tbuckley/cabot-search huggingface dataset:
Transthyretin (Prealbumin) in Health and Disease: Nutritional Implications
Authors: Y Ingenbleek, V Young
Journal: Annual Review of Nutrition (1994)

The name "transthyretin" reflects the dual physiological roles of this tetrameric unglycosylated plasma protein. TTR is one of three specific carrier proteins involved in the transport of both thyroid hormones and of retinol through the mediation of RBP. TTR is a product of the visceral compartment, and its hepatic synthesis is exquisititely sensitive to both the adequacy and levels of protein and energy intakes--hence the proposal of TTR as a nutritional marker. To date, 38 TTR variants have been described, most of which are associated with variable degrees of cardiac and/or neural tissue amyloid deposits. All known variants arise from a single AA substitution due to single point mutation in the coding region of the TTR gene. Under acute stress conditions, the synthesis of TTR, RBP, and CBG is abruptly depressed by a cytokine-directed orchestration of new metabolic priorities, with a redistribution of organ and tissue protein pools. It is proposed that TTR, RBP, and CBG behave as acute-booster reactants (ABRs), actively participating in the cascade of metabolic events characterizing the stress reaction along pathways best explained by the free hormone/vitamin hypothesis. The latter is governed by the law of mass action--the spontaneous dissociation and instant uptake by hepatocytes of the ligands freed from their specific carrier proteins, which creates a transient hyperthyroid, hyperretinoid, and hypercortisolic climate. This response generally does not exceed four or five days because the initial impact of injury normally subsides, but it may last longer if complications occur. The magnitude and adequacy of the stress responses depend on the preceding nutritional status as assessed by TTR plasma levels and are proportionate to the severity of insult. Clinical, animal, and molecular studies concur to demonstrate the dualistic stimulatory or inhibitory effects triggered by the ligands, whose unmetabolized fractions are excreted in the urinary output. Thyroid hormones and retinoids appear to control the early maturation processes and the synthesis of primary transcripts, whereas cortisol preferentially modulates the secondary responses and confers a protective effect on healthy tissues. During acute stress, the evolutionary patterns of visceral proteins and inflammatory markers exhibit compulsory mirror images. However, they change in independent ways under more chronic circumstances. A relatively simple biochemical micromethod based on the simultaneous measurement of plasma TTR, albumin, CRP, and orosomucoid aggregated into a PINI is proposed for the early recognition and follow-up of both nutritional and inflammatory facets of the disease spectrum.
Sorting out the cell biology of Alzheimer’s disease: focus on BACE1 and APP
Authors: Wim Annaert
Journal: Molecular Neurodegeneration (2012)

Background Amyloid b (Ab) peptides, the primary constituents of senile plaques and a hallmark in Alzheimer’s disease pathology, are generated through the sequential cleavage of amyloid precursor protein (APP) by BACE1 and g-secretase. Evidence is accumulating that the early endosome constitutes a major compartment for APP processing; however, the mechanisms of how BACE1 encounters APP are largely unknown.
Whole-Grain, Bran, and Cereal Fiber Intakes and Markers of Systemic Inflammation in Diabetic Women
Authors: Lu Qi, Rob M. van Dam, Simin Liu, Mary Franz, Christos Mantzoros, Frank B. Hu
Journal: Diabetes Care (2006)

OBJECTIVE—To evaluate the dietary predictors for the markers of systemic inflammation and endothelial dysfunction in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—We examined whether intakes of whole grains and dietary fiber were associated with inflammatory indicators among 902 diabetic women in the Nurses’ Health Study. RESULTS—After adjustment for age, BMI, lifestyle, and dietary covariates, intakes of whole grains and bran were both associated with significantly decreasing trends of C-reactive protein (CRP) (P for trend = 0.03 and 0.007, respectively) and tumor necrosis factor-α receptor 2 (TNF-R2) (P for trend = 0.017 and 0.06). High intake of cereal fiber was also inversely associated with the lower levels of CRP (P for trend = 0.03) and TNF-R2 (P for trend = 0.01). The concentrations of CRP and TNF-R2 were 18 and 8% lower in the highest quintile of cereal fiber as compared with the lowest quintile. Dietary glycemic index was positively associated with CRP (P for trend = 0.04) and TNF-R2 (P for trend = 0.0008) levels. The concentrations of CRP and TNF-R2 were 32 and 11% higher, respectively, in the highest quintile of dietary glycemic index as compared with the lowest quintile. CONCLUSIONS—Our data indicate that whole grains and a low-glycemic index diet may reduce systemic inflammation among women with type 2 diabetes.
Steps and Time to Process Clinical Trials at the Cancer Therapy Evaluation Program
Authors: David M. Dilts, Alan B. Sandler, Steven K. Cheng, Joshua S. Crites, Lori B. Ferranti, Amy Y. Wu, Shanda Finnigan, Steven Friedman, Margaret Mooney, Jeffrey Abrams
Journal: Journal of Clinical Oncology (2009)

To examine the processes and document the calendar time required for the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) and Central Institutional Review Board (CIRB) to evaluate and approve phase III clinical trials.Process steps were documented by (1) interviewing CTEP and CIRB staff regarding the steps required to activate a trial from initial concept submission to trial activation by a cooperative group, (2) reviewing standard operating procedures, and (3) inspecting trial records and documents for selected trials to identify any additional steps. Calendar time was collected from initial concept submission to activation using retrospective data from the CTEP Protocol and Information Office.At least 296 distinct processes are required for phase III trial activation: at least 239 working steps, 52 major decision points, 20 processing loops, and 11 stopping points. Of the 195 trials activated during the January 1, 2000, to December 31, 2007, study period, a sample of 167 (85.6%) was used for gathering timing data. Median calendar days from initial formal concept submission to CTEP to trial activation by a cooperative group was 602 days (interquartile range, 454 to 861 days). This time has not significantly changed over the past 8 years. There is a high variation in the time required to activate a clinical trial.Because of their complexity, the overall development time for phase III clinical trials is lengthy, process laden, and highly variable. To streamline the process, a solution must be sought that includes all parties involved in developing trials.
Is It Ethical to Use Enhancement Technologies to Make Us Better than Well?
Authors: Arthur Caplan, Carl Elliott
Journal: PLoS Medicine (2004)

A variety of biomedical technologies are being developed that can be used for purposes other than treating disease. Such "enhancement technologies" can be used to improve our appearance and regulate our emotions, with the goal of feeling "better than well." While these technologies can help people adapt to their rapidly changing lifestyles, their use raises important ethical issues.
Assessment of hospitalised cancer patients' needs by the Needs Evaluation Questionnaire
Authors: M. Tamburini, L. Gangeri, C. Brunelli, E. Beltrami, P. Boeri, C. Borreani, C. Fusco Karmann, M. Greco, G. Miccinesi, L. Murru, P. Trimigno
Journal: Annals of Oncology (2000)
Abnormal glomerular response to atrial natriuretic peptide in rats with aortocaval fistulas.
Authors: L L Norling, B A Thornhill, R L Chevalier
Journal: Journal of the American Society of Nephrology (1996)

Heart failure is characterized by a blunted natriuretic and diuretic response to atrial natriuretic peptide (ANP). To investigate this, a rat model of compensated high-output heart failure was used to determine whether glomerular response to ANP differs in animals with high cardiac output compared with control animals. An aortocaval (AC) fistula was made below the level of the renal arteries in male Sprague-Dawley rats. At 6 wk, one group of AC fistula (N = 6) and control rats (N = 6) was injected with radiolabeled microspheres for determination of hemodynamic parameters, including cardiac output, renal blood flow, and vascular resistance. Rats with AC fistulas had significant changes in cardiac output (218 +/- 17 versus 57 +/- 11 mL/min, P < or = 0.0001), renal blood flow (3.4 +/-0.7 versus 8.4 +/- 1.9 mL/min Left, P < or = 0.05; 3.0 +/- 0.4 versus 7.2 +/- 1.9 mL/min Right, P < or = 0.05), and total vascular resistance (0.6 +/- 0.1 versus 2.7 +/- 0.4 mm Hg/mL per min, P < 0.001) compared with control animals, respectively. In another group of animals, after 6 wk, glomeruli were isolated from kidneys. Extracellular (EC) and intracellular (IC) cGMP was measured as an indication of glomerular response to ANP. Early glomerular response to ANP (10(-8)mol/L) showed a similar acute 13- to 18-fold rise in IC cGMP after 30 sec exposure to ANP (P < or = 0.0001 versus no ANP; N = 4 AC fistula rats and N = 4 control rats). During 1-h incubations with ANP, glomerular response was characterized by a five- to sevenfold increase in EC cGMP. However, glomeruli of AC fistula rats produced significantly less EC cGMP than did those of control animals (21.3 +/- 2.5 versus 44 +/- 4.9 fMol cGMP/2000 glomeruli, P < = 0.005; N = 5 AC fistula rats and N = 5 control rats, respectively). Probenecid-sensitive transport of EC cGMP between AC fistula and control rats (86% decrease versus 82% decrease) was similar. However, glomeruli from AC fistula animals had significantly less phosphodiesterase activity compared with control animals (3.6 +/- 0.4 versus 5.4 +/- 0.7 nMol cGMP/mg protein per min, P < or = 0.01; N = 4 AC fistula rats and N = 5 control rats, respectively). It is speculated that reduced glomerular generation of cGMP in response to ANP contributes to sodium retention in heart failure, but may be compensated for in part by decreased phosphodiesterase-mediated hydrolysis of cGMP.
Sildenafil and Exercise Capacity in Heart Failure—In Reply
Authors: Margaret M. Redfield, Barry A. Borlaug
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells.
Authors: Alexander S Brodsky, Clifford A Meyer, Ian A Swinburne, Giles Hall, Benjamin J Keenan, Xiaole S Liu, Edward A Fox, Pamela A Silver
Journal: Genome biology (2005)

Abstract Background Transcription by RNA polymerase II is regulated at many steps including initiation, promoter release, elongation and termination. Accumulation of RNA polymerase II at particular locations across genes can be indicative of sites of regulation. RNA polymerase II is thought to accumulate at the promoter and at sites of co-transcriptional alternative splicing where the rate of RNA synthesis slows. Results To further understand transcriptional regulation at a global level, we determined the distribution of RNA polymerase II within regions of the human genome designated by the ENCODE project. Hypophosphorylated RNA polymerase II localizes almost exclusively to 5' ends of genes. On the other hand, localization of total RNA polymerase II reveals a variety of distinct landscapes across many genes with 74% of the observed enriched locations at exons. RNA polymerase II accumulates at many annotated constitutively spliced exons, but is biased for alternatively spliced exons. Finally, RNA polymerase II is also observed at locations not in gene regions. Conclusion Localizing RNA polymerase II across many millions of base pairs in the human genome identifies novel sites of transcription and provides insights into the regulation of transcription elongation. These data indicate that RNA polymerase II accumulates most often at exons during transcription. Thus, a major factor of transcription elongation control in mammalian cells is the coordination of transcription and pre-mRNA processing to define exons.
Changes in the Glycemic Profiles of Women With Type 1 and Type 2 Diabetes During Pregnancy
Authors: Helen R. Murphy, Gerry Rayman, Katherine Duffield, Karen S. Lewis, Susan Kelly, Balroop Johal, Duncan Fowler, Rosemary C. Temple
Journal: Diabetes Care (2007)

To examine the changes in glycemic excursions that occur during pregnancy using continuous glucose monitoring and to compare patterns of glycemia in pregnant women with type 1 and type 2 diabetes.An observational data analysis was performed from a prospective randomized study of continuous glucose monitoring in 57 women with pregestational type 1 (n = 40) or type 2 (n = 17) diabetes with 7-day continuous glucose monitoring system profiles during each trimester. Serial glucose measurements were divided into periods of euglycemia (70-140 mg/dl), hyperglycemia (>140 mg/dl), and hypoglycemia (<70 mg/dl). Generalized linear mixed effects models were fitted to the repeated measures data to determine how these glycemic characteristics varied during gestation and by diabetes type.A total of 180 continuous glucose profiles were examined (140 type 1 diabetes, 40 type 2 diabetes), providing 20,433 h of data for analysis (16,117 h type 1 diabetes, 4,316 type 2 diabetes). Women with type 2 diabetes spend approximately 33% less time hyperglycemic throughout pregnancy than women with type 1 diabetes (P = 0.005), with a significantly more rapid reduction in time spent hyperglycemic in early pregnancy (P = 0.02). Although women with type 2 diabetes spend less overall time hypoglycemic (P = 0.04), their risk of nocturnal hypoglycemia is equivalent to that of women with type 1 diabetes (blood glucose level <70 mg/dl, P = 0.9; blood glucose level <50 mg/dl, P = 0.2).Continuous glucose monitoring reveals clear differences in the level of glycemic control that exist in women with type 1 and type 2 diabetes. These data will guide therapeutic interventions aimed at optimizing glycemic control and improving the pregnancy outcomes of both type 1 and type 2 diabetes.
Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain specific.
Authors: W Gilmore, J Correale, L P Weiner
Journal: The Journal of Experimental Medicine (1994)

Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 (A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. They are widely used as models of human demyelinating diseases such as multiple sclerosis (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effects of MHV infection on target cell functions in the CNS are not well understood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection. Changes in class I expression in infected cells may contribute to the immunopathogenesis of MHV infection in the CNS. In this communication, a large panel of MHV strains was tested for their ability to stimulate class I expression in primary astrocytes in vitro. The data show that the more hepatotropic strains, such as MHV-A59, MHV-1, MHV-2, MHV-3, MHV-D, MHV-K, and MHV-NuU, were potent inducers of class I expression in astrocytes during acute infection, measured by radioimmunoassay. The Kb molecule was preferentially expressed over Db. By contrast, JHMV and several viral strains derived from it did not stimulate the expression of class I molecules. Assays of virus infectivity indicated that the class I-inducing activity did not correlate with the ability of the individual viral strain to replicate in astrocytes. However, exposure of the viruses or the supernatants from infected astrocytes to ultraviolet light abolished the class I-inducing activity, indicating that infectious virus is required for class I expression. These data also suggest that class I expression was induced directly by virus infection, and not by the secretion of a soluble substance into the medium by infected astrocytes. Finally, analyses of A59/JHMV recombinant viral strains suggest that class I-inducing activity resides in one of the A59 structural genes.
Human Insulin–Induced Lipoatrophy
Authors: Alberto J. S. Ramos, Marcella A. Farias
Journal: Diabetes Care (2006)

Before the development of purified insulin in the 1970s, lipoatrophy was a common complication of insulin therapy (1,2). With the arrival of human insulin, lipoatrophy has decreased dramatically, becoming a rare problem in clinical practice. Lipoatrophies are considered an adverse immunological side effect of insulin therapy, and in some cases they are mediated by a local high production of tumor necrosis factor-α, which leads to a dedifferentiation of adipocytes in the subcutaneous tissue. The treatment with corticosteroids is useful because of its immunomodulating properties and also because it is able to produce a differentiation of adipocytes (2–4).

In most reported cases of insulin-induced lipoatrophies, there were attempts of changing the injection areas without any evidence of improvement (5–8). Kumar et al. (9) in a single-blind study used small amounts of dexamethasone, adding 4 μg/unit to insulin injections, in nine patients with marked lipoatrophy in both thighs. A mix of insulin and dexamethasone was injected into one thigh and insulin without dexamethasone was injected into the other. This way, each patient was her own control subject. Six patients showed significant improvement. None used …
Detection of novel non-M2-related antimitochondrial antibodies in patients with anti-M2 negative primary biliary cirrhosis
Authors: M Feuchtinger, S Christ, B Preuss, J Dengjel, S Duman, S Stevanovic, R Klein
Journal: Gut (2009)

<h3>Objective:</h3> In 95% of patients with primary biliary cirrhosis (PBC) antimitochondrial antibodies (AMAs) can be detected reacting with at least one of the five components of the M2 antigen identified as the 2-oxoacid dehydrogenase complex (OADC). However, among our PBC sera 15–20% are anti-M2 negative by ELISA and western blotting but in the immunofluorescence test (IFT) they show the typical AMA staining. The aim of the present study was to characterise the target antigen(s) of these non-M2-related AMAs. <h3>Patients and methods:</h3> We analysed sera from 27 patients with clinically and histologically proven PBC being AMA positive by the IFT but anti-M2 negative by ELISA and western blotting. They were tested by western blotting against various 100 000 <i>g</i> supernatants obtained after sonication of mitochondria from rat liver, bovine heart and pig kidney. These were further separated by isopycnic sucrose density centrifugation using different sucrose density fractions. <h3>Results:</h3> Fourteen of the 27 AMA positive/anti-M2 negative sera (52%) reacted in the western blotting with a 60 kDa protein and eight (29%) with an 80 kDa protein, both present in the 100 000 <i>g</i> supernatant from bovine heart mitochondria accumulating at sucrose densities of 1.14–1.16. An identity of these determinants with any of the M2-related antigens could be excluded. In the 60 kDa band components of the mitochondrial enzymes F<sub>1</sub>F<sub>0</sub>-ATPase, ubiquinone cytochrome c reductase and acyl CoA dehydrogenase were detected by MALDI–TOF analysis; the 80 kDa protein could not be further characterised. <h3>Conclusions:</h3> AMA positive/anti-M2 negative PBC sera contain antibodies to further mitochondrial antigens at 60 and 80 kDa which do not correspond to any of the M2 determinants. Those antibodies can be detected to a lesser extent in sera from patients with classical anti-M2 positive PBC but not in patients with other hepatic and non-hepatic disorders and may, therefore, represent additional marker antibodies for the serological diagnosis of PBC.
Dendritic Cells Pulsed with an Anti-Idiotype Antibody Mimicking Carcinoembryonic Antigen (CEA) Can Reverse Immunological Tolerance to CEA and Induce Antitumor Immunity in CEA Transgenic Mice
Authors: Asim Saha, Sunil K. Chatterjee, Kenneth A. Foon, F. James Primus, Sunil Sreedharan, Kartik Mohanty, Malaya Bhattacharya-Chatterjee
Journal: Cancer Research (2004)

Abstract In this report, we have studied the immunogenicity of the nominal antigen, carcinoembryonic antigen (CEA), and that of an anti-idiotype antibody, 3H1, which mimics CEA and can be used as a surrogate for CEA. We have demonstrated that immunization of CEA transgenic mice with bone marrow-derived mature dendritic cells (DC) loaded with anti-idiotype 3H1 or CEA could reverse CEA unresponsiveness and result in the induction of CEA-specific immune responses and the rejection of CEA-transfected MC-38 colon carcinoma cells, C15. Immunized mice splenocytes proliferated in an antigen-specific manner by a mechanism dependent on the functions of CD4, MHC II, B7–2, CD40, CD28, and CD25. However, immune splenic lymphocytes isolated from 3H1-DC-vaccinated mice when stimulated in vitro with 3H1 or CEA secreted significantly higher levels of Th1 cytokines than did CEA-DC vaccinated mice. DC vaccination also induced antigen-specific effector CD8+ T cells capable of expressing interluekin-2, IFN-γ, and tumor necrosis factor (TNF)-α and displayed cytotoxic activity against C15 cells in an MHC class I-restricted manner. 3H1-DC vaccination resulted in augmented CTL responses and the elevated expression of CD69, CD25, and CD28 on CD8+ CTLs. The immune responses developed in 3H1-DC-immunized mice resulted in rejection of C15 tumor cells in nearly 100% of experimental mice, whereas only 40% of experimental mice immunized with CEA-DC were protected from C15 tumor growth. These findings suggest that under the experimental conditions used, 3H1-DC vaccination was better than CEA-DC vaccination in breaking immune tolerance to CEA and inducing protective antitumor immune responses in this murine model transgenic for human CEA.
Is the human brain only responsive?
Authors: Rumyana Kristeva-Feige, Bernd Feige
Journal: Behavioral and Brain Sciences (1995)

Abstract Posner &amp; Raichle's (1994) book is a fascinating and readable account of the studies the authors have conducted on the localization of cognitive functions in the brain mainly using PET and EEC evoked potential methods. Our criticism concerns the underrepresentation of some imaging techniques (magnetoencephalography) and some forms of brain activity (spontaneous activity). Furthermore, the book leaves the reader with the impression that the brain only responds to external events.