tbuckley/cabot-search huggingface dataset:
Worming away from allergies
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

NFATc1 self-promotes to build boneSelf-promotion is the way to get ahead during bone development, according to Asagiri and colleagues.They show on page 1261 that the inducible transcription factor NFATc1 must turn on its own expression for bone-resorbing osteoclasts to form.NFATc1 drives osteoclast-specific gene expression and is essential for the development of these cells in vitro.But whether NFATc1 is required in vivo was unknown, as deletion of the NFATc1 gene is lethal in mice.Another open questions was whether NFATc2-NFATc1's closest relative-can drive osteoclast formation in the absence of NFATc1.Asagiri and colleagues now show that NFATc1 is indeed essential for osteoclast formation in vivo, as only NFATc1-expressing stem cells rescued osteoclast development when transferred into osteoclast-deficient mice.NFATc1-deficient stem cells failed at this task, despite having normal expression of NFATc2.Transcriptional regulation explained why only NFATc1 could do the job.Stimulation of bone marrow cells with the osteoclast growth factor RANKL (receptor activator of NF-B ligand) caused the NFATc2 protein in the cellalong with RANKL-induced NF-B proteins-to pile onto the NFATc1 promoter at the expense of the NFATc2 promoter.This binding induced the expression of NFATc1, which then bound back to its own promoter, thus amplifying NFATc1 production.The NFATc1 promoter also hoarded histone acetylases, whose DNA modifications facilitate transcription.The authors are now analyzing the chromatin structure of the two promoters, which might help explain why these proteins avoid the NFATc2 promoter.
Glyburide Decreases Insulin Requirement, Increases (β-Cell Response to Mixed Meal, and Does Not Affect Insulin Sensitivity: Effects of Short- and Long-Term Combined Treatment in Secondary Failure to Sulfonylurea
Authors: Mark Gutniak, Sven-Gunnar Karlander, Suad Efendić
Journal: Diabetes Care (1987)

In 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea, a double-blind randomized study was performed comparing two regimes: insulin plus placebo (IP) and insulin plus glyburide (IG). The protocol included two hospitalization periods (days 1–18 and 78–85) and follow-up at the outpatient clinic for 325 days. The metabolic control was kept as tight as possible. The subjects underwent normoglycemic clamp studies and meal tests with determination of insulin, C-peptide, glucagon, somatostatin, and gastric inhibitory polypeptide in plasma. On IG, they demonstrated marked and long-lasting improvement of metabolic control: HbA1c decreased from 11.1 ± 0.3% on day 3 to 8.3 ± 0.4% (P &amp;lt; .001) on day 78 and 9.1 ± 0.5% (P &amp;lt; .001) on day 325. In subjects on IP, the corresponding values were 10.3 ± 0.5, 8.4 ± 0.4 (P &amp;lt; .001), and 8.9 ± 0.5% (P &amp;lt; .05). Body weight increased by 6.0 ± 1.5 kg (P &amp;lt; .005) on IG and 2.9 ± 2.1 kg (NS) on IP. The daily insulin requirement decreased on IG from 62.5 ± 12.9 U/day on day 7 to 33.5 ± 8.8 U/ day on day 83 and 34.6 ± 8.9 U/day on day 325. On IP the insulin requirement was almost constant: 62.0 ± 10.7 U/day on day 7, 55.5 ± 7.7 U/day on day 83, and 54.7 ± 7.9 U/day on day 325. Insulin sensitivity measured with the hyperinsulinemic clamp (plasma insulin ≈130 μU/ml) was similar on IP and IG at the initiation of the study and was unchanged on days 18 and 85. A key observation of this study, although the mechanism is unclear, is that isoglycemic-meal-related insulin requirement was diminished by insulin treatment, indicating improvement of meal-related insulin sensitivity. Glyburide increased basal and meal- but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release. We conclude that in NIDDM, IG regime promptly and continuously decreased insulin requirement and improved metabolic control. This effect is, at least during the first 3 mo, mainly due to enhanced insulin secretion. IG and IP treatment had no effect on insulin sensitivity during hyperinsulinemic-normoglycemic clamp, whereas meal-related insulin sensitivity was augmented.
ACTH-Secreting Pheochromocytoma with False-Negative ACTH Immunohistochemistry
Authors: Maria Francesca Cassarino, Alberto Giacinto Ambrogio, Luca Pagliardini, Martina De Martin, Valeria Barresi, Francesco Cavagnini, Francesca Pecori Giraldi
Journal: Endocrine Pathology (2012)
A Critical Temporal Window for Selectin-dependent CD4+ Lymphocyte Homing and Initiation of Late-Phase Inflammation in Contact Sensitivity
Authors: John M. Hwang, Jun Yamanouchi, Pere Santamaria, Paul Kubes
Journal: The Journal of Experimental Medicine (2004)

Contact sensitivity (CS) is an inflammatory disorder characterized by early and late phases of leukocyte recruitment. We used a noninvasive intravital microscopy technique allowing for the direct visualization of leukocyte rolling and adhesion on blood vessel endothelium. By blocking specific adhesion molecules, we elucidated the molecular mechanisms mediating early leukocyte recruitment to be E- and P-selectin and demonstrated that leukocyte recruitment in the late phase had a different adhesive profile (mainly α4-integrin). Complete blockade of E- and P-selectin within the first 2 h of leukocyte–endothelial cell interactions (but not later) eliminated selectin-independent leukocyte recruitment at 24 h. Despite the predominance of neutrophils in the early phase, specific elimination of CD4+ lymphocytes in the early phase eliminated the late response. CD4+ lymphocytes homed to skin via E- and P-selectin within the early phase and induced the late phase response. Addition of these same CD4+ lymphocytes 2 h after antigen challenge was too late for these cells to home to the skin and induce late phase responses. Our data clearly demonstrate that the antigen-challenged microenvironment is only accessible to CD4+ lymphocytes for the first 2 h, and that this process is essential for the subsequent recruitment of other leukocyte populations in late phase responses.
Limbic Hyperreactivity in Bipolar II Disorder
Authors: Gregory S. Berns, Megan Martin, Shawnette M. Proper
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors' goal was to determine whether patients with bipolar II disorder had altered regional brain responses to novel motor sequences. METHOD: Regional cerebral blood flow was measured with positron emission tomography in 13 patients with bipolar II disorder and 14 healthy comparison subjects. Participants performed a serial reaction time task in which they were visually cued to press one of four buttons at a time. The order of button presses was determined by a complex sequence that was changed in the latter half of the study. RESULTS: In the comparison subjects a spatial attention circuit in the superior parietal lobe and supplementary motor area was activated in response to the introduction of the new sequence. Patients did not display this activation pattern; instead, a widespread limbic network was activated in response to the new sequence. CONCLUSIONS: The attentional resources of patients with bipolar II disorder are not reallocated when they are confronted with a nonemotional motor task; rather, their performance is altered through activation of limbic circuitry.
Advanced Glycation End Products and Endothelial Dysfunction in Type 2 Diabetes
Authors: Kathryn C.B. Tan, Wing-Sun Chow, Victor H.G. Ai, Christine Metz, Richard Bucala, Karen S.L. Lam
Journal: Diabetes Care (2002)

OBJECTIVE—Data from experimental studies have suggested that the increased formation of advanced glycation end products (AGEs) is one of the causes of endothelial dysfunction in diabetes. This study was performed to investigate whether changes in endothelium-dependent vasodilation, a marker of endothelial function, were related to serum AGEs concentrations in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—For this study, 170 patients with type 2 diabetes and 83 healthy nondiabetic control subjects of similar age were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay. Endothelium-dependent and -independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. RESULTS—Serum AGEs were increased in diabetic patients compared with control subjects (4.6 ± 0.7 vs. 3.1 ± 0.8 unit/ml; P &amp;lt; 0.01), and both endothelium-dependent (5.1 ± 2.5 vs. 9.1 ± 4.1%; P &amp;lt; 0.01) and endothelium-independent vasodilation (13.2 ± 4.6 vs. 16.4 ± 5.5%; P &amp;lt; 0.01) were impaired. On univariate analysis of all subjects, serum AGEs correlated with endothelium-dependent vasodilation (r = −0.51, P &amp;lt; 0.01); a weaker association was found with endothelium-independent vasodilation (r = −0.24, P &amp;lt; 0.01). On multiple regression analyses including age, sex, smoking status, and plasma lipids, only serum AGEs remained a significant independent determinant of endothelium-dependent vasodilation (r2 = 0.34, P &amp;lt; 0.01). CONCLUSIONS—Increased serum concentrations of AGEs in patients with type 2 diabetes is associated with endothelial dysfunction, independent of other cardiovascular risk factors. Further studies to determine whether treatment targeting AGEs will lead to an amelioration of endothelial dysfunction are warranted.
Relationship between Erythropoietin and Chronic Heart Failure in Patients on Chronic Hemodialysis
Authors: Junko Kumagai, Noriaki Yorioka, Hideki Kawanishi, Misaki Moriishi, Yutaka Komiya, Yukiteru Asakimori, Naoko Takahashi, Shinichiro Tsuchiya
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In the present study, the relationship between the blood erythropoietin level and cardiac function was investigated in 15 patients on chronic hemodialysis who developed chronic heart failure. Another 45 patients without cardiac dysfunction were selected as a control group that was matched for gender, age, and the duration of dialysis. The erythropoietin level was 256.3 ± 481.8 mU/ml in the heart failure group, which was significantly higher than that in the control group (17.0 ± 10.0 mU/ml, P <0.01). Eight of the 15 patients in the heart failure group maintained a hematocrit of more than 30% without receiving recombinant human erythropoietin therapy, whereas 29 of the 45 patients in the control group required erythropoietin. In the heart failure group, the erythropoietin level was significantly correlated with the levels of atrial natriuretic peptide and brain natriuretic peptide (P < 0.01). These results suggest that heart failure can increase the erythropoietin level in proportion to the severity of cardiac dysfunction, even in patients on long-term dialysis.
The Role of Assisted Circulation in Cardiac Resuscitation
Authors: John H. Kennedy
Journal: JAMA (1966)

Heart-lung machines now used for cardiac surgery should be considered for use as an extended form of cardiopulmonary resuscitation in selected patients. Of eight patients in whom cardiac arrest had proved refractory to open- or closed-heart cardiac massage, all but one were resuscitated and survived hours to days. One patient recovered completely.
Short Communication: Angiotensin II Type 1 Receptor–Mediated Upregulation of Calcineurin Activity Underlies Impairment of Cardioprotective Signaling in Diabetic Hearts
Authors: Hiroyuki Hotta, Tetsuji Miura, Takayuki Miki, Nobuhiko Togashi, Takuto Maeda, Seok Jai Kim, Masaya Tanno, Toshiyuki Yano, Atsushi Kuno, Takahito Itoh, Takahiro Satoh, Yoshiaki Terashima, Satoko Ishikawa, Kazuaki Shimamoto
Journal: Circulation Research (2009)

The diabetic heart is resistant to ischemic preconditioning because of diabetes-associated impairment of phosphatidylinositol 3-kinase (PI3K)-Akt signaling. The mechanism by which PI3K-Akt signaling is impaired by diabetes remains unclear.Here, we examined the hypothesis that phosphorylation of Jak2 upstream of PI3K is impaired in diabetic hearts by an angiotensin II type 1 (AT1) receptor-mediated mechanism.Infarct size (as percentage of risk area) after 20-minute ischemia/2-hour reperfusion was larger in a rat model of type 2 diabetes (Otsuka-Long-Evans-Tokushima fatty [OLETF] rat) than in its control (Long-Evans-Tokushima-Otsuka [LETO] rat) (60.4+/-1.6% versus 48.4+/-1.3%). Activation of Jak2-mediated signaling by erythropoietin or DADLE ([D-Ala2, D-Leu5]-enkephalin acetate), a delta-opioid receptor agonist, limited infarct size in LETO rats (27.7+/-3.4% and 24.8+/-5.0%) but not in OLETF rats (53.9+/-5.3% and 55.0+/-2.2%). Blockade of the AT1 receptor by valsartan or losartan for 2 weeks restored the myocardial response of OLETF rats to erythropoietin-induced infarct size limitation (39.4+/-4.9% and 31.2+/-7.5). In OLETF rats, erythropoietin failed to phosphorylate both Jak2 and Akt, and calcineurin activity was significantly higher than in LETO rats. Two-week treatment with valsartan normalized calcineurin activity in OLETF rats and restored the response of Jak2 to erythropoietin. This effect of AT1 receptor blockade was mimicked by inhibition of calcineurin by FK506.These results suggest that the diabetic heart is refractory to protection by Jak2-activating ligands because of AT1 receptor-mediated upregulation of calcineurin activity.
Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer
Authors: Karyn B. Stitzenberg, Hanna K. Sanoff, Dolly C. Penn, Michael O. Meyers, Joel E. Tepper
Journal: Journal of Clinical Oncology (2013)

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer.All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment.LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy.Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.
It's a Knockout!
Authors: Anna V Anagnostopoulos, Robert B Scharpf
Journal: Trends in Genetics (1998)

Abstract  `It's a Knockout!' provides an update of some of the latest mouse knockouts in TBASE (Refs [1, 2]). The column provides a concise phenotypic profile of novel mutants, and renders their complete characterization directly accessible to Web users via unique and unchanging accession numbers (TG-nnn-nn-nnn). Where possible, interesting knockouts will be grouped according to gene families, application or phenotypic similarities.
Effects of auranofin and myochrysine on intestinal transport and morphology in the rat.
Authors: H V Ammon, S A Fowle, J A Cunningham, R A Komorowski, R F Loeffler
Journal: Gut (1987)

Auranofin (SKF-D 39162) is an oral gold preparation for the treatment of rheumatoid arthritis. One of its major side effects is diarrhoea. To determine one possible mechanism for this we compared the effects of auranofin and myochrysine on intestinal water and solute transport in the rat. Jejunal perfusion with 2 mM auranofin (n = 5) induced fluid and electrolyte secretion and inhibited glucose absorption (p less than 0.01). Auranofin (0.2 mM) induced fluid secretion in the jejunum (n = 5; p less than 0.01) and colon (n = 6; p less than 0.01). In contrast, 2 mM myochrysine enhanced jejunal water and electrolyte absorption (n = 6; p less than 0.02). Both compounds enhanced absorption of mannitol (p less than 0.01). Perfusion of 0.2 mM auranofin for two hours had no significant effect on mucosal c-AMP levels (n = 4). After perfusion for two hours with 2 mM auranofin the jejunal mucosa showed severe injury by light and scanning electronmicroscopy while myochrysine had no apparent effect. The damage after perfusion with 0.2 mM auranofin for two hours was less severe. Auranofin was more rapidly absorbed than myochrysine (p less than 0.05). These effects provide an explanation for the diarrhoea associated with auranofin therapy.
Norepinephrine Metabolites as Biochemical Criteria for Classifying Depressive Disorders and Predicting Responses to Treatment: Preliminary Findings
Authors: JOSEPH J. SCHILDKRAUT
Journal: American Journal of Psychiatry (1973)

Preliminary findings suggest that levels of norepinephrine metabolites, particularly 3-methoxy-4-hydroxyphenylglycol (MHPG), excreted in urine may provide biochemical criteria for classifying at least some types of depressive disorders and possibly also for predicting the differential responses to treatment with various tricyclic antidepressant drugs.
E2F1 Overexpression Correlates with Thymidylate Synthase and Survivin Gene Expressions and Tumor Proliferation in Non–Small-Cell Lung Cancer
Authors: Cheng-long Huang, Dage Liu, Jun Nakano, Hiroyasu Yokomise, Masaki Ueno, Kyuichi Kadota, Hiromi Wada
Journal: Clinical Cancer Research (2007)

We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase (TS) and Survivin, in case of non-small-cell lung cancer (NSCLC).One hundred twenty-seven cases of resected NSCLC were analyzed. Quantitative reverse transcription-PCR was done to evaluate the gene expression of E2F1, TS, and Survivin. Immunohistochemistry was done to investigate the protein expression of E2F1, TS, and Survivin. The Ki-67 proliferation index and the apoptotic index using the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling method were also evaluated.E2F1 gene expression significantly correlated with the Ki-67 proliferation index (r = 0.487; P < 0.0001), although no correlation was observed between E2F1 gene expression and the apoptotic index. With regard to E2F1 target genes, E2F1 gene expression significantly correlated with TS gene expression (r = 0.709; P < 0.0001) and Survivin gene expression (r = 0.403; P < 0.0001). The overall survival rate was significantly lower in patients with high-E2F1 tumors than in those with low-E2F1 tumors (P = 0.0027), especially among patients with stage II to III NSCLCs (P = 0.0188). A Cox regression analysis showed that the E2F1 status was a significant prognostic factor for NSCLC patients (hazard ratio, 2.052; P = 0.0261).The present study revealed that E2F1 gene expression correlates with TS and Survivin gene expressions and tumor proliferation. During the progression of NSCLC, E2F1 overexpression could produce more aggressive tumors with a high proliferation rate and chemoresistance.
Hereditary defect of hepatobiliary cysteinyl leukotriene elimination in mutant rats with defective hepatic anion excretion
Authors: Michael Huber, Albrecht Guhlmann, Peter L. M. Jansen, Dietrich Keppler
Journal: Hepatology (1987)

Hepatobiliary and renal elimination of cysteinyl leu-kotrienes were investigated in a mutant rat strain with a hereditary defect in the hepatobiliary excretion of conjugated bilirubin, dibromosulfophthalein and oua-bain. After intravenous injection of [3H]leukotriene C4, the initial half-life of radioactivity circulating in blood was 79 ± 15 sec (S.D.) in transport mutant rats as compared to 31 ± 6 sec (S.D.) in normal Wistar rats. The intrahepatic leukotriene radioactivity was increased 5-fold after 1 hr in mutant rats, while the biliary elimination of [3H]Ieukotrienes was reduced to 1.8% of control. In normal rats, 77 ± 7% (S.D.) of the administered leukotriene radioactivity were recovered in bile within 1 hr. The total recovery of radioactivity from bile, urine, liver, intestine, stomach, kidneys, muscular system and blood 1 hr after intravenous [3H]leukotriene C4 was 89 ± 6% (S.D.) in normal rats and 46 ± 4% (S.D.) in transport mutants. Enterohepatic circulation was studied after intraduodenal administration of N-acetyl-[3H]leukotriene E4, a major cysteinyl leukotriene metabolite in rat bile. In transport mutants, hepatobiliary elimination of the intestinally absorbed [3H]leukotriene was reduced to 5%, whereas urinary excretion was not significantly affected. [3H]Leukotriene metabolites in bile, liver and urine were separated by reversed-phase high-performance liquid chromatography. The proportion of N-acetyl-[3H]leukotriene E4 relative to polar leukotriene metabolites was higher in the bile of transport mutants as compared to control Wistar rats when analyzed within 30 to 60 min after intravenous injection of [3H]leukotriene C4. Our results indicate that the cysteinyl leukotrienes are physiological substrates of the can-alicular transport system for organic anions such as dibromosulfophthalein. The transport mutant rats serve to characterize the hepatobiliary excretion system for cysteinyl leukotrienes.
Mind – your head!
Authors: R. P. Ingvaldsen, H. T. A. Whiting
Journal: Behavioral and Brain Sciences (1995)

Abstract Gray takes an information-processing paradigm as his departure point, invoking a comparator as part of the system. He concludes that consciousness is to be found “in” the comparator but is unable to point to how the comparison takes place. Thus, the comparator turns out not to be an entity arising out of brain research per se, but out of the logic of the paradigm. In this way, Gray both reinvents dualism and remains trapped in the language game of his own model – ending up dealing with the unknowable.
Response to "Reply to [18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma" by Hutterer et al.
Authors: M. Hutterer, M. Nowosielski, D. Putzer, C. l. Fougere, I. J. Virgolini, A. H. Jacobs,, G. Stockhammer
Journal: Neuro-Oncology (2013)

infiltrating zone of gliomas.
In vitro absorption of 1-chloro 2,4-dinitrobenzene (DNCB) through human, hooded rat and mouse epidermis
Authors: R.C. SCOTT, M.A. THOMPSON, R.J. WARD, J. RAMSEY, C. RHODES
Journal: British Journal of Dermatology (1986)

Journal Article In vitro absorption of 1‐chloro 2,4‐dinitrobenzene (DNCB) through human, hooded rat and mouse epidermis R.C. SCOTT, R.C. SCOTT Central Toxicology Laboratory, Imperial Chemical Industries Plc, Alderley Park, Macclesfield, Cheshire SK10 4TJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.A. THOMPSON, M.A. THOMPSON Central Toxicology Laboratory, Imperial Chemical Industries Plc, Alderley Park, Macclesfield, Cheshire SK10 4TJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.J. WARD, R.J. WARD Central Toxicology Laboratory, Imperial Chemical Industries Plc, Alderley Park, Macclesfield, Cheshire SK10 4TJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. RAMSEY, J. RAMSEY Central Toxicology Laboratory, Imperial Chemical Industries Plc, Alderley Park, Macclesfield, Cheshire SK10 4TJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar C. RHODES C. RHODES Central Toxicology Laboratory, Imperial Chemical Industries Plc, Alderley Park, Macclesfield, Cheshire SK10 4TJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s31, 1 August 1986, Pages 47–48, https://doi.org/10.1111/j.1365-2133.1986.tb02108.x Published: 01 August 1986