tbuckley/cabot-search huggingface dataset:
Granulocyte-specific antinuclear factors in synovial fluids and sera from patients with rheumatoid arthritis.
Authors: A Wiik, E Jensen, J Friis
Journal: Annals of the Rheumatic Diseases (1974)

The prevalence of antinuclear factors (ANF) found in sera and synovial fluids (SF) of patients with rheuma- toid arthritis (RA) varies from one study to another, chiefly according to the technique used.The im- portance of sensitivity has been emphasized by Ritchie who found ANF in 89 % of undiluted RA sera, employing rat liver as nuclear substrate and an antihuman immunoglobulin conjugate detecting the three main classes of immunoglobulins (Ig) (Ritchie, 1967).As 61 % of normal control sera contained low titres of ANF (<16) a titre of 16 was selected as the upper normal limit.Titres above 16 were found in 32 % of the RA sera.The choice of nuclear substrate is also important, since some ANF in RA show limited reactivity (Elling, Graudal, and Faber, 1968).Using human blood leucocytes and an antihuman Ig conjugate these authors found ANF reacting predominantly or solely with polymorphonuclear nuclei in 64 % of RA sera and 62 % of paired joint fluids.Previous cross absorption experiments on ANF positive RA and systemic lupus erythematosus sera using thyroid and leucocyte nuclei had shown the specificity of granu- locyte-specific ANF (GS-ANF) (Elling, 1966).Such antibodies were thus detected in virtually all RA sera and about one-third of systemic lupus erythematosus sera.
Culture result of smear-positive sputum samples after 2 months of antituberculous treatment
Authors: C-S. Lim, C-H. Lee, Y-J. Chien, J-Y. Wang, L-N. Lee, C-J. Yu, P-C. Yang
Journal: European Respiratory Journal (2009)

To the Editors: 

The correlation between sputum smear for acid-fast bacilli (AFB) and culture for Mycobacterium tuberculosis is usually good before antituberculous treatment (ATT), but it is not so good after treatment has started. In previous studies, up to 23.5% of patients had sputum that remained smear positive after 2 months of ATT 1. Old age, high bacillary load, presence of pulmonary cavitary lesions, treatment interruption and emergence of resistant strains are risk factors of persistent smear positivity. Determining whether these sputum samples contain viable tuberculosis (TB) bacilli is crucial because it indicates higher rates of relapse 2, 3. Meanwhile, for patients without viable TB bacilli, modifying treatment regimens and isolation appears to be redundant. However, the results of mycobacterial culture are only available after 2 weeks, even when using fluorometric liquid culture technique. Despite having good sensitivity and specificity, commercialised nucleic acid amplification tests are expensive and do not discriminate between viable and dead bacilli and, therefore, are not recommended for TB patients receiving ATT. Thus, we conducted a study to identify clinical factors for predicting the culture results of the persistent smear-positive sputum samples in a 2,100 bed, tertiary-care referral centre in northern Taiwan and an 800 bed local teaching hospital in southern Taiwan.

In the two hospitals, all sputum specimens were processed by adding NaOH-citrate- N -acetyl-l-cysteine at room temperature for 15 min. After centrifugation, the precipitate was resuspended 4. Before October 2006, smears for AFB of the processed samples were stained using the Kinyoun method. From November 2006, the smear was stained with auramine-rhodamine fluorochrome 5. Smears were graded according to guidelines established by the American Thoracic Society 6 and the highest smear grading was recorded. All collected …
Neuropeptide Y-Related Peptides and their Receptors--Are the Receptors Potential Therapeutic Drug Targets?
Authors: C Wahlestedt, D J Reis
Journal: The Annual Review of Pharmacology and Toxicology (1993)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Erythrocyte‐oxidized glutathione transport in pyrimidine 5′‐nucleotidase deficiency
Authors: Takahito Kondo, Yoshinori Ohtsuka, Michiro Shimada, Yoshikazu Kawakami, Yasuhiko Hiyoshi, Yoshiro Tsuji, Hisaichi Fujii, Shiro Miwa
Journal: American Journal of Hematology (1987)

Abstract The oxidized form of glutathione transport was studied in human erythrocytes in pyrimidine 5′‐nucleotidase (P5N) deficiency, a disorder in which the amounts of CTP and UTP in the erythrocytes are elevated. The inhibition of ATP‐requiring oxidized glutathione (GSSG) transport by CTP and UTP is believed to play a role in elevating the levels of the reduced form of glutathione (GSH) in the erythrocytes of patients with P5N deficiency. The current investigation was undertaken to determine if GSSG transport actually decreases in the erythrocytes of such patients. Erythrocytes from a 17‐year‐old patient and a 13‐year‐old patient with P5N deficiency hemolytic anemia and from ten normal subjects were used as materials for the experiment. Erythrocytes, which had been previously incubated with [ 3 H]glycine, were incubated at 37°C, and the rate of [ 3 H]GSSG transported by the cells was estimated. The velocity of GSSG transport out of the erythrocytes was quite low in the patients, 3.17–3.65 nmol GSSG/ml erythrocytes/hr at 37°C in one case, and 3.30 nmol GSSG/ml erythrocytes/hr in the other case, vs that in the normal controls (6.00 ± 0.80 nmol GSSG/ml erythrocytes/hr; mean ± SD). The activity of γ‐glutamylcysteine synthetase and glutathione synthetase did not decrease in the patients. Decreased transport activity of GSSG in addition to a normal synthesis rate for GSH may explain the increased concentration of erythrocyte GSH in P5N deficiency.
Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity
Authors: Gudmar Thorleifsson, G Bragi Walters, Daniel F Gudbjartsson, Valgerdur Steinthorsdottir, Patrick Sulem, Anna Helgadottir, Unnur Styrkarsdottir, Solveig Gretarsdottir, Steinunn Thorlacius, Ingileif Jonsdottir, Thorbjorg Jonsdottir, Elinborg J Olafsdottir, Gudridur H Olafsdottir, Thorvaldur Jonsson, Frosti Jonsson, Knut Borch-Johnsen, Torben Hansen, Gitte Andersen, Torben Jorgensen, Torsten Lauritzen, Katja K Aben, André LM Verbeek, Nel Roeleveld, Ellen Kampman, Lisa R Yanek, Lewis C Becker, Laufey Tryggvadottir, Thorunn Rafnar, Diane M Becker, Jeffrey Gulcher, Lambertus A Kiemeney, Oluf Pedersen, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2008)
20-Year Outcomes Following Conservative Management of Clinically Localized Prostate Cancer
Authors: Peter C Albertsen, James A Hanley, Judith Fine
Journal: JAMA (2005)

The appropriate therapy for men with clinically localized prostate cancer is uncertain. A recent study suggested an increasing prostate cancer mortality rate for men who are alive more than 15 years following diagnosis.To estimate 20-year survival based on a competing risk analysis of men who were diagnosed with clinically localized prostate cancer and treated with observation or androgen withdrawal therapy alone, stratified by age at diagnosis and histological findings.A retrospective population-based cohort study using Connecticut Tumor Registry data supplemented by hospital record and histology review of 767 men aged 55 to 74 years with clinically localized prostate cancer diagnosed between January 1, 1971, and December 31, 1984. Patients were treated with either observation or immediate or delayed androgen withdrawal therapy, with a median observation of 24 years.Probability of mortality from prostate cancer or other competing medical conditions, given a patient's age at diagnosis and tumor grade.The prostate cancer mortality rate was 33 per 1000 person-years during the first 15 years of follow-up (95% confidence interval [CI], 28-38) and 18 per 1000 person-years after 15 years of follow-up (95% CI, 10-29). The mortality rates for these 2 follow-up periods were not statistically different, after adjusting for differences in tumor histology (rate ratio, 1.1; 95% CI, 0.6-1.9). Men with low-grade prostate cancers have a minimal risk of dying from prostate cancer during 20 years of follow-up (Gleason score of 2-4, 6 deaths per 1000 person-years; 95% CI, 2-11). Men with high-grade prostate cancers have a high probability of dying from prostate cancer within 10 years of diagnosis (Gleason score of 8-10, 121 deaths per 1000 person-years; 95% CI, 90-156). Men with Gleason score of 5 or 6 tumors have an intermediate risk of prostate cancer death.The annual mortality rate from prostate cancer appears to remain stable after 15 years from diagnosis, which does not support aggressive treatment for localized low-grade prostate cancer.
Natural Killer Cells License Dendritic Cell Cross-Presentation of B Lymphoma Cell–Associated Antigens
Authors: Tao Dao, Marta Gomez-Nunez, Christophe Antczak, Barry Kappel, Jaspreet Singh Jaggi, Tatyana Korontsvit, Victoriya Zakhaleva, David A. Scheinberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Presentation of exogenous antigen by MHC class I molecules, or cross-presentation, is a property of dendritic cells, which is considered crucial for the priming of cytotoxic T-cell response to tumor antigens. However, the precise mechanisms of this process are not fully understood. Experimental Design and Results: We show here in a human in vitro system, using B lymphoma cells as a tumor model, that the cross-presentation of cell-associated antigens to T cells by dendritic cells requires “help” from natural killer cells. When autologous dendritic cells that had taken up apoptotic B lymphoma cells and induced to a fully mature state were used to stimulate nonadherent cells of peripheral blood mononuclear cells from healthy donors, they induced strong cytotoxicity against B lymphoma cells in a HLA-A0201-restricted manner. The cells failed to induce cytotoxicity, however, when purified T cells were used as effector cells. Depletion of CD56+ cells, but not CD14+ or CD19+ cells, abrogated the cytotoxicity of nonadherent cells, showing that the help was provided by natural killer cells. Further, when natural killer cells were present in the cultures, a strong and persistent production of interleukin-18, but not interleukin-12 and interleukin-15, was observed. Blocking interleukin-18 significantly reduced the cytotoxicity of nonadherent cells against B lymphoma cells. Conclusions: These results suggest that capture of tumor cells and a full maturation status of dendritic cells are not sufficient to cross-prime CD8 T cells. Effective cross-priming requires further activation of dendritic cells by natural killer cells and an abundant production of interleukin-18, which, along with other yet undefined mechanisms, contribute to the generation of CTL response against B-cell lymphoma.
The Experience of Recurrent Cancer
Authors: J. W. Worden
Journal: CA A Cancer Journal for Clinicians (1989)

Although the medical community contin ues to make progress in the treatment of cancer, recurrence of cancer is still both frequent and generally considered to be a poor prognostic sign.For such patients, many of whom are diagnosed with recur rent disease after long periods of remission, the long-range hope for cure must be re vised, and the initial optimism and ultimate outcome are far more limited than at first diagnosis.Along with the return of the dis ease, therefore, comes a return of the dis tress experienced at the time of the original diagnosis and the concurrent concerns that such a return can signal.There are few studies in the extensive literature on psychosocial oncology that look specifically at the psychosocial impact of recurrence.'3It has been assumed that recurrence is more distressing, disabling, and discouraging than the shock of the first diagnosis of cancer.It has also been as sumed that patients with recurrent cancer
Prognostic Impact of Deficient DNA Mismatch Repair in Patients With Stage III Colon Cancer From a Randomized Trial of FOLFOX-Based Adjuvant Chemotherapy
Authors: Frank A. Sinicrope, Michelle R. Mahoney, Thomas C. Smyrk, Stephen N. Thibodeau, Robert S. Warren, Monica M. Bertagnolli, Garth D. Nelson, Richard M. Goldberg, Daniel J. Sargent, Steven R. Alberts
Journal: Journal of Clinical Oncology (2013)

Purpose The association of deficient DNA mismatch repair (dMMR) with prognosis in patients with colon cancer treated with adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy remains unknown. Patients and Methods Resected, stage III colon carcinomas from patients (N = 2,686) randomly assigned to FOLFOX ± cetuximab (North Central Cancer Treatment Group N0147 trial) were analyzed for mismatch repair (MMR) protein expression and mutations in BRAF V600E (exon 15) and KRAS (codons 12 and 13). Association of biomarkers with disease-free survival (DFS) was determined using Cox models. A validation cohort (Cancer and Leukemia Group B 88903 trial) was used. Results dMMR was detected in 314 (12%) of 2,580 tumors, of which 49.3% and 10.6% had BRAF V600E or KRAS mutations, respectively. MMR status was not prognostic overall (adjusted hazard ratio [HR], 0.82; 95% CI, 0.64 to 1.07; P = .14), yet significant interactions were found between MMR and primary tumor site (P interaction = .009) and lymph node category (N1 v N2; P interaction = .014). Favorable DFS was observed for dMMR versus proficient MMR proximal tumors (HR, 0.71; 95% CI, 0.53 to 0.94; P = .018) but not dMMR distal tumors (HR, 1.71; 95% CI, 0.99 to 2.95; P = .056), adjusting for mutations and covariates. Any survival benefit of dMMR was lost in N2 tumors. Mutations in BRAF V600E (HR, 1.37; 95% CI, 1.08 to 1.70; P = .009) or KRAS (HR, 1.44; 95% CI, 1.21 to 1.70; P &lt; .001) were independently associated with worse DFS. The observed MMR by tumor site interaction was validated in an independent cohort of stage III colon cancers (P interaction = .037). Conclusion The prognostic impact of MMR depended on tumor site, and this interaction was validated in an independent cohort. Among dMMR cancers, proximal tumors had favorable outcome, whereas distal or N2 tumors had poor outcome. BRAF or KRAS mutations were independently associated with adverse outcome.
Sodium-Hydrogen Exchanger, Cardiac Overload, and Myocardial Hypertrophy
Authors: Horacio E. Cingolani, Irene L. Ennis
Journal: Circulation (2007)

O verload of neonatal and adult cardiomyocytes and mul- ticellular myocardial preparations, which include whole hearts, are accompanied by an enhanced activity of the Na ϩ /H ϩ exchanger 1 (NHE-1).Exogenous administration of prohypertrophic agents such as angiotensin II (Ang II), endothelin-1 (ET-1), and ␣ 1 -adrenergic agonists also stimulates NHE-1 activity, which leads to an increased concentration of intracellular Na ϩ ([Na ϩ ] i ).Moreover, inhibition of NHE-1 activity prevents the increase in [Na ϩ ] i , induces the regression of cardiac hypertrophy, and exerts beneficial effects in experimental heart failure.The present review summarizes the current knowledge of the causative factors and pathophysiological correlation of cardiac overload and NHE-1 activity.
Metabolic Effects of Replacing Sucrose by Isomaltulose in Subjects With Type 2 Diabetes
Authors: Stefanie Brunner, Ines Holub, Stephan Theis, Andrea Gostner, Ralph Melcher, Petra Wolf, Ulrike Amann-Gassner, Wolfgang Scheppach, Hans Hauner
Journal: Diabetes Care (2012)

OBJECTIVE To test the hypothesis that replacement of sucrose with isomaltulose in sweet foods and beverages improves metabolic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS One hundred ten patients with type 2 diabetes were randomized to receive sweet foods containing either 50 g/day isomaltulose or sucrose for 12 weeks as part of their habitual diet under free-living conditions. HbA1c at 12 weeks was the primary outcome parameter. RESULTS In the final analysis comprising 101 patients, isomaltulose did not significantly affect HbA1c at 12 weeks (sucrose: 7.39 ± 0.78%; isomaltulose: 7.24 ± 0.76%; regression coefficient [b]: 0.02 [95% CI: −0.21 to 0.25], P = 0.844). Triglycerides at 12 weeks were significantly lower in the isomaltulose versus the sucrose group (b: 34.01 [6.59–61.44], P = 0.016). Other secondary parameters did not significantly differ between groups. CONCLUSIONS Isomaltulose did not influence glycemic control assessed as HbA1c in type 2 diabetes under free-living conditions but was associated with lower triglyceride levels.
Serological Documentation of Maternal Influenza Exposure and Bipolar Disorder in Adult Offspring
Authors: Sarah E. Canetta, Yuanyuan Bao, Mary Dawn T. Co, Francis A. Ennis, John Cruz, Masanori Terajima, Ling Shen, Christoph Kellendonk, Catherine A. Schaefer, Alan S. Brown
Journal: American Journal of Psychiatry (2014)

The authors examined whether serologically confirmed maternal exposure to influenza was associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features.The study used a nested case-control design in the Child Health and Development Study birth cohort. In all, 85 individuals with bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 comparison subjects in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay.No association was observed between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serological influenza exposure was related to a significant fivefold greater risk of bipolar disorder with psychotic features.The results suggest that maternal influenza exposure may increase the risk for offspring to develop bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, these results may suggest that prenatal influenza is a risk factor for psychosis rather than for a specific psychotic disorder diagnosis.
Association of <i>CRP</i> Genetic Variation and CRP Level With Elevated PTSD Symptoms and Physiological Responses in a Civilian Population With High Levels of Trauma
Authors: Vasiliki Michopoulos, Alex O. Rothbaum, Tanja Jovanovic, Lynn M. Almli, Bekh Bradley, Barbara O. Rothbaum, Charles F. Gillespie, Kerry J. Ressler
Journal: American Journal of Psychiatry (2014)

Objective: Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the proinflammatory marker C-reactive protein (CRP) are elevated in individuals with posttraumatic stress disorder (PTSD). Furthermore, single-nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP level, risk for cardiovascular disease, and obesity. The authors examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a civilian population with high levels of trauma. Method: Cross-sectional data and DNA samples were collected from 2,698 individuals recruited from an inner-city public hospital that serves a primarily African American, low-socioeconomic-status population. A subgroup of 187 participants participated in further interviews, testing, and physiological measures; of these, 135 were assessed using the fear-potentiated startle paradigm to assess fear-related phenotypes of PTSD. Results: One SNP within the CRP gene, rs1130864, was significantly associated with increased PTSD symptoms (N=2,692), including “being overly alert” as the most significant individual symptom (N=2,698). Additionally, CRP genotype was associated with the odds of PTSD diagnosis (N=2,692). This SNP was also associated with increased CRP level (N=137), and high CRP levels (>3 mg/L) were positively associated with PTSD symptoms (N=187) and fear-potentiated startle to a safety signal (N=135). Conclusions: Together, these data indicate that genetic variability in the CRP gene is associated with serum CRP level and PTSD symptom severity, including that of hyperarousal symptoms. Elevated CRP levels were also associated with exacerbated fear-related psychophysiology and PTSD symptom ratings and diagnosis. These findings suggest a potential mechanism by which an increased proinflammatory state may lead to heightened PTSD symptoms.
Thrombospondin-2 Is Essential for Myocardial Matrix Integrity
Authors: Blanche Schroen, Stephane Heymans, Umesh Sharma, W. Matthijs Blankesteijn, Saraswati Pokharel, Jack P.M. Cleutjens, J. Gordon Porter, Chris T.A. Evelo, Rudy Duisters, Rick E.W. van Leeuwen, Ben J.A. Janssen, Jacques J.M. Debets, Jos F.M. Smits, Mat J.A.P. Daemen, Harry J.G.M. Crijns, Paul Bornstein, Yigal M. Pinto
Journal: Circulation Research (2004)

Cardiac hypertrophy can lead to heart failure (HF), but it is unpredictable which hypertrophied myocardium will progress to HF. We surmised that apart from hypertrophy-related genes, failure-related genes are expressed before the onset of failure, permitting molecular prediction of HF. Hearts from hypertensive homozygous renin-overexpressing (Ren-2) rats that had progressed to early HF were compared by microarray analysis to Ren-2 rats that had remained compensated. To identify which HF-related genes preceded failure, cardiac biopsy specimens were taken during compensated hypertrophy and we then monitored whether the rat progressed to HF or remained compensated. Among 48 genes overexpressed in failing hearts, we focused on thrombospondin-2 (TSP2). TSP2 was selectively overexpressed only in biopsy specimens from rats that later progressed to HF. Moreover, expression of TSP2 was increased in human hypertrophied hearts with decreased (0.19+/-0.01) versus normal ejection fraction (0.11+/-0.03 [arbitrary units]; P<0.05). Angiotensin II induced fatal cardiac rupture in 70% of TSP2 knockout mice, with cardiac failure in the surviving mice; this was not seen in wild-type mice. In TSP2 knockout mice, angiotensin II increased matrix metalloproteinase (MMP)-2 and MMP-9 activity by 120% and 390% compared with wild-type mice (P<0.05). In conclusion, we identify TSP2 as a crucial regulator of the integrity of the cardiac matrix that is necessary for the myocardium to cope with increased loading and that may function by its regulation of MMP activity. This suggests that expression of TSP2 marks an early-stage molecular program that is activated uniquely in hypertrophied hearts that are prone to fail.