tbuckley/cabot-search huggingface dataset:
Inhibition of Tumor Growth by Ribozyme-Mediated Suppression of Aberrant Epidermal Growth Factor Receptor Gene Expression
Authors: Hitoshi Yamazaki, Hiroshi Kijima, Yoshiyuki Abe, Yoshiro Oshika, Takashi Tsuchida, Tetsuji Tokunaga, Norikazu Tamaoki, Masato Nakamura, Atsushi Tsugu, Yasuyuki Ohnishi, Yoshito Ueyama
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene is frequently associated with malignant gliomas. One type of EGFR mutation in primary gliomas results in overexpression of an aberrant EGFR messenger RNA (mRNA) that lacks sequences of exons II through VI of the human EGFR gene. We observed that the aberrantly spliced EGFR mRNA contains a ribozyme cleavable sequence (5*-AAG GUA AUU-3*) created by the joining of EGFR exon I to exon VII. We hypothesized that an appropriately designed ribozyme RNA could mediate site-specific cleavage of the aberrant EGFR mRNA and reduce the growth of aberrant EGFR-producing tumor cells. Methods: We synthesized aberrant EGFR mRNA substrates and a sequence-specific hammerhead ribozyme (abEGFR-rib) to examine the ribozyme's activity in vitro. We also constructed an abEGFR-rib plasmid and introduced it into ERM5-1 cells, which are murine NIH3T3 cells transfected to express an aberrant EGFR complementary DNA. We measured the growth potential of the cotransfected cells in culture and in nude mice. Results: The synthesized abEGFR-rib efficiently and specifically cleaved aberrant EGFR mRNA substrates in vitro. Expression of the transfected abEGFR-rib suppressed expression of aberrant EGFR mRNA in ERM5-1 cells and reduced the growth of tumors formed by the cotransfected cells in nude mice. Finally, the incorporation of bromodeoxyuridine, a measure of mitotic activity, was also decreased in abEGFR-ribproducing ERM5-1 cells in vivo. Conclusion: Ribozymes targeted to aberrant EGFR mRNA can inhibit the growth of tumors formed by cells that express this mRNA.
Biochemical basis of heart function: 1. relation of catecholamine stores and contractile force in an isolated rat heart
Authors: N. S. Dhalla, K. J. R. Naidu, B. Bhagat, K. Cristensen
Journal: Cardiovascular Research (1971)

Under different experimental conditions, endogenous noradrenaline and contractile force of the isolated rat heart were measured concomitantly. Neither substrate-depleted nor hypoxic hearts, which failed to generate contractility, showed a proportional decline in noradrenaline concentration. The catecholamine stores decreased but the contractile force was maintained in hearts perfused with medium containing glucose for 2 hr. In hearts from animals treated with reserpine, catecholamine stores were markedly reduced and contractility increased while, in hearts from animals treated with nialamide, catecholamine stores were increased without any change in contractility. Essentially a good correlation was noted between results concerning catecholamine stores measured by chemical and histochemical techniques. The data do not suggest any relation between endogenous noradrenaline stores and myocardial contractility.
Researchers' offices raided over banned AIDS drug
Authors: P. Sidley
Journal: BMJ (1997)

South Africa's drug regulatory authority, the Medicines Control Council, has raided the offices and home of two researchers who developed a controversial drug, Virodene, to treat AIDS. They were looking for evidence of the sale and manufacture of Virodene, which has been banned.

Although nothing was found, the council has asked the police to investigate the possibility of laying charges against the developers. Virodene hit the headlines earlier this year as a cheap possible cure to AIDS (8 February, p 450). Its active ingredient is an industrial solvent known as P058. …
Service Versus Education in Residency
Authors: Jon S. Du Bois
Journal: Annals of Internal Medicine (1991)

Letters1 December 1991Service Versus Education in ResidencyJon S. Du Bois, MDJon S. Du Bois, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-11-914_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:In their recent article, Hayward and colleagues (1) address the balance between service and clinical education in residency training by examining characteristics of "burdensome non-medical chores" (2) known as "scutwork." They successfully defined numerous procedural and clerical duties, which were viewed by residents as having little educational value and as being peripheral to their physician role. As anticipated, there were differences between faculty and residents' perceptions of scutwork, with faculty tending to underestimate scut content and to overestimate educational merit. Interestingly, for residents, the scut content of a service often depended on the clinical context and specific...References1. HaywardRockwoodSheehanBass RKGE. A phenomenology of scut. Ann Intern Med. 1991;115:372-6. LinkGoogle Scholar2. . Response to the New York State Advisory Committee on Emergency Services: Position Paper. Washington, D.C.: Association of Program Directors in Internal Medicine; 1987. Google Scholar3. Wallice E. Service vs education in internal medicine residency: need for a solution. Arch Intern Med. 1988; 148:1296. CrossrefMedlineGoogle Scholar4. Squires B. Fatigue and stress in medical students, interns and residents: it's time to act. Can Med Assoc J. 1989;140:18-9. Google Scholar5. KatzSchroeder MS. The sounds of the hospital: paging patterns in three teaching hospitals. N Engl J Med. 1988;319:1585-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New England Medical Center Hospitals Boston, MA 02111 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1991Volume 115, Issue 11Page: 914-914KeywordsPerceptionResidency Issue Published: 1 December 1991 PDF DownloadLoading ...
Categorical Programs for Heart Disease, Cancer and Stroke
Authors: Alex M. Burgess, Theodore Colton, Osler L. Peterson
Journal: New England Journal of Medicine (1965)

THE report of the President's Commission on Heart Disease, Cancer and Stroke, published in late 1964, has proposed a program to effect a reduction of unnecessary deaths from heart disease, cancer and stroke, through the establishment of a network of centers for investigation, training and treatment. Evidence, mostly in the form of death rates, was presented to demonstrate the major importance of these three causes of death. The Commission stated that the federal Government has the responsibility of assuring immediate application of scientific advances to medical care. These proposals must be evaluated critically in relation to both the realism of . . .
THE EFFECT OF GLUTATHIONE IN DELAYING GRISEOFULVIN-INDUCED PORPHYRIA IN MICE
Authors: C. W. I. OWENS
Journal: British Journal of Dermatology (1964)

Journal Article THE EFFECT OF GLUTATHIONE IN DELAYING GRISEOFULVIN‐INDUCED PORPHYRIA IN MICE Get access C. W. I. OWENS, B.Sc. C. W. I. OWENS, B.Sc. Research Assistant, Department of Chemical Pathology, University College Hospital Medical School, London, W.C.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 2, 1 February 1964, Pages 81–85, https://doi.org/10.1111/j.1365-2133.1964.tb14479.x Published: 01 February 1964
Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines
Authors: David G. Maloney
Journal: Journal of Clinical Oncology (2005)

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.
Receptor Affinity and Extracellular Domain Modifications Affect Tumor Recognition by ROR1-Specific Chimeric Antigen Receptor T Cells
Authors: Michael Hudecek, Maria-Teresa Lupo-Stanghellini, Paula L. Kosasih, Daniel Sommermeyer, Michael C. Jensen, Christoph Rader, Stanley R. Riddell
Journal: Clinical Cancer Research (2013)

The adoptive transfer of T cells modified to express a chimeric antigen receptor (CAR) comprised of an extracellular single-chain antibody (scFV) fragment specific for a tumor cell surface molecule, and linked to an intracellular signaling module, has activity in advanced malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a tumor-associated molecule expressed in prevalent B-lymphoid and epithelial cancers and is absent on normal mature B cells and vital tissues, making it a candidate for CAR T-cell therapy.We constructed ROR1-CARs from scFVs with different affinities and containing extracellular IgG4-Fc spacer domains of different lengths, and evaluated the ability of T cells expressing each CAR to recognize ROR1(+) hematopoietic and epithelial tumors in vitro, and to eliminate human mantle cell lymphoma (MCL) engrafted into immunodeficient mice.ROR1-CARs containing a short "Hinge-only" extracellular spacer conferred superior lysis of ROR1(+) tumor cells and induction of T-cell effector functions compared with CARs with long "Hinge-CH2-CH3" spacers. CARs derived from a higher affinity scFV conferred maximum T-cell effector function against primary CLL and ROR1(+) epithelial cancer lines in vitro without inducing activation-induced T-cell death. T cells modified with an optimal ROR1-CAR were equivalently effective as CD19-CAR-modified T cells in mediating regression of JeKo-1 MCL in immunodeficient mice.Our results show that customizing spacer design and increasing affinity of ROR1-CARs enhances T-cell effector function and recognition of ROR1(+) tumors. T cells modified with an optimized ROR1-CAR have significant antitumor efficacy in a preclinical model in vivo, suggesting they may be useful to treat ROR1(+) tumors in clinical applications.
Objective Analysis of Tomographic Ventilation–Perfusion Scintigraphy in Pulmonary Embolism
Authors: Benjamin Harris, Dale Bailey, Susan Miles, Elizabeth Bailey, Kerry Rogers, Paul Roach, Paul Thomas, Michael Hensley, Gregory G. King
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Ventilation-perfusion scintigraphy is highly sensitive for pulmonary embolism (PE), but its clinical usefulness is limited by its nondiagnostic rate. Objective analysis of single photon emission computed tomography (SPECT) three-dimensional scintigraphy may improve its diagnostic performance compared with subjective interpretation.To determine the diagnostic accuracy of objective SPECT analysis in PE.We determined the ventilation/perfusion (V(.)/Q(.)) relationship using SPECT scintigraphy in a retrospective cohort of 73 patients. Measures of V(.)/Q(.) heterogeneity (logSD(Q(.)), logSD(V(.)), logSD(VQR)), including a novel parameter, the weighted median V(.)/Q(.) value, were calculated. Using receiver operating characteristic (ROC) analysis, each parameter's diagnostic accuracy was determined. The weighted median V(.)/Q(.) value was then assessed prospectively in a second cohort of 50 patients.In cohort 1, all parameters of V(.)/Q(.) heterogeneity were higher in patients with PE (p < 0.002). The weighted median V(.)/Q(.) had the highest area under the ROC curve (0.93; 95% confidence interval, 0.87-0.98). When applied to the prospective cohort, the area under the ROC curve was 0.87 (95% confidence interval, 0.75-0.99), with diagnostic cutoff values having negative and positive predictive values of 96 and 83%, respectively. In the retrospective and prospective cohorts, 82 and 73% of initially reported intermediate or low probability scans had diagnostic weighted median V(.)/Q(.) values, with 90 and 100% accuracy, respectively.Objective analysis of SPECT scintigraphy has a high diagnostic accuracy in patients with suspected PE. Objective analysis has the potential to reduce the number of nondiagnostic scan results, and may be useful for quantifying V(.)/Q(.) mismatch in other pulmonary disorders.
Reynolds Risk Score for men predicted cardiovascular events more accurately than traditional risk factors only
Authors: Keane K. Lee
Journal: Annals of Internal Medicine (2009)

Source Citation Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR. C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men. Circulation. 2008;118:2243-51. 18997194
A Case for Evolutionary Genomics and the Comprehensive Examination of Sequence Biodiversity
Authors: David D. Pollock, Jonathan A. Eisen, Norman A. Doggett, Michael P. Cummings
Journal: Molecular Biology and Evolution (2000)

Comparative analysis is one of the most powerful methods available for understanding the diverse and complex systems found in biology, but it is often limited by a lack of comprehensive taxonomic sampling. Despite the recent development of powerful genome technologies capable of producing sequence data in large quantities (witness the recently completed first draft of the human genome), there has been relatively little change in how evolutionary studies are conducted. The application of genomic methods to evolutionary biology is a challenge, in part because gene segments from different organisms are manipulated separately, requiring individual purification, cloning, and sequencing. We suggest that a feasible approach to collecting genome-scale data sets for evolutionary biology (i.e., evolutionary genomics) may consist of combination of DNA samples prior to cloning and sequencing, followed by computational reconstruction of the original sequences. This approach will allow the full benefit of automated protocols developed by genome projects to be realized; taxon sampling levels can easily increase to thousands for targeted genomes and genomic regions. Sequence diversity at this level will dramatically improve the quality and accuracy of phylogenetic inference, as well as the accuracy and resolution of comparative evolutionary studies. In particular, it will be possible to make accurate estimates of normal evolution in the context of constant structural and functional constraints (i.e., site-specific substitution probabilities), along with accurate estimates of changes in evolutionary patterns, including pairwise coevolution between sites, adaptive bursts, and changes in selective constraints. These estimates can then be used to understand and predict the effects of protein structure and function on sequence evolution and to predict unknown details of protein structure, function, and functional divergence. In order to demonstrate the practicality of these ideas and the potential benefit for functional genomic analysis, we describe a pilot project we are conducting to simultaneously sequence large numbers of vertebrate mitochondrial genomes.
Ginseng and mastalgia.
Authors: M N Dukes
Journal: BMJ (1978)

reports on bronchodilator infusions which were given as initial therapy for acute asthma and for short periods only, where it would be a simple matter to change treatment for those who failed to respond.We cannot really contest his views on the ethical committee, which may apply criteria more stringent than elsewhere.The information presented in our paper suggested that a salbutamol infusion of 10 g/min is no more effective than the amino- phylline infusion, and Professor Grant may well be correct to state, as we inferred, that with adequate administration of nebulised bronchodilator drugs an intravenous infusion may not make a significant contribution to airway function.The analysis for significant differences in lung function between the two infusion groups included all the patients up to the time of withdrawal from the study if before 36 h.Dr Anderson assumes incorrectly that the data on those patients withdrawn before 36 h were not included in these analyses.The fact that of the six patients withdrawn from the salbutamol group before 36 h, two were responding faster than the group as a whole makes the response between the two groups less marked than Dr Anderson suggests.
THYROIDITIS DURING TREATMENT WITH CORTISONE
Authors: Eugene F. Traut
Journal: JAMA (1952)

Corticotropin (ACTH) and cortisone are known to affect thyroid function. Forsham reported experiments demonstrating a slowed iodine uptake in normal people taking cortisone or corticotropin. The decreased thyroid function may not be reflected in an increase of cholesterol in the blood, according to Conn. Hypothyroidism in patients receiving corticotropin or cortisone may also not be demonstrable by the usual method of measuring basal metabolism because of the known calorigenic effect of corticotropin and cortisone. Of the many complications of corticoid therapy, thyroiditis has not been reported to date.  REPORT OF A CASE  J. R. was first seen in December, 1949. He had been disabled by severe rheumatoid arthritis for months. All the joints in his extremities were painful, tender, and swollen. Large subcutaneous nodules were present below the elbows. While he was under observation in West Suburban Hospital, coronary thrombosis developed. Six weeks after the coronary episode he consulted another
Landmark article June 8, 1946: A clinical syndrome following exposure to atomic bomb explosions. By Paul D. Keller
Authors: P. D. Keller
Journal: JAMA (1987)

The information presented in this report was obtained from studies on 21 patients who were admitted to the Osaka University Hospital in late August and early September 1945 suffering from an alarming malady designated atomic bomb disease by the Japanese. I observed, examined and followed approximately half of the patients, while information on the remaining patients was taken from the hospital records. The patients selected for presentation do not include those receiving severe blast injuries or extensive external burns at the time of the explosion. Included are patients who received minor or no injuries or burns during those catastrophic days at Hiroshima and Nagasaki but who subsequently developed severe clinical manifestations, which in 5 instances resulted in death. Seventeen of the patients herein presented experienced the atomic bombing at Hiroshima, Japan, on August 6, 1945, while the remaining 4 were victims of the Nagasaki explosion on Aug. 9, 1945. The
1031-31 Prognosis of Patients with Symptomatic Heart Failure (HF) Considered Too Well for Cardiac Transplantation (Htx): Predictors of Adverse Outcome
Authors: Peter R. Rickenbacher, Pedro T. Trindade, Guy A. Haywood, Randall H. Vagelos, John S. Schroeder, Kathy Willson, Lisa Prikaszky, Michael B. Fowler
Journal: Journal of the American College of Cardiology (1995)
Diabetes may be independent risk factor for hyperkalaemia
Authors: P. R Jarman
Journal: BMJ (2003)

A very large Turkish family with syndactyly type II (synpolydactyly (SPD)) is described, which originated from and is mainly concentrated in the village of Derbent, Afyon. The kindred consists of 425 subjects over seven generations, of whom 182 are affected. It appears that a founder effect in this village has led to this extensive kindred. This condition is inherited as an autosomal dominant trait with variable expressivity and an estimated penetrance of 96%. Penetrance is different between the upper (96%) and lower (69.5%) extremities. No excess of affected males or females or other associated features were documented in this condition. Variations in the involvement of one or both hands, upper or lower extremities, bone and soft tissue, as well as variation in the affected subjects of two successive generations were documented. We also noted that metacarpal and metatarsal involvement and middle phalangeal hypoplasia of the feet are the consistent features of SPD and, therefore, should be considered as characteristic of this phenotype. We observed four different phenotypes in various branches of the Derbent kindred: (1) subjects presenting typical features of SPD; (2) subjects exhibiting both pre- and post-axial polydactyly simultaneously; (3) persons manifesting postaxial polydactyly type A; and (4) subjects born to two affected parents with severe hand and foot deformities that have not been previously described in any other SPD families (that is, homozygotes). A total of 27 affected offspring were born to two such affected parents, of whom seven are expected to be homozygous for the SPD gene. This group is presented in an accompanying paper in this issue of the Journal. A molecular study is currently under way to identify the chromosomal location of the defective gene.