tbuckley/cabot-search huggingface dataset:
75Se HCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit.
Authors: G Sciarretta, G Fagioli, A Furno, G Vicini, L Cecchetti, B Grigolo, A Verri, P Malaguti
Journal: Gut (1987)

The purpose of this study was to evaluate whether bile acid malabsorption assessed by the 75SeHCAT test, had a pathogenetic role in functional chronic diarrhoea and to ascertain whether the small bowel transit time (SBTT) could be correlated with the 75SeHCAT test results. The test was based on the counting of the abdominal retention of a 75-selenium labelled homotaurocholic acid. The 75SeHCAT test was carried out in a control group of 23 healthy adults and in 46 patients, 38 of whom were suffering from irritable bowel syndrome (IBS) of diarrhoeic form and eight patients who had undergone cholecystectomy and were suffering from chronic diarrhoea. Faecal bile acid loss was determined in nine patients, and in 14, serum bile acid increase after a standard meal was measured. In 17, SBTT was studied by hydrogen breath test after lactulose administration (21 g in 300 ml water). In 15 patients, choledochocaecal transit time was estimated by Tc99m-HIDA (111 MBq) cholescintigraphy. In 20 of 46 subjects, 75SeHCAT retention was below normal level, and in 19 cholestyramine administration relieved diarrhoea. 75SeHCAT results were related to faecal bile acid loss, while no correlation was found with serum bile acids and SBTT. The data suggest a possible wider use of the 75SeHCAT test in chronic diarrhoea to estimate bile acid malabsorption in irritable bowel syndrome, diarrhoeic form, and provide an effective treatment. In our patients small bowel transit velocity does not seem to be a pathogenetic factor of bile acid malabsorption.
Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives
Authors: Francesco Ferraguti, Luca Crepaldi, Ferdinando Nicoletti
Journal: Pharmacological Reviews (2008)

Almost 25 years after the first report that glutamate can activate receptors coupled to heterotrimeric G-proteins, tremendous progress has been made in the field of metabotropic glutamate receptors. Now, eight members of this family of glutamate receptors, encoded by eight different genes that share distinctive structural features have been identified. The first cloned receptor, the metabotropic glutamate (mGlu) receptor mGlu1 has probably been the most extensively studied mGlu receptor, and in many respects it represents a prototypical subtype for this family of receptors. Its biochemical, anatomical, physiological, and pharmacological characteristics have been intensely investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of receptors that couple to phospholipase C and mobilize Ca<sup>2+</sup> from intracellular stores. Several alternatively spliced variants of mGlu1 receptors, which differ primarily in the length of their C-terminal domain and anatomical localization, have been reported. Use of a number of genetic approaches and the recent development of selective antagonists have provided a means for clarifying the role played by this receptor in a number of neuronal systems. In this article we discuss recent advancements in the pharmacology and concepts about the intracellular transduction and pathophysiological role of mGlu1 receptors and review earlier data in view of these novel findings. The impact that this new and better understanding of the specific role of these receptors may have on novel treatment strategies for a variety of neurological and psychiatric disorders is considered.
Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Authors: Jeremy S. Duffield, Stuart J. Forbes, Christothea M. Constandinou, Spike Clay, Marina Partolina, Srilatha Vuthoori, Shengji Wu, Richard Lang, John P. Iredale
Journal: Journal of Clinical Investigation (2005)

Macrophages perform both injury-inducing and repair-promoting tasks in different models of inflammation, leading to a model of macrophage function in which distinct patterns of activation have been proposed. We investigated macrophage function mechanistically in a reversible model of liver injury in which the injury and recovery phases are distinct. Carbon tetrachloride--–induced liver fibrosis revealed scar-associated macrophages that persisted throughout recovery. A transgenic mouse (CD11b-DTR) was generated in which macrophages could be selectively depleted. Macrophage depletion when liver fibrosis was advanced resulted in reduced scarring and fewer myofibroblasts. Macrophage depletion during recovery, by contrast, led to a failure of matrix degradation. These data provide the first clear evidence that functionally distinct subpopulations of macrophages exist in the same tissue and that these macrophages play critical roles in both the injury and recovery phases of inflammatory scarring.
Investigation of the Hepatic Arterial "Space" under Various Conditions of Flow in the Isolated Perfused Dog Liver
Authors: C. D. FIELD, W. H. ANDREWS
Journal: Circulation Research (1968)

A radioactive isotope dilution technique, in which two radioactive tracers were used simultaneously, was employed to investigate the nature of the hepatic arterial vascular bed or arterial vascular "space" in 22 isolated perfused canine livers. The technique continuously monitored the blood leaving the liver for radioactivity so that no assumptions had to be made regarding the representative nature of samples. The concept of an arterial vascular space was defined in terms of the mean circulation time of labeled red cells through the perfused organ, and the variation of this parameter with variations in arterial flow was considered; agreement with other published work was shown. The experiments on the size of the arterial vascular space showed a linear relationship between the arterial fraction of the blood occupying the total hepatic vascular bed and the arterial fraction of the total hepatic blood flow. The evidence from these experiments supported the idea that the artery and the portal vein share a large proportion of the total hepatic vascular bed.
Lung as reservoir for antidepressants in pharmacokinetic drug interactions
Authors: Tetsuya Suhara, Yasuhiko Sudo, Katsuya Yoshida, Yoshiro Okubo, Hiroshi Fukuda, Takayuki Obata, Kyosan Yoshikawa, Kazutoshi Suzuki, Yasuhito Sasaki
Journal: The Lancet (1998)
Pleural sarcoidosis: one case presenting with an eosinophilic effusion.
Authors: D V Durand, A Dellinger, C Guerin, J C Guerin, R Levrat
Journal: Thorax (1984)

Pleural manifestations are rare in sarcoidosis, occurring in about 1 % of a cumulative series.'They include pleural effusions, pleural thickening, and spontaneous pneumo- thorax.We present a case of pleural sarcoidosis presenting as an eosinophilic effusion.Specific pleural lesions were established by thoracoscopy and biopsy, which showed appearances suggesting serous dissemination of sarcoid granulation tissue.
Community-based intervention to increase HIV testing and case detection in people aged 16–32 years in Tanzania, Zimbabwe, and Thailand (NIMH Project Accept, HPTN 043): a randomised study
Authors: Michael Sweat, Stephen Morin, David Celentano, Marta Mulawa, Basant Singh, Jessie Mbwambo, Surinda Kawichai, Alfred Chingono, Gertrude Khumalo-Sakutukwa, Glenda Gray, Linda Richter, Michal Kulich, Andrew Sadowski, Thomas Coates
Journal: The Lancet Infectious Diseases (2011)
Muscarinic Signaling in the Brain
Authors: Alexander Thiele
Journal: Annual Review of Neuroscience (2013)

Muscarinic signaling affects attention, action selection, learning, and memory through multiple signaling cascades, which act at different timescales and which alter ion channels in cell type-specific manners. The effects of muscarinic signaling differ between cortical layers and between brain areas. Muscarinic signaling adds flexibility to the processing mode of neuronal networks, thereby supporting processing according to task demands. This review outlines possible scenarios to describe how it contributes to cellular mechanisms of attention and how it affects channeling of information in different neuronal circuits.
Plasma Connective Tissue Growth Factor Is an Independent Predictor of End-Stage Renal Disease and Mortality in Type 1 Diabetic Nephropathy
Authors: Tri Q. Nguyen, Lise Tarnow, Anders Jorsal, Noelynn Oliver, Peggy Roestenberg, Yasuhiko Ito, Hans-Henrik Parving, Peter Rossing, Frans A. van Nieuwenhoven, Roel Goldschmeding
Journal: Diabetes Care (2008)

We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes.Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic patients with persistent normoalbuminuria. Follow-up time was 12.8 years. Prediction of end-stage renal disease (ESRD) and mortality by plasma CTGF was analyzed in conjunction with conventional risk factors.Plasma CTGF was higher in patients with nephropathy than in patients with normoalbuminuria (median 381 [interquartile range 270-630] vs. 235 [168-353] pmol/l). In patients with nephropathy, elevated plasma CTGF was an independent predictor of ESRD (covariate-adjusted hazard ratio [HR] 1.6 [95% CI 1.1-2.5]) and correlated with the rate of decline in glomerular filtration rate (GFR) (cumulative R = 0.46). Area under the receiver operating characteristic curve for prediction of ESRD was 0.72. Plasma CTGF above a cutoff level of 413 pmol/l predicted ESRD with a sensitivity of 73% and a specificity of 63% and was associated with a higher rate of decline in GFR (mean +/- SD 5.4 +/- 4.9 vs. 3.3 +/- 3.5 ml/min per 1.73 m(2) per year). Moreover, in patients with nephrotic range albuminuria (>3 g/day), plasma CTGF was the only predictor of ESRD (covariate-adjusted HR 4.5 [2.0-10.4]). Plasma CTGF was an independent predictor also of overall mortality (covariate-adjusted HR 1.4 [1.1-1.7]). In contrast, in normoalbuminuric patients, plasma CTGF did not correlate with clinical parameters and did not predict outcome.Plasma CTGF contributes significantly to prediction of ESRD and mortality in patients with type 1 diabetic nephropathy.
Proteomic and Metabolomic Analysis of Vascular Smooth Muscle Cells
Authors: Manuel Mayr, Richard Siow, Yuen-Li Chung, Ursula Mayr, John R. Griffiths, Qingbo Xu
Journal: Circulation Research (2004)

Recent developments of proteomic and metabolomic techniques provide powerful tools for studying molecular mechanisms of cell function. Previously, we demonstrated that neointima formation was markedly increased in vein grafts of PKCδ-deficient mice compared with wild-type controls. To clarify the underlying mechanism, we performed a proteomic and metabolomic analysis of cultured vascular smooth muscle cells (SMCs) derived from PKCδ +/+ and PKCδ −/− mice. Using 2-dimensional electrophoresis and mass spectrometry, we identified &gt;30 protein species that were altered in PKCδ −/− SMCs, including enzymes related to glucose and lipid metabolism, glutathione recycling, chaperones, and cytoskeletal proteins. Interestingly, nuclear magnetic resonance spectroscopy confirmed marked changes in glucose metabolism in PKCδ −/− SMCs, which were associated with a significant increase in cellular glutathione levels resulting in resistance to cell death induced by oxidative stress. Furthermore, PKCδ −/− SMCs overexpressed RhoGDIα, an endogenous inhibitor of Rho signaling pathways. Inhibition of Rho signaling was associated with a loss of stress fiber formation and decreased expression of SMC differentiation markers. Thus, we performed the first combined proteomic and metabolomic study in vascular SMCs and demonstrate that PKCδ is crucial in regulating glucose and lipid metabolism, controlling the cellular redox state, and maintaining SMC differentiation.
PATHOLOGIC REACTIONS OF MARITAL PARTNERS TO IMPROVEMENT OF PATIENTS
Authors: RICHARD N. KOHL
Journal: American Journal of Psychiatry (1962)

During the past 20 years there has been an increasing number of reports concerning treatment of the family rather than treatment of the individual exclusively. The importance of treating the marital partner as well as the patient is emphasized in the present study by the relatively frequent pathologic reactions of marital partners to patients's improvement or recovery. Just as a patients' failure to respond to treatment may give rise to anxiety, guilt or hostility in his marital partner, so may his improvement lead to similar pathologic reactions. Treatment of the marital partner as well as the patient is indicated when the former reacts to the patient's obvious progress by resisting his improvement or by development of a clinical illness. In such cases the wellbeing of one partner appears to be directly related to the illness of the other and it is not uncommon to find that the less sick marital partner is the first to seek treatment voluntarily. Such pathologic reactions are often predictable and when so, treatment of the marital partner should be instituted as early as possible. The success or failure of the patient's treatment is dependent upon the therapist's ability to deal effectively with both the conscious and unconscious hostility of the marital partner, his resistence to treatment and recovery of the patient, his dependence upon the existence of the patient's illness and the occurrence of his own pathologic reaction to the patient's improvement. The occurrence of specific pathologic reactions by marital partners to patients' improvement or recovery affords an excellent opportunity for further investigation of the etiology and treatment, as well as the prevention of complementary illnesses in marriage.
Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia
Authors: Miriam Sonnet, Rainer Claus, Natalia Becker, Manuela Zucknick, Jana Petersen, Daniel B Lipka, Christopher C Oakes, Mindaugas Andrulis, Amelie Lier, Michael D Milsom, Tania Witte, Lei Gu, Soo-Zin Kim-Wanner, Peter Schirmacher, Michael Wulfert, Norbert Gattermann, Michael Lübbert, Frank Rosenbauer, Michael Rehli, Lars Bullinger, Dieter Weichenhan, Christoph Plass
Journal: Genome Medicine (2014)

Abstract Background Aberrant DNA methylation is frequently found in human malignancies including acute myeloid leukemia (AML). While most studies focus on later disease stages, the onset of aberrant DNA methylation events and their dynamics during leukemic progression are largely unknown. Methods We screened genome-wide for aberrant CpG island methylation in three disease stages of a murine AML model that is driven by hypomorphic expression of the hematopoietic transcription factor PU.1. DNA methylation levels of selected genes were correlated with methylation levels of CD34+ cells and lineage negative, CD127-, c-Kit+, Sca-1+ cells; common myeloid progenitors; granulocyte-macrophage progenitors; and megakaryocyte-erythroid progenitors. Results We identified 1,184 hypermethylated array probes covering 762 associated genes in the preleukemic stage. During disease progression, the number of hypermethylated genes increased to 5,465 in the late leukemic disease stage. Using publicly available data, we found a significant enrichment of PU.1 binding sites in the preleukemic hypermethylated genes, suggesting that shortage of PU.1 makes PU.1 binding sites in the DNA accessible for aberrant methylation. Many known AML associated genes such as RUNX1 and HIC1 were found among the preleukemic hypermethylated genes. Nine novel hypermethylated genes, FZD5 , FZD8 , PRDM16 , ROBO3 , CXCL14 , BCOR , ITPKA , HES6 and TAL1 , the latter four being potential PU.1 targets, were confirmed to be hypermethylated in human normal karyotype AML patients, underscoring the relevance of the mouse model for human AML. Conclusions Our study identified early aberrantly methylated genes as potential contributors to onset and progression of AML.
Emergence of Drug Resistance Is Associated with an Increased Risk of Death among Patients First Starting HAART
Authors: Robert S Hogg, David R Bangsberg, Viviane D Lima, Chris Alexander, Simon Bonner, Benita Yip, Evan Wood, Winnie W. Y Dong, Julio S. G Montaner, P. Richard Harrigan
Journal: PLoS Medicine (2006)

Background The impact of the emergence of drug-resistance mutations on mortality is not well characterized in antiretroviral-naïve patients first starting highly active antiretroviral therapy (HAART). Patients may be able to sustain immunologic function with resistant virus, and there is limited evidence that reduced sensitivity to antiretrovirals leads to rapid disease progression or death. We undertook the present analysis to characterize the determinants of mortality in a prospective cohort study with a median of nearly 5 y of follow-up. The objective of this study was to determine the impact of the emergence of drug-resistance mutations on survival among persons initiating HAART. Methods and Findings Participants were antiretroviral therapy naïve at entry and initiated triple combination antiretroviral therapy between August 1, 1996, and September 30, 1999. Marginal structural modeling was used to address potential confounding between time-dependent variables in the Cox proportional hazard regression models. In this analysis resistance to any class of drug was considered as a binary time-dependent exposure to the risk of death, controlling for the effect of other time-dependent confounders. We also considered each separate class of mutation as a binary time-dependent exposure, while controlling for the presence/absence of other mutations. A total of 207 deaths were identified among 1,138 participants over the follow-up period, with an all cause mortality rate of 18.2%. Among the 679 patients with HIV-drug-resistance genotyping done before initiating HAART, HIV-drug resistance to any class was observed in 53 (7.8%) of the patients. During follow-up, HIV-drug resistance to any class was observed in 302 (26.5%) participants. Emergence of any resistance was associated with mortality (hazard ratio: 1.75 [95% confidence interval: 1.27, 2.43]). When we considered each class of resistance separately, persons who exhibited resistance to non-nucleoside reverse transcriptase inhibitors had the highest risk: mortality rates were 3.02 times higher (95% confidence interval: 1.99, 4.57) for these patients than for those who did not exhibit this type of resistance. Conclusions We demonstrated that emergence of resistance to non-nucleoside reverse transcriptase inhibitors was associated with a greater risk of subsequent death than was emergence of protease inhibitor resistance. Future research is needed to identify the particular subpopulations of men and women at greatest risk and to elucidate the impact of resistance over a longer follow-up period.
High-Throughput Screening Identifies Novel Agents Eliciting Hypersensitivity in Fanconi Pathway–Deficient Cancer Cells
Authors: Eike Gallmeier, Tomas Hucl, Jonathan R. Brody, David A. Dezentje, Khola Tahir, Jana Kasparkova, Viktor Brabec, Kurtis E. Bachman, Scott E. Kern
Journal: Cancer Research (2007)

Inactivation of the Fanconi anemia (FA) pathway occurs in diverse human tumors among the general population and renders those tumors hypersensitive to DNA interstrand-cross-linking (ICL) agents. The identification of novel agents to which FA pathway-deficient cells were hypersensitive could provide new therapeutic opportunities and improve our molecular understanding of the FA genes. Using high-throughput screening, we assessed the growth of isogenic human cancer cells that differed only in the presence or absence of single FA genes upon treatment with 880 active drugs and 40,000 diverse compounds. We identified several compounds to which FA pathway-deficient cells were more sensitive than FA pathway-proficient cells, including two groups of structurally related compounds. We further investigated the compound eliciting the strongest effect, termed 80136342. Its mechanism of action was distinct from that of ICL agents; 80136342 did not cause increased chromosomal aberrations, enhanced FANCD2 monoubiquitination, H2AX phosphorylation, p53 activation, or ICL induction. Similar to ICL agents, however, 80136342 caused a pronounced G(2) arrest in FA pathway-deficient cells. When applied in combination with ICL agents, 80136342 had at least additive toxic effects, excluding interferences on ICL-induced toxicity and facilitating a combinational application. Finally, we identified one particular methyl group necessary for the effects of 80136342 on FA-deficient cells. In conclusion, using high-throughput screening in an isogenic human FA cancer model, we explored a novel approach to identify agents eliciting hypersensitivity in FA pathway-deficient cells. We discovered several attractive candidates to serve as lead compounds for evaluating structure-activity relationships and developing therapeutics selectively targeting FA pathway-deficient tumors.
47Calcium absorption in parenchymatous and biliary liver disease
Authors: M. J. Whelton, A. K. Kehayoglou, J. E. Agnew, L. A. Turnberg, S. Sherlock
Journal: Gut (1971)

As measured by whole body retention of isotopic calcium given in milk, absorption of calcium was impaired in 10 patients with chronic parenchymal non-biliary liver disease who were icteric. Mean absorption was normal in 15 patients with parenchymal liver disease who were anicteric although some individual patients absorbed less than any of the controls. Depressed absorption of calcium was seen in 10 patients with primary biliary cirrhosis and seven patients with intra- or extra-hepatic biliary obstructive disease. The most likely cause for this malabsorption is reduced bile salt secretion into the intestinal lumen which impairs vitamin D and fat absorption. The finding that parenteral vitamin D increased calcium absorption to normal levels in five patients with primary biliary cirrhosis suggests that deficiency of this vitamin is a major and correctable factor leading to calcium malabsorption in such patients. Precipitation of calcium salts by excess intraluminal fat appears to be a further possible factor reducing calcium absorption in these patients. These findings emphasize the importance of parenteral vitamin D therapy in patients with chronic obstructive biliary diseases. They also suggest that certain patients with chronic parenchymatous liver disease, particularly those who are icteric, may also occasionally require therapy with vitamin D.
Notes on Certain Changes in the Cardio-Vascular System which are Induced by Treatment According to the Schott Methods
Authors: W. B. Thorne
Journal: BMJ (1896)

TMUDIx' JLnTTaI 653.aspira-tion on tlle aortic blood is ehecked by more or less perfect valves, while the increased tone of the arterial system brought about by the drug promotes the resiliency and aspirative power of the latter.What, then, is the rational treatment of aortic incompetency ?Marey and Chauveau demonstrated by experiment on the horse that destruction of the aortic sigmoid valves eaused a rise in intraventricular pressure due to the reflux of blood, and that this was associated with increased frequency of the heart's action.16Ottomar Rosenbachl7 also showed that no artificial destruction of valves, or even the introduction into the heart of various obstacles,, materially affected the blood pressure in the arteries.Marey's and Rosenbach's observations are not incompatible.The increased frequency of action noted by the former in the presence of increased intracardiae pressure, together with the constant action of the forces of gravitation and aspiration, serve to maintain arterial pressure, notwithstanding the greater labour thrown upon the heart.The therapeutic indications given by these results is that the aortically incompetent heart should be quickened, not retarded, until, after aequired compensation, the organ