tbuckley/cabot-search huggingface dataset:
Adrenoceptor recovery after heart failure in the dog
Authors: G. Larosa, P. W Armstrong, P. Seeman, C. Forster
Journal: Cardiovascular Research (1993)

Journal Article β Adrenoceptor recovery after heart failure in the dog Get access Giulia Larosa, Giulia Larosa Department of Medicine, Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada: G Larosa, P W Armstrong, C Forster; Department of Pharmacology, University of Toronto, Ontario, Canada: P Seeman. Correspondence to Giulia Larosa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul W Armstrong, Paul W Armstrong Department of Medicine, Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada: G Larosa, P W Armstrong, C Forster; Department of Pharmacology, University of Toronto, Ontario, Canada: P Seeman. Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip Seeman, Philip Seeman Department of Medicine, Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada: G Larosa, P W Armstrong, C Forster; Department of Pharmacology, University of Toronto, Ontario, Canada: P Seeman. Search for other works by this author on: Oxford Academic PubMed Google Scholar Christine Forster Christine Forster Department of Medicine, Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada: G Larosa, P W Armstrong, C Forster; Department of Pharmacology, University of Toronto, Ontario, Canada: P Seeman. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 3, March 1993, Pages 489–493, https://doi.org/10.1093/cvr/27.3.489 Published: 01 March 1993 Article history Received: 14 May 1992 Accepted: 23 September 1992 Published: 01 March 1993
The Effect of Gastric Bypass on the Pharmacokinetics of Serotonin Reuptake Inhibitors
Authors: Giselle G. Hamad, Joseph C. Helsel, James M. Perel, Gina M. Kozak, Mary C. McShea, Carolyn Hughes, Andrea L. Confer, Dorothy K. Sit, Carol A. McCloskey, Katherine L. Wisner
Journal: American Journal of Psychiatry (2012)

Morbidly obese patients treated with serotonin reuptake inhibitors for mood and anxiety disorders frequently relapse following gastric bypass surgery. Of 12 patients followed, drug absorption 1 month postoperatively dropped to an average of 54% of preoperative levels (range: 36%–80%) in eight patients but returned to baseline levels by 6 months for six patients. Those who relapsed into depression with low blood levels frequently failed to lose weight as well.
Herbal medicines for the treatment of COPD: a systematic review
Authors: R. Guo, M. H. Pittler, E. Ernst
Journal: European Respiratory Journal (2006)

The aim of the current study was to systematically assess the effectiveness of herbal medicines in treating chronic obstructive pulmonary disease (COPD). Randomised clinical trials (RCTs) testing herbal medicines against any type of control intervention in patients with COPD and assessing clinically relevant outcomes were included. The selection of studies, data extraction and validation were performed independently by at least two reviewers. Methodological quality was evaluated using the Jadad score. Effect sizes and their 95% confidence intervals were calculated. Fourteen eligible RCTs, testing 14 different herbal medicines, were located. Herbal medicines were compared against placebo or no treatment in six trials. Significant intergroup differences for one or more outcome were reported for several herbal medicines including Panax ginseng and Salvia miltiorrhiza . In seven RCTs, which compared herbal medicines with other herbal medicines, the results were mixed. A single trial compared a herbal medicine ( Hedera helix leaf extract) with a conventional treatment (ambroxol tablet) and reported no significant difference between groups. Due to the heterogeneity of the data, statistical pooling was not performed. The median methodological quality score was 2 out of a possible maximum 5. The effectiveness of herbal medicines for treating chronic obstructive pulmonary disease is not established beyond reasonable doubt. Currently, the evidence from randomised clinical trials is scarce and often methodologically weak. Considering the popularity of herbal medicine among chronic obstructive pulmonary disease patients, rigorously designed studies seem warranted.
1-Antitrypsin deficiency {middle dot} 6: New and emerging treatments for 1-antitrypsin deficiency
Authors: R A Sandhaus
Journal: Thorax (2004)

Alpha-1-antitrypsin (AAT) deficiency is a genetic condition that increases the risk of developing lung and liver disease, as well as other associated conditions. Most treatment of affected individuals is not specifically directed at AAT deficiency but focuses on the resultant disease state. The only currently available specific therapeutic agent-namely, intravenous augmentation with plasma derived AAT protein-is marketed in a limited number of countries. Treatments aimed at correcting the underlying genetic abnormality, supplementing or modifying the gene product, and halting or reversing organ injury are now beginning to emerge. These innovative approaches may prove effective at modifying or eliminating diseases association with AAT deficiency.
Pharmacogenetics of Drug Dependence: Role of Gene Variations in Susceptibility and Treatment
Authors: Jibran Y. Khokhar, Charmaine S. Ferguson, Andy Z.X. Zhu, Rachel F. Tyndale
Journal: The Annual Review of Pharmacology and Toxicology (2010)

Drug dependency is a highly prevalent mental health disorder that imposes a significant burden on those directly affected, health care systems, and society in general. There is substantial heritability in the susceptibility to drug addiction, which indicates that there are genetic risk factors. Variation in the human genome is abundant and can directly affect drug dependency phenotypes, for example, by altering the function of a gene product or by altering gene expression. Pharmacogenetic studies can assess the effects of genetic variation on the risk for a particular phenotype (e.g., being an alcoholic). In addition, pharmacogenetic variability in treatment efficacy and adverse reactions can be investigated to identify particular genetic variants associated with altered responses. This review highlights examples of genetic variations that are important in the development and maintenance of specific drug dependencies as well as those that affect the response to treatment.
Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity
Authors: Michal Marzec, Monika Kasprzycka, Raymond Lai, Andrew B. Gladden, Pawel Wlodarski, Ewa Tomczak, Peter Nowell, Samuel E. DePrimo, Seth Sadis, Stephen Eck, Stephen J. Schuster, J. Alan Diehl, Mariusz A. Wasik
Journal: Blood (2006)
Secretion of Tumor-Specific Antigen by Myeloma Cells Is Required for Cancer Immunosurveillance by CD4+ T Cells
Authors: Alexandre Corthay, Katrin U. Lundin, Kristina Berg Lorvik, Peter O. Hofgaard, Bjarne Bogen
Journal: Cancer Research (2009)

Tumor-specific CD4(+) T cells orchestrate the adaptive immune responses against cancer. We have previously shown that CD4(+) T cells recognize MHC class II-negative myeloma cells indirectly by collaborating with tumor-infiltrating macrophages. We, here, hypothesize that this critical step may be dependent on secretion of tumor-specific antigens by cancer cells. This was investigated using T-cell receptor-transgenic mice, in which CD4(+) T cells mediate rejection of syngeneic MOPC315 myeloma cells. We analyzed the immune response against myeloma cell variants, which either secrete or retain intracellularly a tumor-specific idiotypic (Id) antigen. Our results reveal that CD4(+) T cells helped by macrophages are capable of detecting nonsecreted tumor antigens from MHC class II-negative cancer cells. However, Id secretion was required for successful myeloma immunosurveillance. Antigen secretion resulted in stronger priming of naive myeloma-specific CD4(+) T cells in tumor-draining lymph nodes. Secretion of antigen by at least some cancer cells within a tumor was shown to facilitate immunosurveillance. Treatment by local injection of purified tumor-specific antigen successfully enhanced immunity against nonsecreting myeloma cells. Collectively, the data indicate that antigen concentration within the tumor extracellular matrix must reach a certain threshold to allow successful cancer immunosurveillance by CD4(+) T cells.
MicroRNA let-7 Modulates the Immune Response to Mycobacterium tuberculosis Infection via Control of A20, an Inhibitor of the NF-κB Pathway
Authors: Manish Kumar, Sanjaya Kumar Sahu, Ranjeet Kumar, Arijita Subuddhi, Ranjan Kumar Maji, Kuladip Jana, Pushpa Gupta, Johanna Raffetseder, Maria Lerm, Zhumur Ghosh, Geert van Loo, Rudi Beyaert, Umesh D. Gupta, Manikuntala Kundu, Joyoti Basu
Journal: Cell Host & Microbe (2015)
Occurrence of Second Cancers in Patients Treated With Radiotherapy for Rectal Cancer
Authors: Helgi Birgisson, Lars Påhlman, Ulf Gunnarsson, Bengt Glimelius
Journal: Journal of Clinical Oncology (2005)

To analyze the occurrence of second cancers in patients with rectal cancer treated with external radiotherapy (RT) in addition to surgery.The analyses were based on the Uppsala Trial (completed in 1985), with patients randomly assigned to preoperative RT to all stages or postoperative RT for stage II and III cancers, and the Swedish Rectal Cancer Trial (completed in 1990), with patients randomly assigned to preoperative RT or surgery alone. Patients from the trials were matched against the Swedish Cancer Registry.A total of 115 (7%) of the 1,599 patients developed 122 second cancers. More patients treated with RT developed a second cancer (relative risk [RR], 1.85; 95% CI, 1.23 to 2.78). A significant increased risk for second cancers in the RT group was seen in organs within or adjacent to the irradiated volume (RR, 2.04; 95% CI, 1.10 to 3.79) but not outside the irradiated volume (RR, 1.78; 95% CI, 0.97 to 3.27). For the Swedish Rectal Cancer Trial, 20.3% of the RT patients got either a local recurrence or a second cancer, compared with 30.7% of the non-RT patients (RR, 0.55; 95% CI, 0.44 to 0.70).An increased risk of second cancers was found in patients treated with RT in addition to surgery for a rectal cancer, which was mainly explained by an increase in the risk of second cancers in organs within or adjacent to the irradiated volume. However, a favorable effect of radiation seemed to dominate, as shown by the reduced risk of the sum of local recurrences and second cancers.
Centrifugal lipodystrophy of the face mimicking progressive lipodystrophy
Authors: Y. Hagari, R. Sasaoka, S. Nishiura, M. Ishihara, M. Mihara, S. Shimao
Journal: British Journal of Dermatology (1992)

We report a Japanese boy with centrifugal lipodystrophy. The initial lesion developed on the forehead as an area of erythema which showed centrifugal spread and central fading to leave a residual depression. Three years later, similar erythematous lesions appeared on the cheeks, and he developed a cadaverous appearance. A central depression on the upper trunk was surrounded by an erythematous border and there was right cervical lymphadenopathy. Histological examination revealed inflammatory changes in the subcutaneous fat. Although this patient showed the characteristics of both centrifugal and progressive lipodystrophy (partial lipodystrophy), we consider that he has centrifugal lipodystrophy of the face because of the overall features of the lesions.
Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis.
Authors: J K Liao, M A Bettmann, T Sandor, J I Tucker, S M Coleman, M A Creager
Journal: Circulation Research (1991)

The purpose of this study was to assess the effect of atherosclerosis on the regulation of limb blood flow. To examine this issue, the reactivity of resistance and conduit vessels was evaluated in 11 patients with peripheral atherosclerotic disease and six control subjects. Responsiveness of resistance vessels was measured by venous occlusion plethysmography. Responsiveness of conduit vessels was determined by quantitative angiography to measure the diameter of the superficial femoral artery. To distinguish endothelium-dependent vasodilation from that caused by direct smooth muscle relaxation, each participant received intra-arterial infusions of methacholine and nitroprusside, respectively. Flow-mediated dilation of the superficial femoral artery was determined during reactive hyperemia. Vasoconstrictor function was determined by the infusion of phenylephrine. Methacholine reduced calf vascular resistance in the control subjects but not in the patients with atherosclerosis (-64 +/- 11% versus 6 +/- 18%, p less than 0.01). Nitroprusside decreased calf vascular resistance comparably in each group (-51 +/- 5% versus -42 +/- 4%, p = NS). The vasoconstrictor effect of phenylephrine was similar in each group (105 +/- 30% versus 108 +/- 22%, p = NS). In the superficial femoral artery, the vasodilator responses to both methacholine (20 +/- 4% versus 1 +/- 4%, p less than 0.05) and nitroprusside (19 +/- 4% versus 5 +/- 4%, p less than 0.05) were blunted in the atherosclerotic patients as was the vasoconstrictive response to phenylephrine (-15 +/- 1% versus -1 +/- 5%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Cooperation between signalling pathways leading to survival, proliferation or death of B cells
Authors: D. Szili, A. Hancz, J. Pozsgay, H. Zoltan, G. Koncz, G. Sarmay
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Antigen driven positive selection of B cells depends on signals from B cell receptor (BCR) and a plethora of positive and negative regulating receptors determining B cells’ fate. Fas/CD95 mediated signals kill bystander or autoreactive B cells, while the receptor for B cell activating factor of tumour necrosis factor family (BAFF-R) mediates survival signals for transitional/mature B cells. Toll-like receptor 9 (TLR9) induced signals stimulate B cells and may enhance the antigen-specific B cell response. The study aim was to reveal the collaboration between these signalling pathways in human B cells. <h3>Materials and methods</h3> B cells were isolated from peripheral blood of normal blood donors by negative selection, and stimulated by various combinations of ligands binding to BCR, BAFFR, TLR9 and Fas. Kinase activities were tested by protein profiler microarray and Western blot. Proliferation of 5-(and 6)-Carboxyfluorescein diacetate succinimidyl ester (CFSE) loaded cells was tested by flow cytometry, antibody production was measured by ELISA. Apoptosis was evaluated by determining the ratio of subdiploid cells by flow cytometry. <h3>Results</h3> The authors found that BAFF induced a small but significant reduction of Fas-mediated cell death; however, BAFF and BCR mediated rescue signals did not cooperate. TLR9 mediated signals significantly reduced apoptosis, and the rescuing effect of TLR9 was sensitive for inhibitors of protein kinase C and p38. TLR9 synergised with BCR not only in inhibiting apoptosis but also in inducing proliferation, indicating that TLR9 may support B cell growth in the presence and in absence of antigen. Antibody synthesis was also enhanced by the co-signals of TLR9 and BAFF-R. To reveal the mechanism behind the collaboration between various signals in B cells, phosphorylation of crucial signalling molecules was tested. Proteome profiler microarray has shown that activities of Erk2, JNK, p38 and Rsk1 were synergistically enhanced by the co-stimulation via BCR and TLR9. These results were confirmed by Western blots. Additionally, the authors found that the mitogen-activated protein kinase kinase kinase, transforming growth factor β (TGFβ) activated kinase 1 (Tak1) plays a crucial role in co-signalling. Inhibitor of Tak1 blocked p38 and Rsk1 phosphorylation, and diminished proliferation induced by BCR and TLR9. <h3>Conclusions</h3> These data suggest that BAFF may function independently of BCR, rescuing B cells from Fas-mediated death. It may enhance the risk of autoimmune diseases by promoting the survival of bystander B cells in the germinal centre. TLR9 mediates both antiapoptotic and proliferative signals, and it co-operates with BCR-induced signals at the level of Tak1-p38 pathway. Thus TLR9 may significantly contribute to the positive selection, activation and growth of B cells, and thus may help to break tolerance.
Differential contributions of central and effector memory T cells to recall responses
Authors: Alan D. Roberts, Kenneth H. Ely, David L. Woodland
Journal: The Journal of Experimental Medicine (2005)

Although the absolute number of memory CD8+ T cells established in the spleen following antigen encounter remains stable for many years, the relative capacity of these cells to mediate recall responses is not known. Here we used a dual adoptive transfer approach to demonstrate a progressive increase in the quality of memory T cell pools in terms of their ability to proliferate and accumulate at effector sites in response to secondary pathogen challenge. This temporal increase in efficacy occurred in CD62L lo (effector memory) and CD62L hi (central memory) subpopulations, but was most prominent in the CD62L hi subpopulation. These data indicate that the contribution of effector memory and central memory T cells to the recall response changes substantially over time.
FAS Ligand, Bcl-2, Granulocyte Colony-Stimulating Factor, and p38 Mitogen-Activated Protein Kinase
Authors: Andreas Villunger, Lorraine A. O'Reilly, Nils Holler, Jerry Adams, Andreas Strasser
Journal: The Journal of Experimental Medicine (2000)

The short life span of granulocytes, which limits many inflammatory responses, is thought to be influenced by the Bcl-2 protein family, death receptors such as CD95 (Fas/APO-1), stress-activated protein kinases such as p38 mitogen-activated protein kinase (MAPK), and proinflammatory cytokines like granulocyte colony-stimulating factor (G-CSF). To clarify the roles of these various regulators in granulocyte survival, we have investigated the spontaneous apoptosis of granulocytes in culture and that induced by Fas ligand or chemotherapeutic drugs, using cells from normal, CD95-deficient lpr, or vav-bcl-2 transgenic mice. CD95-induced apoptosis, which required receptor aggregation by recombinant Fas ligand or the membrane-bound ligand, was unaffected by G-CSF treatment or Bcl-2 overexpression. Conversely, spontaneous and drug-induced apoptosis occurred normally in lpr granulocytes but were suppressed by G-CSF treatment or Bcl-2 overexpression. Although activation of p38 MAPK has been implicated in granulocyte death, their apoptosis actually was markedly accelerated by specific inhibitors of this kinase. These results suggest that G-CSF promotes granulocyte survival largely through the Bcl-2–controlled pathway, whereas CD95 regulates a distinct pathway to apoptosis that is not required for either their spontaneous or drug-induced death. Moreover, p38 MAPK signaling contributes to granulocyte survival rather than their apoptosis.
Video Testimony of Long-Term Hospitalized Psychiatrically Ill Holocaust Survivors
Authors: Rael D Strous, Mordechai Weiss, Irit Felsen, Boris Finkel, Yuval Melamed, Avraham Bleich, Moshe Kotler, Dori Laub
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Many Holocaust survivors who have both psychotic disorders and residual symptoms of posttraumatic stress disorder (PTSD) remain chronically hospitalized in psychiatric institutions. This study investigated the clinical benefits of a therapeutic process facilitating a detailed videotaped account of traumatic experience (testimony method) in elderly long-term hospitalized Holocaust survivors. METHOD: Twenty-four schizophrenia patients (mean age=72.2 years) who were chronically hospitalized in Israeli state psychiatric hospitals underwent assessment by blind rating with a battery of psychiatric rating scales before and 4 months after extensive videotaped interview. The rating scales included the Positive and Negative Syndrome Scale; Clinical Global Impression (CGI); Mini-Mental State Examination (MMSE); Clinician-Administered PTSD Scale, Form 2; and Structured Interview for Disorders of Extreme Stress. Full pre- and postinterview data were available for 21 patients. RESULTS: Thirty-eight percent of the patients met the criteria for PTSD at the first interview, compared with only 19% at the second interview. The patients had significant reductions in functional impairment and in the severity and intensity of all posttraumatic symptom clusters (intrusion, avoidance, hyperarousal); the avoidance cluster showed the most reduction. Eleven subjects had an improvement of 30% or more in total posttraumatic severity score. No differences in Positive and Negative Syndrome Scale, MMSE, Structured Interview for Disorders of Extreme Stress, and CGI total scores were noted postinterview or between the two preinterview evaluation batteries in the comparison group. Female patients had a higher prevalence of PTSD symptoms. Total Clinician-Administered PTSD Scale, Form 2, scores and total Positive and Negative Syndrome Scale scores were inversely correlated both at baseline and at follow-up. CONCLUSIONS: Study observations suggest clinical benefits of the testimony method in the alleviation of many posttraumatic symptoms, but not psychosis, in a cohort of psychiatrically ill Holocaust survivors, despite an interval of as many as 60 years since the traumatic events. The findings have implications for care and rehabilitation of patients many years after acute traumatic events.
Glioma-Associated Oncogene Family Zinc Finger 1 Expression and Metastasis in Patients With Head and Neck Squamous Cell Carcinoma Treated With Radiation Therapy (RTOG 9003)
Authors: Christine H. Chung, James J. Dignam, M. Elizabeth Hammond, Alexander C. Klimowicz, Stephanie K. Petrillo, Anthony Magliocco, Richard Jordan, Andy Trotti, Sharon Spencer, Jay S. Cooper, Quynh-Thu Le, K. Kian Ang
Journal: Journal of Clinical Oncology (2011)

Purpose Glioma-associated oncogene family zinc finger 1 (GLI1) expression was assessed to determine a potential role of hedgehog (Hh) signaling in head and neck squamous cell carcinoma (HNSCC). Additional proteins known to be modulated by Hh signaling, including beta-catenin (CTNNB1) and epidermal growth factor receptor (EGFR), were also assessed to determine the correlation among these distinct signaling pathways. Patients and Methods Nuclear GLI1 and CTNNB1 expression levels were determined in tumors from patients enrolled on Radiation Therapy Oncology Group (RTOG) 9003, a radiation fractionation trial. The results were also correlated with previously determined EGFR expression. The expression levels were evaluated in relation to three end points: time to metastasis (TTM), time to disease progression (TDP), and overall survival (OS). Results Among 1,068 eligible patients, data on GLI1, CTNNB1, and EGFR were available in 339, 164, and 300 patients, respectively. Although CTNNB1 expression did not differentiate prognosis, GLI1 was associated with poorer outcomes, adjusted for age, TNM stages, and Karnofsky performance score, and the significant influence persisted in a multivariable analysis (quartile 4 [Q4] v Q1 to Q3: TTM hazard ratio [HR], 2.7; 95% CI, 1.5 to 4.9; TDP HR, 1.6; 95% CI, 1.1 to 2.5; OS HR, 1.9; 95% CI, 1.4 to 2.7). The significance of GLI1 persisted in a multivariable analysis that included EGFR expression levels. Conclusion These data suggest that Hh signaling may play an important role in metastasis and that GLI1 could serve as a marker in HNSCC, but the regulatory mechanisms and oncogenic significance need further investigation. Risk classification based on this analysis needs a validation in independent cohorts.