tbuckley/cabot-search huggingface dataset:
Relationships of Upper Gastrointestinal Motor and Sensory Function With Glycemic Control
Authors: Christopher K. Rayner, Melvin Samsom, Karen L. Jones, Michael Horowitz
Journal: Diabetes Care (2001)

Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may, accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes.
Gene-Environment Interaction in Youth Depression: Replication of the 5-HTTLPR Moderation in a Diverse Setting
Authors: Thiago Botter-Maio Rocha, Mara H. Hutz, Angélica Salatino-Oliveira, Júlia P. Genro, Guilherme V. Polanczyk, João Ricardo Sato, Fernando C. Wehrmeister, Fernando C. Barros, Ana M.B. Menezes, Luis Augusto Rohde, Luciana Anselmi, Christian Kieling
Journal: American Journal of Psychiatry (2015)

Objective: Replication of scientific findings is a major challenge in biomedical research. In psychiatry, the identification of measured gene-environment interactions (G×E) has promoted a heated debate over the past decade, with controversial results about its influence on disorders such as major depression. The authors sought to replicate a 2003 study on G×E in youth depression in a large birth cohort from a diverse setting. Method: Using data from the 1993 Pelotas Birth Cohort Study, and adopting a design as similar as possible to that of the original study, the authors tested whether the relationship between childhood maltreatment and a subsequent depressive episode diagnosis was moderated by 5-HTTLPR genotype. Of 5,249 individuals assessed at birth and followed up to age 18, data on the evaluation for depressive episodes in early adulthood, on childhood maltreatment, and on genotype were available for 3,558 participants, of whom 2,392 remained after conservative screening for previous depressive symptoms. Associations were investigated with logistic regression analyses and controlling for potential confounders. Results: The results replicated important findings of the original study, this time in a sample of young adults from a middle-income country: there was a differential dose-response relationship between childhood maltreatment and major depression according to 5-HTTLPR genotype. Conclusions: After following a research strategy as comparable as possible to that of the original study, the results corroborated the existence of a measured G×E, now in a large sample from a different sociocultural context. These findings provide further evidence that a genetic variant in the 5-HTTLPR moderates the link between childhood maltreatment and youth depression.
Cardiovascular aspects of obstructive sleep apnoea and their relevance to the assessment of the efficacy of nasal continuous positive airway pressure therapy
Authors: R. J O Davies
Journal: Thorax (1998)

Wright et al 1 set out to assess the “health effects” of obstructive sleep apnoea (OSA) and the evidence for the efficacy of continuous positive airway pressure (CPAP) in this disorder. In their assessment they concentrated particularly on whether or not OSA causes cardiovascular disease. The review included more than 70 papers examining cardiovascular end points and less than 30 pertaining to daytime sleepiness and quality of life. It was structured to emphasise these cardiovascular issues and appeared to imply that these factors are the important reasons for the treatment of sleep apnoea. In fact this is incorrect. Patients with sleep apnoea are treated primarily to control disabling daytime sleepiness and to improve quality of life. Heated debates about possible links with cardiovascular disease continue but these are not primarily relevant to the efficacy of CPAP treatment. By getting this balance wrong, the review by Wright et al 1 was seriously flawed; by asking the wrong question it inevitably produced a misleading answer.

Wright et al 1 first dealt with “health effects” and then separately with “CPAP efficacy” and the present discussion is structured similarly. Most of the available cardiovascular evidence relates to systemic arterial blood pressure and hence this dominates what follows. The discussion of arterial blood pressure deals first with blood pressure at night in patients with OSA and then separately with daytime awake blood pressure, since the patterns and mechanisms of any blood pressure changes are different in these two states.

Figure 1 shows the disturbance of blood pressure and cardiac output which occurs during obstructive apnoeas. The blood pressure trace shows repeated falls during apnoea followed by a sharp rise in the period following the apnoea which is coincident with arousal on the electroencephalogram. The magnitude of the rise in blood pressure following apnoea can be …
Role of Advanced Glycation End Products in Diabetic Nephropathy
Authors: Josephine M. Forbes, Mark E. Cooper, Matthew D. Oldfield, Merlin C. Thomas
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Nonenzymatic reactions between sugars and the free amino groups on proteins, lipids, and nucleic acids result in molecular dysfunction through the formation of advanced glycation end products (AGE). AGE have a wide range of chemical, cellular, and tissue effects through changes in charge, solubility, and conformation that characterize molecular senescence. AGE also interact with specific receptors and binding proteins to influence the expression of growth factors and cytokines, including TGF-β1 and CTGF, thereby regulating the growth and proliferation of the various renal cell types. It seems that many of the pathogenic changes that occur in diabetic nephropathy may be induced by AGE. Drugs that either inhibit the formation of AGE or break AGE-induced cross-links have been shown to be renoprotective in experimental models of diabetic nephropathy. AGE are able to stimulate directly the production of extracellular matrix and inhibit its degradation. AGE modification of matrix proteins is also able to disrupt matrix–matrix and matrix–cell interactions, contributing to their profibrotic action. In addition, AGE significantly interact with the renin-angiotensin system. Recent studies have suggested that angiotensin-converting enzyme inhibitors are able to reduce the accumulation of AGE in diabetes, possibly via the inhibition of oxidative stress. This interaction may be a particularly important pathway for the development of AGE-induced damage, as it also can be attenuated by antioxidant therapy. In addition to being a consequence of oxidative stress, it is now clear that AGE can promote the generation of reactive oxygen species. It is likely that therapies that inhibit the formation of AGE will form an important part of future therapy in patients with diabetes, acting synergistically with conventional approaches to prevent diabetic renal injury. E-mail: [email protected]
Association of the H-Y male antigen with beta2-microglobulin on human lymphoid and differentiated mouse teratocarcinoma cell lines.
Authors: M Fellous, E Günther, R Kemler, J Wiels, R Berger, J L Guenet, H Jakob, F Jacob
Journal: The Journal of Experimental Medicine (1978)

The expression of the H-Y antigen has been tested on several human lymphoid lines and mouse teratocarcinoma cell lines during differentiation. The human male lymphoid cell line Raji is a very useful target for studies of the H-Y antigen by lymphocytotoxicity test with rat anti-H-Y sera. With a few exceptions, all cells carrying the Y chromosome were H-Y positive. One of the exceptions is the human Daudi cell line which, besides lacking H-Y antigen, also lacks beta2-microglobulin. We have studied a possible association between the H-Y antigen, beta2-microglobulin, and HLA antigen with redistribution experiments. The results strongly suggest that H-Y antigen is not associated with HLA antigens but with beta2-microglobulin.
Simultaneous β1 integrin-EGFR Targeting and Radiosensitization of Human Head and Neck Cancer
Authors: Iris Eke, Katja Zscheppang, Ellen Dickreuter, Linda Hickmann, Ercole Mazzeo, Kristian Unger, Mechthild Krause, Nils Cordes
Journal: JNCI Journal of the National Cancer Institute (2015)

Signaling from integrins and receptor tyrosine kinases (RTKs) contributes substantially to therapy resistance of malignant tumors. We investigated simultaneous β1 integrin-epidermal growth factor receptor (EGFR) targeting plus radiotherapy in human head and neck squamous cell carcinomas (HNSCCs). Ten HNSCC cell lines were grown in three-dimensional laminin-rich extracellular matrix cell cultures and two of them as tumor xenografts in nude mice (n = 12–16 per group). Targeting of β1 integrin and EGFR with monoclonal inhibitory antibodies (AIIB2 and cetuximab, respectively) was combined with x-ray irradiation. Clonogenic survival, tumor growth, and tumor control (evaluated by Kaplan-Meier analysis), apoptosis, phosphoproteome (interactome, network betweeness centrality analysis), receptor expression (immunohistochemistry), and downstream signaling (western blotting) were assessed. Various mutants of the integrin signaling mediator focal adhesion kinase (FAK) were employed for mechanistic studies. All statistical tests were two-sided. Compared with β1 integrin or EGFR single inhibition, combined β1 integrin-EGFR targeting resulted in enhanced cytotoxicity and radiosensitization in eight out of 10 tested HNSCC cell lines, which responded with an FAK dephosphorylation after β1 integrin inhibition. In vivo, simultaneous anti-β1 integrin/anti-EGFR treatment and radiotherapy of UTSCC15 responder xenografts enabled better tumor control compared with anti-EGFR monotherapy and irradiation (hazard ratio [HR] = 6.9, 95% confidence interval [CI] = 1.6 to 30.9, P = .01), in contrast to the SAS nonresponder tumor model (HR = 0.9, 95% CI = 0.4 to 2.3, P = .83). Mechanistically, a protein complex consisting of FAK- and Erk1-mediated prosurvival signals for radiation resistance, which was effectively compromised by β1 integrin and EGFR blocking. Concomitant targeting of β1 integrin and EGFR seems a powerful and promising approach to overcome radioresistance of HNSCCs.
Diagnostic associations in a large and consecutively identified population positive for anti-SSA and/or anti-SSB: the range of associated diseases differs according to the detailed serotype
Authors: I Peene
Journal: Annals of the Rheumatic Diseases (2002)

To determine the diagnostic distribution in a consecutive anti-SSA and/or anti-SSB positive population.A total of 15 937 serum samples from 10 550 consecutive patients were analysed for antinuclear antibodies (ANAs) on HEp-2 cells. Serum samples positive for ANAs were analysed by immunodiffusion and line immunoassay with recombinant SSA-Ro52, natural SSA-Ro60, and recombinant SSB.Among ANA positive patients in whom clinical information was available, 181 consecutive patients with anti-SSA and/or anti-SSB antibodies were identified, Disease associations were systemic lupus erythematosus (SLE) (45.3%), primary Sjögren's syndrome (pSS) (14.4%), scleroderma (8.8%), RA (7.7%), cutaneous lupus (7.7%), and dermatomyositis (2.2%). The ratio of diagnoses differed according to the anti-SSA/anti-SSB serotype. Scleroderma and dermatomyositis were enriched among mono-Ro52 reactive serum samples (34.2% and 10.5% respectively). Single reactivity towards Ro60 or anti-Ro60 with anti-Ro52 predisposed for SLE (80.0% and 52.2% respectively). Triple reactivity towards Ro52, Ro60, and SSB was primarily linked with SLE (55.8%) followed by pSS (20.9%). Anti-SSA on immunodiffusion increased the chance for SLE (62.8%), whereas isolated anti-SSB reactivity on immunodiffusion was less indicative for SLE (14.3%) and predisposed more for cutaneous lupus (23.8%) and pSS (33.3%).The diagnostic range associated with anti-SSA or anti-SSB reactivity differs significantly according to the detailed serotype defined by line immunoassay and immunodiffusion.
Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method
Authors: Ting-Chao Chou
Journal: Cancer Research (2010)

Abstract This brief perspective article focuses on the most common errors and pitfalls, as well as the do's and don'ts in drug combination studies, in terms of experimental design, data acquisition, data interpretation, and computerized simulation. The Chou-Talalay method for drug combination is based on the median-effect equation, derived from the mass-action law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. This general equation encompasses the Michaelis-Menten, Hill, Henderson-Hasselbalch, and Scatchard equations in biochemistry and biophysics. The resulting combination index (CI) theorem of Chou-Talalay offers quantitative definition for additive effect (CI = 1), synergism (CI &amp;lt; 1), and antagonism (CI &amp;gt; 1) in drug combinations. This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively. Cancer Res; 70(2); 440–6
Rift Valley fever - a threat for Europe?
Authors: V Chevalier, M Pépin, L Plée, R Lancelot
Journal: Eurosurveillance (2010)

Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants, caused by a Phlebovirus (Bunyaviridae). It is widespread in Africa and has recently spread to Yemen and Saudi Arabia. RVF epidemics are more and more frequent in Africa and the Middle East, probably in relation with climatic changes (episodes of heavy rainfall in eastern and southern Africa), as well as intensified livestock trade. The probability of introduction and large-scale spread of RVF in Europe is very low, but localized RVF outbreaks may occur in humid areas with a large population of ruminants. Should this happen, human cases would probably occur in exposed individuals: farmers, veterinarians, slaughterhouse employees etc. Surveillance and diagnostic methods are available, but control tools are limited: vector control is difficult to implement, and vaccines are only available for ruminants, with either a limited efficacy (inactivated vaccines) or a residual pathogenic effect. The best strategy to protect Europe and the rest of the world against RVF is to develop more efficient surveillance and control tools and to implement coordinated regional monitoring and control programmes.
Complete sequence, gene arrangement, and genetic code of mitochondrial DNA of the cephalochordate Branchiostoma floridae (Amphioxus) [published erratum appears in Mol Biol Evol 1999 Jul;16(7):1010]
Authors: J. L. Boore, L. L. Daehler, W. M. Brown
Journal: Molecular Biology and Evolution (1999)

We have determined the 15,083-nucleotide (nt) sequence of the mitochondrial DNA (mtDNA) of the lancelet Branchiostoma floridae (Chordata: Cephalochordata). As is typical in metazoans, the mtDNA encodes 13 protein, 2 rRNA, and 22 tRNA genes. The gene arrangement differs from the common vertebrate arrangement by only four tRNA gene positions. Three of these are unique to Branchiostoma, but the fourth is in a position that is primitive for chordates. It shares the genetic code variations found in vertebrate mtDNAs except that AGA = serine, a code variation found in many invertebrate phyla but not in vertebrates (the related codon AGG was not found). Branchiostoma mtDNA lacks a vertebrate-like control region; its largest noncoding region (129 nt) is unremarkable in sequence or base composition, and its location between ND5 and tRNAG differs from that usually found in vertebrates. It also lacks a potential hairpin DNA structure like those found in many (though not in all) vertebrates to serve as the second-strand (i.e., L-strand) origin of replication. Perhaps related to this, the sequence corresponding to the DHU arm of tRNAC cannot form a helical stem, a condition found in a few other vertebrate mtDNAs that also lack a canonical L-strand origin of replication. ATG and GTG codons appear to initiate translation in 11 and 2 of the protein-encoding genes, respectively. Protein genes end with complete (TAA or TAG) or incomplete (T or TA) stop codons; the latter are presumably converted to TAA by post-transcriptional polyadenylation.
Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human fibroblasts.
Authors: M Kiehntopf, F Herrmann, M A Brach
Journal: The Journal of Experimental Medicine (1995)

Tumor necrosis factor (TNF) alpha participates in the regulation of the acute-phase, immune, and inflammatory responses. Target genes known to be transcriptionally activated by TNF-alpha include the granulocyte (G)-colony-stimulating factor (CSF) gene, the granulocyte/macrophage (GM)-CSF gene, as well as the interleukin (IL) 6 gene. Functional nuclear factor (NF)-IL6 recognition sites have been identified in regulatory regions of these genes by transient transfection studies using deleted promoter constructs. In addition, NF-IL6 is known to form heterodimeric complexes with the NF-kappa B transcription factor, which is also engaged in the transcriptional regulation of these genes. The indispensable importance of NF-IL6 for regulating gene expression of proinflammatory cytokine genes in response to inflammatory stimuli in vivo remains, however, unclear. We here report, by using both antisense (AS) oligodesoxyribonucleotide (ODN) and ribozyme (RZ)-mediated specific elimination of NF-IL6 transcripts in human fibroblasts, that TNF-alpha-induced synthesis of G-CSF, but not of GM-CSF or IL-6, is abolished in the absence of functional NF-IL6 in vivo. Both AS ODN and RZ targeting of the NF-IL6 transcript eliminate NF-IL6 protein, as shown in Western blot analysis and electrophoretic mobility shift assays. Similarly, fibroblasts exposed to either the AS NF-IL6 ODN or the NF-IL6 RZ, but not to the sense or nonsense ODN or a mutated ribozyme, also failed to respond with functional activation of NF-IL6 as assayed in transient transfection studies using heterologous promoter constructs harboring the NF-IL6 recognition site. In contrast, protein synthesis, DNA-binding activity, and transcriptional activation capacity of the NF-kappa B transcription factor is not impaired upon exposure to either ODN or RZ. Fibroblasts that had been cultured in the presence of the AS NF-IL6 ODN or the NF-IL6RZ failed to synthesize G-CSF protein in response to TNF-alpha, while TNF-alpha-inducible transcription and release of GM-CSF and IL-6 was preserved.
Ménière's Attack: Vertigo
Authors: Barbara Ellen Baldwin
Journal: Annals of Internal Medicine (2012)

Ad Libitum4 December 2012Ménière's Attack: VertigoBarbara Ellen BaldwinBarbara Ellen BaldwinFrom Spokane, WA 99204.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-11-201212040-00017 Audio Reading - “Ménière's Attack: Vertigo” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Piano Man," by C.S. Williams, "Heart Surgeon," by B. Butka, and "Ménière's Attack," by B.E. Baldwin. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Instantly, nothing is still.The otolithic organs restin the vestibule,a crista ampullaris foreach semicircular canal.These tiniest of parts lieto the body in motion.Nystagmus calls for help,balance impossiblein a pen click's snap.Eyes, muscles, and bone,send conflicting reports.Movement isn't possible.Ground and sky crazy-whirl,in a ride not easily escaped.Someone in white drivescalmly in the right direction.Nothing is real, just reeling.That someone says:“Stare right throughthat apple,on the dashboard.”One bite is missing,in the normal world.Focus and fear marry.The horizon line,keeps tilting, tilting,on this one-person,out of control plane.details of their ... Author, Article, and Disclosure InformationAffiliations: From Spokane, WA 99204.Current Author Address: Barbara Ellen Baldwin; e-mail, [email protected]. PreviousarticleNextarticle Advertisement Audio Reading - “Ménière's Attack: Vertigo” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Piano Man," by C.S. Williams, "Heart Surgeon," by B. Butka, and "Ménière's Attack," by B.E. Baldwin. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 4 December 2012Volume 157, Issue 11Page: 831KeywordsBoneChartsFearMusclesNystagmusVertigo ePublished: 4 December 2012 Issue Published: 4 December 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A Strategy in The Design of Micellar Shape for Cancer Therapy
Authors: Tao Chen, Xing Guo, Xian Liu, Shuai Shi, Jie Wang, Chunli Shi, Zhiyong Qian, Shaobing Zhou
Journal: Advanced Healthcare Materials (2012)

For cancer therapy, optimization of carrier features is necessary to effectively deliver the targeting agents to tumor sites. Biodegradable poly(ether-anhydrides) micelles with filamentous, rod-like, and spherical shapes are fabricated. Their size and morphology are characterized by AFM and TEM. The encapsulation of doxorubicin hydrochloride (DOX) into the micelles does not impact their shape. The effect of micellar shape on the drug loading capacity and encapsulation efficiency, as well as in vitro drug release, is investigated. The cellular uptakes are evaluated using fluorescence microscopy, confocal laser scanning microscopy and flow cytometry on co-cultures of human hepatoblastoma cell line (HepG2), lung epithelial cancer cell line (A549), and human nasopharyngeal epidermoid carcinoma cells (KB) and fibroblast normal cells mixed with the different shapes of DOX-loaded micelles. The results show that the spherical DOX-loaded micelles are more readily taken up by all types of cells. The impact of micellar shape on in vivo antitumor function is also assessed from changes of tumor volume, body weight loss, and survival rate of 4T1-bearing mice and the immunostaining of tumor sections for analysis of tumor cell proliferation. The results reveal that the filamentous DOX-loaded micelles possess the highest safety to body and the best therapeutic effects to artificial solid tumors. Therefore, the filamentous shape is deemed the most suitable morphology for design and engineering of drug vehicles for cancer therapy.