tbuckley/cabot-search huggingface dataset:
S15 Detection of bacteria in sputum following experimental rhinovirus infection is more common in COPD than controls subjects
Authors: J. I. M. Footitt, P. Mallia, M. B. Trujillo-Torralbo, A. Jepson, S. L. Johnston
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> There is increasing evidence that the majority of acute exacerbations of COPD (AECOPD) are caused by virus infection, and rhinoviruses are the most frequently identified species. Bacteria are also responsible for AECOPD but the relationship between these two is poorly understood. To investigate this further bacterial culture was performed in sputum samples collected from GOLD stage II COPD subjects (n=9) and non-obstructed smoking (n=10) and non-smoking (n=11) controls enrolled in a rhinovirus challenge study. <h3>Methods</h3> Rhinovirus infection was confirmed with quantitative PCR performed on nasal lavage and sputum samples collected at baseline and days 3, 5, 9, 12, 15, 21 and 42 post virus inoculation. Semi-quantitative bacterial detection was performed in sputum samples by a CPA-accredited microbiological laboratory. Any subject that had bacteria detected on or after day 9 was defined as “bacteria positive” and those with none detected were defined “bacteria negative”. Species frequently associated with respiratory illness were defined as pathogenic (<i>S pneumoniae, H influenzae, M catarrhalis</i> and <i>S aureus</i>) and any others as non-pathogenic. <h3>Results</h3> No bacteria were detected in baseline sputum samples. Peak virus load occurred on day 9 with maximum bacterial colonies identified on day 15. There were significantly more bacteria positive subjects in the COPD group (67%) with the majority of control subjects (81%) being classified as bacteria negative, (Abstract S15 figure 1, χ<sup>2</sup> p=0.04). COPD subjects with bacteria detected at any time point in the study had significantly more pathogenic species in their sputum samples (n=8/8) compared to controls (n=1/9), (χ<sup>2</sup> p=0.0001). No non-pathogenic bacteria were detected in COPD subjects. <h3>Conclusions</h3> Detection of bacteria is common after rhinovirus infection, with the peak occurring 6 days after maximum virus load. COPD subjects are more likely to have pathogenic bacteria detected than controls following virus infection. Mechanisms responsible for this phenomenon merit further investigation.
Mechanism of action of carbocyclic thromboxane A2 and its interaction with prostaglandin I2 and verapamil in isolated arteries.
Authors: N Toda
Journal: Circulation Research (1982)

Carbocyclic thromboxane A2 (10(-9) to 10(-7) M) produced a concentration-dependent contraction of helical strips of dog cerebral, coronary, mesenteric, renal, and femoral arteries and of monkey cerebral, coronary, and mesenteric arteries. Contraction induced by low concentrations of carbocyclic thromboxane A2 tended to be greater in cerebral arterial strips. Even after 60 minutes of exposure to Ca++-free media, approximately one-half of the contractile response of dog cerebral and mesenteric arteries to 10(-8) M carbocyclic thromboxane A2 was retained. The contractile response was attenuated by diphloretin phosphate, a prostaglandin antagonist, and was potentiated by aspirin. In dog cerebral arterial strips contracted with carbocyclic thromboxane, the relaxant response to prostaglandin I2 was less than the response seen in mesenteric and coronary arteries, whereas, in contrast, the response to verapamil was greater in cerebral arteries. Concentration-relaxation curves for papaverine did differ appreciably. It may be concluded that contractions induced by carbocyclic thromboxane are associated with the release of Ca++ from intracellular storage sites and, in addition, the increase in transmembrane Ca++ influx. Greater susceptibility of cerebral arteries to verapamil may indicate that the Ca++ antagonist is of use to relieve the persistent contraction of cerebroarterial smooth muscle. Prostaglandin I2 appears to counteract effectively the action of potent vasoconstrictors, such as thromboxane A2 and its carbocyclic analog, in various vascular beds.
Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL)
Authors: Andre Franke, Tobias Balschun, Christian Sina, David Ellinghaus, Robert Häsler, Gabriele Mayr, Mario Albrecht, Michael Wittig, Eva Buchert, Susanna Nikolaus, Christian Gieger, H Erich Wichmann, Jurgita Sventoraityte, Limas Kupcinskas, Clive M Onnie, Maria Gazouli, Nicholas P Anagnou, David Strachan, Wendy L McArdle, Christopher G Mathew, Paul Rutgeerts, Séverine Vermeire, Morten H Vatn, Michael Krawczak, Philip Rosenstiel, Tom H Karlsen, Stefan Schreiber
Journal: Nature Genetics (2010)
THE ORGANIC BACKGROUND OF OBSESSIONS AND COMPULSIONS
Authors: Paul Schilder
Journal: American Journal of Psychiatry (1938)

1. Seven cases of obsession neurosis are presented in which definite organic signs were disclosed by neurological examination. These signs remind of symptoms observed in epidemic encephalitis. However, it is not probable that one deals in these cases with mild encephalitis, of the epidemic type. They may be due to constitutional factors and to early traumatic toxic and infectious processes. 2. In two cases, the type of motility and activity hinted to similar organic factors. In other cases, the psychic symptomatology pointed to an underlying motor impulse disturbance. 3. Compulsion neurosis cases of this type show a particular relation to numbers and counting. There is the tendency to iteration and compulsions based upon it. The attitude towards space is changed. The motor drives are in close relation to sadistic attitudes. 4. Similar disturbances and a similar psychic symptomatology are present in the obsessions and compulsions observed in post encephalitic cases in which the organic change in the motor impulses is obvious. 5. Organic factors influencing the state of consciousness may have an influence in some obsession neurotic cases. 6. Psychotherapy has to consider the importance of the motor factors in compulsions and their relations to sadistic attitudes. They have to be appreciated in connection with the libidinous situation. In the majority of the cases treated, good results were obtained.
A giant epidermoid cyst demonstrated by magnetic resonance imaging
Authors: T. Yamamoto, T. Nishikawa, T. Fujii, K. Mizuno
Journal: British Journal of Dermatology (2001)

Journal Article A giant epidermoid cyst demonstrated by magnetic resonance imaging Get access T. Yamamoto, T. Yamamoto Department of Orthopaedic Surgery, Kobe University School of Medicine, 7–5‐1 Kusunoki‐cho, Chuo‐ku, Kobe 650–0017, Japan Correspondence: E‐mail: yamatetu@med.kobe‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar T. Nishikawa, T. Nishikawa Department of Orthopaedic Surgery, Kobe University School of Medicine, 7–5‐1 Kusunoki‐cho, Chuo‐ku, Kobe 650–0017, Japan Correspondence: E‐mail: yamatetu@med.kobe‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar T. Fujii, T. Fujii Department of Orthopaedic Surgery, Kobe University School of Medicine, 7–5‐1 Kusunoki‐cho, Chuo‐ku, Kobe 650–0017, Japan Correspondence: E‐mail: yamatetu@med.kobe‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Mizuno K. Mizuno Department of Orthopaedic Surgery, Kobe University School of Medicine, 7–5‐1 Kusunoki‐cho, Chuo‐ku, Kobe 650–0017, Japan Correspondence: E‐mail: yamatetu@med.kobe‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 1, 1 January 2001, Pages 217–218, https://doi.org/10.1046/j.1365-2133.2001.03997.x Published: 01 January 2001
Multilocus Analysis of Nucleotide Variation of Oryza sativa and Its Wild Relatives: Severe Bottleneck during Domestication of Rice
Authors: Qihui Zhu, Xiaoming Zheng, Jingchu Luo, Brandon S. Gaut, Song Ge
Journal: Molecular Biology and Evolution (2007)

Varying degrees of reduction of genetic diversity in crops relative to their wild progenitors occurred during the process of domestication. Such information, however, has not been available for the Asian cultivated rice (Oryza sativa) despite its importance as a staple food and a model organism. To reveal levels and patterns of nucleotide diversity and to elucidate the genetic relationship and demographic history of O. sativa and its close relatives (Oryza rufipogon and Oryza nivara), we investigated nucleotide diversity data from 10 unlinked nuclear loci in species-wide samples of these species. The results indicated that O. rufipogon and O. nivara possessed comparable levels of nucleotide variation (θsil = 0.0077∼0.0095) compared with the relatives of other crops. In contrast, nucleotide diversity of O. sativa was as low as θsil = 0.0024 and even lower (θsil = 0.0021 for indica and 0.0011 for japonica), if we consider the 2 subspecies separately. Overall, only 20–10% of the diversity in the wild species was retained in 2 subspecies of the cultivated rice (indica and japonica), respectively. Because statistic tests did not reject the assumption of neutrality for all 10 loci, we further used coalescent to simulate bottlenecks under various lengths and population sizes to better understand the domestication process. Consistent with the dramatic reduction in nucleotide diversity, we detected a severe domestication bottleneck and demonstrated that the sequence diversity currently found in the rice genome could be explained by a founding population of 1,500 individuals if the initial domestication event occurred over a 3,000-year period. Phylogenetic analyses revealed close genetic relationships and ambiguous species boundary of O. rufipogon and O. nivara, providing additional evidence to treat them as 2 ecotypes of a single species. Lowest linkage disequilibrium (LD) was found in the perennial O. rufipogon where the r2 value dropped to a negligible level within 400 bp, and the highest in the japonica rice where LD extended to the entirely sequenced region (∼900 bp), implying that LD mapping by genome scans may not be feasible in wild rice due to the high density of markers needed.
Expression of Indoleamine 2,3-Dioxygenase in Tumor Endothelial Cells Correlates with Long-term Survival of Patients with Renal Cell Carcinoma
Authors: Rainer Riesenberg, Christoph Weiler, Oliver Spring, Martin Eder, Alexander Buchner, Tanja Popp, Mirna Castro, Robert Kammerer, Osamu Takikawa, Rudolf A. Hatz, Christian G. Stief, Alfons Hofstetter, Wolfgang Zimmermann
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The inflammatory enzyme indoleamine 2,3-dioxygenase (IDO) participates in immune tolerance and tumor immune escape processes by degradation of the essential amino acid tryptophan and formation of toxic catabolites. Here, we analyzed the role of IDO in tumor growth and disease progression in patients with clear cell renal cell carcinoma (RCC). Experimental Design: Expression of IDO mRNA was analyzed by quantitative reverse transcription-PCR in 55 primary and 52 metastatic RCC, along with 32 normal kidneys. Western blot and immunohistochemistry analyses were used to semiquantitatively determine IDO proteins in a subset of tumor samples, in RCC cell lines, and microvessel endothelial cells. IDO expression was correlated with expression of the proliferation marker Ki67 in tumor cells and survival of patients with tumor. Results: More than 75% of the clear cell RCC in comparison to normal kidney contained elevated levels of IDO mRNA, which correlated with their IDO protein content. Low IDO mRNA levels in primary tumors represented an unfavorable independent prognostic factor (hazard ratio, 3.8; P = 0.016). Unexpectedly, immunohistochemical analyses revealed that IDO is nearly exclusively expressed in endothelial cells of newly formed blood vessels and is virtually absent from tumor cells, although RCC cells could principally synthesize IDO as shown by in vitro stimulation with IFN-γ. A highly significant inverse correlation between the density of IDO-positive microvessels and the content of proliferating Ki67-positive tumor cells in primary and metastatic clear cell RCC was found (P = 0.004). Conclusions: IDO in endothelial cells might limit the influx of tryptophan from the blood to the tumor or generate tumor-toxic metabolites, thus restricting tumor growth and contributing to survival.
High <i>SEPT9_v1</i> Expression in Human Breast Cancer Cells Is Associated with Oncogenic Phenotypes
Authors: Maria E. Gonzalez, Esther A. Peterson, Lisa M. Privette, Janice L. Loffreda-Wren, Linda M. Kalikin, Elizabeth M. Petty
Journal: Cancer Research (2007)

Abstract Altered expression of the human septin gene, SEPT9, and its murine homologue, Sept9, has been implicated in neoplasia. However, their role(s) in oncogenesis remains poorly understood. We found amplification of SEPT9 in 67% of breast cancer cells (BCC) when compared with immortalized human mammary epithelial cells (IHMEC) as well as high levels of SEPT9 expression in the majority (61%) of the BCCs studied, unlike IHMECs. Expression profiling of variant SEPT9 transcripts and translated products revealed that high expression of the variant, SEPT9_v1, in contrast to other variants, was widespread in BCCs (55% of the BCCs) but not in IHMECs. High expression of SEPT9_v1 was also observed in primary breast cancer samples by immunohistochemical studies. We subsequently examined the phenotypic consequences of SEPT9_v1 expression in human breast cells. Retroviral expression of SEPT9_v1 in IHMEC cell culture models showed that SEPT9_v1 accelerated growth kinetics, stimulated cell motility, promoted invasion in Matrigel Transwell assays, increased genomic instability with the development of aneuploidy, and stimulated morphologic changes. Significant cytokinesis defects and disruption of tubulin microfilaments were also observed by immunofluorescence when SEPT9_v1 was ectopically expressed in IHMECs. Furthermore, SEPT9_v1 markedly enhanced neoplastic transformation in Hs578T cells, a BCC with no endogenous expression of the SEPT9_v1 isoform. Small interfering RNA–mediated and short hairpin RNA–mediated inhibition of SEPT9_v1 expression in two BCCs with high levels of endogenous SEPT9_v1 expression inhibited neoplastic growth properties of the cells. Taken together, our findings suggest that increased SEPT9_v1 expression contributes to the malignant pathogenesis of some breast tumors. [Cancer Res 2007;67(18):8554–11]
Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome
Authors: Dag Sulheim, Even Fagermoen, Anette Winger, Anders Mikal Andersen, Kristin Godang, Fredrik Müller, Peter C. Rowe, J. Philip Saul, Eva Skovlund, Merete Glenne Øie, Vegard Bruun Wyller
Journal: JAMA Pediatrics (2014)

IMPORTANCE Chronic fatigue syndrome (CFS) is a disabling condition with unknown disease mechanisms and few treatment options.OBJECTIVE To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function.DESIGN, SETTING, AND PARTICIPANTS Participants were enrolled from a single referral center recruiting nationwide in Norway.A referred sample of 176 adolescents with CFS was assessed for eligibility; 120 were included (34 males and 86 females; mean age, 15.4 years).A volunteer sample of 68 healthy adolescents serving as controls was included (22 males and 46 females; mean age, 15.1 years).The CSF patients and healthy controls were assessed cross-sectionally at baseline.Thereafter, patients with CFS were randomized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks; double-blinding was provided.Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.INTERVENTIONS Clonidine hydrochloride capsules (25 μg or 50 μg twice daily for body weight <35 kg or >35 kg, respectively) vs placebo capsules for 9 weeks.MAIN OUTCOMES AND MEASURES Number of steps per day.RESULTS At baseline, patients with CFS had a lower number of steps per day (P < .001),digit span backward score (P = .002),and urinary cortisol to creatinine ratio (P = .001),and a higher fatigue score (P < .001),heart rate responsiveness (P = .02),plasma norepinephrine level (P < .001),and serum C-reactive protein concentration (P = .04)compared with healthy controls.There were no significant differences regarding blood microbiology evaluation.During intervention, the clonidine group had a lower number of steps per day (mean difference, -637 steps; P = .07),lower plasma norepinephrine level (mean difference, -42 pg/mL; P = .01),and lower serum C-reactive protein concentration (mean ratio, 0.69; P = .02)compared with the CFS placebo group. CONCLUSIONS AND RELEVANCEAdolescent CFS is associated with enhanced sympathetic nervous activity, low-grade systemic inflammation, attenuated hypothalamus-pituitaryadrenal axis function, cognitive impairment, and large activity reduction, but not with common microorganisms.Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity; thus, sympathetic and inflammatory enhancement may be compensatory mechanisms.Low-dose clonidine is not clinically useful in CFS.
Noninvasive Positive-Pressure Ventilation for Respiratory Failure after Extubation
Authors: Andrés Esteban, Fernando Frutos-Vivar, Niall D. Ferguson, Yaseen Arabi, Carlos Apezteguía, Marco González, Scott K. Epstein, Nicholas S. Hill, Stefano Nava, Marco-Antonio Soares, Gabriel D'Empaire, Inmaculada Alía, Antonio Anzueto
Journal: New England Journal of Medicine (2004)

The need for reintubation after extubation and discontinuation of mechanical ventilation is not uncommon and is associated with increased mortality. Noninvasive positive-pressure ventilation has been suggested as a promising therapy for patients with respiratory failure after extubation, but a single-center, randomized trial recently found no benefit. We conducted a multicenter, randomized trial to evaluate the effect of noninvasive positive-pressure ventilation on mortality in this clinical setting.
Hodgkin lymphoma: 2011 update on diagnosis, risk‐stratification, and management
Authors: Stephen M. Ansell
Journal: American Journal of Hematology (2011)

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8,500 new patients annually and representing approximately 11% of all lymphomas in the United States.HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL.An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence are used to optimize therapy for patients with limited or advanced stage disease.Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy.High-dose chemotherapy (HDCT) followed by an autologous stem-cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered.
Effects of endothelin on peptide-dependent cyclic adenosine monophosphate accumulation along the nephron segments of the rat.
Authors: K Tomita, H Nonoguchi, F Marumo
Journal: Journal of Clinical Investigation (1990)

We investigated the tubular action of endothelin in rat nephron segments. The effects of endothelin on arginine vasopressin (AVP)-, parathyroid hormone-, glucagon-, calcitonin-, and isoproterenol-dependent cAMP accumulation were studied. The following nephron segments were microdissected: glomerulus (Gl), proximal convoluted tubule (PCT), cortical and medullary thick ascending limbs of Henle's loop (cTAL and mTAL, respectively), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD). Endothelin dose dependently (10(-8)-10(-10)M) inhibited AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD. This effect was independent of the presence or absence of phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, Ca channel blocker nicardipine, or indomethacin, but was abolished in the presence of protein kinase C inhibitor H-7. Protein kinase C stimulator dioctanoyl glycerol mimicked the effect of endothelin. On the other hand, endothelin had no inhibitory effect on AVP-dependent cAMP accumulation in cTAL or mTAL, parathyroid hormone-dependent cAMP accumulation in Gl and PCT, or glucagon-, calcitonin-, and isoprotereol-dependent cAMP accumulation in OMCD. We conclude that endothelin specifically inhibits AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD through activating protein kinase C. This effect possibly has a role in maintaining urine volume to counteract the decrease in GFR caused by endothelin itself.
A Research Agenda for Malaria Eradication: Drugs
Journal: PLoS Medicine (2011)

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission.