tbuckley/cabot-search huggingface dataset:
Phenomenology of Mania: Evidence for Distinct Depressed, Dysphoric, and Euphoric Presentations
Authors: Steven C. Dilsaver, Y. Richard Chen, Arif M. Shoaib, Alan C. Swann
Journal: American Journal of Psychiatry (1999)

A substantial number of manic episodes include conspicuous depressive symptoms. Manic episodes have been clinically classified a posteriori using preset criteria. The aim of this study was to investigate the possibility that there might be a natural division of manic episodes into clinical types.One hundred and five inpatients met Research Diagnostic Criteria and DSM-III-R criteria for manic episodes and were rated before institution of pharmacological treatment. The authors conducted a factor analysis of 37 behavior rating items from the Schedule for Affective Disorders and Schizophrenia. The resulting factors were used as independent variables in a cluster analysis of the patients.This analysis revealed four factors corresponding to manic activation, depressed state, sleep disturbance, and irritability/paranoia. Cluster analysis separated the patients into two groups. One included patients with major depressive disorder and mania. Blind, a priori clinical classification into classic and mixed mania (mania plus depression) showed that all of the patients in the depressed cluster, and about 40% of those in the nondepressed cluster, were in a mixed state according to clinical criteria. Comparison of the clinically mixed and nonmixed patients in the nondepressed cluster revealed that the mixed patients in that cluster had higher scores for items related to anger, worry, dysphoria, and irritability.These data suggest that manic episodes can be naturalistically classified as classic (predominately euphoric), dysphoric, or depressed.
Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis
Authors: Assieh Saadatpour, Guoji Guo, Stuart H Orkin, Guo-Cheng Yuan
Journal: Genome biology (2014)

A fundamental challenge for cancer therapy is that each tumor contains a highly heterogeneous cell population whose structure and mechanistic underpinnings remain incompletely understood. Recent advances in single-cell gene expression profiling have created new possibilities to characterize this heterogeneity and to dissect the potential intra-cancer cellular hierarchy. Here, we apply single-cell analysis to systematically characterize the heterogeneity within leukemic cells using the MLL-AF9 driven mouse model of acute myeloid leukemia. We start with fluorescence-activated cell sorting analysis with seven surface markers, and extend by using a multiplexing quantitative polymerase chain reaction approach to assay the transcriptional profile of a panel of 175 carefully selected genes in leukemic cells at the single-cell level. By employing a set of computational tools we find striking heterogeneity within leukemic cells. Mapping to the normal hematopoietic cellular hierarchy identifies two distinct subtypes of leukemic cells; one similar to granulocyte/monocyte progenitors and the other to macrophage and dendritic cells. Further functional experiments suggest that these subtypes differ in proliferation rates and clonal phenotypes. Finally, co-expression network analysis reveals similarities as well as organizational differences between leukemia and normal granulocyte/monocyte progenitor networks. Overall, our single-cell analysis pinpoints previously uncharacterized heterogeneity within leukemic cells and provides new insights into the molecular signatures of acute myeloid leukemia.
On widening the explanatory gap
Authors: A. H. C. van der Heijden, P. T. W. Hudson, A. G. Kurvink
Journal: Behavioral and Brain Sciences (1997)

The explanatory gap refers to the lack of concepts for understanding “how it is that . . . a state of consciousness comes about as a result of irritating nervous tissue.” By assuming that there are colours in the outside world, Block needlessly widens this gap and Lycan and Kitcher simply fail to see the gap. When such assumptions are abandoned, an unnecessary and incomprehensible constraint disappears. It then becomes clear that the brain can use its own neural language for representing aspects of the outside world. While this may not close the gap, it becomes clearer where we need new concepts.
Demonstration of bronchial eosinophil activity in seasonal allergic rhinitis by induced plasma exudation combined with induced sputum
Authors: L. Greiff, M. Andersson, C. Svensson, M. Linden, P. Wollmer, C. G A Persson
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Patients with seasonal allergic rhinitis may develop bronchial hyperresponsiveness during the active disease period. Eosinophil activation may occur in the bronchial mucosa and may be reflected by increased sputum levels of eosinophil cationic protein (ECP), especially when ECP binding proteins such as α<sub>2</sub>-macroglobulin pass through the lamina propria and across the epithelium into the airway lumen. A study was therefore undertaken to determine histamine airway responsiveness (FEV<sub>1</sub>) and bronchovascular responsiveness (exudation of α<sub>2</sub>-macroglobulin) to histamine in subjects with seasonal allergic rhinitis, and to explore whether sputum ECP levels are increased by the use of induced exudation followed by induced sputum. <h3>METHOD</h3> Eleven patients with seasonal allergic rhinitis were examined before and during a birch pollen season. Sputum was induced by inhalation of 4.5% saline twice before and twice during the pollen season. Histamine inhalations were given before the second of each pair of sputum inductions at increasing concentrations until FEV<sub>1</sub> was reduced by 20%. Sputum levels of α<sub>2</sub>-macroglobulin and ECP were determined as indices of bronchial exudation of plasma and activation of bronchial eosinophils, respectively. <h3>RESULTS</h3> Bronchomotor responsiveness increased during the pollen season (median difference in the reduction of FEV<sub>1</sub> 9% (95% confidence interval (CI) –3 to 26)) but histamine induced exudation of plasma was not increased. Baseline sputum levels of α<sub>2</sub>-macroglobulin and ECP did not increase. Histamine induced exudation of α<sub>2</sub>-macroglobulin was associated with increased sputum levels of ECP exclusively during the pollen season (median difference 8.2 ng/ml (95% CI 0.4 to 562.0)). <h3>CONCLUSION</h3> Bronchial hyperresponsiveness in seasonal allergic rhinitis may not be associated with bronchovascular exudative hyperresponsiveness. Sputum levels of ECP were increased only during the season, and only after induced exudation (potentially moving ECP to the mucosal surface). It is suggested that the combined method of induced exudation and induced sputum may significantly improve the yield of some markers of inflammation in sputum samples.
PROTECTIVE ANTIBODIES IN THE SERUM OF SYPHILITIC RABBITS
Authors: Thomas B. Turner
Journal: The Journal of Experimental Medicine (1939)

1. When an emulsion containing virulent Treponema pallidum is added to serum from normal rabbits and from untreated immune syphilitic rabbits that have been infected with a homologous strain of T. pallidum the mixture incubated at 37 degrees C., and injected intracutaneously into normal rabbits, typical syphilitic lesions commonly develop at the sites of inoculation of the normal serum-spirochete mixture, while at the sites of inoculation of immune serum-spirochete mixtures usually either no lesion develops or else the incubation period of the resulting lesions is shorter and the lesions remain smaller than those produced by normal serum-spirochete mixtures. 2. In a series of preliminary experiments, of 56 areas inoculated with serum-spirochete mixtures, in 42 the suppressive action of the syphilitic serum was manifest, in 10 areas questionable evidence of protection was noted, and in 4 areas there was no evidence that the syphilitic serum had exerted a suppressive or protective action. 3. The protective action of syphilitic serum seems to have been lessened by heating to 56 degrees C. 4. The results of the protection test in three other series of experiments were as follows: (a) Of 12 areas in 6 rabbits inoculated with normal serum-spirochete mixtures typical syphilitic lesions developed, while in the same number of areas inoculated with immune serum-spirochete mixtures there was complete or partial suppression of lesions in all. (b) Of 45 areas inoculated with serum from 10 different immune syphilitic rabbits, definite evidence of protection was observed in 37, questionable evidence in 5, and no evidence of protection in 3. (c) Of 8 areas in 4 rabbits inoculated with immune serum-spirochete mixtures no lesions developed during the period of observation, while of 8 areas in the same rabbits inoculated with one of two normal serum-spirochete mixtures typical syphilitic lesions developed in each.
How Notch heals a broken heart
Authors: Mitch Leslie
Journal: The Journal of Experimental Medicine (2008)

The Notch pathway helps a developing heart get into shape. Croquelois et al. reveal on page 3173 that the pathway also helps a damaged heart reshape itself and keep pumping.






Figure 1

Notch1's absence increases the number of suicidal cells (green) in the stressed heart.




Weakened by a heart attack or the protracted stress of hypertension, the heart rebuilds itself as it struggles to maintain blood flow. To provide more pumping power, cardiomyocytes swell. Some studies suggest that heart stem cells begin proliferating to replace lost cardiomyocytes. Because the Notch pathway helps control self-renewal by other organs, Croquelois et al. thought it might also have a hand in heart remodeling.

When Notch1 was absent, they found, mice with stressed hearts showed signs of over-exuberant repair including thicker ventricular walls, increased fibrosis, and more of the telltale proteins fashioned by swollen cardiomyocytes. The mice and their heart muscle cells also had a higher-than-normal death rate. Loss of Notch also spurred more heart stem cells to differentiate. Notch might allow the heart to conserve these cells.

The Notch pathway triggers stem cell proliferation in skeletal muscle, and the pathway short-circuits as we age. The researchers say that it's possible the same deterioration occurs in the older heart, explaining why elderly people are more vulnerable to heart failure.
A Novel Founder CHEK2 Mutation is Associated with Increased Prostate Cancer Risk
Authors: Cezary Cybulski, Tomasz Huzarski, Bohdan Górski, Bartłomiej Masojć, Marek Mierzejewski, Tadeusz Dębniak, Bartłomiej Gliniewicz, Joanna Matyjasik, Elżbieta Złowocka, Grzegorz Kurzawski, Andrzej Sikorski, Michał Posmyk, Marek Szwiec, Ryszard Czajka, Steven A. Narod, Jan Lubiński
Journal: Cancer Research (2004)

Variants in the CHEK2 have been found to be associated with prostate cancer risk in the United States and Finland. We sequenced CHEK2 gene in 140 Polish patients with prostate cancer and then genotyped the three detected variants in a larger series of prostate cancer cases and controls. CHEK2 truncating mutations (IVS2 + 1G>A or 1100delC) were identified in 9 of 1921 controls (0.5%) and in 11 of 690 (1.6%) unselected patients with prostate cancer [odds ratio (OR) = 3.4; P = 0.004]. These mutations were found in 4 of 98 familial prostate cases (OR = 9.0; P = 0.0002). The missense variant I157T was also more frequent in men with prostate cancer (7.8%) than in controls (4.8%), but the relative risk was more modest (OR = 1.7; P = 0.03). I157T was identified in 16% of men with familial prostate cancer (OR = 3.8; P = 0.00002). Loss of the wild-type CHEK2 allele was not observed in any of prostate cancers from five men who carried CHEK2-truncating mutations. Our results provide evidence that the two truncating mutations of CHEK2 confer a moderate risk of prostate cancer in Polish men and that the missense change appears to confer a modest risk.
HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA-DQA1 locus can be a potential melanoma risk factor
Authors: D. Planelles, E. Nagore, A. Moret, R. Botella-Estrada, E. Vila, C. Guillén, J.A. Montoro
Journal: British Journal of Dermatology (2005)

Journal Article HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA‐DQA1 locus can be a potential melanoma risk factor Get access D. Planelles, D. Planelles Laboratory of Histocompatibility‐Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65‐A, 46014‐Valencia, Spain *Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain D. Planelles. E‐mail: planelles_dol@gva.es Search for other works by this author on: Oxford Academic Google Scholar E. Nagore, E. Nagore Laboratory of Histocompatibility‐Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65‐A, 46014‐Valencia, Spain *Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Moret, A. Moret Laboratory of Histocompatibility‐Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65‐A, 46014‐Valencia, Spain *Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain Search for other works by this author on: Oxford Academic Google Scholar R. Botella‐Estrada, R. Botella‐Estrada Laboratory of Histocompatibility‐Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65‐A, 46014‐Valencia, Spain *Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain Search for other works by this author on: Oxford Academic Google Scholar E. Vila, E. Vila Laboratory of Histocompatibility‐Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65‐A, 46014‐Valencia, Spain *Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain Search for other works by this author on: Oxford Academic Google Scholar C. Guillén, C. Guillén Laboratory of Histocompatibility‐Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65‐A, 46014‐Valencia, Spain *Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain Search for other works by this author on: Oxford Academic Google Scholar J.A. Montoro J.A. Montoro Laboratory of Histocompatibility‐Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65‐A, 46014‐Valencia, Spain *Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 2, 1 February 2006, Pages 261–266, https://doi.org/10.1111/j.1365-2133.2005.06896.x Published: 01 February 2006 Article history Accepted: 22 April 2005 Published: 01 February 2006
TNF Receptor-2 Facilitates an Immunosuppressive Microenvironment in the Liver to Promote the Colonization and Growth of Hepatic Metastases
Authors: Boram Ham, Ni Wang, Zarina D'Costa, Maria Celia Fernandez, France Bourdeau, Patrick Auguste, Martin Illemann, Rikke Loevendahl Eefsen, Gunilla Høyer-Hansen, Ben Vainer, Maximilien Evrard, Zu-Hua Gao, Pnina Brodt
Journal: Cancer Research (2015)

Abstract Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. TNF signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked. In this study, we explored how TNF signaling influences the efficiency of liver metastasis by colon and lung carcinoma in mice that are genetically deficient for the TNF receptor TNFR2. We found a marked reduction in liver metastases that correlated with a greatly reduced accumulation at metastatic sites of CD11b+GR-1+ myeloid cells with enhanced arginase activity, identified as myeloid-derived suppressor cells (MDSC). Reduced infiltration of MDSC coincided with a reduction in the number of CD4+FoxP3+ T regulatory cells in the tumors. Reconstitution of TNFR2-deficient mice with normal bone marrow, or adoptive transfer of TNFR2-expressing MDSC into these mice, was sufficient to restore liver metastasis to levels in wild-type mice. Conversely, treatment with TNFR2 antisense oligodeoxynucleotides reduced liver metastasis in wild-type mice. Clinically, immunohistochemical analysis of liver metastases from chemotherapy-naïve colon cancer patients confirmed the presence of CD33+HLA-DR−TNFR2+ myeloid cells in the periphery of hepatic metastases. Overall, our findings implicate TNFR2 in supporting MDSC-mediated immune suppression and metastasis in the liver, suggesting the use of TNFR2 inhibitors as a strategy to prevent metastatic progression to liver in colon, lung, and various other types of cancer. Cancer Res; 75(24); 5235–47. ©2015 AACR.
The Contemporary Concept of Significant Versus Insignificant Prostate Cancer
Authors: Guillaume Ploussard, Jonathan I. Epstein, Rodolfo Montironi, Peter R. Carroll, Manfred Wirth, Marc-Oliver Grimm, Anders S. Bjartell, Francesco Montorsi, Stephen J. Freedland, Andreas Erbersdobler, Theodorus H. van der Kwast
Journal: European Urology (2011)
Olea europaea pollen lipids activate invariant natural killer T cells by upregulating CD1d expression on dendritic cells
Authors: Beatriz Abós-Gracia, Manuel Gómez del Moral, Juan López-Relaño, Vanesa Viana-Huete, Lourdes Castro, Mayte Villalba, Eduardo Martínez-Naves
Journal: Journal of Allergy and Clinical Immunology (2012)
Response of nitric oxide pathway to l-arginine infusion at the altitude of 4,350 m
Authors: J-C. Schneider, I. Blazy, M. Déchaux, D. Rabier, N.P. Mason, J-P. Richalet
Journal: European Respiratory Journal (2001)

It was hypothesized that hypoxia may inhibit nitric oxide (NO) production by reducing the availability of endothelial NO synthase (NOS III) substrate. To evaluate the effect of l-arginine on the NO release in high altitude, 11 subjects were infused with l-arginine (0.5 g·kg −1 ) during 30 min in normoxia and after 36 h at 4,350 m (hypoxia). The l-citrulline and cyclic guanosine monophosphate (cGMP) concentrations were measured to investigate NO synthesis and guanylyl cyclase activity respectively. l-citrulline concentration, arterial oxygen saturation ( S a,O 2 ), systemic blood pressure, heart rate and acute mountain sickness (AMS) score were measured at rest and 15, 30 and 45 min after starting infusion. The results showed that baseline l-citrulline was lower in hypoxia (p&lt;0.05). l-arginine infusion increased l-citrulline concentration in both conditions. However, in hypoxia l-citrulline concentration remained lower than in normoxia (p&lt;0.05). The concentration of cGMP was lower in hypoxia (p&lt;0.05). In hypoxia, S a,O 2 increased from 15 min after the start of the infusion to 45 min (p&lt;0.05). Blood pressure and heart rate were not affected by l-arginine infusion. Subjects who experienced symptoms of AMS showed a slight decrease in AMS score with l-arginine. The decreased l-citrulline suggests a hypoxia-induced impairment of nitric oxide synthase III or a decrease in l-arginine availability. The improvement of arterial oxygen saturation by pretreatment with l-arginine could be ascribed to an enhancement of the ventilation/perfusion ratio. Collectively, these results are consistent with a decrease in nitric oxide production in hypoxia that could be antagonized by supplying nitric oxide synthase cosubstrate.
Sexual Function and Endocrine Profile in Fertile Women With Type 1 Diabetes
Authors: Andrea Salonia, Roberto Lanzi, Marina Scavini, Marina Pontillo, Elisa Gatti, Giovanna Petrella, Giada Licata, Rossella E. Nappi, Emanuele Bosi, Alberto Briganti, Patrizio Rigatti, Francesco Montorsi
Journal: Diabetes Care (2006)

Aims of this study were 1) to assess sexual function and endocrine profile among fertile type 1 diabetic women during the follicular and luteal phases of the menstrual cycle, 2) to compare these results with those obtained among healthy fertile women who served as control subjects, and 3) to explore the correlations between sexual function and endocrine milieu among patients and control subjects during the follicular and luteal phases of the menstrual cycle.Fifty fertile women with type 1 diabetes and 47 healthy control subjects completed a semistructured medical interview and filled in self-administered validated instruments to evaluate sexual function, depression, and sexual distress. Venous blood samples were drawn to measure glycated hemoglobin and an endocrine profile during either the follicular or the luteal phase of the menstrual cycle.Type 1 diabetic women had decreased sexual function and increased sexual distress compared with control subjects during the luteal, but not the follicular, phase of the menstrual cycle. During the follicular phase, patients had lower estrogenic basal tone, lower "weak" androgen (namely Delta4-androstenedione and dehydroepiandrosterone sulfate) production, and lower free-triiodothyronine and free-thyroxine levels compared with control subjects. During the luteal phase, total testosterone levels were higher in patients than control subjects, while 17beta-estradiol and progesterone levels were lower in patients than control subjects.Among type 1 diabetic women, sexual function and sexual distress vary according to the phase of the menstrual cycle. This finding may have implications on the clinical assessment of sexual function in type 1 diabetic women.
Enhancement of liposomal stability and cellular drug uptake by incorporating tributyrin into celecoxib-loaded liposomes
Authors: Sung Nam Kang, Soon-Seok Hong, Soo-Yeon Kim, Heungchan Oh, Mi-Kyung Lee, Soo-Jeong Lim
Journal: Asian Journal of Pharmaceutical Sciences (2013)

Tributyrin, a triglyceride analog of short chain fatty acid butyrate, can act as a prodrug of an anticancer agent butyrate. In view of other reports that demonstrated the improved characteristics of conventional liposomes by incorporating small amount of non-phospholipids such as Tween 80, herein we sought to investigate whether the incorporation of tributyrin into the liposomal layers may provide additional advantages for liposomes as an anticancer drug carrier. Liposomes were prepared with dimyristoylphosphatidylcholine as a main phospholipid with or without addition of tributyrin. Celecoxib was loaded in liposomes as a model anticancer drug. Tween 80-incorporated liposomes were also prepared for comparison. Tributyrin-incorporated liposomes were ineffective in enhancing the skin permeation of celecoxib compared to Tween 80-incorporated ones. However, tributyrin-incorporated liposomes enhanced the entrapped celecoxib concentration to an extent comparable to Tween 80-incorporated ones. Furthermore, tributyrin-incorporated liposomes exhibited much higher stability compared to Tween 80-incorporated ones. Finally, the cellular uptake of celecoxib loaded in tributyrin-incorporated liposomes into mouse melanoma cells were more than 10-fold higher compared to that loaded in conventional- and Tween 80-incorporated liposomes. Taken together, the incorporation of tributyrin into conventional liposomes loaded with anticancer drugs may provide an advanced anticancer drug carrier delivering both drug and tributyrin.
Targeted In Vivo Mutations of the AMPA Receptor Subunit GluR2 and Its Interacting Protein PICK1 Eliminate Cerebellar Long-Term Depression
Authors: Jordan P. Steinberg, Kogo Takamiya, Ying Shen, Jun Xia, Maria E. Rubio, Sandy Yu, Wenying Jin, Gareth M. Thomas, David J. Linden, Richard L. Huganir
Journal: Neuron (2006)