tbuckley/cabot-search huggingface dataset:
The Tachykinin Peptide Family
Authors: C. Severini
Journal: Pharmacological Reviews (2002)

The tachykinin peptide family certainly represents one of the largest peptide families described in the animal organism. So far, more than 40 tachykinins have been isolated from invertebrate (insects, worms, and molluscs), protochordate, and vertebrate (skin, gastrointestinal tract, peripheral and central nervous system) tissues. Substance P (SP), first identified by bioassay as early as 1931 but sequenced only in 1971, several years after the elucidation of the structure of eledoisin from molluscan tissues and of physalaemin from amphibian skin, may be considered as a prototype of the tachykinins. Hitherto, as many as 19 tachykinins have been isolated from amphibian integument, and eight additional peptides have been isolated from amphibian gut and brain. Counterparts of skin tachykinins in mammalian tissues are SP, neurokinin A, and neurokinin B. Three main receptor subtypes for the tachykinins have been identified (NK1, NK2, and NK3), but their number is probably destined to increase. It is obvious that the peripheral and central effects of the tachykinins may substantially vary depending on the activation of different receptor subtypes. Matters are further complicated by the frequent capacity of the single tachykinins to bind, although with different affinity, to more receptors. It has been recognized that tachykinins have a variety of effects in physiological and pathological conditions, and there is evidence suggesting intrinsic neuroprotective and neurodegenerative properties of these neuropeptides. This review provides an update on the current body of knowledge regarding tachykinin occurrence and distribution in the animal kingdom, from the lowest invertebrates to man, and the physiological and pharmacological actions of tachykinins outlining the pregnant importance of this large peptide family.
Circulating KL-6 Predicts the Outcome of Rapidly Progressive Idiopathic Pulmonary Fibrosis
Authors: AKIHITO YOKOYAMA, NOBUOKI KOHNO, HIRONOBU HAMADA, MITSUNORI SAKATANI, EINOSUKE UEDA, KEIICHI KONDO, YUTAKA HIRASAWA, KUNIO HIWADA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Searching for early predictive markers of the therapeutic effects of high-dose corticosteroids ("pulse therapy") on patients with rapidly progressing idiopathic pulmonary fibrosis (IPF), we evaluated 14 such patients, who had received weekly pulse therapy for at least 3 wk. Eight patients responded to the treatment and survived. However, six patients failed to respond, and all of them died within 3 mo after treatment. Serum levels of KL-6 (MUC1 mucin), neutrophil elastase (NE), and lactate dehydrogenase (LDH) were measured before, and at 1 wk and 3 wk after treatment. Levels of KL-6 decreased significantly in patients who lived, whereas KL-6 levels tended to increase in patients who died. The values of NE did not change significantly. LDH levels decreased significantly at 1 wk, and tended to decrease at 3 wk in patients who lived. However, in patients who died, they did not significantly change. At the first cycle of treatment when clinical effects may not be evident, the decrease in KL-6 but not LDH levels was significantly related to a favorable outcome, whereas their increase was related to a poor outcome. Results suggest that monitoring with KL-6 may contribute to early clinical decisions for alternative therapy in the management of rapidly progressing IPF.
Correlation of lung surface area to apoptosis and proliferation in human emphysema
Authors: K. Imai, B. A. Mercer, L. L. Schulman, J. R. Sonett, J. M. D'Armiento
Journal: European Respiratory Journal (2005)

Pulmonary emphysema is associated with alterations in matrix proteins and protease activity. These alterations may be linked to programmed cell death by apoptosis, potentially influencing lung architecture and lung function. To evaluate apoptosis in emphysema, lung tissue was analysed from 10 emphysema patients and six individuals without emphysema (normal). Morphological analysis revealed alveolar cells in emphysematous lungs with convoluted nuclei characteristic of apoptosis. DNA fragmentation was detected using terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) and gel electrophoresis. TUNEL revealed higher apoptosis in emphysematous than normal lungs. Markers of apoptosis, including active caspase-3, proteolytic fragment of poly (ADP-ribose) polymerase, Bax and Bad, were detected in emphysematous lungs. Linear regression showed that apoptosis was inversely correlated with surface area. Emphysematous lungs demonstrated lower surface areas and increased cell proliferation. There was no correlation between apoptosis and proliferation, suggesting that, although both events increase during emphysema, they are not in equilibrium, potentially contributing to reduced lung surface area. In summary, cell-based mechanisms associated with emphysematous parenchymal damage include increased apoptosis and cell proliferation. Apoptosis correlated with airspace enlargement, supporting epidemiological evidence of the progressive nature of emphysema. These data extend the understanding of cell dynamics and structural changes within the lung during emphysema pathogenesis.
A Phase IV, Open-label assessment of the treatment of actinic keratoses with diclofenac sodium 3% topical gel
Authors: Darrell S Rigel, Neal Swanson, John Wolf, Stacy Smith
Journal: Journal of the American Academy of Dermatology (2004)

Objectives: To determine the complete response rate (CR), cosmetic outcome (CO), recurrence rate and incidence of adverse events (AE) of Photodynamic Therapy with Methyl Aminolevulinate (MAL PDT) in patients with difficult to treat Basal Cell Carcinoma (BCC) due to large lesion size or location in the H-zone, or risk factors for surgery.Methods: Patients received 2 treatments with MAL PDT one week apart.After lesion preparation and 3 hours of occlusion with MAL cream, the lesion was illuminated with 75J/cm 2 of red light (570-670nm).If there was a non-complete response after 3 months, the lesion was re-treated.Results: One hundred and two patients were treated; 95 patients with 148 lesions were included in the PP analysis.55% of the lesions were very large, 19% located in the H-zone.3 patients were included because of surgical risk factors alone.23% of the patients received 2 treatment cycles.The histologically confirmed complete response rate after 3 months was 89% (131/148 lesions).9 lesions (6%) recurred within 12 months.65% of patients with CR had good or excellent CO according to investigators, 98% according to patients.Seventy-nine percent of patients reported AEs, mainly local photoxic reactions (erythema and burning sensation/pain).Symptoms were transient and mostly of mild severity.Conclusions: MAL PDT was effective in patients with "difficult to treat" BCC and the cosmetic outcome was mostly good or excellent.MAL PDT was well tolerated and may be a good alternative to conventional modalities which carry risks of disfigurement or inferior cosmetic outcome.Follow up is underway to determine long-term recurrence rate.
Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: Final results of BSG 98 prospective trial
Authors: Didier Frappaz, Matthias Schell, Philippe Thiesse, Perrine Marec-Bérard, Carmine Mottolese, David Perol, Christophe Bergeron, Thierry Philip, Anne Claire Ricci, Sophie Galand-Desme, Alexandru Szathmari, Christian Carrie
Journal: Neuro-Oncology (2008)

Radiation therapy remains the only treatment that provides clinical benefit to children with diffuse brainstem tumors. Their median survival, however, rarely exceeds 9 months. The authors report a prospective trial of frontline chemotherapy aimed at delaying radiation until time of clinical progression. The aim was to investigate the possibility that radiotherapy would maintain its activity in children whose disease progressed after chemotherapy. Twenty-three patients took part in this protocol, the BSG 98 protocol, which consisted of frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules. Each cycle included three courses delivered monthly; the first course was 1,3-bis(2-chloroethyl)-1-nitrosoureacisplatin, and the second and third were high-dose methotrexate. Three patients underwent one cycle; 5 patients each, two and three cycles; and 10 patients, four cycles. Twenty of the 23 patients eventually received local radiation therapy. A historical cohort of 14 patients who received at least local radiation therapy served as controls. Four patients experienced severe iatrogenic infections, and 11 patients required platelet transfusions. Median survival increased significantly in patients participating in the protocol compared to that in the historical controls (17 months, 95% confidence interval [CI], 10-23 months, vs. 9 months, 95% CI, 8-10 months; p = 0.022), though hospitalization was prolonged (57 vs. 25 days, p = 0.001). Although frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules significantly increases overall median survival, its cost from infection and hospitalization deserves honest discussion with the children and their parents.
Chronic thromboembolic pulmonary hypertension at the crossroad
Authors: Marius M. Hoeper
Journal: European Respiratory Journal (2014)

Chronic thromboembolic pulmonary hypertension (CTPEH) is one of the few forms of pulmonary hypertension for which we have a clear and undisputed solution, i.e. pulmonary endarterectomy (PEA). In the vast majority of patients, PEA markedly improves or even cures the disease [1]. Over the years, surgeons have continuously improved their skills and are now reaching beyond the level of the subsegmental vessels. Patients, who would have been considered inoperable a couple of years ago, are now undergoing surgery and are surviving and doing well! In San Diego (CA, USA), considered the epicentre of the PEA universe, the in-hospital mortality for the most recent 500 surgeries in this field was 2.2% with no mortalities among the last 260 procedures; despite the patients presenting with more peripheral disease and more co-morbidities [2]. Recent reports from other centres are comparable [3, 4].

So, why even think about alternative therapies? Well, first of all, some patients are not operable, not even in the most experienced of centres. Occasionally, small-vessel disease dominates the picture and in such cases PEA is not a good option given a high risk of persistent pulmonary hypertension and a high mortality [5–7]. In fact, even after successful PEA, up to …
Strength training and detraining effects on muscular strength, anaerobic power, and mobility of inactive older men are intensity dependent
Authors: I G Fatouros, A Kambas, I Katrabasas, K Nikolaidis, A Chatzinikolaou, D Leontsini, K Taxildaris
Journal: British Journal of Sports Medicine (2005)

Although strength training (ST) enhances physical function in the elderly, little is known about the effect of training intensity on training and detraining adaptations in musculoskeletal fitness.To determine the effect of exercise intensity on strength, anaerobic power, and mobility of older men subjected to a 24 week ST protocol followed by prolonged detraining.Fifty two healthy but inactive older men (mean (SD) age 71.2 (4.1) years) were assigned to a control (n = 14), low intensity training (LIST; n = 18; 55% 1RM), or high intensity training (HIST; n = 20; 82% 1RM) group. They carried out a 24 week, whole body (10 exercises, two to three sets/exercise) ST programme followed by a 48 week detraining period. Upper and lower body strength, anaerobic power (Wingate testing), and mobility (timed up and go, walking, climbing stairs) were measured at baseline and immediately after training and during detraining.Although low intensity training improved (p<0.05) strength (42-66%), anaerobic power (10%), and mobility (5-7%), high intensity training elicited greater (p<0.05) gains (63-91% in strength, 17-25% in anaerobic power, 9-14% in mobility). All training induced gains in the LIST group had been abolished after four to eight months of detraining, whereas in the HIST group strength and mobility gains were maintained throughout detraining. However, anaerobic power had returned to baseline levels after four months of detraining in both groups.Higher intensity training protocols induce greater gains in strength, anaerobic power, and whole body physical function of older men. Moreover, higher intensity training may maintain the gains for more prolonged periods after training ceases.
Endothelial, inducible and neuronal nitric oxide synthase in congenital pulmonary lymphangiectasis
Authors: T. Hoehn, M. William, A. R. McPhaden, H. Stannigel, E. Mayatepek, R. M. Wadsworth
Journal: European Respiratory Journal (2006)

Abnormal growth and development of lymphatic pulmonary structures leads to severe hypoxia in congenital pulmonary lymphangiectasis (CPL). This case study aims to determine the cellular source and topographical distribution of the nitric oxide synthases in CPL. It studies the post mortem tissue of a term newborn with the clinical course and histological findings of CPL and three controls without pulmonary pathology. It was found that endothelial cells of pulmonary arteries and lymphatic structures stained significantly more for endothelial nitric oxide synthase protein in the CPL patient compared to the controls. The authors conclude that synthesis of endothelial nitric oxide synthase is upregulated in vascular and lymphatic endothelial cells in congenital pulmonary lymphangiectasis.
Distinct Roles for Signals Relayed through the Common Cytokine Receptor γ Chain and Interleukin 7 Receptor α Chain in Natural T Cell Development
Authors: Alina Boesteanu, A. Dharshan De Silva, Hiroshi Nakajima, Warren J. Leonard, Jacques J. Peschon, Sebastian Joyce
Journal: The Journal of Experimental Medicine (1997)

The commitment, differentiation, and expansion of mainstream α/β T cells during ontogeny depend on the highly controlled interplay of signals relayed by cytokines through their receptors on progenitor cells. The role of cytokines in the development of natural killer (NK)1+ natural T cells is less clearly understood. In an approach to define the role of cytokines in the commitment, differentiation, and expansion of NK1+ T cells, their development was studied in common cytokine receptor γ chain (γc) and interleukin (IL)-7 receptor α (IL-7Rα)–deficient mice. These mutations block mainstream α/β T cell ontogeny at an early prethymocyte stage. Natural T cells do not develop in γc-deficient mice; they are absent in the thymus and peripheral lymphoid organs such as the liver and the spleen. In contrast, NK1+ T cells develop in IL-7Rα–deficient mice in the thymus, and they are present in the liver and in the spleen. However, the absolute number of NK1+ T cells in the thymus of IL-7Rα–deficient mice is reduced to ∼10%, compared to natural T cell number in the wild-type thymus. Additional data revealed that NK1+ T cell ontogeny is not impaired in IL-2– or IL-4–deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development. From these data, we conclude that commitment and/or differentiation to the NK1+ natural T cell lineage requires signal transduction through the γc, and once committed, their expansion requires signals relayed through the IL-7Rα.
Therapeutic benefits of increasing natriuretic peptide levels
Authors: H Peter Brunner-La Rocca
Journal: Cardiovascular Research (2001)

Natriuretic peptides play an important role in water and salt homeostasis and in the regulation of the cardiovascular system. In recent years, exogenous administration of natriuretic peptides has primarily been used to improve our understanding of the role of natriuretic peptides. Also, it became evident that natriuretic peptides may be used therapeutically. Because of their peptide character, they cannot be administered orally and, therefore, may be used for short-term intravenous therapy only. In recent years, inhibitors of neutral endopeptidase, which degrades natriuretic peptides to inactive metabolites, have been investigated. This review focuses on the potential benefits of increasing natriuretic peptide levels, either through exogenous administration or inhibiting the degradation of endogenous natriuretic peptides.
Primary chemotherapy for clinical stage II nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients.
Authors: C J Logothetis, D A Swanson, F Dexeus, C Chong, S Ogden, A G Ayala, A C von Eschenbach, D E Johnson, M L Samuels
Journal: Journal of Clinical Oncology (1987)

Fifty patients with clinical stage II nonseminomatous germ cell tumor of the testis (NSGCTT) were treated with primary chemotherapy followed by a retroperitoneal lymph node dissection (RPLND) in selected patients. The study population included 34 patients with retroperitoneal masses and elevated levels of serum biomarkers (alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [BHCG] ), five with needle aspiration biopsy-proven retroperitoneal metastases but normal levels of biomarkers, and 11 in whom there were rising levels of serum biomarkers but no radiographic evidence of retroperitoneal metastases. Forty-eight patients (96%) achieved a complete response (CR), with a mean disease-free survival of 132 weeks (range, 55 to 273 weeks). Two patients developed recurrent disease. One died and one achieved a second CR with further therapy (48 + weeks). Postchemotherapy RPLND was required in 11 patients (22%). Patients with embryonal carcinoma had a lower frequency of RPLND (8%) than patients with teratomatous elements in their primary tumor [36%, P = .014]. To reduce the frequency of double therapy (surgery +/- chemotherapy), we propose individualized therapy. Patients presenting with clinical stage II embryonal carcinoma of the testis should receive primary chemotherapy. Patients with clinical stage II NSGCTT and teratomatous elements in their primary tumor continue to require an RPLND. Those patients with intermediate volume disease (greater than 2 cm less than or equal to 5 cm in maximum diameter) may be treated with an RPLND only. Patients with higher volume teratomatous elements (greater than 5 cm less than or equal to 10 cm in maximum diameter) are likely to require the combination of chemotherapy and surgery.
INDUCTION OF A PRIMARY ANTIHAPTEN RESPONSE IN VIVO BY A GRAFT-VS.-HOST REACTION
Authors: J. A. Hamilton, J. F. A. P. Miller
Journal: The Journal of Experimental Medicine (1973)

A primary anti-NIP PFC response can be elicited by a GVH reaction provided certain structural requirements of the NIP-carrier are met. NIP-coated F(1) erythrocytes and NIP-coated parental erythrocytes give rise to substantial anti-NIP PFC responses in F(1) mice after the injection of parental spleens. These conjugates do not of themselves give rise to an anti-NIP PFC response and, in fact, normally give rise to NIP-specific tolerance. In contrast the GVH reaction is not able to enhance the primary anti-NIP PFC response to immunogenic NIP-conjugates.
Television Watching, Leisure Time Physical Activity, and the Genetic Predisposition in Relation to Body Mass Index in Women and Men
Authors: Qibin Qi, Yanping Li, Andrea K. Chomistek, Jae H. Kang, Gary C. Curhan, Louis R. Pasquale, Walter C. Willett, Eric B. Rimm, Frank B. Hu, Lu Qi
Journal: Circulation (2012)

Background— Previous studies on gene-lifestyle interaction and obesity have focused mostly on the FTO gene and physical activity, whereas little attention has been paid to sedentary behavior as indicated by television (TV) watching. Methods and Results— We analyzed interactions between TV watching, leisure time physical activity, and genetic predisposition in relation to body mass index (BMI) in 7740 women and 4564 men from 2 prospective cohorts: The Nurses' Health Study and the Health Professionals Follow-up Study. Data on physical activity and TV watching were collected 2 years before assessment of BMI. A weighted genetic risk score was calculated on the basis of 32 established BMI-associated variants. In both women and men, the genetic associations with BMI strengthened with increased hours of TV watching. An increment of 10 points in the weighted genetic risk score was associated with 0.8 (SE, 0.4), 0.8 (SE, 0.2), 1.4 (SE, 0.2), 1.5 (SE, 0.2), and 3.4 (SE, 1.0) kg/m 2 higher BMI across the 5 categories of TV watching (0–1, 2–5, 6–20, 21–40, and &gt;40 h/wk; P for interaction=0.001). In contrast, the genetic association with BMI weakened with increased levels of physical activity. An increment of 10 points in the weighted genetic risk score was associated with 1.5 (SE, 0.2), 1.3 (SE, 0.2), 1.2 (SE, 0.2), 1.2 (SE, 0.2), and 0.8 (SE, 0.2) kg/m 2 higher BMI across the quintiles of physical activity. The interactions of TV watching and physical activity with genetic predisposition in relation to BMI were independent of each other. Conclusions— A sedentary lifestyle, indicated by prolonged TV watching, may accentuate the predisposition to elevated adiposity, whereas greater leisure time physical activity may attenuate the genetic association.
Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism
Authors: Katherine Wesseling-Perry, Renata C. Pereira, Shobha Sahney, Barbara Gales, He-Jing Wang, Robert Elashoff, Harald Jüppner, Isidro B. Salusky
Journal: Kidney International (2010)
Activation of Natural Killer T Cells Ameliorates Postinfarct Cardiac Remodeling and Failure in Mice
Authors: Mochamad Ali Sobirin, Shintaro Kinugawa, Masashige Takahashi, Arata Fukushima, Tsuneaki Homma, Taisuke Ono, Kagami Hirabayashi, Tadashi Suga, Putri Azalia, Shingo Takada, Masaru Taniguchi, Toshinori Nakayama, Naoki Ishimori, Kazuya Iwabuchi, Hiroyuki Tsutsui
Journal: Circulation Research (2012)

Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies have determined the pathophysiological role of iNKT cells in post-MI LV remodeling.The purpose of this study was to examine whether the activation of iNKT cells might affect the development of LV remodeling and failure.After creation of MI, mice received the injection of either α-galactosylceramide (αGC; n=27), the activator of iNKT cells, or phosphate-buffered saline (n=31) 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI+αGC than MI+PBS (59% versus 32%, P<0.05). LV cavity dilatation and dysfunction were significantly attenuated in MI+αGC, despite comparable infarct size, accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis. The infiltration of iNKT cells were increased during early phase in noninfarcted LV from MI and αGC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. AntienIL-10 receptor antibody abrogated these protective effects of αGC on MI remodeling. The administration of αGC into iNKT cell-deficient Jα18(-/-) mice had no such effects, suggesting that αGC was a specific activator of iNKT cells.iNKT cells play a protective role against post-MI LV remodeling and failure through the enhanced expression of cardioprotective cytokines such as IL-10.