tbuckley/cabot-search huggingface dataset:
Ultraviolet A1 phototherapy
Authors: R.S. Dawe
Journal: British Journal of Dermatology (2003)

Long-wavelength ultraviolet A (340-400 nm; UVA1) therapy is currently available in only a few dermatology departments. Equipment capable of delivering this waveband has been available since 1981, but it is only over the past decade that increasing numbers of studies assessing the potential of this as a therapy have been published. High-dose UVA1, which requires expensive and space-occupying apparatus, is effective as a monotherapy for acute flares of atopic dermatitis, but it has not yet been formally assessed as an adjunct, rather than as an alternative to conventional therapies including potent and very potent topical corticosteroids. Low-dose (which can be administered using a standard phototherapy cubicle fitted with appropriate lamps) and medium-dose UVA1 may be less effective for this indication. Another condition for which UVA1 is effective, and is particularly promising because we have no reliably effective treatment already, is localized scleroderma. It also appears to be effective in systemic lupus erythematosus (although it is not yet clear when it is indicated, and its safety needs to be assessed in more patients) and in polymorphic light eruption (although there have been no studies suggesting that UVA1 will have any advantages over standard prophylactic phototherapies). Open studies and case series suggest that UVA1 may prove beneficial for various other diseases, including cutaneous T-cell lymphoma, lichen sclerosus, keloids, systemic sclerosis and hand dermatitis. In the centres where it is available, UVA1 has already proved a useful addition to the range of phototherapies previously available. However, much more research is needed to confirm its efficacy for many of its potential indications, and to determine when and how it should be used.
Mycophenolate Mofetil versus Azathioprine for Prevention of Chronic Allograft Dysfunction in Renal Transplantation
Authors: Giuseppe Remuzzi, Paolo Cravedi, Marco Costantini, Mariadomenica Lesti, Maria Ganeva, Giulia Gherardi, Bogdan Ene-Iordache, Eliana Gotti, Donato Donati, Maurizio Salvadori, Silvio Sandrini, Giuseppe Segoloni, Stefano Federico, Paolo Rigotti, Vito Sparacino, Piero Ruggenenti
Journal: Journal of the American Society of Nephrology (2007)

The Mycophenolate Steroids Sparing (MYSS) study found that in renal transplant recipients who were on immunosuppressive therapy with the cyclosporine microemulsion Neoral, mycophenolate mofetil (MMF) was not better than azathioprine in preventing acute rejection at 21 mo after transplantation and was 15 times more expensive. The MYSS Follow-up Study, an extension of MYSS, was aimed at comparing long-term outcome of 248 MYSS patients according to their original randomization to MMF (1 g twice daily) or azathioprine (75 to 100 mg/d). Primary outcome was estimated GFR at 5 yr after transplantation. Mean 5-yr GFR difference between azathioprine and mycophenolate was 4.67 ml/min per 1.73 m(2) (95% confidence interval [CI] -0.43 to 9.77 ml/min per 1.73 m(2); P = 0.07). GFR from month 6 (mean +/- SEM: 54.3 +/- 1.6 versus 53.9 +/- 1.5 ml/min per 1.73 m(2); P = 0.83) to month 72 after transplantation (49.5 +/- 2.2 versus 47.3 +/- 2.4 ml/min per 1.73 m(2); P = 0.50); GFR slopes (mean +/- SEM: -1.10 +/- 0.56 versus -1.23 +/- 0.31 ml/min per 1.73 m(2) per year; P = 0.83); and 72-mo patient mortality (4.0 versus 4.0% [P = 0.95]; HR 0.96; 95% CI 0.28 to 3.31; P = 0.95), graft loss (6.8 versus 6.1% [P = 0.82]; HR 0.89; 95% CI 0.32 to 2.46; P = 0.83), incidence of persistent proteinuria (25.0 versus 27.4%; P = 0.72), late (>6 mo after transplantation) rejections (25.3 versus 21.2%; P = 0.53), and adverse events were similar on azathioprine (n = 124) and MMF (n = 124), respectively. Outcomes in the two groups were comparable also among patients with or without steroid therapy, considered separately. In kidney transplantation, the long-term risk/benefit profile of MMF and azathioprine therapy in combination with cyclosporine Neoral is similar. In view of the cost, standard immunosuppression regimens for kidney transplantation should perhaps include azathioprine rather than MMF.
Downregulation of MicroRNA-30 Facilitates Podocyte Injury and Is Prevented by Glucocorticoids
Authors: Junnan Wu, Chunxia Zheng, Yun Fan, Caihong Zeng, Zhaohong Chen, Weisong Qin, Changming Zhang, Wanfen Zhang, Xiao Wang, Xiaodong Zhu, Mingchao Zhang, Ke Zen, Zhihong Liu
Journal: Journal of the American Society of Nephrology (2013)

MicroRNAs (miRNAs) are essential for podocyte homeostasis, and the miR-30 family may be responsible for this action. However, the exact roles and clinical relevance of miR-30s remain unknown. In this study, we examined the expression of the miR-30 family in the podocytes of patients with FSGS and found that all members are downregulated. Treating cultured human podocytes with TGF-β, LPS, or puromycin aminonucleoside (PAN) also downregulated the miR-30 family. Podocyte cytoskeletal damage and apoptosis caused by treatment with TGF-β or PAN were ameliorated by exogenous miR-30 expression and aggravated by miR-30 knockdown. Moreover, we found that miR-30s exert their protective roles by direct inhibition of Notch1 and p53, which mediate podocyte injury. In rats, treatment with PAN substantially downregulated podocyte miR-30s and induced proteinuria and podocyte injury; however, transfer of exogenous miR-30a to podocytes of PAN-treated rats ameliorated proteinuria and podocyte injury and reduced Notch1 activation. Finally, we demonstrated that glucocorticoid treatment maintains miR-30 expression in cultured podocytes treated with TGF-β, LPS, or PAN and in the podocytes of PAN-treated rats. Glucocorticoid-sustained miR-30 expression associated with reduced Notch1 activation and alleviated podocyte damage. Taken together, these findings demonstrate that miR-30s protect podocytes by targeting Notch1 and p53 and that the loss of miR-30s facilitates podocyte injury. In addition, sustained miR-30 expression may be a novel mechanism underlying the therapeutic effectiveness of glucocorticoids in treating podocytopathy.
Impaired Notch signalling: the unifying mechanism explaining the pathogenesis of hidradenitis suppurativa (acne inversa)
Authors: B.C. Melnik, G. Plewig
Journal: British Journal of Dermatology (2012)

Journal Article Impaired Notch signalling: the unifying mechanism explaining the pathogenesis of hidradenitis suppurativa (acne inversa) Get access B.C. Melnik, B.C. Melnik Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Sedanstrasse 115, D‐49090 Osnabrück, Germany Search for other works by this author on: Oxford Academic Google Scholar G. Plewig G. Plewig Clinic and Policlinic for Dermatology and Allergology, University of Munich, Frauenlobstrasse 9‐11, D‐80337 Munich, Germany E‐mail: melnik@t-online.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 4, 1 April 2013, Pages 876–878, https://doi.org/10.1111/bjd.12068 Published: 01 April 2013
The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis
Authors: Daniel J. Brat, Anita C. Bellail, Erwin G. Van Meir
Journal: Neuro-Oncology (2005)

Interleukin-8 (IL-8, or CXCL8), which is a chemokine with a defining CXC amino acid motif that was initially characterized for its leukocyte chemotactic activity, is now known to possess tumorigenic and proangiogenic properties as well. In human gliomas, IL-8 is expressed and secreted at high levels both in vitro and in vivo, and recent experiments suggest it is critical to glial tumor neovascularity and progression. Levels of IL-8 correlate with histologic grade in glial neoplasms, and the most malignant form, glioblastoma, shows the highest expression in pseudopalisading cells around necrosis, suggesting that hypoxia/anoxia may stimulate expression. In addition to hypoxia/anoxia stimulation, increased IL-8 in gliomas occurs in response to Fas ligation, death receptor activation, cytosolic Ca2+, TNF-α, IL-1, and other cytokines and various cellular stresses. The IL-8 promoter contains binding sites for the transcription factors NF-κB, AP-1, and C-EBP/NF-IL-6, among others. AP-1 has been shown to mediate IL-8 upregulation by anoxia in gliomas. The potential tumor suppressor ING4 was recently shown to be a critical regulator of NF-κB-mediated IL-8 transcription and subsequent angiogenesis in gliomas. The IL-8 receptors that could contribute to IL-8-mediated tumorigenic and angiogenic responses include CXCR1 and CXCR2, both of which are G-protein coupled, and the Duffy antigen receptor for cytokines, which has no defined intracellular signaling capabilities. The proangiogenic activity of IL-8 occurs predominantly following binding to CXCR2, but CXCR1 appears to contribute as well through independent, small-GTPase activity. A precise definition of the mechanisms by which IL-8 exerts its proangiogenic functions requires further study for the development of effective IL-8-targeted therapies.
A Case of Lobar Pneumonia, with a Hyperpyrexial Temperature of 109 F: Recovery
Authors: J. K. Couch
Journal: BMJ (1896)

I 212 y,T a-.I LOBAR PNEUMONIA.'HYPERPYREXIA.[Oc. 2 S This is, of course, a rough and ready way, but in accurate work much experience in examining microscopically the bacteria will be necessary.If anyone wants examinations made they can have them done at the Oxygen Home, 35, St.George's Square, Pimlico, London, S.W.We have gone some two steps further still.We have cul- tivated what we call favourable micro-organisms in pure air, pure oxygen and varying strengths of oxygen, and find that the favourable micro-organisms grow best and stain easiest after cultivation in from 25 to 50 per cent. of pure oxygen mixed with purified air.It is found in practice that a solution as strong as 75 per cent. of pure oxygen, mixed with pure air, is too stimulating for any ordinary cases, and that with a weaker solution wounds heal better.There are thus two elements to be taken into consideration in regulating the quantity of oxygen to be used:i.The condition and behaviour of the micro-organisms, favourable and unfavourable when cultivated on agar.2. The condition -and behaviour of the micro-organisms, favourable or unfavourable, when growing on a wounded or ulcerated surface.Secondly we have taken the case of W.Here the hand was healing with great rapidity and the leg slowly.We took
INCREASED REACTIVITY OF MOUSE SPLEEN CELLS SENSITIZED IN VITRO AGAINST SYNGENEIC TUMOR CELLS IN THE PRESENCE OF A THYMIC HUMORAL FACTOR
Authors: Claude Carnaud, David Ilfeld, Itzhak Brook, Nathan Trainin
Journal: The Journal of Experimental Medicine (1973)

Unprimed mouse spleen cells cultured in vitro on syngeneic tumor cell monolayers have been previously shown to become specifically sensitized and to mediate cytotoxicity against the same type of tumor cells. This complete in vitro system of cell-mediated response has been presently used to test the effect of a thymic humoral factor (THF) upon the differentiation process leading to the generation of specifically committed lymphocytes. Culture media were supplemented with 2% THF during either the sensitization or effector phase, or both phases of the reaction. Whereas the addition of THF during both phases or during sensitization only resulted in a significant increase in the cytotoxicity index, THF added during the effector phase was ineffective. The behavior of unsensitized spleen cells and of spleen cells sensitized against nonrelated transplantation antigens remained unmodified by THF. After showing that the entire reaction is mediated by lymphocytes of thymic origin, THF was directly tested on T or B spleen cells. It was found that only T cells reacted to THF by an increased cytotoxic capacity, while B cells remained inactive after addition of THF. It was therefore concluded that THF activates a postthymic population of lymphoid cells, transforming them into fully competent lymphocytes.
High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine
Authors: Costa Bachas, Gerrit Jan Schuurhuis, Iris H. I. M. Hollink, Zinia J. Kwidama, Bianca F. Goemans, C. Michel Zwaan, Marry M. van den Heuvel-Eibrink, Eveline S. J. M. de Bont, Dirk Reinhardt, Ursula Creutzig, Valerie de Haas, Yehuda G. Assaraf, Gertjan J. L. Kaspers, Jacqueline Cloos
Journal: Blood (2010)
Normative data on snoring: a comparison between younger and older adults
Authors: RA Stoohs, HC Blum, M Haselhorst, HW Duchna, C Guilleminault, WC Dement
Journal: European Respiratory Journal (1998)

Snoring is a common sleep-related behaviour. Increased body mass index (BMI), cranio-facial anatomical features, and older age have been linked to the occurrence of snoring. While mostly middle-aged populations have been studied for the occurrence of snoring and sleep-related breathing abnormality, this study was designed to assess the subjective report of snoring and the objective measurement of snoring at the two extremes of human age. The study design called for measurement of snoring in two age groups (college students; n=155 and older subjects; mean age 64.1 yrs n=134) with a mean age difference of 45 yrs. Snoring was assessed with a validated recording device. A validated questionnaire was used to subjectively assess snoring and obtain relevant sleep-related information. Students and older subjects differed in the self-report of snoring. While 83% of students reported "never" or "rarely" snoring only 35% of older subjects fell into these categories. Measurement of snoring during sleep revealed that students spent more time during sleep with continuous snoring than older subjects. In older subjects, a reduction in continuous snoring was accompanied by an increase in apnoeic snoring. Subjective snoring frequency correlated with continuous snoring in students only. A positive family history of snoring increased the odds ratio for self-reported snoring but not for recorded snoring. It has been shown that snoring frequency can vary depending on age and that the congruency between perceived snoring frequency and recorded snoring is influenced by the age of an individual.
A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study
Authors: G. Grignani, E. Palmerini, P. Dileo, S.D. Asaftei, L. D’Ambrosio, Y. Pignochino, M. Mercuri, P. Picci, F. Fagioli, P.G. Casali, S. Ferrari, M. Aglietta
Journal: Annals of Oncology (2011)
ARSENICAL COMPOUNDS IN THE TREATMENT OF BLACKHEAD IN TURKEYS
Authors: Ernest Edward Tyzzer
Journal: The Journal of Experimental Medicine (1923)

The natural form of blackhead, although very fatal to young turkeys, is favorably influenced by treatment with certain of the newer arsenical compounds. Neoarsphenamine injected intravenously in toxic doses has a somewhat favorable effect on the course of the spontaneous disease and evidently lowers the mortality. Its instability, its pronounced toxicity for young turkeys, as well as the difficulty of obtaining amounts suitable for the cases to be treated on any one occasion, serve to make its employment impracticable. Less favorable results were obtained with atoxyl. Arsenious acid fed daily in small doses failed to prevent blackhead and possibly increased the incidence of infection. In larger doses it failed to cure spontaneous blackhead. Tryparsamide may be injected in cases of spontaneous blackhead in doses as high as 1 gm. per kilo of body weight either intravenously or subcutaneously without serious toxic effect. Prompt clinical improvement usually follows and the mortality is undoubtedly greatly lowered. With inoculated blackhead recovery is more difficult to obtain. Birds treated by injections of either neoarsphenamine or atoxyl failed to recover. There were two recoveries among three tryparsamidetreated cases. An attempt to cure inoculated blackhead at an advanced stage by the injection of tryparsamide failed. The study of the lesions of treated turkeys shows that tryparsamide, and to some extent neoarsphenamine, have a more pronounced effect on the liver lesions than on the disease in the lung, which accounts for the discrepancy in the results of the treatment of spontaneous and inoculated blackhead. There is histological evidence of prompt absorption of necrotic liver parenchyma; moreover, the protozoa are destroyed more rapidly in the liver than in the lung. Tryparsamide has the most pronounced curative action on blackhead infection of any of the drugs thus far tested. Either intravenous or subcutaneous injection of appropriate doses of this drug at the first appearance of symptoms should serve to cure the majority of cases of blackhead.
PHOSIDA (phosphorylation site database): management, structural and evolutionary investigation, and prediction of phosphosites
Authors: Florian Gnad, Shubin Ren, Juergen Cox, Jesper V Olsen, Boris Macek, Mario Oroshi, Matthias Mann
Journal: Genome biology (2007)

PHOSIDA http://www.phosida.com, a phosphorylation site database, integrates thousands of high-confidence in vivo phosphosites identified by mass spectrometry-based proteomics in various species. For each phosphosite, PHOSIDA lists matching kinase motifs, predicted secondary structures, conservation patterns, and its dynamic regulation upon stimulus. Using support vector machines, PHOSIDA also predicts phosphosites.
Fibulin-5 Suppresses Lung Cancer Invasion by Inhibiting Matrix Metalloproteinase-7 Expression
Authors: Wen Yue, Quanhong Sun, Rodney Landreneau, Chuanyue Wu, Jill M. Siegfried, Jian Yu, Lin Zhang
Journal: Cancer Research (2009)

The high mortality rate of lung cancer is largely due to the spread of disease to other organs. However, the molecular changes driving lung cancer invasion and metastasis remain unclear. In this study, we identified fibulin-5, a vascular ligand for integrin receptors, as a suppressor of lung cancer invasion and metastasis. Fibulin-5 was silenced by promoter hypermethylation in a majority of lung cancer cell lines and primary tumors. It inhibited lung cancer cell invasion and down-regulated matrix metalloproteinase-7 (MMP-7), which promoted lung cancer cell invasion. Knockdown of fibulin-5 was sufficient to stimulate cell invasion and MMP-7 expression. The expression levels of fibulin-5 and MMP-7 were inversely correlated in lung tumors. Suppression of MMP-7 expression by fibulin-5 was mediated by an integrin-binding RGD motif via the extracellular signal-regulated kinase (ERK) pathway. Furthermore, overexpression of fibulin-5 in H460 lung cancer cells inhibited metastasis in mice. Collectively, these results suggest that epigenetic silencing of fibulin-5 promotes lung cancer invasion and metastasis by activating MMP-7 expression through the ERK pathway.
Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans
Authors: R. J. Havel, J. P. Kane, E. O. Balasse, N. Segel, L. V. Basso
Journal: Journal of Clinical Investigation (1970)

Transport of free fatty acids from the blood into the splanchnic region and their conversion to triglycerides of very low density lipoproteins, together with estimates of splanchnic oxidation of free fatty acids to ketones and to carbon dioxide and water, have been made in the postabsorptive state in seven normolipemic subjects, six with primary endogenous hyperlipemia and one each with primary dysbetalipoproteinemia and mixed hyperlipemia. Net systemic transport of free fatty acids into the blood was the same in normolipemic and hyperlipemic groups, but a greater fraction was taken up in the splanchnic region in the latter. Transport into the blood in very low density lipoproteins of triglyceride fatty acids derived from free fatty acids was proportional and bore the same relationship to splanchnic uptake of free fatty acids in the two groups. In normolipemic subjects, near equilibration of specific activities after 4 hr infusion of palmitate-1-(14)C showed that almost all triglyceride fatty acids of very low density lipoproteins and acetoacetate were derived from free fatty acids taken up in the splanchnic region. In the hyperlipemic subjects, equilibration of free fatty acidcarbon with acetoacetate was almost complete, but not with triglyceride fatty acids, owing at least in part to increased pool size. Comparison of the rate of equilibration of triglyceride fatty acids-(14)C with rate of inflow transport from the splanchnic region, together with other data, indicated that most of the circulating triglyceride fatty acids of very low density lipoproteins in hyperlipemic subjects were also derived from free fatty acids. Although mean inflow transport of triglyceride fatty acids was greater in the hyperlipemic subjects, it correlated poorly with their concentration and it appeared that efficiency of mechanisms for extrahepatic removal must be a major determinant of the concentration of triglycerides in blood plasma of the normolipemic as well as the hyperlipemic subjects. Estimates of splanchnic respiratory quotient supported the concept that oxidation of free fatty acids accounts for almost all of splanchnic oxygen consumption in the postabsorptive state. Splanchnic oxygen consumption was greater in the hyperlipemics, but fractional oxidation of free fatty acids to ketones was higher in normolipemic subjects. Calculations of splanchnic balance indicate that a larger fraction of free fatty acids was stored in lipids of splanchnic tissues in the hyperlipemics. No differences were found between the two groups in net splanchnic transport of glucose, lactate, or glycerol.
Intratracheal Administration of Activated Protein C Inhibits Bleomycin-induced Lung Fibrosis in the Mouse
Authors: HIROKI YASUI, ESTEBAN C. GABAZZA, SHIGENORI TAMAKI, TETSU KOBAYASHI, OSAMU HATAJI, HISAMICHI YUDA, SHINO SHIMIZU, KOJI SUZUKI, YUKIHIKO ADACHI, OSAMU TAGUCHI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

It is well recognized that activation of the coagulation system plays an important role in bleomycin (BLM)-induced lung injury and fibrosis. The protein C (PC) pathway is an important regulator of the coagulation system. In this study, we evaluated the bronchoalveolar lavage fluid (BALF) concentration of activated PC (APC) and the therapeutic effect of the intratracheal administration of APC on BLM-induced lung fibrosis in mice. APC levels in BALF were significantly lower in BLM-treated animals than in the saline-treated group. Fibrotic changes were progressive in mice treated with BLM and intratracheal instillation of vehicle (BLM/Veh) after 14 and 21 d of BLM infusion. Compared with the BLM/Veh group, histologic findings on Days 14 and 21 in mice treated with BLM and intratracheal instillation of APC (BLM/APC) showed less fibrotic lesions in the subpleural and central areas of the lung. The mean Aschcroft's fibrosis score in the BLM/Veh group was significantly (p < 0.05) higher than in the BLM/APC group. The lung hydroxyproline content on Day 21 was significantly higher (p < 0.05) in the BLM/Veh group (1.78 +/- 0.07 micromol/lung weight) than in the BLM/APC (1.30 +/- 0.06 micromol/lung weight) group. The ratio of plasminogen activator activity to thrombin level in BALF was significantly increased in the BLM/APC group compared with the BLM/ Veh group on Day 21. The expression of tumor necrosis factor-alpha and interleukin-1beta was significantly decreased in the lungs of the BLM/APC group compared with the BLM/Veh group on Day 14 after BLM infusion. These results showed that intratracheal APC administration inhibits the development of lung fibrosis in BLM-induced lung injury, giving further support to the important role that the PC pathway plays in the mechanism of lung fibrosis.