tbuckley/cabot-search huggingface dataset:
Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Reward System
Authors: Natsuko Tsujino, Takeshi Sakurai
Journal: Pharmacological Reviews (2009)

Recent studies have implicated the orexin system as a critical regulator of sleep/wake states as well as feeding behavior and reward processes. Orexin deficiency results in narcolepsy in humans, dogs, and rodents, suggesting that the orexin system is particularly important for maintenance of wakefulness. In addition, orexin deficiency also cause abnormalities in energy homeostasis and reward systems. Orexin activates waking active monoaminergic and cholinergic neurons in the hypothalamus and brainstem regions to maintain a long, consolidated waking period. Orexin neurons receive abundant input from the limbic system. Orexin neurons also have reciprocal links with the hypothalamic arcuate nucleus, which regulates feeding. Moreover, the responsiveness of orexin neurons to peripheral metabolic cues, such as leptin and glucose, suggest that these neurons have important role as a link between the energy homeostasis and vigilance states. Orexin neurons also have a link with the dopaminergic reward system in the ventral tegmental nucleus. These findings suggest that the orexin system interacts with systems that regulate emotion, reward, and energy homeostasis to maintain proper vigilance states. Therefore, this system may be a potentially important therapeutic target for treatment of sleep disorder, obesity, emotional stress, and addiction.
Hydration in Four Hours Around the Cisplatin Infusion May Be Critical for Preventing Cisplatin-Induced Nephrotoxicity
Authors: T. Yamaguchi, K. Imaizumi, S. Morikawa, T. Minezawa, T. Okamura, M. Morishita, S. Uozu, M. Hayashi, T. Nakanishi, M. Okazawa
Journal: Annals of Oncology (2013)
Methotrexate and bone marrow suppression: Drug errors may be implicated in death
Authors: M. L Grove
Journal: BMJ (2003)

EDITOR—Two points arise from the lesson of the week by Sosin and Handa on methotrexate toxicity.1

Firstly, bone marrow toxicity with methotrexate is a late complication of treatment. Only one of the cases described (case 2) had been treated for less than 12 months, and the authors suspect he had been taking methotrexate daily rather than weekly as would have …
Putting optometry at the heart of community eye healthcare
Authors: James M Gilchrist
Journal: BMJ (2015)

GPs who feel overburdened or limited in their ability to assess eye and vision problems should be able to refer patients to primary care practitioners with specialist expertise in ocular and visual assessment.1

Optometrists are well equipped and experienced in assessing sight threatening conditions—such as cataract, glaucoma, diabetes related eye problems, macular degeneration, and less common diseases. They …
Uroporphyrin I Stimulation of Collagen Biosynthesis in Human Skin Fibroblasts
Authors: George Varigos, John R. Schiltz, David R. Bickers
Journal: Journal of Clinical Investigation (1982)

Porphyria cutanea tarda and erythropoietic porphyria are disorders of heme synthesis that originate in the liver and bone marrow, respectively. Each is characterized by increased accumulation of uroporphyrin, I, by cutaneous photosensitivity, and in some patients by indurated plaques and scarring that resemble scleroderma. These scleroderma-like lesions occur in light-exposed and light-protected body areas. In these studies we evaluated the role of uroporphyrin I and of light in evoking the scleroderma-like cutaneous changes. Normal human skin fibroblasts were exposed to uroporphyrin I and to 400 nm radiation and the effect of these agents on collagen accumulation by the cells was determined. Radioactive tracer studies showed that uroporphyrin I caused a specific increase in the accumulation of newly synthesized collagen by fibroblast monolayer cultures, as verified by [3H]hydroxyproline and collagenase digestion assays. Collagen accumulation was stimulated 1.5- to 2.7-fold by uroporphyrin I, whereas noncollagenous protein accumulation was unchanged. The increased collagen accumulation was time and uroporphyrin I-concentration-dependent, and occurred both in the presence or absence of ultraviolet light exposure. Further studies demonstrated that the increased accumulation was not the result of decreased rates of collagen degradation nor was it due to changes in cell population growth parameters (generation times and saturation densities). No changes in morphology of the treated cells occurred. These studies indicate that porphyrins possess previously undemonstrated biological effects that are independent of their photosensitizing properties. This novel dark effect of uroporphyrin I may account for the sclerodermatous lesions seen in the skin of patients with porphyria cutanea tarda and erythropoietic porphyria.
ACTIVATION OF THE ALTERNATE COMPLEMENT PATHWAY BY AUTOLOGOUS RED CELL STROMA
Authors: Thomas R. Poskitt, H. Philip Fortwengler, Beverly J. Lunskis
Journal: The Journal of Experimental Medicine (1973)

The present study demonstrates the ability of human autologous RBC stroma to activate the alternate complement pathway (C3-Activator system, properdin system), as evidenced by the generation of C3-Activator (C3A) from C3-Proactivator (C3PA) when RBC ghosts and sonicated ghosts are incubated with autologous serum. Intact RBC's, hemoglobin, and concentrated platelet stroma, on the other hand, are inactive in this regard. We postulate that this in vitro activity of RBC stroma may occur intravascularly when erythrocytes are damaged by immune or nonimmune mechanisms. The ensuing interaction of activated complement components with platelets leading to release of platelet factor three (PF-3) may constitute a mechanism for activation of the coagulation system during acute hemolytic episodes.
Optical Neural Interfaces
Authors: Melissa R. Warden, Jessica A. Cardin, Karl Deisseroth
Journal: Annual Review of Biomedical Engineering (2014)

Genetically encoded optical actuators and indicators have changed the landscape of neuroscience, enabling targetable control and readout of specific components of intact neural circuits in behaving animals. Here, we review the development of optical neural interfaces, focusing on hardware designed for optical control of neural activity, integrated optical control and electrical readout, and optical readout of population and single-cell neural activity in freely moving mammals.
Abstract LB-14: Endogenous expression of oncogenic PI3K mutation leads to accumulation of pro- and antiapoptotic proteins at mitochondria
Authors: Nelly Buron, Mathieu Porceddu, Chris Torrance, Darrin Disley, Annie Borgne-Sanchez
Journal: Cancer Research (2010)

Abstract The phosphatidylinositol 3-kinase subunit PI3K is frequently mutated in human cancers and therefore represents an interesting therapeutic target. Cancer resistance to therapies is often related to expression of anti-apoptotic Bcl-2 family members which negatively regulate mitochondrial cell death. We investigated the influence of PI3K mutations on Bcl-2 family proteins both at the cellular and mitochondrial level. We used human breast epithelial cell lines with an endogenous “knock-in” PI3K mutation (HME-1 cells harbouring the H1047R activating mutation) from which we purified the mitochondria to homogeneity (95%). We first characterized these mitochondria for their sensitivity to reference compounds (Calcium, t-Bid) on 3 parameters: swelling, m loss and cytochrome c release. Mitochondrial preparations from wild-type and mutated HME-1 were analysed for their protein pattern in Bcl-2 family members. We observed accumulation of anti-apoptotic (Bcl-xl and Bcl-2) and pro-apoptotic (Bad) proteins in mitochondria isolated from PI3K mutated cells. We showed that the excess of anti-apoptotic proteins at the mitochondria does not change their sensitivity to the Bcl-2 family inhibitor, ABT-737. Investigations with PI3K-inhibitors are currently undergoing to determine the mitochondrial on-target biomarker for drug development. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-14.
The epidermal growth factor–like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans
Authors: Martin Stacey, Gin-Wen Chang, John Q. Davies, Mark J. Kwakkenbos, Ralph D. Sanderson, Jörg Hamann, Siamon Gordon, Hsi-Hsien Lin
Journal: Blood (2003)
Influence of carotid baroreceptors on vascular responses to carotid chemoreceptor stimulation in the dog.
Authors: G Mancia
Journal: Circulation Research (1975)

The modification by the carotid baroreceptors of the vascular responses to chemoreceptor stimulation was studied in anesthetized, artificially ventilated, vagotomized dogs. The carotid bifurcations were vascularly isolated and perfused with blood at constant pressures of 134, 215, and 51 mm Hg to cause intermediate, maximal, and minimal inhibition, respectively, of the vasomotor center. At each pressure, stimulation of the carotid chemoreceptors was achieved by perfusion with hypoxic hypercapnic blood. With intermediate inhibition, the chemoreceptor stimulation increased the aortic pressure by 50% and decreased the hind-limb and kidney blood flow (perfusion at constant pressure) by 59% and 19%, respectively. At carotid sinus pressures of 215 and 51 mm Hg, the effects of chemoreceptor stimulation were absent or markedly attenuated. With intermediate sinus pressure, chemoreceptor stimulation decreased the perfusion pressure of the saphenous vein by 27% (perfusion at constant flow). When the sinus pressure was increased to 215 mm Hg, the tone of the vein did not change, but chemoreceptor stimulation was without effect. The present study indicates a central interaction (which may be presynaptic) between the chemoreceptor and baroreceptor inputs such that the vascular responses to chemoreceptor stimulation are inhibited when the carotid sinus activity is maximal or minimal.
Volume of emphysema.
Authors: P Turner, W F Whimster
Journal: Thorax (1981)

A method of determining the volume of emphysema in excised lungs is presented, with its validation. This method is based on macroscopic point counting using a perforated grid but only the holes (points) overlying emphysema need be counted to produce results within a percentage standard error of 5%. Application of the method shows that an adequate assessment of emphysema cannot be made from one lung slice alone, and that the amount of emphysema found in one lung cannot be used to predict the amount of emphysema in the other lung.
Exercise Training Improves Exercise Capacity and Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Frank Edelmann, Götz Gelbrich, Hans-Dirk Düngen, Stefan Fröhling, Rolf Wachter, Raoul Stahrenberg, Lutz Binder, Agnieszka Töpper, Diana Jahandar Lashki, Silja Schwarz, Christoph Herrmann-Lingen, Markus Löffler, Gerd Hasenfuss, Martin Halle, Burkert Pieske
Journal: Journal of the American College of Cardiology (2011)
Differences between pig tissues in the expression of major transplantation antigens: possible relevance for organ allografts.
Authors: H S Davies, J E Taylor, M R Daniel, C Wakerley
Journal: The Journal of Experimental Medicine (1976)

Evidence is presented that there are differences between pig liver and kidney parenchymal cells in the expression of major histocompatibility complex antigens. Analogues of I-region antigens of the mouse are detectable on kidney cells and some peripheral blood leukocytes (PBL) but not on liver, platelets, and other PBL. Such differences between liver and kidney may explain (a) the fate of these organs as allografts and (b) the donor-specific protection of kidney by liver. Other antigens peculiar to skin and kidney have been detected but require further characterization.
Preventable Hospitalizations and Access to Health Care
Authors: Andrew B. Bindman
Journal: JAMA (1995)

<h3>Objective.</h3> —To examine whether the higher hospital admission rates for chronic medical conditions such as asthma, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and diabetes in low-income communities resulted from community differences in access to care, prevalence of the diseases, propensity to seek care, or physician admitting style. <h3>Design.</h3> —Analysis of California hospital discharge data. We calculated the hospitalization rates for these five chronic conditions for the 250 ZIP code clusters that define urban California. We performed a random-digit telephone survey among adults residing in a random sample of 41 of these urban ZIP code clusters stratified by admission rates and a mailed survey of generalist and emergency physicians who practiced in the same 41 areas. <h3>Setting.</h3> —Community based. <h3>Participants.</h3> —A total of 6674 English- and Spanish-speaking adults aged 18 through 64 years residing in the 41 areas were asked about their access to care, their chronic medical conditions, and their propensity to seek health care. Physician admitting style was measured with written clinical vignettes among 723 generalist and emergency physicians practicing in the same communities. <h3>Main Outcome Measures.</h3> —We compared respondents' reports of access to medical care in an area with the area's cumulative admission rate for these five chronic conditions. We then tested whether access to medical care remained independently associated with preventable hospitalization rates after controlling for the prevalence of the conditions, health care seeking, and physician practice style. <h3>Results.</h3> —Access to care was inversely associated with the hospitalization rates for the five chronic medical conditions (<i>R</i><sup>2</sup>=0.50;<i>P</i>&lt;.001). In a multivariate analysis that included a measure of access, the prevalence of conditions, health care seeking, and physician practice style to predict cumulative hospitalization rates for chronic medical conditions, both self-rated access to care (<i>P</i>&lt;.002) and the prevalence of the conditions (<i>P</i>&lt;.03) remained independent predictors. <h3>Conclusion.</h3> —Communities where people perceive poor access to medical care have higher rates of hospitalization for chronic diseases. Improving access to care is more likely than changing patients' propensity to seek health care or eliminating variation in physician practice style to reduce hospitalization rates for chronic conditions. (<i>JAMA</i>. 1995;274:305-311)
EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria
Authors: S. Ozen, A. Pistorio, S. M. Iusan, A. Bakkaloglu, T. Herlin, R. Brik, A. Buoncompagni, C. Lazar, I. Bilge, Y. Uziel, D. Rigante, L. Cantarini, M. O. Hilario, C. A. Silva, M. Alegria, X. Norambuena, A. Belot, Y. Berkun, A. I. Estrella, A. N. Olivieri, M. G. Alpigiani, I. Rumba, F. Sztajnbok, L. Tambic-Bukovac, L. Breda, S. Al-Mayouf, D. Mihaylova, V. Chasnyk, C. Sengler, M. Klein-Gitelman, D. Djeddi, L. Nuno, C. Pruunsild, J. Brunner, A. Kondi, K. Pagava, S. Pederzoli, A. Martini, N. Ruperto
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> To validate the previously proposed classification criteria for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). <h3>Methods</h3> Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and κ-agreement) and nominal group technique consensus evaluations. <h3>Results</h3> 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. <h3>Conclusion</h3> European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.
Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis
Authors: Michael Safaee, Michael C. Oh, Orin Bloch, Matthew Z. Sun, Gurvinder Kaur, Kurtis I. Auguste, Tarik Tihan, Andrew T. Parsa
Journal: Neuro-Oncology (2012)

Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.
Selective Estrogen Receptor Modulators: Clinical Spectrum*
Authors: Felicia Cosman, Robert Lindsay
Journal: Endocrine Reviews (1999)

I. Introduction II. Breast Effects A. Women with primary breast cancer without metastases B. Women with metastatic disease C. Breast cancer prevention III. Reproductive System Effects A. Ovary B. Uterus C. Vagina D. Neuroendocrine IV. Skeletal Effects: Bone Mass, Bone Metabolism, and Fracture Occurrence A. Tamoxifen B. Raloxifene V. Vascular System Effects: Intermediate Markers and Disease Outcomes A. Intermediate markers B. Vascular disease outcomes VI. Central Nervous System Effects A. Cognitive function and mood B. Eye disease VII. Hepatic Effects VIII. Miscellaneous Effects IX. Conclusion
Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors
Authors: Cheryl L. Rock, Shirley W. Flatt, Tim E. Byers, Graham A. Colditz, Wendy Demark-Wahnefried, Patricia A. Ganz, Kathleen Y. Wolin, Anthony Elias, Helen Krontiras, Jingxia Liu, Michael Naughton, Bilgé Pakiz, Barbara A. Parker, Rebecca L. Sedjo, Holly Wyatt
Journal: Journal of Clinical Oncology (2015)

Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is the largest weight loss intervention trial among survivors of breast cancer to date.In this multicenter trial, 692 overweight/obese women who were, on average, 2 years since primary treatment for early-stage breast cancer were randomly assigned to either a group-based behavioral intervention, supplemented with telephone counseling and tailored newsletters, to support weight loss or a less intensive control intervention and observed for 2 years. Weight and blood pressure were measured at 6, 12, 18, and 24 months. Longitudinal mixed models were used to analyze change over time.At 12 months, mean weight loss was 6.0% of initial weight in the intervention group and 1.5% in the control group (P<.001). At 24 months, mean weight loss in the intervention and control groups was 3.7% and 1.3%, respectively (P<.001). Favorable effects of the intervention on physical activity and blood pressure were observed. The weight loss intervention was more effective among women older than 55 years than among younger women.A behavioral weight loss intervention can lead to clinically meaningful weight loss in overweight/obese survivors of breast cancer. These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival.