tbuckley/cabot-search huggingface dataset:
WITHDRAWN: Cardiovascular roles of nitric oxide: A review of insights from nitric oxide synthase gene disrupted mice
Authors: V LIU, P HUANG
Journal: Cardiovascular Research (2007)

Nitric oxide (NO) is a gaseous molecule that plays many key roles in the cardiovascular system. Each of the enzymes that generate NO—neuronal, inducible and endothelial NO synthase—has been genetically disrupted in mice. This review discusses the cardiovascular phenotypes of each of the NO synthase (NOS) gene knockout mice, and the insights gained into the roles of NO in the cardiovascular system. Mice lacking the endothelial isoform are hypertensive, have endothelial dysfunction and show a more severe outcome in response to vascular injury, to stroke and cerebral ischaemia, and to diet-induced atherosclerosis. Mice lacking the neuronal isoform show a less severe outcome in response to stroke and cerebral ischaemia but have increased diet-induced atherosclerosis. Mice lacking the inducible isoform show reduced hypotension to septic shock. Together, NOS gene knockout mice have been useful tools that complement our other approaches to studying the multiple roles of NO in the cardiovascular system.
Correlation between β-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma
Authors: Madeleine Austinat, Ruediger Dunsch, Christian Wittekind, Andrea Tannapfel, Rolf Gebhardt, Frank Gaunitz
Journal: Molecular Cancer (2008)

Abstract Aberrant Wnt-signaling caused by mutants of β-catenin, a key regulator of the canonical Wnt-signaling pathway, is frequently detected in cancer. Only recently, it was suggested that in hepatocellular carcinoma (HCC) the expression of the target gene glutamine synthetase (GS) is a highly reliable marker for the identification of β-catenin mutations. In order to prove this hypothesis, 52 samples from human hepatocellular carcinomas were analysed for the activation of β-catenin and the expression of GS. In total, 45 samples stained positive for cytoplasmic/nuclear β-catenin. A strong correlation between expression of GS and activated β-catenin (100% of nuclear and 84% of cytosolic) was found. However, among 35 GS positive tumors that were analysed for β-catenin mutations no mutations were detected in 25 GS-positive carcinomas although 24 out of the 25 carcinomas exhibited at least abnormal expression of β-catenin. Since the mutational analysis identified 9 different point mutations of the β-catenin gene including the rare mutation H36P and the yet unknown mutation P44A it was asked whether these mutations may differently effect β-catenin target genes. Therefore, expression plasmids for different mutations were constructed and cotransfected with the TOP-flash luciferase reporter and a reporter carrying the GS-5'-enhancer. The experiments confirmed that there are differences between different β-catenin target sequences and different β-catenin mutations. In addition, the failure that the endogenous expression of GS in GS-negative cells was not induced by the transient transfection experiment indicated that the effect of β-catenin on the GS-5'-enhancer is only one aspect of gene activation induced by β-catenin.
Risks and benefits of combining immunosuppressives and biological agents in inflammatory bowel disease: is the synergy worth the risk?
Authors: S. B Hanauer
Journal: Gut (2007)

Since the introduction of infliximab to treat Crohn's disease, combination therapy with immunosuppressants has reduced immunogenicity, without impacting efficacy. The availability of novel anti-TNF agents and potential combined toxicities question the risk/benefit of combination therapies.
Plasma asymmetric dimethylarginine and retinal vessel diameters in middle-aged men
Authors: Virpi Hemminki, Juha Laakso, Mika Kähönen, Väinö Turjanmaa, Hannu Uusitalo, Terho Lehtimäki, Inkeri Ruokonen, Reijo Laaksonen, Heini Huhtala, Hannu Päivä
Journal: Metabolism (2007)
Effect of Polyethylene Glycol Linker Chain Length of Folate-Linked Microemulsions Loading Aclacinomycin A on Targeting Ability and Antitumor Effect <i>In vitro</i> and <i>In vivo</i>
Authors: Tomonori Shiokawa, Yoshiyuki Hattori, Kumi Kawano, Yukino Ohguchi, Hiroko Kawakami, Kazunori Toma, Yoshie Maitani
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To establish a novel formulation tumor-targeted drug carrier of lipophilic antitumor antibiotics, aclacinomycin A (ACM), folate-linked microemulsions were prepared and investigated both in vitro and in vivo. Experimental Design: Three kinds of folate-linked microemulsions with different polyethylene glycol (PEG) chain lengths loading ACM were formulated with 0.24 mol% folate-PEG2000-distearoylphosphatidylethanolamine (DSPE), folate-PEG5000-DSPE, and folate-lipid (without PEG linker) in microemulsions. In vitro studies were done in a human nasopharyngeal cell line, KB, which overexpresses the folate receptor (FR), and a human hepatoblastoma cell line, [FR(−)] HepG2. In vivo experiments were done in a KB xenograft by systemic administration of folate-linked microemulsions loading ACM. Results: The association of folate-linked microemulsions to KB cells could be blocked by 2 mmol/L free folic acid. Selective FR-mediated cytotoxicity of folate-linked microemulsions loading ACM was obtained in KB but not in HepG2 cells. The association of the folate-PEG5000-linked microemulsion and folate-PEG2000-linked microemulsion with the cells was 200- and 4-fold higher, whereas their cytotoxicity was 90- and 3.5-fold higher than those of nonfolate microemulsion, respectively. The folate-PEG5000-linked microemulsions showed 2.6-fold higher accumulation in solid tumors 24 hours after i.v. injection and greater tumor growth inhibition than free ACM. Conclusion: These findings suggest that a folate-linked microemulsion is feasible for tumor-targeted ACM delivery. This study shows that folate modification with a sufficiently long PEG chain on emulsions is an effective way of targeting emulsion to tumor cells.
Case of General Anasarca, with Albuminous Urine, in an Infant Ten Weeks Old
Authors: W. B. Herapath
Journal: BMJ (1848)

extremely small, having suffered gradual compression 'during the increase of the tumour.The tumour I sent to a pupil studying at King's,ollege, and it was examined by Mr. Bowman of thatInstitution, who pronounced it to be a decidedly fungoid growth.In some portions the blood-vessels had,given way, constituting fungus hbematodes, and other parts presented the character of miedullary sarcoma.A sec- tion examined under the microscope presented a number of healtlhy nucleated cells, interspersed vith some that were diseased; the latter were larger than the former, and contained within them smaller cells.In the substance of the tumour numerous fibrous bands .mightbe discerned with the naked eye.The tumour was highly organized, and very vascular.Mr. Bowman thought the case extremely interesting from the unusual size of the tumour, the slowness of its growth, *(ten years,) and the absence of any disturbance in the functions of the brain.This last circumstance is perhaps the chief peculiarity connected with this case, and when we think that for a considerable time, nearly the whole of the left hemisphere of the brain was -obliterated, and occupied by a malignant tumour, 'vithout interfering with the operations of the mind, 4he fact seems explicable only on the views of Foville and Wigan,-that the two hemispheres constitute two distinct brains, (connected, it is true,) but each, individually, capable of carrying on the various mental -operations independently of the other, just as we see in the eyes, ears, &c.In addition to the analogies presented by the special -senses in support of the theory of the duality of the mind, numerous facts, bitherto inexplicable in health, 'but mnore especially in disease, point to this source for an explanation.The phenomena of insanity, which lave occupied the thoughts of the profoundest minds, -and are still involved in mystery, afford many instances -corroborative of Dr. Wigan's views.He considers 'each brain as a perfect whole, in thought, sentiment, and volition ; and also, that when one of them is *destroyed, the other can perfor#all the functions of the mind.Each brain carries on its own processes independently, and, like the two strings of a piano-forte, producing only one note.In bothcases, it is only when they are out of harmony that the fact is observed, that that which is apparently one is really an harmonious -combination of two distinct actions.A discrepancy in the action of the two brains,-a mixture of two trains of thought produces confusion, incoherence, and
Greater Effect of Diabetes on LDL size in Women Than in Men
Authors: Steven M Haffner, Leena Mykkänen, Michael P Stern, Michael Paidi, Barbara V Howard
Journal: Diabetes Care (1994)

OBJECTIVE Coronary heart disease (CHD) is increased two- to fourfold in subjects with NIDDM compared with normoglycemic subjects. This excess risk is only partially explained by conventional risk factors. We studied the effect of non-insulin-dependent diabetes mellitus (NIDDM) on the size of low-density lipoproteins (LDL). RESEARCH DESIGN AND METHODS We examined the effect of NIDDM on LDL size and subclass pattern B (LDL size &amp;lt; 253.5 Å) in 95 diabetic subjects and 371 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. RESULTS LDL size (Å) was significantly lower in diabetic subjects (men: 252.2 ± 1.8; women: 254.7 ± 1.3) than in nondiabetic subjects (men: 256.1 ± 0.8; women: 259.7 ± 0.7) (P = 0.007). After the use of analysis of covariance to adjust for triglyceride and high-density lipoprotein cholesterol, LDL size was still significantly lower in diabetic women than in nondiabetic women. In men, however, diabetes was no longer significantly associated with LDL size after similar adjustments. Fasting glucose was more strongly correlated with LDL size in women (r = −0.30) than in men (r = −0.18). CONCLUSIONS We conclude that LDL size is significantly lower in diabetic subjects of both sexes than in nondiabetic subjects, but that diabetic dyslipidemia accounts for the association in diabetic men. The stronger association between LDL size and diabetes in women than in men may partially explain the greater relative risk of CHD observed in women with NIDDM in some studies.
SIMPLE VERSUS RADICAL MASTECTOMY
Authors: M.Maureen Roberts, L.H. Blumgart, Marianne Davies, J.M. Henk, A.P.M. Forrest, H. Campbell, E.N. Gleave, P.B. Kunkler, R. Shields, M. Hulbert, C.W. Jamieson, R.A. Sellwood
Journal: The Lancet (1973)
Withering Away--25,000 Years of Genetic Decline Preceded Cave Bear Extinction
Authors: M. Stiller, G. Baryshnikov, H. Bocherens, A. Grandal d'Anglade, B. Hilpert, S. C. Munzel, R. Pinhasi, G. Rabeder, W. Rosendahl, E. Trinkaus, M. Hofreiter, M. Knapp
Journal: Molecular Biology and Evolution (2010)

The causes of the late Pleistocene megafaunal extinctions are still enigmatic. Although the fossil record can provide approximations for when a species went extinct, the timing of its disappearance alone cannot resolve the causes and mode of the decline preceding its extinction. However, ancient DNA analyses can reveal population size changes over time and narrow down potential causes of extinction. Here, we present an ancient DNA study comparing late Pleistocene population dynamics of two closely related species, cave and brown bears. We found that the decline of cave bears started approximately 25,000 years before their extinction, whereas brown bear population size remained constant. We conclude that neither the effects of climate change nor human hunting alone can be responsible for the decline of the cave bear and suggest that a complex of factors including human competition for cave sites lead to the cave bear's extinction.
Aortic Root Characteristics of Human Pulmonary Autografts
Authors: G. S. Carr-White, A. Afoke, E. J. Birks, S. Hughes, A. O'Halloran, S. Glennen, S. Edwards, M. Eastwood, M. H. Yacoub
Journal: Circulation (2000)

After pulmonary autograft replacement of the aortic valve and root, the pulmonary artery (PA) wall is subjected to higher pressures. Concern exists that this may lead to structural and functional changes in the implanted autograft and subsequent aortic root dilatation and neoaortic regurgitation. We therefore assessed root dimensions and neoaortic regurgitation, morphological structure, and mechanical behavior in patients who underwent the Ross operation.Seventy-four patients who were randomized to undergo aortic valve replacement with an aortic homograft or a pulmonary autograft were followed up echocardiographically for up to 4 years and had their aortic root dimensions measured at the level of the annulus, sinuses, and sinotubular junction. In a separate series of 18 patients who underwent pulmonary autograft surgery and 8 normal organ donors, samples from the PA and aorta were analyzed for medial wall thickness, distribution of the staining of collagen and elastin, and elastin fragmentation. Finally, stress-strain curves were obtained from samples of the PA and aorta from 9 patients who underwent pulmonary autograft surgery and from 1 patient in whom a 4-month-old autograft was explanted. No patient in either group had aortic dilatation at any level of >20% or more than mild aortic regurgitation at up to 4 years of follow-up. The aortic media was thicker in both autografts and normal donors (P:<0.01), and there was a trend for the PA media to be thicker in the autograft group. Elastic fiber in all aortas showed little or no variation, whereas in the PA, there was considerable variation in fragmentation. Patients with higher preoperative PA pressures tended to have lower fragmentation scores (chi(2) P:<0.01). The lower stiffness modulus, higher stiffness modulus, and maximum tensile strength of the aorta was 34% to 38% higher than that of the PA (P:<0.01); however, the 4-month-old autograft appeared to show adaptation in mechanical behavior.In our series of patients, there was no significant progressive dilatation of the aortic root. We demonstrated differences in the anatomic structure and mechanical behavior of the PA in vitro and highlighted histological and mechanical modes of adaptation.
3-D Visualization in Biomedical Applications
Authors: Richard A. Robb
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Visualizable objects in biology and medicine extend across a vast range of scale, from individual molecules and cells through the varieties of tissue and interstitial interfaces to complete organs, organ systems, and body parts. These objects include functional attributes of these systems, such as biophysical, biomechanical, and physiological properties. Visualization in three dimensions of such objects and their functions is now possible with the advent of high-resolution tomographic scanners and imaging systems. Medical applications include accurate anatomy and function mapping, enhanced diagnosis, accurate treatment planning and rehearsal, and education/training. Biologic applications include study and analysis of structure-to-function relationships in individual cells and organelles. The potential for revolutionary innovation in the practice of medicine and in biologic investigations lies in direct, fully immersive, real-time multisensory fusion of real and virtual information data streams into online, real-time visualizations available during actual clinical procedures or biological experiments. Current high-performance computing, advanced image processing, and high-fidelity rendering capabilities have facilitated major progress toward realization of these goals. With these advances in hand, there are several important applications of three-dimensional visualization that will have a significant impact on the practice of medicine and on biological research.
Change in liver blood flow and blood content in dogs during direct and reflex alteration of hepatic sympathetic nerve activity.
Authors: J J Carneiro, D E Donald
Journal: Circulation Research (1977)

A mean decrease of 60% in liver blood volume was recorded by a plethysmographic technique during electrical stimulation of the hepatic nerves in anesthetized, vagotomized dogs. A decrease in pressure in the vascularly isolated carotid sinus to 40 mm Hg, from a mean control of 144 mm Hg, decreased liver blood volume by a mean of 16%; arterial blood pressure increased by a mean of 77 mm Hg. Carotid sinus hypotension was accompanied by respective mean increases of 16% and 1.4% in hepatic arterial and portal venous blood flows, and of 45% and 22% in arterial and portal resistances. Increase in sinus pressure to 240 mm Hg increased liver blood volume by a mean of 20%; arterial blood pressure decreased by 90 mm Hg. Sinus hypertension was accompanied by respective mean decreased of 10% and 1.5% in hepatic arterial and portal venous blood flows, and of 44% and 18% in arterial and portal resistances. Interruption of afferent vagal traffic from cardiopulmonary receptors was maximally effective in decreasing liver blood volume at a carotid sinus pressure of 40 mm Hg and was ineffective at carotid sinus pressures greater than 160 mm Hg. Combined withdrawal of carotid and cardiopulmonary vasomotor inhibition decreased liver blood volume by 42%; of this 37% was due to the cardiopulmonary and 63% to the carotid baroreflex. The study showed the canine liver to function as a blood reservoir by active mobilization of a portion of its blood volume.
Assessing Glycemic Control in Maintenance Hemodialysis Patients With Type 2 Diabetes
Authors: Sara Kazempour-Ardebili, Varunika L. Lecamwasam, Thushara Dassanyake, Andrew H. Frankel, Frederick W.K. Tam, Anne Dornhorst, Gary Frost, Jeremy J.O. Turner
Journal: Diabetes Care (2009)

In response to the comment by Riveline and Hadjadj (1) on the work presented in our article “Assessing Glycemic Control in Maintenance Hemodialysis Patients With Type 2 Diabetes” (2), we would like to acknowledge the following:
Fat-suppression magnetic resonance imaging in the diagnosis of late-onset axial spondyloarthropathy
Authors: S. Shankaranarayana, A. L. Tan, J. Madden, D. McGonagle
Journal: Annals of the Rheumatic Diseases (2007)

between mycobacterial infections and PM is interesting, especially if there was a latent infection present in most of the cases, although this cannot be confirmed from their records.A weak causal relationship with 'reactive myositis' caused by a former or latent mycobacterial infection cannot be ruled out.We conclude that the possibility of mycobacterial infection has to be kept in mind when diagnosing and treating patients with myositis.
Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice
Authors: A. La Marca, S. K. Sunkara
Journal: Human Reproduction Update (2013)

The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic strategies that have been proposed in IVF after this prediction. A systematic review of the existing literature was performed by searching Medline, EMBASE, Cochrane library and Web of Science for publications in the English language related to AFC, AMH and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Literature available to May 2013 was included. The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of AMH and AFC to predict response to COS were included in this review. The literature review demonstrated that AFC and AMH, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized COS protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the GnRH antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The selection of the appropriate and individualized gonadotrophin dose is also of paramount importance for effective COS and subsequent IVF outcomes. Personalized IVF offers several benefits; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response. The deployment of therapeutic strategies based on selective use of GnRH analogues and the fine tuning of the gonadotrophin dose on the basis of potential ovarian response in every single woman can allow for a safer and more effective IVF practice.
Chromosome Instability Accounts for Reverse Metastatic Outcomes of Pediatric and Adult Synovial Sarcomas
Authors: Pauline Lagarde, Joanna Przybyl, Céline Brulard, Gaëlle Pérot, Gaelle Pierron, Olivier Delattre, Raf Sciot, Agnieszka Wozniak, Patrick Schöffski, Philippe Terrier, Agnès Neuville, Jean-Michel Coindre, Antoine Italiano, Daniel Orbach, Maria Debiec-Rychter, Frédéric Chibon
Journal: Journal of Clinical Oncology (2013)

Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS.One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach.CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology.