tbuckley/cabot-search huggingface dataset:
The intracellular target of butyrate's actions: HDAC or HDON'T?
Authors: P R GIBSON
Journal: Gut (2000)

See articles on pages 493 and 507 

Butyrate, the four-carbon short chain fatty acid, has special significance for clinicians and scientists interested in large bowel physiology. It is normally present in the colonic lumen at millimolar concentrations as a product of bacterial fermentation of luminal carbohydrates and is readily taken up by the colonic epithelium to be used as a major energy source via β-oxidation. Butyrate affects key functions of the colonic epithelium in vivo or at least in vitro in models of the colonic epithelium. These functions include promotion of sodium and water absorption, improvement of tight junction permeability, and acceleration of epithelial restitution. Thus, butyrate plays an important role in the maintenance of colonic mucosal health.

Butyrate has also been implicated in the pathogenesis of colonic diseases, especially colorectal cancer and ulcerative colitis. Butyrate's role in the pathogenesis of ulcerative colitis has been a fascinating saga. In 1981, Roediger first reported that epithelial cells isolated from the rectum of patients with ulcerative colitis exhibited impaired β-oxidation of butyrate.1 His “energy-deficiency” hypothesis created more attention when diversion colitis, which may histologically resemble ulcerative colitis, was shown to be largely caused by a deficient supply of short chain fatty acids in the lumen.2 Whether a defect in β-oxidation has specificity for ulcerative colitis and indeed whether it …
A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart
Authors: Osamu Seguchi, Seiji Takashima, Satoru Yamazaki, Masanori Asakura, Yoshihiro Asano, Yasunori Shintani, Masakatsu Wakeno, Tetsuo Minamino, Hiroya Kondo, Hidehiko Furukawa, Kenji Nakamaru, Asuka Naito, Tomoko Takahashi, Toshiaki Ohtsuka, Koichi Kawakami, Tadashi Isomura, Soichiro Kitamura, Hitonobu Tomoike, Naoki Mochizuki, Masafumi Kitakaze
Journal: Journal of Clinical Investigation (2007)

Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v), which is involved in the development of human cardiomyopathy, is an important structural protein that affects physiologic cardiac sarcomere formation and heart development. Integrated cDNA expression analysis of failing human myocardia uncovered a novel protein kinase, cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well correlated with the pulmonary arterial pressure of patients with heart failure. In cultured cardiomyocytes, knockdown of cardiac-MLCK by specific siRNAs decreased MLC2v phosphorylation and impaired epinephrine-induced activation of sarcomere reassembly. To further clarify the physiologic roles of cardiac-MLCK in vivo, we cloned the zebrafish ortholog z–cardiac-MLCK. Knockdown of z–cardiac-MLCK expression using morpholino antisense oligonucleotides resulted in dilated cardiac ventricles and immature sarcomere structures. These results suggest a significant role for cardiac-MLCK in cardiogenesis.
Combined immunoradiotherapy induces long-term remission of CNS relapse of peripheral, diffuse, large-cell lymphoma after allogeneic stem cell transplantation: Case study
Authors: Christian Lotze, Frank Schüler, William H. Krüger, Carsten Hirt, Michael Kirsch, Silke Vogelgesang, Christian A. Schmidt, Gottfried Dölken
Journal: Neuro-Oncology (2005)

Relapse of peripheral non-Hodgkin's lymphoma (NHL) in the central nervous system commonly has a poor prognosis. Graft-versus-leukemia effects (GvL) contribute substantially to eradication of hematological malignancies after allogeneic stem cell transplantation. Few data are available describing GvL activity within the brain. We report the case of a man allografted for peripheral NHL. On day +83 after transplantation a CNS relapse of the lymphoma occurred. The brain was irradiated with 44 Gy, anti-CD20 antibodies were given, and the immunosuppression was withdrawn. Subsequently, limited-stage, chronic graft-versus-host disease occurred. The lymphoma regressed completely, and the patient has been in continuous complete remission for 30 months. The favorable course suggests substantial contribution of immunomodulation to excellent outcome.
Erythropoietin Increases Asymmetric Dimethylarginine in Endothelial Cells
Authors: Fortunato Scalera, Jan T. Kielstein, Jens Martens-Lobenhoffer, Sylvia C. Postel, Michael Ta[Combining Diaeresis]ger, Stefanie M. Bode-Bo[Combining Diaeresis]ger
Journal: Journal of the American Society of Nephrology (2005)

Recombinant human erythropoietin therapy frequently causes hypertension in humans and animals with chronic renal failure. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase, and its accumulation has been associated with reducing NO bioavailability and increasing superoxide generation. Whether epoetin beta (EPO) or darbepoetin alpha (NESP) can modify the levels of ADMA in endothelial cells was investigated. Endothelial cells from the third passage were incubated for 24 h in the presence of various concentrations of EPO or NESP (0, 0.1, 1, 10, 50, 100, and 200 U/ml). The levels of ADMA, allantoin, nitrate, and nitrite in conditioned media and the activity of dimethylarginine dimethylaminohydrolase (DDAH), the content of thiols and reactive oxygen species in endothelial cells, were determined. When endothelial cells were exposed to EPO or NESP, ADMA concentration in the cell culture medium increased significantly in a dose-dependent manner versus control. This effect was associated with a reduced activity of DDAH, the enzyme that degrades ADMA. Furthermore, EPO- or NESP-induced accumulation of ADMA was accompanied by a significant reduction of NO synthesis and an increase in oxidative stress. Both allantoin, a marker of oxygen free radical generation, and reactive oxygen species increased significantly after EPO or NESP treatment compared with control. The antioxidant pyrrolidine dithiocarbamate preserved DDAH activity and reduced ADMA accumulation in the same way as the co-incubation with anti-EPO neutralizing antibody. EPO and NESP posttranslationally impair DDAH activity via increased oxidative stress, causing ADMA as an important cardiovascular risk factor to accumulate and inhibit NO synthesis.
Intensive Glycemic Control in the ACCORD and ADVANCE Trials
Authors: Robert G. Dluhy, Graham T. McMahon
Journal: New England Journal of Medicine (2008)

Diabetes is associated with a reduced lifespan, largely as a consequence of cardiovascular disease.13 Although diabetes significantly increases the risk of cardiovascular events,1 the relative increase in events for each percent increase in glycated hemoglobin is modest.4 Microvascular complications of diabetes remain the leading causes of blindness and renal failure in the developed world and are much more closely associated with hyperglycemia than with macrovascular complications.4 Though there is a link between hyperglycemia and cardiovascular risk, there is less evidence that glucose lowering is associated with reduction in risk. Patients with type 2 diabetes whose glycated hemoglobin levels were . . .
Retrospective Cost-effectiveness Analysis of Screening Mammography
Authors: Natasha K. Stout, Marjorie A. Rosenberg, Amy Trentham-Dietz, Maureen A. Smith, Stephen M. Robinson, Dennis G. Fryback
Journal: JNCI Journal of the National Cancer Institute (2006)

Many guidelines recommend screening mammography every 1-2 years for women older than 40 years; more than 70% of women now participate in routine screening. No studies have examined the societal impact of screening practices over the past decade in the United States on costs and quality-adjusted life-years (QALYs). We performed a retrospective cost-effectiveness analysis comparing actual and alternative screening mammography scenarios.We used a discrete-event simulation model of breast cancer epidemiology to estimate the costs and the number of QALYs that were associated with observed screening mammography patterns in the United States from 1990 to 2000 for women aged 40 years or older. We also estimated costs and QALYS for no screening and for 64 alternative screening scenarios. Incremental cost-effectiveness ratios were computed. Sensitivity analyses were performed on key parameters.Actual U.S. screening patterns from 1990 to 2000 accrued 947.5 million QALYs and cost $166 billion over the lifetimes of the screened women, resulting in a gain of 1.7 million QALYs for an additional cost of $62.5 billion compared with no screening. Among those polices that were not dominated--i.e., for which no alternative existed that produced more QALYs for lower costs--screening all women aged 40-80 years annually per some U.S. guidelines was the most expensive option, costing $58,000 per additional QALY gained compared with the next most costly alternative, screening all women aged 45-80 years annually. Many alternative screening scenarios generated more QALYs for less cost (with savings up to $6 billion) than actual screening patterns over the study period. Sensitivity analysis showed that conclusions about the cost-effectiveness of screening mammography policies were highly sensitive to small, short-term detrimental effects on quality of life from the screening test itself.Choosing among the efficient policies to guide current screening recommendations requires consideration of costs to promote participation in screening and measurement of acute quality-of-life effects of mammography.
Thalidomide-Associated Hyperglycemia and Diabetes
Authors: Ram D. Pathak, Kandaswamy Jayaraj, Lawrence Blonde
Journal: Diabetes Care (2003)

A 70-year-old patient with refractory multiple myeloma, renal failure, and colon cancer was admitted with severe hyperglycemia (612 mg/dl). During the previous 3 weeks he had developed polyuria, polydipsia, fatigue, and a 2-kg weight loss. He had no personal or family history of diabetes. He had developed stress-related hyperglycemia during hospitalization for colon cancer surgery 4 years earlier. He was treated with insulin in the hospital and discharged on medical nutrition therapy. He was diagnosed with multiple myeloma 3 months later and was treated with chemotherapy and steroids for 12 months. His plasma glucose levels ranged from 98 to 114 mg/dl during this period. He was not treated with glucocorticoids or antidiabetic agents for the next 3 …
Increasing Incidence of Late Second Malignancies After Conditioning With Cyclophosphamide and Total-Body Irradiation and Autologous Bone Marrow Transplantation for Non-Hodgkin’s Lymphoma
Authors: Jennifer R. Brown, Heather Yeckes, Jonathan W. Friedberg, Donna Neuberg, Helen Kim, Lee M. Nadler, Arnold S. Freedman
Journal: Journal of Clinical Oncology (2005)

Although the risk of myelodysplastic syndrome (MDS) has been well-described following autologous bone marrow transplantation (ABMT), the risk of solid tumors has been poorly characterized. We report the incidence and outcome of solid tumors at 10-year follow-up in a large cohort of uniformly treated patients who underwent ABMT for non-Hodgkin's lymphoma (NHL).Between 1982 and 1997, 605 patients underwent ABMT for B-cell NHL, with uniform conditioning with cyclophosphamide and total-body irradiation followed by reinfusion of autologous bone marrow purged with anti-B-cell monoclonal antibodies. Current information on relapse of disease and second malignancies was obtained via an institutional review board-approved questionnaire sent to the referring oncologists.Forty-two solid tumors, six non-MDS hematologic malignancies, 39 nonmelanoma skin cancers, and 68 cases of MDS/acute myelogenous leukemia (AML) were observed at a median follow-up of 9.5 years. A cumulative incidence model using death as a competing risk found that the 10-year incidence of second malignancy is 21%, with 10.0% non-MDS malignancies. The projected incidence of all malignancies at 15 years is 29%. The principal risk factor for second malignancy is increased age at ABMT (P = .0002). In the entire cohort, 9.6% of patients have died of second malignancy.Lengthy follow-up demonstrates a significant incidence of second malignancies after ABMT for NHL. Although the incidence of MDS/AML starts to plateau, the incidence of solid tumors continues to rise. Second malignancies are responsible for a significant fraction of overall mortality following ABMT.
Cardiovascular Effects of Tricyclic Antidepressants
Authors: A H Glassman
Journal: Annual Review of Medicine (1984)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Fat Chance Getting an Obstetrician in South Florida? Ethics and Discrimination in Obstetrics and Gynecology
Authors: Glenn McGee
Journal: The American Journal of Bioethics (2011)

The practice of obstetrics and gynecology is uniquely rewarding. Even an ‘uneventful’ pregnancy engages the Ob/Gyn in the transformation of the human body and mind, in the relationship between sexu...
Proliferative activity in peripheral and coronary atherosclerotic plaque among patients undergoing percutaneous revascularization.
Authors: J G Pickering, L Weir, J Jekanowski, M A Kearney, J M Isner
Journal: Journal of Clinical Investigation (1993)

We evaluated the proliferative activity of human atherosclerotic lesions associated with active symptoms of ischemia, by assessing the expression of the proliferating cell nuclear antigen (PCNA). We confirmed in vitro that PCNA, an essential component of the DNA synthesis machinery, is selectively expressed in proliferating human vascular smooth muscle cells. 37 atherosclerotic lesions (18 primary and 19 restenotic) retrieved by directional atherectomy from either coronary or peripheral arteries were then studied for the expression of PCNA, using in situ hybridization or immunohistochemistry. Among plaques studied by in situ hybridization, 7 out of 11 primary and 11 out of 11 restenotic lesions contained PCNA-positive cells. The mean rate of proliferation (percent of PCNA-positive cells) was 7.2 +/- 10.8% in primary lesions and 20.6 +/- 18.2% in restenotic lesions (P < 0.05). Among specimens studied by immunohistochemistry, five out of seven primary and eight out of eight restenotic lesions contained proliferating cells. The mean rate of proliferation was again higher in the restenotic (15.2 +/- 13.6%) than primary (3.6 +/- 3.5%) lesions (P < 0.05). Proliferating cells were detected as late as 1 yr after angioplasty. We conclude that cellular proliferation is a feature of atherosclerotic lesions which are associated with symptoms of ischemia, but that it is more prominent in restenosis compared to primary lesions. These findings have implications for therapies aimed at limiting lesion growth, particularly after percutaneous revascularization.
Repeated low-dose skin exposure is an effective sensitizing stimulus, a factor to be taken into account in predicting sensitization risk
Authors: P. Paramasivan, C. Lai, C. Pickard, M. Ardern-Jones, E. Healy, P.S. Friedmann
Journal: British Journal of Dermatology (2009)

Background Contact sensitization by ingredients in personal products is an important clinical problem. It is not clear how sensitization is induced by the generally low concentrations at which they occur but it might be the result of repeated exposure. Objectives To compare the strength of contact sensitization induced by a single exposure to 2,4‐dinitrochlorobenzene (DNCB) (60 μg cm−2) or three repeated exposures to a subsensitizing dose (10 μg cm−2). Methods Two groups (n =10) of healthy adult volunteers were randomized to receive either a single patch of DNCB 60 μg cm−2 or three once‐weekly applications to the same site of 10 μg cm−2 DCNB. Four weeks after the last application, sensitization was quantified by measurement of responses (skinfold thickness) to a graded series of four challenge doses. Results All the volunteers were sensitized and the strength of the responses was virtually identical between the groups. Conclusions The same degree of sensitization was induced by three exposures to DNCB 10 μg cm−2 as by one exposure to 60 μg cm−2 of DNCB. Thus repeated exposure to low doses of contact sensitizers may increase the sensitizing potency. This must be taken into account in future risk assessments.
Modulation of gene expression by leflunomide and prednisone during treatment of early rheumatoid arthritis
Authors: S. Soldano, B. Villaggio, F. Gallo, P. Montagna, R. Brizzolara, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2010)

Many genes encoding human leucocyte antigen molecules or involved in the activation and resistance of apoptosis of T cells have a role in the susceptibility to rheumatoid arthritis (RA) and are also responsible for the heterogeneous response to conventional disease-modifying antirheumatic drugs (DMARDs) such as leflunomide (LEF).1 LEF has a cellular antiproliferative action on activated inflammatory cells and halts important steps in the pathogenesis of RA, reducing joint inflammation.2 Combined with glucocorticoids such …
Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population
Authors: Ako Fukami, Hisashi Adachi, Sho-ichi Yamagishi, Takanori Matsui, Shin-ichiro Ueda, Kazuo Nakamura, Mika Enomoto, Maki Otsuka, Shun-ichi Kumagae, Yasuki Nanjo, Eita Kumagai, Eishi Esaki, Kyoko Murayama, Yuji Hirai, Tsutomu Imaizumi
Journal: Metabolism (2009)
Low dose cabergoline induced interstitial pneumonitis
Authors: W. Frank, R. Moritz, B. Becke, R. Pauli
Journal: European Respiratory Journal (1999)

Certain dopaminergic anti-Parkinson drugs (ergolines) have repeatedly been identified as a cause of pleuropulmonary disease with a focus on serosal cell damage. Recently, a pathogenetic link between ergolines and prior asbestos exposure was suggested, as regards the development of pleural pathology. This report describes a patient with idiopathic Parkinson9s disease, who was on a multiple drug regimen including low dose cabergoline. The patient developed a febrile illness with widespread bilateral lung infiltrations nonresponsive to beta-lactam and macrolide antibiotics. Bronchoalveolar lavage and transbronchial lung biopsy showed a "hypersensitivity-like" interstitial lung disease, which cleared almost completely within 2 months after simple drug withdrawal. Circumstantial evidence suggests a so far undescribed adverse lung reaction to cabergoline, devoid of the more usual pleural changes.
The miR-144/451 locus is required for erythroid homeostasis
Authors: Kasper D. Rasmussen, Salvatore Simmini, Cei Abreu-Goodger, Nenad Bartonicek, Monica Di Giacomo, Daniel Bilbao-Cortes, Rastislav Horos, Marieke Von Lindern, Anton J. Enright, Dónal O’Carroll
Journal: The Journal of Experimental Medicine (2010)

The process of erythropoiesis must be efficient and robust to supply the organism with red bloods cells both under condition of homeostasis and stress. The microRNA (miRNA) pathway was recently shown to regulate erythroid development. Here, we show that expression of the locus encoding miR-144 and miR-451 is strictly dependent on Argonaute 2 and is required for erythroid homeostasis. Mice deficient for the miR-144/451 cluster display a cell autonomous impairment of late erythroblast maturation, resulting in erythroid hyperplasia, splenomegaly, and a mild anemia. Analysis of gene expression profiles from wild-type and miR-144/451–deficient erythroblasts revealed that the miR-144/451 cluster acts as a “tuner” of gene expression, influencing the expression of many genes. MiR-451 imparts a greater impact on target gene expression than miR-144. Accordingly, mice deficient in miR-451 alone exhibited a phenotype indistinguishable from miR-144/451–deficient mice. Thus, the miR-144/451 cluster tunes gene expression to impart a robustness to erythropoiesis that is critical under conditions of stress.
Long-term follow-up of chemonaive patients with asymptomatic metastatic colorectal cancer treated with enzastaurin in a window of opportunity phase II study
Authors: B. Glimelius, K.L. Spindler, J.-E. Frödin, Å. Berglund, P. Byström, C. Qvortrup, A. Jakobsen, P. Pfeiffer
Journal: Annals of Oncology (2009)
8 FACTORS PREDICTIVE OF RELAPSE IN GENOTYPE 2 AND 3 PTS TREATED FOR 12 WEEKS WITH PEGIFN ALFA 2B AND WEIGHT BASED RIBAVIRIN COMBINATION
Authors: A. Mangia, N. Minerva, D. Bacca, R. Cozzolongo, E. Agostinacchio, F. Sogari, F. Vinelli, G. Scotto, G.L. Ricci, M. Romano, V. Carretta, D. Petruzzellis, V. Piazzolla, F. Spirito, A. Andriulli
Journal: Journal of Hepatology (2008)
What's important in the doctor-patient relationship?
Authors: A. Kubacki
Journal: Journal of the Royal Society of Medicine (2003)

While most of the published research into the doctor-patient relationship focuses on communication skills and behaviours, the paper by Dr Lings and colleagues (April 2003 JRSM1) provides further insight into the non-behavioural aspects of these relationships. Their findings point to ‘liking’ as a key factor of the doctor-patient relationship. This concept, however (or ‘interpersonal attraction’ as it is sometimes called), is not new to the realms of psychological research on the doctor-patient relationship. Like and Zyzanski2 found positive associations between how much the physician liked the patient and both the doctor's and the patient's satisfaction with the visit. Hall et al. 3 expanded the investigation of doctors' liking of patients and again reported a positive association between physician liking and patient satisfaction as well as finding that physicians report higher liking of patients who were male and in good health. This might lead to the notion that liking and satisfaction are synonymous, however Hall et al. 4 now suggest that liking is not simply redundant with satisfaction and is indeed an important psychological characteristic of the doctor-patient relationship. They also reported a reciprocity in terms of liking, whereby how much each liked the other was related to how much each was liked.

Given the evidence that liking and satisfaction may be single entities, 4 where does that leave rapport? If liking is being defined as ‘having an easy and comfortable relationship with the doctor’1 and it includes ‘warmth, respect, interest and enthusiasm for seeing the patient’, 2 how is this different from the concept of rapport? Is liking merely redundant of rapport or is liking at the crux of establishing a good rapport between doctors and patients? Determining the relation between liking and rapport may be another step in the process of clarifying the non-behavioural aspects important in doctor-patient communication.
BAD Ser128 Is Not Phosphorylated by c-Jun NH2-Terminal Kinase for Promoting Apoptosis
Authors: Jiyan Zhang, Jing Liu, Chenfei Yu, Anning Lin
Journal: Cancer Research (2005)

Abstract The phosphorylation and regulation of the proapoptotic Bcl-2 family protein BAD by c-Jun NH2-terminal kinase (JNK) is controversial. JNK can suppress interleukin-3 withdrawal-induced apoptosis via phosphorylation of BAD at Thr201. However, it has also been reported that JNK promotes apoptosis through phosphorylation of BAD at Ser128. Here, we report that JNK is not a BAD Ser128 kinase. JNK phosphorylates murine BAD (mBAD), but not human BAD (hBAD), in which Ser91 is equivalent to Ser128 in mBAD. In contrast, Cdc2, which phosphorylates Ser128, phosphorylates both mBAD and hBAD. Replacement of Ser128 by alanine has no effects on BAD phosphorylation by JNK in vitro and in vivo. Two-dimensional phosphopeptide mapping in combination with phosphoamino acid analysis reveals that JNK does not phosphorylate BAD at Ser128. Elimination of Ser128 phosphorylation has no effects on the proapoptotic activity of BAD in apoptosis induced by UV via JNK or growth factor withdrawal. Thus, our results show that Ser128 is not phosphorylated by JNK for promoting cell death.