tbuckley/cabot-search huggingface dataset:
The Role of Hypocretins (Orexins) in Sleep Regulation and Narcolepsy
Authors: Shahrad Taheri, Jamie M. Zeitzer, Emmanuel Mignot
Journal: Annual Review of Neuroscience (2002)

▪ Abstract The hypocretins (orexins) are two novel neuropeptides (Hcrt-1 and Hcrt-2), derived from the same precursor gene, that are synthesized by neurons located exclusively in the lateral, posterior, and perifornical hypothalamus. Hypocretin-containing neurons have widespread projections throughout the CNS with particularly dense excitatory projections to monoaminergic centers such as the noradrenergic locus coeruleus, histaminergic tuberomammillary nucleus, serotoninergic raphe nucleus, and dopaminergic ventral tegmental area. The hypocretins were originally believed to be primarily important in the regulation of appetite; however, a major function emerging from research on these neuropeptides is the regulation of sleep and wakefulness. Deficiency in hypocretin neurotransmission results in the sleep disorder narcolepsy in mice, dogs, and humans. The hypocretins are also uniquely positioned to link sleep, appetite, and neuroendocrine control. The aim of this review is to describe and discuss the current knowledge regarding the hypocretin neurotransmitter system in narcolepsy and normal sleep.
Expression of xenobiotic-metabolizing enzymes in human pulmonary tissue: possible role in susceptibility for ILD
Authors: J Hukkanen, O Pelkonen, H Raunio
Journal: European Respiratory Journal (2001)

The lung is a major target for all inhaled toxicants. Many inhaled chemicals are not hazardous as such, but are biotransformed to reactive intermediates. Therefore, the pathogenesis of interstitial and other lung diseases is intimately linked to exposure to environmental and other chemicals, which may be causative or modifying factors in the cellular pathways and mechanisms mediating oxidative stress and cell protection in the pulmonary tissue. Several different xenobiotic-metabolizing cytochrome P450 (CYP) and phase II enzymes ( i.e. conjugation enzymes including several transferases) are present in the human lung and lung-derived cell lines, possibly contributing to in situ activation and inactivation of chemical toxicants. This paper describes the expression and localization of individual CYP‐forms in the lung. Interindividual differences in the expression of these enzymes may contribute to the risk of developing interstitial and other lung diseases initiated by agents that require metabolic activation.
Vildagliptin Improves Endothelium-Dependent Vasodilatation in Type 2 Diabetes
Authors: Pleun C.M. van Poppel, Mihai G. Netea, Paul Smits, Cees J. Tack
Journal: Diabetes Care (2011)

To investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes.Sixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m(2), HbA(1c) 6.97 ± 0.61) on oral blood glucose-lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator).Infusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL(-1) ⋅ min(-1) in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL(-1) ⋅ min(-1), respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside.Four weeks' treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications.
Drug Prices and Value for Money
Authors: David A. Henry, Suzanne R. Hill, Anthony Harris
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of a Long-acting β<sub>2</sub>-Agonist over Three Months on Airway Wall Vascular Remodeling in Asthma
Authors: BERNADETTE E. ORSIDA, CHRIS WARD, XUN LI, ROS BISH, JOHN W. WILSON, FRANK THIEN, E. HAYDN WALTERS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

There are few data regarding the potential effects of antiasthma treatment on indices of airway remodeling, such as the increased subepithelial airway vascularity in patients with asthma. We studied 45 symptomatic subjects with asthma who were receiving treatment with low dose inhaled corticosteroids (ICS) (range 200-500 microg twice a day) and 28 normal subjects without asthma as a control population. Subjects underwent bronchoscopy with airway biopsy and subjects with asthma were then randomized to receive supplementary inhaled salmeterol 50 microg twice a day, fluticasone propionate 100 microg twice a day, or placebo for 3 mo in addition to their baseline ICS. Biopsy of the airway was then repeated. The biopsies were analyzed for vascular structures in the subepithelial lamina propria. Sufficient biopsy material was available for analysis of vascularity in 34 of the subjects with asthma and 28 of the normal subjects. We confirmed that airways of subjects with asthma had a significant increase in the number of vessels/mm2 of lamina propria compared with airways of normal subjects (524 +/- 137 vessels/mm2, n = 34 versus 425 +/- 130 vessels/mm2, n = 28; p = 0.004). There was a decrease in the density of vessels of lamina propria after treatment only in the salmeterol group compared with baseline (before, 535 +/- 153 vessels/mm2 versus after, 400 +/- 142 vessels/mm2; n = 12; p = 0.04). There was no significant change within the fluticasone (n = 11) or placebo (n = 11) treatment groups, but also no significant differences between the groups. Notably, no treatment was associated with increased airway wall vascularity. The demonstrated fall in vessel number within the salmeterol-treated group may suggest an advantageous effect of long-acting beta2-agonists on this manifestation of airway remodeling over the 3-mo time scale of this study, which is complementary to the action of ICS on airway vascularity.
The effects of selected probiotic strains on the development of eczema (the PandA study)
Authors: L. Niers, R. Martín, G. Rijkers, F. Sengers, H. Timmerman, N. Van Uden, H. Smidt, J. Kimpen, M. Hoekstra
Journal: Allergy (2009)

Modification of the intestinal microbiota by administration of probiotic bacteria may be a potential approach to prevent allergic disease. We aimed to study primary prevention of allergic disease in high-risk children by pre- and postnatal supplementation of selected probiotic bacteria.In a double-blind, randomized, placebo-controlled trial, a mixture of probiotic bacteria selected by in-vitro experiments (Bifidobacterium bifidum, Bifidobacterium lactis, and Lactococcus lactis; Ecologic Panda) was prenatally administered to mothers of high-risk children (i.e. positive family history of allergic disease) and to their offspring for the first 12 months of life.Parental-reported eczema during the first 3 months of life was significantly lower in the intervention group compared with placebo, 6/50 vs 15/52 (P = 0.035). After 3 months, the incidence of eczema was similar in both groups. Cumulative incidence of parental-reported eczema at 1 and 2 years was 23/50 (intervention) vs 31/48 (placebo) and 27 (intervention) vs 34 (placebo), respectively. The number needed to treat was 5.9 at age 3 and 12 months and 6.7 at age 2 years. The intervention group was significantly more frequently colonized with higher numbers of Lc. lactis. Furthermore, at age 3 months, in vitro production of IL-5 (146 pg/ml vs 72 pg/ml; P = 0.04) was decreased in the probiotic-group compared with the placebo-group.This particular combination of probiotic bacteria shows a preventive effect on the incidence of eczema in high-risk children, which seems to be sustained during the first 2 years of life. In addition to previous studies, the preventive effect appears to be established within the first 3 months of life.
Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration
Authors: R J Verburg
Journal: Annals of the Rheumatic Diseases (2005)

To determine clinical and immunological correlates of high dose chemotherapy (HDC) + autologous stem cell transplantation (ASCT) in patients with severe rheumatoid arthritis (RA), refractory to conventional treatment.Serial samples of peripheral blood and synovial tissue were obtained from seven patients with RA treated with HDC and autologous peripheral blood grafts enriched for CD34+ cells. Disease activity was assessed with the Disease Activity Score (DAS), serum concentrations of C reactive protein (CRP), and human immunoglobulin (HIg) scans, and the extent of immunoablation was determined by immunophenotyping of peripheral blood mononuclear cells, and immunohistochemistry and double immunofluorescence of synovium.Clinical responders (n = 5) had a larger number of cells at baseline expressing CD3, CD4, CD27, CD45RA, CD45RB, and CD45RO in synovium (p < 0.05), higher activity on HIg scans (p = 0.08), and a trend towards higher concentrations of CRP in serum than non-responders (n = 2). Subsequent remissions and relapses in responders paralleled reduction and re-expression, respectively, of T cell markers. A relatively increased expression of CD45RB and CD45RO on synovial CD3+ T cells was seen after HDC + ASCT. No correlations were found between DAS and changes in B cells or macrophage infiltration or synoviocytes.HDC + ASCT results in profound but incomplete immunoablation of both the memory and naïve T cell compartment, which is associated with longlasting clinical responses in most patients. The findings provide strong circumstantial evidence for a role of T cells in established RA, and demonstrate a role for the synovium in post-transplantation T cell reconstitution.
Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S
Authors: Thanyaphong Na Nakorn, David Traver, Irving L. Weissman, Koichi Akashi
Journal: Journal of Clinical Investigation (2002)

Whole-body irradiation at the minimal lethal dose causes bone marrow failure and death within 12–18 days. To identify the principal components of the hematopoietic system that are radioprotective, we transplanted lethally irradiated mice with purified progenitors: common myeloid progenitors (CMPs), megakaryocyte/erythrocyte-restricted progenitors (MEPs), or granulocyte/monocyte-restricted progenitors (GMPs). Transplanted CMPs gave rise to cells both of the granulocyte/monocyte (GM) series and the megakaryocyte/erythrocyte series, whereas GMPs or MEPs showed reconstitution of only GM or ME cells, respectively. CMPs and MEPs but not GMPs protected mice in a dose-dependent manner, suggesting that erythrocytes, platelets, or both are the critical effectors of radioprotection. Accordingly, CMPs and MEPs formed robust colonies in recipient bone marrow and spleen, whereas GMPs formed small colonies that rapidly disappeared. Direct comparisons of spleen CFU (CFU-S) potentials among each progenitor subset showed that MEPs contain the vast majority of day 8 CFU-S activity, suggesting that day 8 CFU-S are the precursors of radioprotective cell subsets. All animals radioprotected for 30 days subsequently survived for at least 6 months post-transplant, and showed only host-derived hematopoiesis after 30 days. These findings suggest that rare hematopoietic stem cells survive myeloablation that can eventually repopulate irradiated hosts if myeloerythroid-restricted progenitors transiently rescue ablated animals through the critical window of bone marrow failure.
Metronomic Oral Topotecan with Pazopanib Is an Active Antiangiogenic Regimen in Mouse Models of Aggressive Pediatric Solid Tumor
Authors: Sushil Kumar, Reza Bayat Mokhtari, Reihaneh Sheikh, Bing Wu, Libo Zhang, Ping Xu, Shan Man, Indhira Dias Oliveira, Herman Yeger, Robert S. Kerbel, Sylvain Baruchel
Journal: Clinical Cancer Research (2011)

Low dose metronomic (LDM) chemotherapy, combined with VEGF signaling pathway inhibitors, is a highly effective strategy to coordinately inhibit angiogenesis and tumor growth in many adult preclinical cancer models. We have tested the efficacies of daily oral LDM topotecan alone and in combination with pazopanib, a VEGF receptor inhibitor, in three pediatric extracranial solid tumor mouse models.In vitro dose-response study of topotecan and pazopanib was conducted on several neuroblastoma, osteosarcoma, and rhabdomyosarcoma cell lines. In vivo antitumor efficacies of the LDM topotecan and pazopanib as single agents and in combination were tested on 4 subcutaneous xenograft models and on 2 neuroblastoma metastatic models. Circulating angiogenic factors such as circulating endothelial cells (CEC), circulating endothelial pro genitor cells (CEP), and microvessel densities were used as surrogate biomarker markers of antiangiogenic activity.In vitro, topotecan caused a dose-dependent decrease in viabilities of all cell lines, while pazopanib did not. In vivo, combination of topotecan + pazopanib (TP + PZ) showed significant antitumor activity and significant enhancement in survival compared with the respective single agents in all models. Reductions in viable CEP and/or CEC levels and tumor microvessel density were correlated with tumor response and therefore confirmed the antiangiogenic activity of the regimens. Pharmacokinetic studies of both drugs did not reveal any drug-drug interaction.Metronomic administration of TP + PZ showed a statistically significant antitumor activity compared with respective single agents in pediatric tumor mouse models and represent a valid option as a maintenance therapy in aggressive pediatric solid tumors.
A Phase 2 Trial of Dasatinib in Patients with Advanced HER2-Positive and/or Hormone Receptor–Positive Breast Cancer
Authors: Erica L. Mayer, Jean-Francois Baurain, Joseph Sparano, Lewis Strauss, Mario Campone, Pierre Fumoleau, Hope Rugo, Ahmad Awada, Oumar Sy, Antonio Llombart-Cussac
Journal: Clinical Cancer Research (2011)

SRC-family kinases (SFK) are involved in numerous oncogenic signaling pathways. A phase 2 trial of dasatinib, a potent oral tyrosine kinase inhibitor of SFKs, was carried out in patients with human epidermal growth factor receptor 2-positive (HER2+) and/or hormone receptor-positive (HR+) advanced breast cancer.Patients with measurable tumors and progression after chemotherapy and HER2 and/or HR-targeted agents in adjuvant or metastatic settings (maximum of two prior metastatic setting regimens) received twice daily dasatinib. Primary endpoint was Response Evaluation Criteria in Solid Tumors-defined response rate. Secondary endpoints included toxicity and limited pharmacokinetics.Seventy patients (55 years median age) were treated, 83% of HER2+ patients had received prior HER2-directed therapy, and 61% of HR+ patients had received prior endocrine therapy in the advanced setting. Dasatinib starting dose was reduced from 100 to 70 mg twice daily to limit toxicity. Median therapy duration was 1.8 months in both dose groups and most discontinuations were due to progression. Of 69 evaluable patients, three had confirmed partial responses and six had stable disease for 16 weeks or more (disease control rate = 13.0%); all nine of these tumors were HR+ (two were also HER2+). The most common drug-related toxicities were gastrointestinal complaints, headache, asthenia, and pleural effusion. Grade 3-4 toxicity occurred in 37% of patients and was comparable between doses; drug-related serious adverse events were less frequent with 70 mg twice daily than 100 mg twice daily.Limited single-agent activity was observed with dasatinib in patients with advanced HR+ breast cancer.
Points: Emphysema--beginning of an understanding
Authors: R G Dalton
Journal: BMJ (1980)

Social class and private referrals Patients opting Total referred for private Social class population referral 1 5 % 9% 2 22-9% 40°% 3 56-6% 440°o 4 12-1% 6°,' 5 3-2°1% N= 694(100%) N= 139(100°o)health insurance schemes.Of 43 domiciliary visits by specialists, 10 (23 %) were carried out in private consultations although only six (14%) patients belonged to a private health insurance scheme.I agree that much more information is required about private practice in this country but I submit that the statistics presented here are rather more "central" than "peripheral."
ALS and NIV: A four-year experience in the "NEMO" centre in Italy. A retrospective study
Authors: Barbara Garabelli, Elisa De Mattia, Marino Iatomasi, Elisabetta Roma, Elisa Falcier, Christian Lunetta, Fabrizio Rao
Journal: European Respiratory Journal (2013)

INTRODUCTION

In literature, bulbar ALS patients (pts) have always been related to worse NIV tolerance and survival. There is no clear agreement on NIV parameters to be used.

AIM

To describe the NIV path in ALS pts attending in the “Nemo” centre, to compare survival differences between onsets, to outline the relationship between respiratory, disability (ALS FRS-R) and NIV parameters.

METHOD

Our database includes 535 ALS pts, 147 attained our centre between 2008 and 2011 and had their respiratory function been tested from baseline to NIV adaptation and use, until exitus or tracheostomy. From this group, we enrolled 78 pts in a randomized way. Parametric tests were used to compare groups.

RESULTS

Bulbar pts have the higher diaphragmatic impairment and the worst orthostatic/clinostatic FVC (p=0,038), nevertheless with EPAP titration higher than 4 cmH2O (5,73 ± 1,53) and a proper care of bulbar impairment they can have good tolerance and survive as long as general population. In these pts clinostatic FVC relates directly to ALS FRS-R bulbar and respiratory scores (p<0,01).

![Figure][1] 



CONCLUSION

EPAP set higher than 4 cm H2O to reduce ODI, normalize VT and increase SpO2 in NIV permits better tolerance and adherence in all pts. This allows bulbar pts to have a duration of illness from NIV adaptation comparable to other onsets. ALSFRS-R is an accurate measure of respiratory impairment.

 [1]: pending:yes
Fetal microchimerism in normal breast in healthy women and women with breast cancer.
Authors: AD Walline, V Gadi
Journal: Cancer Research (2009)

Abstract Abstract #5048 Introduction: A lasting legacy of a fetus to his mother is a small number of stably persistent allogeneic cells, a phenomenon known as fetal microchimerism. We have been testing the hypothesis that fetal microchimerism is protective against cancer in the mother by participation in immune surveillance. Prior studies demonstrated that fetal microchimerism in the peripheral blood is associated with protection from breast cancer (Cancer Res, 67(19):9035-8 and PLoS ONE, 3(3):e1706). Here we examine whether the same association of fetal microchimerism extends to the tissue of interest, the breast.&amp;#x2028; Methods: Total genomic DNA was extracted from frozen normal breast tissue adjacent to invasive disease in women with breast cancer. Control tissues were from reduction mammoplasty procedures performed for women with no prior history of invasive breast cancer. The presence of male DNA, presumably from a prior male fetus, was tested with a quantitative PCR assay for the Y chromosome gene, DYS14. Proportions of tissues harboring fetal microchimerism were compared between women with and without prior history of invasive breast cancer.&amp;#x2028; Results: At present, tissues from 19 women with cancer and 19 without have been tested for the presence and quantity of fetal microchimerism using the DYS14 assay. Fetal microchimerism was detected less frequently in tissues from women with cancer (26%) than without (63%). The odds ratio for this protective association of fetal microchimerism with breast cancer is 0.21 (0.04-1.0 95% confidence interval; p=0.05). A trend towards larger median quantities of fetal microchimerism was noted in control tissues versus normal breast from cancer patients (0.34 versus 0 fetal genomes/million maternal cells, p&amp;gt;0.05).&amp;#x2028; Conclusions: Preliminary results suggest that the negative association of breast cancer and fetal microchimerism observed previously in the blood is also reflected at the level of the tissue of interest. These results merit further investigation in the breast tissue of controls to identify the phenotype of the cells detected. Furthermore, the findings here provide further support to the overall hypothesis that fetal microchimerism may participate in immune surveillance against breast cancer in healthy women. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5048.