. who were awarded the Joslin Medal between 1997 and 2003. The Committee on Human Subjects at the JDC approved this study. The patients were questioned regarding the presence and absence of eye, kidney, and peripheral neuropathy.

### Clinical validation of retinopathy

Self-reported retinopathy was validated by comparing retinal clinical examination and fundus photography (seven-standard field), in a subset ( n = 92, 28%) of the 326 subjects, to the questionnaire, with the worse eye used for analysis. Grading was performed by two experienced ophthalmologists and discrepancies adjudicated by consensus. Descriptive analyses were performed using the Statistical Analysis System (version 8.2; SAS, Cary, NC). The Cochran-Armitage test was used to test for trends of categorical …
Deregulation of cell growth by the K1 gene of Karposi's sarcoma-associated herpesvirus
Authors: Heuiran Lee, Ronald Veazey, Kenneth Williams, Mengtao Li, Jie Guo, Frank Neipel, Bernhard Fleckenstein, Andrew Lackner, Ronald C. Desrosiers, Jae U. Jung
Journal: Nature Medicine (1998)
Broad based training is actively discouraged in UK postgraduate medical education
Authors: P. Kumar
Journal: BMJ (2014)

Greenway’s report highlights the frustrating contradictions that are embedded in postgraduate medical education and training in the UK.1 It rightly emphasises the need for more “broad based” clinicians to cope with the ever increasing demands of an ageing population.

However, trainees are actively discouraged from becoming more broad based. Those who try to gain clinical experience across a variety …
Inappropriate drug prescribing in elderly people is common
Authors: Scott Gottlieb
Journal: BMJ (2004)

Prescribing drugs to elderly patients that are known to be associated with side effects in older people seems relatively common, despite warnings about such drugs.

Researchers, led by Lesley Curtis of Duke University Medical Center in Durham, North Carolina, and colleagues, investigated the extent that potentially inappropriate drugs are prescribed for elderly patients who are not in hospital ( Archives of Internal Medicine 2004;164: 1621-5).

Inappropriate medications were identified according to criteria set by physicians and pharmacologists, as defined by a list known as the Beers revised list …
Our National Department of Health.
Authors: L. P. H. Bahrenburg
Journal: JAMA (1900)

Pemberville, Ohio, March 6, 1900. <h3>To the Editor:</h3> For a long time past I have noticed in our professional journals letters and reports of remarks made on the subject of a proposed national board of health to be established as an individual cabinet department. All these have been of considerable interest to me and, although the majority evince a deplorable ignorance of the public health functions even now being exercised by our Government, they are nevertheless a source of great satisfaction in that they show an awakened interest in the profession in this, our most important and altruistic duty to our land. It is quite evident that but a very small minority of our professional brethren are informed as to the existence of the U. S. Marine-Hospital Service, and apparently a still smaller number are at all acquainted with the scope of its usefulness or with the fidelity with which
Bottom‐Up Engineering of Well‐Defined 3D Microtissues Using Microplatforms and Biomedical Applications
Authors: Geon Hui Lee, Jae Seo Lee, Xiaohong Wang, Sang Hoon Lee
Journal: Advanced Healthcare Materials (2015)

During the last decades, the engineering of well‐defined 3D tissues has attracted great attention because it provides in vivo mimicking environment and can be a building block for the engineering of bioartificial organs. In this Review, diverse engineering methods of 3D tissues using microscale devices are introduced. Recent progress of microtechnologies has enabled the development of microplatforms for bottom‐up assembly of diverse shaped 3D tissues consisting of various cells. Micro hanging‐drop plates, microfluidic chips, and arrayed microwells are the typical examples. The encapsulation of cells in hydrogel microspheres and microfibers allows the engineering of 3D microtissues with diverse shapes. Applications of 3D microtissues in biomedical fields are described, and the future direction of microplatform‐based engineering of 3D micro‐tissues is discussed.
Incisions and Esophagectomy
Authors: Andrew C. Chang
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
1223 MICE DEFICIENT IN HLJ1 EXHIBIT IMPAIRED ER STRESS MEDIATED FATTY LIVER AND DEFECTS IN LIVER RESPONSES TO ENVIRONMENTAL TOXICS
Authors: M.H. Chien, T.C. Lin, K.Y. Su, P.C. Yang, H.Y. Chen, K.C. Li, S.L. Yu
Journal: Journal of Hepatology (2012)
Continuous Subcutaneous Insulin Infusion in Adults: Glycemic Advantage is Predicted by Venous Plasma C-Peptide Concentrations
Authors: N W Rodger, J Dupre, C L B Canny, W F Brown
Journal: Diabetes Care (1985)

Continuous subcutaneous insulin infusion (CSII) has been compared with conventional insulin injection treatment (CIT) supplemented by self-monitoring of capillary blood glucose (SMBG) in 18 nonobese adults with insulin-dependent diabetes mellitus (IDDM). Mean daily insulin dosage and rates of hypoglycemia were similar during CSII (duration of treatment 36 ± 2 wk mean ± SE) and CIT (31 ± 1.6 wk). On the basis of fasting C-peptide concentrations and postintravenous glucagon increments of &amp;lt; 0.1 pmol/ml, subjects were classified C-peptide negative (CP NEG) (N = 11), or C-peptide positive (CP POS) (N = 7). Relative to CIT, CP NEG subjects on CSII had significant decreases in premeal/bedtime and postmeal plasma glucose concentrations and glycosylated hemoglobin (percent of total). CP POS patients during each of CSII and CIT showed glycemic responses equivalent to those of CP NEG patients on CSII. In neither group could results be explained on the basis of improved beta cell function. Thus, therapeutic advantage of CSII was not apparent in IDDM adults retaining significant C-peptide activity.
THE CARE OF THE CRIPPLE
Authors: F. J. GAENSLEN
Journal: JAMA (1925)

The care of the cripple, it is generally conceded, is a problem of no small proportions. Much has been accomplished and much still remains to be done. The purpose of the address which it is my privilege to present is to offer a brief survey of the situation as it stands today, as an aid in the determination, if possible, of the directions along which further efforts may be most fruitful. While my remarks bear on the problem of the cripple in general, I have in mind especially the child cripple. The ultimate goal of all our efforts should be the prevention of dependence on family or state and all that that implies, the motives being both humanitarian and economic.  It would seem logical, in the first place, to ascertain the total number of cripples and the annual addition to the cripple population; also whether or not all reasonable effort
Interactions between selenium compounds and those of mercury or cadmium.
Authors: J Parizek
Journal: Environmental Health Perspectives (1978)

Two types of mechanisms are considered in this discussion of the interactions between compounds of selenium and those of cadmium or mercury: one based on a direct chemical reaction between compounds of these elements and the other based on metabolic changes induced by selenium administration and modifying the dose-effect relationship indirectly, without a reaction between selenium and the metallic compound. The second type of metabolic changes induced by selenium may explain why an increased selenium intake provides protection not only against methylmercury but also against the toxicity of methylated selenium compounds. A better understanding of the underlying mechanisms would help in assessing the importance of these interactions for man.
Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G‐CSF
Authors: Mike G. Martin, Kristan M. Augustin, Geoffrey L. Uy, John S. Welch, Lindsay Hladnik, Sagun Goyal, Divya Tiwari, Ryan S. Monahan, Richard M. Reichley, Amanda F. Cashen, Keith Stockerl‐Goldstein, Peter Westervelt, Camille N. Abboud, John F. DiPersio, Ravi Vij
Journal: American Journal of Hematology (2009)

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m(2) on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18-70) and 47 years (range 20-68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG-I and FLAG-IM. The complete remission (CR) rate in the FLAG-I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG-IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event-free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG-I over FLAG-IM. The patients who received G-CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G-CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G-CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.
Theories of male and female aggression
Authors: Kirsti M. J. Lagerspetz
Journal: Behavioral and Brain Sciences (1999)

Sociobiology has ignored the results of psychology, which is the discipline between biology and society. Campbell's target article fills some of the gaps beautifully, but the fact that women's direct and physical aggression has increased during the past 20 years, undermines Campbell's evolutionary explanation of female aggression. The two classical types of theoretical explanations of aggression are that (1) aggression is a drive and (2) aggression is instrumental behavior. Expressive aggression, assumed to be typical of women, is no more drive aggression than is men's aggression.
Letter: Hazard of air embolism with multiple infusion apparatus.
Authors: S J Tovey
Journal: BMJ (1975)

as safe as Dr Jackson-Moore believes them to be; they undoubtedly have great promnise.Nevertlheless, at the present time we would reconmmend for at-risk patients an up-to-date inactivated vaccine rather than live A/England vaccine.-ED,BM7.Thrombocytopenia during treatment with clonazepam SIR,-We think it is desirable to publicise as a matter of some urgency a potentially dangerous thrombocytopenia developing probably as a reaction to the drug clonaze- pam (Rivotril).
STROKE IN PATIENTS WITH AORTIC STENOSIS: THE SIMVASTATIN AND EZETIMIBE IN AORTIC STENOSIS STUDY
Authors: Anders M. Greve, Morten Dalsgaard, Casper Bang, Kenneth Egstrup, Simon Ray, Kurt Boman, Anne B. Rosseb, Christa Gohlke-Baerwolf, Richard Devereux, Lars Kober, Kristian Wachtell
Journal: Journal of the American College of Cardiology (2014)
Gruppe und Aggression
Authors: G. Ammon
Journal: Psychotherapy and Psychosomatics (1972)

Based on the observation of 183 patients suffering from conflicts of the early mother-child-symbiosis the author examines the role of the family in the rise of destructive aggression. Destructive aggression is caused by the loss of social functions of the family which becomes the stage of a dammed up aggression. Identification and communication are thus made impossible. The therapeutic technique is the analytic group therapy, which allows to put family dynamics here and now on the stage rendering possible a direct therapeutic working through. The social problem of the family will be solved by its investigation and by searching for ways of a new organisation.
Incidence of acute symptomatic toxoplasma retinochoroiditis in south London according to country of birth
Authors: R E Gilbert, M R Stanford, H Jackson, R E Holliman, M D Sanders
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To determine the incidence of acute symptomatic toxoplasma retinochoroiditis presenting to ophthalmologists for patients born in Britain and elsewhere. <b>Design</b>: Population based, cross sectional study. <b>Setting</b>: 11 districts in south Greater London. <b>Subjects</b>: All patients presenting to NHS ophthalmologists with symptoms due to acute toxoplasma retinochoroiditis in 1992-3. <b>Main outcome measure</b>: Intraocular inflammation in association with a retinochoroidal scar, active adjoining retinitis, and IgG serum antibodies to toxoplasma. <b>Results</b>: The estimated incidence of acute symptomatic retinochoroiditis for all people born in Britain was 0.4/100 000/year and for black people born in west Africa 57/100 000/year. If a mean of two symptomatic episodes per lifetime is assumed, 100 people born in Britain may be affected each year, about a fifth of the estimated 500-600 congenitally infected people born each year. <b>Conclusions</b>: A substantial proportion of people with acute symptomatic toxoplasma retinochoroiditis were born outside the country, and the number born in Britain was smaller than the number previously estimated to develop retinochoroidal lesions due to congenital toxoplasmosis. These findings suggest that prenatal screening for toxoplasmosis in Britain may be of limited benefit. <h3>Key messages</h3> Key messages Prevention of toxoplasma retinochoroiditis is considered to be a major benefit of prenatal screening as previous studies have suggested that 80% of congenitally infected children would eventually develop retinochoroiditis This report shows that the incidence of symptomatic toxoplasma retinochoroiditis is nearly 100 times higher in black people born in west Africa than in subjects born in Britain In subjects born in Britain acute symptomatic toxoplasma retinochoroiditis is much less common than expected, affecting about one fifth of the estimated number of congenitally infected people These findings suggest that the potential benefits of prenatal screening for toxoplasma infection in Britain are limited
Assessment of the multiple components of the variability in the adenoma detection rate in sigmoidoscopy screening, and lessons for training
Authors: M. Fracchia, C. Senore, P. Armaroli, R. Ferraris, R. Placido, A. Musso, D. Turco, C. Bellisario, I. Baldi, N. Segnan
Journal: Endoscopy (2010)

See also: Commentaire de travail de M. Fracchia et al., pp. 448Endoscopy 2010; 42(06): 522-522DOI: 10.1055/s-0031-1291862
Preparation for Barium Enema
Authors: Robert A. Rose
Journal: JAMA (1977)

To the Editor.—  The overall diagnostic quality of barium enema roentgenograms is quite poor. We are missing 35% to 60% of notable pathologic findings; most of these findings would be readily demonstrable with good-quality roentgenograms.  At least two areas must be addressed.   I will dispense with the part about which we can do little, and that is the radiologist, both regarding the care with which the examination is done and the technique used. A difference of opinion exists as to the relative efficacy of air-contrast vis-a-vis high-voltage techniques or both, depending on the reason for the study.  That which we can influence considerably is the patient bowel preparation. Excellent or good patient preparation may be predictably, rather simply, and realistically obtained in 96.7%.2   Patients will comply with intelligent instructions. Both verbal and supplemental written well-thoughtout and clearly presented instructions are necessary. It is suggested that the most interested