tbuckley/cabot-search huggingface dataset:
The diagnosis of Sézary syndrome on peripheral blood by flow cytometry requires the use of multiple markers
Authors: C.-D. Klemke, J. Brade, S. Weckesser, M.M. Sachse, N. Booken, M. Neumaier, S. Goerdt, T.C. Nebe
Journal: British Journal of Dermatology (2008)

Diagnosis of Sézary syndrome (SS)-defining blood involvement is hampered by the lack of Sézary cell-specific markers and nonspecific morphology of the tumour cells.To identify the most reliable and easy to use markers for the diagnosis of SS-defining blood involvement.We studied 17 patients with SS and 11 control patients. We used flow cytometry for the detection of T-cell antigens (CD3, CD4, CD7 and CD8), expression of the Sézary cell-associated marker CD158k and T-cell receptor (TCR)-Vbeta chain. Additionally, Sézary cells were identified by peripheral blood smear for lymphocytes with cerebriform nuclei.It was not possible to diagnose blood involvement in all patients with SS by a single marker or method, although none of the markers was increased in the control population. Sézary cells were detected by blood smears in 13 of 17 (76%), by flow cytometry by their CD4+ CD7- CD3(dim) phenotype (> 1000 cells microL(-1)) in 13 of 17 (76%) and by expression of CD158k in 11 of 17 (65%) patients with SS. A specific T-cell clone was identified by identical TCR-Vbeta chain expression in 12 of 17 (71%) patients with SS. The identification of Sézary cells in individual patients varied for the different markers investigated.The combination of identifying CD4+ CD7- CD3(dim) cells, TCR-Vbeta chain and CD158k expression allowed a definite identification of SS-defining blood involvement in every individual patient. All of these markers can be measured by flow cytometry which would avoid time-consuming analysis of blood smears. These markers would also be suitable to monitor tumour cell load during therapy.
The target cell nucleus is not required for cell-mediated granzyme- or Fas-based cytotoxicity.
Authors: H Nakajima, P Golstein, P A Henkart
Journal: The Journal of Experimental Medicine (1995)

The requirement for target cell nuclei in the two apoptotic death pathways used by cytotoxic lymphocytes was tested using model effector systems in which the granzyme and Fas pathways of target damage are isolated. Mast cell tumors expressing granzymes A and B in addition to cytolysin/perforin lysed tumor target cells about 10-fold more efficiently than comparable effector cells without granzymes. Enucleated cytoplast targets derived from these cells were also lysed with a similar 10-fold effect of granzymes. In contrast to cytoplasts, effector granzyme expression did not influence lysis of red cell targets. The Fas pathway was assessed using the selected cytotoxic T lymphocyte hybridoma subline d11S, which lysed target cells expressing Fas but not those lacking Fas. Similarly, cytoplasts derived from Fas+ but not Fas- cells were also readily lysed by these effector cells. Thus, neither the nucleus itself nor the characteristic apoptotic nuclear damage associated with the two major cell death pathways used by cytotoxic lymphocytes are required for cell death per se.
Effectiveness of a Computerized Insulin Order Template in General Medical Inpatients With Type 2 Diabetes
Authors: Deborah J. Wexler, Peter Shrader, Sean M. Burns, Enrico Cagliero
Journal: Diabetes Care (2010)

OBJECTIVE To determine whether an electronic order template for basal-bolus insulin ordering improves mean blood glucose in hospitalized general medical patients with hyperglycemia and type 2 diabetes. RESEARCH DESIGN AND METHODS We randomly assigned internal medicine resident teams on acute general medical floors to the use of an electronic insulin order template or usual insulin ordering. We measured diabetes care parameters for 1 month on all patients with type 2 diabetes and blood glucose &amp;lt;60 mg/dl or &amp;gt;180 mg/dl treated by these physicians. RESULTS Intervention group patients (n = 65) had mean glucose of 195 ± 66 mg/dl. Control group patients (n = 63) had mean glucose of 224 ± 57 mg/dl (P = 0.004). In the intervention group, there was no increase in hypoglycemia. CONCLUSIONS Access to a computer insulin order template was associated with improved mean glucose levels without increasing hypoglycemia in patients with type 2 diabetes.
Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients
Authors: Mark R. Rigby, Kristina M. Harris, Ashley Pinckney, Linda A. DiMeglio, Marc S. Rendell, Eric I. Felner, Jean M. Dostou, Stephen E. Gitelman, Kurt J. Griffin, Eva Tsalikian, Peter A. Gottlieb, Carla J. Greenbaum, Nicole A. Sherry, Wayne V. Moore, Roshanak Monzavi, Steven M. Willi, Philip Raskin, Lynette Keyes-Elstein, S. Alice Long, Sai Kanaparthi, Noha Lim, Deborah Phippard, Carol L. Soppe, Margret L. Fitzgibbon, James McNamara, Gerald T. Nepom, Mario R. Ehlers
Journal: Journal of Clinical Investigation (2015)

BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D.
Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation
Authors: S. A. Kasseckert, C. Schafer, A. Kluger, D. Gligorievski, J. Tillmann, K.-D. Schluter, T. Noll, H. Sauer, H. M. Piper, Y. Abdallah
Journal: Cardiovascular Research (2009)

Ischaemia–reperfusion provokes barrier failure of the coronary microvasculature, impeding functional recovery of the heart during reperfusion. The aim of the present study was to investigate whether the stimulation of cGMP signalling by activation of soluble guanylyl cyclase (sGC) can reduce reperfusion-induced endothelial intercellular gap formation and to determine whether this is due to an influence on endothelial cytosolic Ca2+ homeostasis during reperfusion. Experiments were performed with cultured coronary endothelial monolayers and isolated saline-perfused rat hearts. HMR1766 (1 µmol/L) or DEAnonoate (0.5 µmol/L) were used to activate sGC. After exposure to simulated ischaemic conditions, reperfusion of endothelial cells led to a pronounced increase in cytosolic calcium levels and intercellular gaps. Stimulation of cGMP signalling during reperfusion increased Ca2+ sequestration in the endoplasmic reticulum (ER) and attenuated the reperfusion-induced increase in cytosolic [Ca2+]. Phosphorylation of phospholamban was also increased, indicating a de-inhibition of the ER Ca2+ pump (SERCA). Reperfusion-induced intercellular gap formation was reduced. Reduction of myosin light chain phosphorylation indicated inactivation of the endothelial contractile machinery. Effects on cytsolic Ca2+ and gaps were abrogated by inhibition of cGMP-dependent protein kinase (PKG) with KT5823. In reperfused hearts, stimulation of cGMP signalling led to decreased oedema development. sGC/PKG activation during reperfusion reduces reperfusion-induced endothelial intercellular gap formation by attenuation of cytosolic calcium overload and reduction of contractile activation in endothelial cells. This mechanism protects the heart against reperfusion-induced oedema.
Whole-body 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) for accurate staging of Hodgkin’s disease
Authors: M. Bangerter, F. Moog, I. Buchmann, J. Kotzerke, M. Griesshammer, M. Hafner, K. Elsner, N. Frickhofen, S.N. Reske, L. Bergmann
Journal: Annals of Oncology (1998)
Trazodone increases arousal threshold in obstructive sleep apnoea
Authors: R. C. Heinzer, D. P. White, A. S. Jordan, Y. L. Lo, L. Dover, K. Stevenson, A. Malhotra
Journal: European Respiratory Journal (2008)

A low arousal threshold is believed to predispose to breathing instability during sleep. The present authors hypothesised that trazodone, a nonmyorelaxant sleep-promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnoea (OSA) patients. In total, nine OSA patients, mean+/-sd age 49+/-9 yrs, apnoea/hypopnoea index 52+/-32 events.h(-1), were studied on 2 nights, one with trazodone at 100 mg and one with a placebo, in a double blind randomised fashion. While receiving continuous positive airway pressure (CPAP), repeated arousals were induced: 1) by increasing inspired CO(2) and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CO(2 )tension (P(ET,CO(2))) was monitored with a nasal catheter. During trazodone nights, compared with placebo nights, the arousals occurred at a higher P(ET,CO(2)) level (mean+/-sd 7.30+/-0.57 versus 6.62+/-0.64 kPa (54.9+/-4.3 versus 49.8+/-4.8 mmHg), respectively). When arousals were triggered by increasing inspired CO(2) level, the maximal oesophageal pressure swing was greater (19.4+/-4.0 versus 13.1+/-4.9 cm H(2)O) and the oesophageal pressure nadir before the arousals was lower (-5.1+/-4.7 versus -0.38+/-4.2 cm H(2)O) with trazodone. When arousals were induced by stepwise CPAP drops, the maximal oesophageal pressure swings before the arousals did not differ. Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate higher CO(2) levels.
COOH-Terminal Truncated HBV X Protein Plays Key Role in Hepatocarcinogenesis
Authors: Ning-Fang Ma, Sze Hang Lau, Liang Hu, Dan Xie, Jun Wu, Jun Yang, Yi Wang, Meng-Chao Wu, Jackie Fung, Xueyan Bai, Chi-Hung Tzang, Li Fu, Mengsu Yang, Yan An Su, Xin-Yuan Guan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: X protein (HBx), a product of hepatitis B virus, has been closely associated with the development of hepatocellular carcinoma (HCC). Based on observations that the COOH-terminal truncated HBx was frequently detected in HCC, the aim of this study is to evaluate the function of COOH-terminal truncated HBx in hepatocarcinogenesis. Experimental Design: Expression pattern of HBx was analyzed by immunohistochemistry on tissue microarray containing 194 pairs of HCCs and their matched nontumor liver tissues. MIHA and HepG2 cells transfected with full-length (X2) and COOH-terminal truncated HBx (X1) were tested for their ability to grow in soft agar and form tumors in vivo. Proliferation and apoptosis were assessed using 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assays, respectively. To gain additional insight, the expression profile of HepG2-X2 and HepG2-X1 were compared using cDNA microarray. Results: COOH-terminal truncated HBx was frequently detected in HCCs (79.3%, n = 111), and our in vitro and in vivo studies showed that the truncated rather than the full-length HBx could effectively transform immortalized liver cell line MIHA. Interestingly, expression profiling revealed differential expression of key genes implicated in the control of cell cycle and apoptosis. Conclusions: These findings strongly suggest that the COOH-terminal truncated HBx plays a critical role in the HCC carcinogenesis via the activation of cell proliferation.
Repeatability of bronchial hyperresponsiveness to adenosine-5'-monophosphate (AMP) by a short dosimeter protocol
Authors: G De Meer
Journal: Thorax (2001)

<h3>BACKGROUND</h3> To study bronchial responsiveness to adenosine 5′-monophosphate (AMP) in population surveys, repeatability of a rapid dosimetric method with quadrupling doses was evaluated. <h3>METHODS</h3> Volunteers with symptoms of airway respiratory allergy or asthma were invited for AMP challenges on two occasions. After each dose the fall in forced expiratory volume in one second (FEV<sub>1</sub>) compared with the post-saline value was determined. The cumulative doses of AMP needed to cause a fall in FEV<sub>1</sub> of 20% (PD<sub>20</sub>), 15% (PD<sub>15</sub>), and 10% (PD<sub>10</sub>) were calculated. Agreement was evaluated by means of kappa values. After excluding systematic differences in PD values on two occasions (<i>t</i> test), repeatability of a single estimation of the chosen PD values was calculated and expressed in doubling doses (DD). <h3>RESULTS</h3> In 28 of 76 subjects a PD<sub>20</sub> was estimated on the two visits, in 29 subjects a PD<sub>15</sub> was estimated, and in 32 a PD<sub>10</sub>was obtained. Kappa values for a positive threshold were 0.89 for a cut off level for a 20% fall in FEV<sub>1</sub>, 0.78 for a 15% fall in FEV<sub>1</sub>, and 0.76 for a fall in FEV<sub>1</sub> of 10%. The PD values did not differ between the two visits and 95% repeatability of a single estimation was ±1.7 DD for PD<sub>20</sub>, ±2.2 DD for PD<sub>15</sub>, and ±2.4 DD for PD<sub>10</sub>. The quadrupling dose method reduced time by 40% in non-hyperresponsive subjects and no adverse effects were observed. <h3>CONCLUSION</h3> The short dosimeter protocol with quadrupling doses for AMP challenges is a rapid, reproducible tool for estimating bronchial responsiveness in population surveys.
Principles of Human Physiology
Authors: Ernest Henry Starling
Journal: BMJ (1946)

The success of Starling's Physiology, as shown by reaching a third edition in eight years, is to be explained by the author's high standing as experimenter and teacher, by the clearness of the statement and well chosen arrangement of the work, and these warrant its use by beginners. There is one curious feature, over 100 pages, or almost one-eleventh of the total space, is devoted to vision. Perhaps, the vagaries of the medical book trade are to blame for this; perhaps, lack of time to condense the material into space proportionate to that of other topics. In strong contrast to this large chapter, the ear and its associated organs are discussed in a few pages. Perhaps, Bárány's work was made too prominent by certain specialists during the war, but that seems all the greater reason why a clear and authoritative summary should be given. Readers of theArchives of Internal
Systematic Review and Meta-analysis of Ovarian Cancers: Estimation of Microsatellite-High Frequency and Characterization of Mismatch Repair Deficient Tumor Histology
Authors: Tuya Pal, Jenny Permuth-Wey, Ambuj Kumar, Thomas A. Sellers
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A meta-analytic approach was used to estimate the frequency of: (a) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and (b) various histologic subtypes of mismatch repair (MMR)-deficient epithelial ovarian cancers. Methods: A systematic search of the Medline electronic database was conducted to identify articles published between January 1, 1966, and December 31, 2007, that examined MMR deficiency in ovarian cancers. Data were extracted on the study population, sample size, MSI-H frequency, and histology of MMR-deficient ovarian tumors. Results: The pooled proportion of MSI-H ovarian cancers was 0.12 [95% confidence interval (CI), 0.08-0.17] from 18 studies with 977 cases. The proportion of histologic subtypes in the pooled analysis from 15 studies with 159 cases was serous at 0.32 (95% CI, 0.20-0.44), mucinous at 0.19 (95% CI, 0.12-0.27), endometrioid at 0.29 (95% CI, 0.22-0.36), clear cell at 0.18 (95% CI, 0.09-0.28), and mixed at 0.24 (95% CI, 0.07-0.47). There was significant heterogeneity between studies. Conclusions: The frequency of the MSI-H phenotype in unselected ovarian cancers approximates 12%. MMR-deficient ovarian cancers also seem to be characterized by an overrepresentation of nonserous histologic subtypes. Knowledge of histologic subtype may aid clinicians in identifying the relatively large proportion of ovarian cancers due to MMR defects; such knowledge has potential implications for medical management.
IFN-α–Stimulated Genes and Epstein-Barr Virus Gene Expression Distinguish WHO Type II and III Nasopharyngeal Carcinomas
Authors: D. Michiel Pegtel, Aravind Subramanian, David Meritt, Ching-Hwa Tsai, Tzung-Shiahn Sheen, Todd R. Golub, David A. Thorley-Lawson
Journal: Cancer Research (2007)

Abstract Nonkeratinizing nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr Virus (EBV) and divided into two subtypes (WHO types II and III) based on histology. We tested whether these subtypes can be distinguished at the molecular genetic level using an algorithm that analyzes sets of related genes (gene set enrichment analysis). We found that a class of IFN-stimulated genes (ISG), frequently associated with the antiviral response, was significantly activated in type III versus type II NPC. Consistent with this, replication of the endogenous EBV was suppressed in type III. A strong association was also seen with a subset of ISGs previously identified in systemic lupus erythematosus, another disease in which ‘normal’ EBV biology is deregulated, suggesting that this pattern of ISG expression may be linked to the increased EBV activity in both diseases. In contrast, unsupervised hierarchical clustering of the complete expression profiles failed to distinguish the two subsets. These results suggest that type II and III NPC have not originated from obviously distinct epithelial precursors; rather, the histologic differences may be a consequence of a differential antiviral response, involving IFNs, to chronic EBV infection. [Cancer Res 2007;67(2):474–81]
S-adenosylmethionine and Catechol-O-methyltransferase in Schizophrenia
Authors: STEVEN MATTHYSSE, ROSS J. BALDESSARINI
Journal: American Journal of Psychiatry (1972)

The authors examined the hypothesis of disordered transmethylation in schizophrenia by comparing S-adenosylmethionine (SAMe) concentration and cathechol-O-methyltransferase (COMT) activities in venous blood of schizophrenic and nonschizophrenic patients. While they did not find a difference in blood SAMe concentration between the groups, they did find a significant correlation between blood COMT activity and SAMe concentration. This suggests that some schizophrenics may methylate biogenic amines more actively than others.
Promotion of Incidence of Adenovirus Type 12 Transplantable Tumors by Carrageenan, a Specific Antimacrophage Agent2
Authors: Eva Lotzová, Ellen R. Richie
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Promotion of Incidence of Adenovirus Type 12 Transplantable Tumors by Carrageenan, a Specific Antimacrophage Agent Get access Eva Lotzová, Ph.D., Eva Lotzová, Ph.D. 4 4Address reprint requests to Dr. Lotzová at her present address: Department of Developmental Therapeutics, M. D. Anderson Hospital, The University of Texas System Cancer Center, Texas Medical Center, Houston, Tex. 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ellen R. Richie, Ph.D. Ellen R. Richie, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 4, April 1977, Pages 1171–1172, https://doi.org/10.1093/jnci/58.4.1171 Published: 01 April 1977 Article history Received: 29 July 1976 Accepted: 14 October 1976 Published: 01 April 1977
Effect of a Successful Intensive Lifestyle Program on Insulin Sensitivity and Glucose Tolerance in Obese Youth
Authors: Melissa Shaw, Mary Savoye, Anna Cali, James Dziura, William V. Tamborlane, Sonia Caprio
Journal: Diabetes Care (2008)

To evaluate the impact on glucose metabolism of a lifestyle program (the Yale Bright Bodies Program) for obese children.Thirteen Bright Bodies and ten clinic-care control subjects who were part of a large randomized clinical trial had 75-g oral glucose tolerance tests at the beginning and end of the 12-month study.Bright Bodies subjects had significantly greater decreases in weight, BMI, and body fat than clinic-care subjects, and the Bright Body subjects' changes in body composition were accompanied by marked improvements in insulin sensitivity (P = 0.009) and glucose tolerance (P = 0.04).An intensive lifestyle program that successfully reduces body weight and body fat can markedly improve insulin sensitivity and glucose metabolism in obese youth.
Inhibitory effects of Helicobacter pylori infection on murine autoimmune gastritis
Authors: M Ohana
Journal: Gut (2003)

Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the effects of H pylori infection on the pathophysiology of AIG in mice.BALB/c nu/nu mice (n=40) with or without H pylori infection received splenocytes from neonatally thymectomised mice to induce AIG. Half of the mice were orally infected with H pylori prior to AIG induction. Histological findings, and local and systemic immune responses were serially evaluated.Two and six months after transfer, parietal cells in uninfected mice were depleted while those in infected mice were well preserved. The degree of gland atrophy (p<0.01), hyperplasia (p<0.01), gastric pH (p<0.05), and serum gastrin levels of infected mice were significantly lower than those of uninfected mice. Serum antiparietal cell antibody levels gradually decreased in infected mice, and were significantly lower than those of uninfected mice at six months (p<0.05). Real time polymerase chain reaction studies revealed significantly higher interleukin 4 (p<0.05) and transforming growth factor beta (p<0.05) gene expression in the gastric mucosa in infected mice than in uninfected mice at both two and six months after AIG induction.H pylori infection inhibited the development of AIG in mice. Th2-type immune responses and transforming growth factor beta in the gastric microenvironment might be involved in the inhibitory effects of H pylori infection on the development of AIG, in which Th1-type responses have an important role.
Interlesion Dependence of the Risk for Restenosis in Patients With Coronary Stent Placement in Multiple Lesions
Authors: Adnan Kastrati, Albert Schömig, Shpend Elezi, Helmut Schühlen, Manfred Wilhelm, Josef Dirschinger
Journal: Circulation (1998)

Little is known about the behavior with regard to restenosis of multiple lesions within the same patient treated with intracoronary stenting. Our objective was to test the hypothesis that there is an intrapatient dependence of restenosis between lesions.Quantitative analysis was carried out on angiograms obtained before, immediately after, and at 6 months after coronary stent placement in 1734 lesions in 1244 patients. We used a specialized logistic regression that not only accounts for intraclass correlation but also quantifies it in the form of odds ratio (OR) as the change in risk of a lesion to develop restenosis if another companion lesion had restenosis. The model was based on 23 patient- and lesion-related variables with binary restenosis (diameter stenosis > or =50%) as end point. The overall restenosis rate was 27.5%: 24.4% for single-lesion, 28.6% for double-lesion, and 33.8% for > or =3-lesion interventions. After adjustment for the influence of significant factors (hypercholesterolemia, systemic arterial hypertension, diabetes mellitus, previous PTCA, ostial lesion, location in left anterior descending coronary artery, number of stents placed, vessel size, stenosis severity, balloon-to-vessel ratio, and final result), the analysis found a significant intrapatient correlation, OR 2.5 (1.8 to 3.6). This means that in patients with multilesion interventions, the risk of a lesion to develop restenosis is 2.5 times higher if a companion lesion has restenosis, independently of the presence or absence of analyzed patient risk factors (eg, diabetes).This study demonstrates that there is a dependence of restenosis between coronary lesions in patients who undergo a multilesion intervention. The likelihood of restenosis for a lesion is higher when another companion lesion has also developed restenosis. Other, as yet unidentified patient factors may be the source of this intrapatient correlation of restenosis.