tbuckley/cabot-search huggingface dataset:
Testing for Colon Neoplasia Susceptibility Variants at the Human COX2 Locus
Authors: C. M. Ulrich, J. D. Potter
Journal: JNCI Journal of the National Cancer Institute (2001)

As reported by eight randomized trials of breast cancer screening conducted over the past 40 years, women aged 50-59 years who are screened for breast cancer have a 20%-30% survival advantage compared with unscreened control subjects.However, when women aged 40-49 years are screened, there is either no advantage or a small disadvantage to the screened population for the first 6-8 years of the trials.After that, an advantage to screening begins to appear.These data have not been explained.Data from all screening trials were presented at a National Institutes of Health Consensus Development Conference in 1997.After review, an expert panel reported that the data did not support an overall recommendation for screening all women aged 40-49 years.The consensus report was then rebuffed by the Director of the National Cancer Institute (Bethesda, MD) as well as by the U.S. Senate, as colorfully documented by Fletcher (1).We have recently published two articles (2,3) that may explain these puzzling trial results.Briefly, analysis of clinical data suggests that the surgical removal of a primary breast tumor from premenopausal lymph node-positive women triggers the growth of temporarily dormant distant disease in approximately 20% of cases.This growth could explain an additional 0.11 deaths per 1000 screened women aged 40-49 years that occurs 2-3 years after the start of screening-approximately what is observed.We proposed that the biologic mechanism of the surgical influence on the metastatic development might be a surge of angiogenesis resulting from the removal of inhibitor(s) or even the appearance of growth factors (2).If our explanation is correct, at least five and perhaps as many as seven of the eight screening trials may no longer be relevant to current practice because they were conducted before adjuvant chemo-
Susceptibility genes and modifiers for cardiac arrhythmias
Authors: S KAAB, E SCHULZEBAHR
Journal: Cardiovascular Research (2005)

The last decade has seen a dramatic increase in the understanding of the molecular basis of arrhythmias. Much of this new information has been driven by genetic studies that focused on rare, monogenic arrhythmia syndromes that were accompanied or followed by cellular electrophysiological or biochemical studies. The marked clinical heterogeneity known from these familial arrhythmia syndromes has led to the development of a multifactorial ("multi-hit") concept of arrhythmogenesis in which causal gene mutations have a major effect on disease expression that is further modified by other factors such as age, gender, sympathetic tone, and environmental triggers. Systematic genetic studies have unraveled an unexpected DNA sequence variance in these arrhythmia genes that has ethnic-specific patterns. Whether this genetic variance may contribute as a second genetic modifier for arrhythmia development is under current investigation. The aim of this article is to review common genetic variation in ion channel genes and to compare these recent findings.
Avoidance of stimulation improves engraftment of cultured and retrovirally transduced hematopoietic cells in primates
Authors: Masaaki Takatoku, Stephanie Sellers, Brian A. Agricola, Mark E. Metzger, Ikunoshin Kato, Robert E. Donahue, Cynthia E. Dunbar
Journal: Journal of Clinical Investigation (2001)

Recent reports suggest that cells in active cell cycle have an engraftment defect compared with quiescent cells. We used nonhuman primates to investigate this finding, which has direct implications for clinical transplantation and gene therapy applications. Transfer of rhesus CD34(+) cells to culture in stem cell factor (SCF) on the CH-296 fibronectin fragment (FN) after 4 days of culture in stimulatory cytokines maintained cell viability but decreased cycling. Using retroviral marking with two different gene transfer vectors, we compared the engraftment potential of cytokine-stimulated cells versus those transferred to nonstimulatory conditions (SCF on FN alone) before reinfusion. In vivo competitive repopulation studies showed that the level of marking originating from the cells continued in culture for 2 days with SCF on FN following a 4-day stimulatory transduction was significantly higher than the level of marking coming from cells transduced for 4 days and reinfused without the 2-day culture under nonstimulatory conditions. We observed stable in vivo overall gene marking levels of up to 29%. This approach may allow more efficient engraftment of transduced or ex vivo expanded cells by avoiding active cell cycling at the time of reinfusion.
ALOGLIPTIN IN PATIENTS WITH TYPE 2 DIABETES AFTER ACUTE CORONARY SYNDROMES: HEART FAILURE OUTCOMES AND CARDIOVASCULAR SAFETY IN HEART FAILURE PATIENTS
Authors: Faiez Zannad, Christopher Cannon, William Cushman, George Bakris, Steven Nissen, Simon Heller, Richard Bergenstal, Venu Menon, Alfonso Perez, Penny Fleck, Richard Oh, Cyrus Mehta, Stuart Kupfer, Craig A. Wilson, William White
Journal: Journal of the American College of Cardiology (2014)
Monocyte‐Targeting Supramolecular Micellar Assemblies: A Molecular Diagnostic Tool for Atherosclerosis
Authors: Eun Ji Chung, Laurie B. Mlinar, Kathryn Nord, Matthew J. Sugimoto, Emily Wonder, Francis J. Alenghat, Yun Fang, Matthew Tirrell
Journal: Advanced Healthcare Materials (2014)

Atherosclerosis is a multifactorial inflammatory disease that can progress silently for decades and result in myocardial infarction, stroke, and death. Diagnostic imaging technologies have made great strides to define the degree of atherosclerotic plaque burden through the severity of arterial stenosis. However, current technologies cannot differentiate more lethal “vulnerable plaques,” and are not sensitive enough for preventive medicine. Imaging early molecular markers and quantifying the extent of disease progression continues to be a major challenge in the field. To this end, monocyte‐targeting, peptide amphiphile micelles (PAMs) are engineered through the incorporation of the chemokine receptor CCR2‐binding motif of monocyte chemoattractant protein‐1 (MCP‐1) and MCP‐1 PAMs are evaluated preclinically as diagnostic tools for atherosclerosis. Monocyte‐targeting is desirable as the influx of monocytes is a marker of early lesions, accumulation of monocytes is linked to atherosclerosis progression, and rupture‐prone plaques have higher numbers of monocytes. MCP‐1 PAMs bind to monocytes in vitro, and MCP‐1 PAMs detect and discriminate between early‐ and late‐stage atherosclerotic aortas. Moreover, MCP‐1 PAMs are found to be eliminated via renal clearance and the mononuclear phagocyte system (MPS) without adverse side effects. Thus, MCP‐1 PAMs are a promising new class of diagnostic agents capable of monitoring the progression of atherosclerosis.
Usefulness of screening large numbers of contacts for tuberculosis: questionnaire based review
Authors: H. Stoddart, N. Noah
Journal: BMJ (1997)

In two separate incidents of tuberculosis that we investigated, 732 contacts were identified and 524 screened. As no further cases of tuberculosis were detected, we began to question the value of screening and conducted a questionnaire survey of colleagues in England and Wales to determine their experience.

In April 1994 we sent a questionnaire to consultants in communicable disease control and medical officers of environmental health in 155 districts in England and Wales. The questionnaire asked for the number of new cases of tuberculosis found in the preceding three years in incidents in which more than 100 contacts had been screened.

Altogether 123 replies (79%) were returned, with 56 incidents reported. West Midlands and North Western regions reported the largest numbers of incidents (eight and six respectively) while South Western …
A clinical study of 23 cases of female anogenital carcinoma
Authors: E.K. Derrick, C.M. Ridley, A. Kobza‐Black, P.H. Mckee, S.M. Neill
Journal: British Journal of Dermatology (2000)

Vulval carcinoma is a relatively rare disorder that may have various aetiologies. Objectives To document the features and outcome in a series of patients with this disorder.Retrospective analysis of patients presenting to a vulval clinic over a 5-year period.Twenty-one women presented with a squamous cell carcinoma (SCC) and two with a verrucous carcinoma (VC). The age range was 43-83 years. Twenty-one had well-established (1-30 years) vulval symptoms prior to developing their tumour. Specific tumour-related symptoms ranged from 3 weeks to 11 months. Eight had had a prior diagnosis of lichen sclerosus (LS) or lichen planus (LP), only two of whom were on regular treatment and follow-up. At presentation, 12 patients had clinical signs of LS, three of LP, and five had some changes of both LS and LP. Two patients had multifocal vulval intraepithelial neoplasia (VIN3). Only one had no evidence of any background vulval skin disease. The commonest histological changes noted in the epithelium either adjacent to or distant from the SCC were those of atrophic LS (n = 8), LS with squamous cell hyperplasia (n = 3), LS with hyperplastic foci and lichenoid infiltrate (n = 4), and LS with differentiated VIN3 (n = 1). Four cases demonstrated the changes of LP, and three showed VIN3. All patients were treated surgically and, in those who had lymphadenectomy, four had positive nodes. There have been two deaths due to metastatic disease, and one further patient has developed a second primary SCC at a different site.An underlying skin disorder prior to the development of their carcinoma was found in 22 of 23 patients with vulval SCC and is therefore an important risk factor.
Bushbaby Growth Hormone Is Much More Similar to Nonprimate Growth Hormones than to Rhesus Monkey and Human Growth Hormones
Authors: Ronald M. Adkins, Anton Nekrutenko, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2001)

Unlike other mammals, Old World primates have five growth hormone–like genes that are highly divergent at the amino acid level from the single growth hormone genes found in nonprimates. Additionally, there is a change in the interaction of growth hormone with its receptor in humans such that human growth hormone functions in nonprimates, whereas nonprimate growth hormone is ineffective in humans. A Southern blotting analysis of the genome of a prosimian, Galago senegalensis, revealed a single growth hormone locus. This single gene was PCR-amplified from genomic DNA and sequenced. It has a rate of nonsynonymous nucleotide substitution less than one fourth that of the human growth hormone gene, while the rates of synonymous substitution in the two species are less different. Human and rhesus monkey growth hormones exhibit variation at a number of amino acid residues that can affect receptor binding. The galago growth hormone is conservative at each of these sites, indicating that this growth hormone is functionally like nonprimate growth hormones. These observations indicate that the amplification and rapid divergence of primate growth hormones occurred after the separation of the higher primate lineage from the galago lineage.
The value of simple tests for peristaltic activity in hiatus hernia
Authors: S. J. A. Powis, J. L. Collis
Journal: Thorax (1970)

A study has been made of oesophageal peristaltic activity as viewed at barium swallows, in an effort to see whether this is helpful in assessing the type and degree of oesophageal lesions associated with hiatus hernia. It has not been possible to establish a clinical usefulness from such testing as the frequency with which peristaltic upset occurs is too marginal.
Iron Metabolism in Patients Undergoing Regular Dialysis Therapy
Authors: B. Brozovich, W. R. Cattell, M. F. Cottrall, M. M. Gwyther, J. M. McMillan, J. S. Malpas, A. Salsbury, N. G. Trott
Journal: BMJ (1971)

Thirteen patients with chronic renal failure maintained on regular renal dialysis were studied. Seven proved to have iron deficiency on the basis of marrow iron studies, reticulocyte iron uptake, and saturation of the serum iron-binding capacity. They absorbed iron when given it by mouth and were able to utilize it for haemoglobin formation. Iron-deficient patients given 600 mg of ferrous sulphate daily for three months showed an increase in haemoglobin, but the failure to replace stores of iron is probably related to their relatively limited ability to absorb iron and the variable but sometimes considerable blood loss occurring with each dialysis.The loss may be occult, and prolonged iron therapy may be required. This is most safely achieved by giving iron by mouth.
Captopril Ameliorates Myocarditis in Acute Experimental Chagas Disease
Authors: Juan S. Leon, Kegiang Wang, David M. Engman
Journal: Circulation (2003)

Background— Captopril, an angiotensin-converting enzyme inhibitor, is commonly prescribed to patients with Chagas heart disease (CHD). There are few human studies and no animal studies on the effects of captopril in CHD. We investigated the effects of captopril on myocarditis and the host immune response to Trypanosoma cruzi in an experimental model of acute CHD. Methods and Results— A/J mice infected with Brazil strain of T cruzi developed acute myocarditis by day 21 after infection, consisting of severe focal inflammation, necrosis, fibrosis, and T cruzi pseudocysts. Administration of captopril (5 mg/L in the water) significantly reduced necrosis and fibrosis in infected mice. Increasing the captopril dose also led to a decrease in inflammation. Captopril did not affect overall mortality but did delay death while having no effect on parasitemia or cardiac parasite load. Treatment did not affect humoral immunity against T cruzi or cardiac myosin (autoimmunity) but did decrease delayed-type hypersensitivity responses against both antigens. Interestingly, increasing the dose of captopril induced mortality in infected mice in a dose-dependent manner. Mortality was apparently not due to T cruzi because neither parasitemia nor cardiac parasitosis was affected. The combination of captopril and infection may have impaired renal function because these mice had increased water consumption, decreased body mass, and increased serum BUN/creatinine ratio. Conclusions— Captopril ameliorates the myocarditis associated with acute T cruzi infection.
Signaling via the prostaglandin E2 receptor EP4 exerts neuronal and vascular protection in a mouse model of cerebral ischemia
Authors: Xibin Liang, Lu Lin, Nathaniel S. Woodling, Qian Wang, Christoph Anacker, Tingting Pan, Milton Merchant, Katrin Andreasson
Journal: Journal of Clinical Investigation (2011)

Stroke is the third leading cause of death in the United States. Fewer than 5% of patients benefit from the only intervention approved to treat stroke. Thus, there is an enormous need to identify new therapeutic targets. The role of inducible cyclooxygenase (COX-2) activity in stroke and other neurologic diseases is complex, as both activation and sustained inhibition can engender cerebral injury. Whether COX-2 induces cerebroprotective or injurious effects is probably dependent on which downstream prostaglandin receptors are activated. Here, we investigated the function of the PGE2 receptor EP4 in a mouse model of cerebral ischemia. Systemic administration of a selective EP4 agonist after ischemia reduced infarct volume and ameliorated long-term behavioral deficits. Expression of EP4 was robust in neurons and markedly induced in endothelial cells after ischemia-reperfusion, suggesting that neuronal and/or endothelial EP4 signaling imparts cerebroprotection. Conditional genetic inactivation of neuronal EP4 worsened stroke outcome, consistent with an endogenous protective role of neuronal EP4 signaling in vivo. However, endothelial deletion of EP4 also worsened stroke injury and decreased cerebral reperfusion. Systemic administration of an EP4 agonist increased levels of activated eNOS in cerebral microvessels, an effect that was abolished with conditional deletion of endothelial EP4. Thus, our data support the concept of targeting protective prostaglandin receptors therapeutically after stroke.
Aids in Screening for Heterozygous Alpha_1-Antitrypsin Deficiency.
Authors: Jack Lieberman
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Aids in Screening for Heterozygous Alpha1-Antitrypsin Deficiency.Jack Lieberman, M.D., F.A.C.P., Charles Mittman, M.D.Jack Lieberman, M.D., F.A.C.P.Search for more papers by this author, Charles Mittman, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-809_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDetection of the carrier state for alpha1-antitrypsin deficiency is valuable for studying the genetic predisposition to chronic obstructive lung disease and as a screening test in preventive medicine. Sera are screened for antitrypsin deficiency by protein electrophoresis on cellulose-acetate membranes followed by an enzymatic assay of inhibitor when the alpha1-globulin is less than 0.2 g%. However, the detection of heterozygotes may conceivably be impaired when other serum protein abnormalities exist or when the antitrypsin level has risen into the low normal range during an acute illness. A survey of patients without obstructive lung disease at the City of Hope Medical... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Duarte, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAlpha-1-Antitrypsin 1 May 1970Volume 72, Issue 5Page: 809-809KeywordsEnzyme assaysGenetic predispositionLungsMembrane proteinsPreventive medicineSerum proteins Issue Published: 1 May 1970 PDF DownloadLoading ...
Patients Leaving Emergency Departments Without Being Seen by a Physician
Authors: Otto J. N. Kunst
Journal: JAMA (1992)

To the Editor.  —I read with interest the articles 1,2 and editorial 3 regarding patients leaving public hospital emergency departments without being seen by a physician and the resultant failure to provide necessary medical care, particularly to the indigent. This becomes even more interesting when juxtaposed to a brief Centers for Disease Control article 4 regarding the 33 million Americans lacking health care coverage.  Has anyone considered how much more strain will be placed on the health care provision system if a universal health care system is instituted and 33 million more potential patients are dumped on the system? How many more delays and outright failures to provide necessary care will then result?  The only alternative would appear to be an expansion of the health care system, both in terms of physical facilities and equipment, physicians, nurses, and other paramedical personnel. However, a major underlying motive of many supporting
STUDIES ON INTRACRANIAL PRESSURE
Authors: J. A. E. Eyster, M. T. Burrows, C. R. Essick
Journal: The Journal of Experimental Medicine (1909)

1. The results of this work form a confirmation of the earlier work of Cushing in all details investigated. 2. The increase of blood pressure that results from an increase of the intracranial pressure above the blood pressure is due in the dog to a vaso-constriction of the vessels of the intestine, the kidney and the limbs. Preceding this constriction there is dilatation. 3. The anastomotic connection between the internal carotid artery within the skull and the ophthalmic branch of the internal maxillary is of a size in the dog approximately equal to the internal carotid outside of the skull. The anatomical relations are such as to indicate that the internal maxillary artery in this animal is a cerebral artery equal in importance to the internal carotid. The anastomotic connection because of its position within the cranial cavity is unaffected except by extreme grades of intracranial compression. 4. The ordinary method of artificial perfusion of the dog's brain as used in physiological investigation appears from this work to be of no value, since there is at least one important path open besides that through the vessels of the brain. 5. The increase of the intracranial pressure above the blood pressure leads to a complete anaemia, superficial and deep, of the blood vessels of the brain. If the intracranial pressure is not greatly increased above the blood pressure, the circle of Willis and some of the larger arterial connections at the base of the brain are more or less well injected. An intracranial pressure somewhat below blood pressure leads apparently to a certain degree of anaemia directly beneath the point of entrance of the intracranial fluid; the condition of the rest of the brain as regards blood supply is normal.
437. Alternative Strategies To Deliver Multiple shRNAs in Order to Simultaneously Inhibit Multiple Targets
Authors: Peter W. Roelvink, Michael W. Graham, David A. Suhy, Linda B. Couto, Sara M. Cunningham, Mark A. Kay, John J. Rossi, Alexander A. Kolykhalov
Journal: Molecular Therapy (2005)

RNA interference is a new promising technology for therapeutic drug development. It can be initiated either by chemically synthesized double-stranded RNA delivered to a cell, or by transcription of a short hairpin RNA (shRNA) in the cell nucleus from a DNA template. We are interested in developing RNAi therapies for HCV, which is difficult infection to treat due to the generation of viral escape mutants. RNAi is uniquely positioned to address this issue because it has the ability to simultaneously inhibit multiple viral targets. This can be accomplished by delivering several shRNAs that target different sequences of the viral genome. One approach to accomplish this is to include several promoter-shRNA cassettes in a single DNA vector. The disadvantages of this strategy are the possible interference of the promoters, potential differences in promoter activity, and vector size limitations. Alternatively, multiple shRNAs could be expressed from a single promoter as a long shRNA precursor. Processing of this pre-shRNA by Drosha/Dicer complex may result in the generation of multiple siRNAs; however it may be difficult to optimize the pre-shRNA sequences for correct processing, and there is the potential for toxic effects attributed to the generation of a long double-stranded RNA. In this work we present a third alternative to express multiple shRNAs from a single promoter which includes the tandem positioning of short shRNAs (19-20 nucl) separated by short spacers. We identified several individual shRNA sequences that efficiently inhibit replication of HCV in the replicon system. We then combined these validated shRNAs in a triple construct under the expression of a single promoter and demonstrated functional activity of each of the individual shRNAs against their cognate targets. Results comparing these different strategies and their implication for shRNA-based drug development will be discussed.
Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) treated with narrowband (TL-01) UVB phototherap
Authors: H. Cameron, R.S. Dawe
Journal: British Journal of Dermatology (1997)

Journal Article Subcorneal pustular dermatosis (Sneddon‐Wilkinson disease) treated with narrowband (TL‐01) UVB phototherap Get access H. Cameron, H. Cameron Department of Dermatology. Ninewells Hospital and Medical School. Dundee DD1 9SY. U.K. Search for other works by this author on: Oxford Academic Google Scholar R.S. Dawe R.S. Dawe Department of Dermatology. Ninewells Hospital and Medical School. Dundee DD1 9SY. U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 1, 1 July 1997, Pages 150–151, https://doi.org/10.1111/j.1365-2133.1997.tb03721.x Published: 01 July 1997