tbuckley/cabot-search huggingface dataset:
Beta-adrenergic stimulation disassembles microtubules in neonatal rat cultured cardiomyocytes through intracellular Ca2+ overload.
Authors: M Hori, H Sato, M Kitakaze, K Iwai, H Takeda, M Inoue, T Kamada
Journal: Circulation Research (1994)

Catecholamine cardiotoxicity is attributable in part to Ca2+ overload. To test whether the cytoskeletal structures of microtubules in cardiomyocytes are reversibly injured by catecholamine through excessive Ca2+ influx, morphological changes in the microtubules of neonatal rat myocytes were studied by immunohistochemical technique during exposure to norepinephrine (NE). In intact myocytes, microtubules appeared as a filamentous network throughout the cytoplasm and around the nucleus. NE exposure (10 mumol/L) for &gt; 30 minutes elicited microtubular disassembly in a duration-dependent fashion without any irreversible change in sarcomere structure, and this abnormality recovered within 24 hours after cessation of stimulation. Microtubular disruption scores obtained by semiquantitative assessment were significantly increased in a dose-dependent manner (10.8 +/- 4.0 in the control condition, 23.4 +/- 4.7 at 60 minutes with 10 mumol/L NE), whereas they were significantly attenuated by pretreatment with propranolol (100 mumol/L; score, 11.8 +/- 3.3) but not with phentolamine (100 mumol/L; score, 26.4 +/- 4.8). Isoproterenol (1 mumol/L) and denopamine (10 mumol/L) mimicked the effects of NE, but phenylephrine did not, indicating that NE-induced microtubular disassembly is mediated by beta 1-adrenergic receptor stimulation. This beta-adrenergic receptor-mediated insult was significantly attenuated by a decrease in Ca2+ concentration in the medium from 2 to 0.5 mmol/L and by pretreatment with diltiazem (1 mumol/L). In contrast, microtubular disassembly was induced by an increase in Ca2+ concentration in the medium and an administration of the Ca2+ ionophore A23187, even without beta-adrenergic receptor stimulation. Involvement of intracellular hypoxia and activation of Ca(2+)-calmodulin-dependent kinase or Ca(2+)-dependent neutral protease were excluded from possible mechanisms; however, inhibition of tubulin polymerization by excessive Ca2+ influx during beta-adrenergic receptor stimulation may be primarily involved. We conclude that microtubular structures that support cellular integrity are reversibly injured by beta-adrenergic receptor stimulation through excessive Ca2+ influx.
Treatment of Metastatic Melanoma with Autologous CD4+ T Cells against NY-ESO-1
Authors: Naomi N. Hunder, Herschel Wallen, Jianhong Cao, Deborah W. Hendricks, John Z. Reilly, Rebecca Rodmyre, Achim Jungbluth, Sacha Gnjatic, John A. Thompson, Cassian Yee
Journal: New England Journal of Medicine (2008)

We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with specificity for the melanoma-associated antigen NY-ESO-1. We infused these cells into a patient with refractory metastatic melanoma who had not undergone any previous conditioning or cytokine treatment. We show that the transferred CD4+ T cells mediated a durable clinical remission and led to endogenous responses against melanoma antigens other than NY-ESO-1.
<i>Klf15</i> Deficiency Is a Molecular Link Between Heart Failure and Aortic Aneurysm Formation
Authors: Saptarsi M. Haldar, Yuan Lu, Darwin Jeyaraj, Daiji Kawanami, Yingjie Cui, Sam J. Eapen, Caili Hao, Yan Li, Yong-Qiu Doughman, Michiko Watanabe, Koichi Shimizu, Helena Kuivaniemi, Junichi Sadoshima, Kenneth B. Margulies, Thomas P. Cappola, Mukesh K. Jain
Journal: Science Translational Medicine (2010)

The co-occurrence of heart failure and aortic aneurysms may be explained by their common dependence on a transcriptional regulator, which now presents a possible therapeutic target.
Inhibition of interleukin-1 responsiveness by type II receptor gene transfer: a surface "receptor" with anti-interleukin-1 function.
Authors: F Re, M Sironi, M Muzio, C Matteucci, M Introna, S Orlando, G Penton-Rol, S K Dower, J E Sims, F Colotta, A Mantovani
Journal: The Journal of Experimental Medicine (1996)

The hypothesis that the type II receptor (RII) acts as a decoy for interleukin-1 (IL-1) was tested by gene transfer in cells expressing only the type I receptor (8387 fibroblasts). RII-transfected cells showed defective responsiveness to IL-1 in terms of NFkappaB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1 beta. Hence defective IL-1 responsiveness of RII-transfected cells requires surface expression of the molecule. RII-transfected cells showed normal responsiveness to TNF, which shares functional properties and elements in the signal transduction pathway with IL-1. Cells transfected with a deletion mutant of RII missing 26 of 29 amino acids of the cytoplasmic portion of the molecule showed impaired responsiveness to IL-2. Cells transfected with full-length or the cytoplasmic deletion mutant of RII released copious amounts of RII in the supernatant. However, transfected cells showed defective responsiveness to brief exposure to IL-1, in the absence of measurable released RII. These results indicate that impairment of the responsiveness to IL-1 following RII gene transfer was dependent upon surface expression of the molecule, specific for IL-1 and unaffected by truncation of the cytoplasmic portion. Thus, the type II "receptor" is a decoy surface molecule, regulated by antiinflammatory signals, whose only known function is to capture and block IL-1.
Reply to M.A. Khattak et al
Authors: Andrew J. Armstron, Daniel J. George, Susan Halabi
Journal: Journal of Clinical Oncology (2013)

these agents. [6][][8][9][10] Data suggest that hypertension secondary to treatment with sunitinib is associated with improvement in clinical outcomes (objective response rate, PFS, and OS) 11 and similar results have been observed with other anti-VEGF agents. 12,13mTOR inhibitors may also have antiangiogenic activity, 14 and treatment-emergent hypertension has been observed as a consequence of treatment with non-VEGF therapy (eg, cytotoxic agents in non-small-lung cancer in which it has been found to be prognostic but not predictive of differential outcome). 15 Therefore, it would be interesting to know from the data set reported by Armstrong et al 1 whether the development of hypertension correlated with survival on therapy or correlated with baseline LDH.In conclusion, the results of the study by Armstrong et al 1 are encouraging and indicate progress toward predicting the clinical outcome of mRCC patients treated with a targeted agent.However, further corroboration of these findings is needed to establish their relevance for clinical practice.
Disrupted hepcidin regulation in HFE -associated haemochromatosis and the liver as a regulator of body iron homoeostasis
Authors: Kim R Bridle, David M Frazer, Sarah J Wilkins, Jeanette L Dixon, David M Purdie, Darrell HG Crawford, V Nathan Subramaniam, Lawrie W Powell, Gregory J Anderson, Grant A Ramm
Journal: The Lancet (2003)
Bilateral rupture of the quadriceps tendon associated with anabolic steroids.
Authors: R Y Liow, S Tavares
Journal: British Journal of Sports Medicine (1995)

Resisted knee extension may rupture the extensor mechanism, the precise site varying with age.In the elderly, the injury is often suprapatellar; in middle life, the patella fractures; in young adults, the patella ligament ruptures.In adolescents, the lesion often lies in the upper tibial apophysis.Simultaneous bilateral quadriceps rupture is rare and only 31 cases have been reported previously.Predisposing factors are often present'.We report a case where anabolic steroid abuse is identified as a predisposing cause. Case reportA 29-year-old competitive body builder presented to us following a jump from a height of 15 feet, landing on both feet with flexed knees.He complained of
‘Is (creno)balneotherapy a drug, a surgical procedure or a non-pharmacological treatment?’ eLetter on EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis
Authors: Romain J Forestier, F Begüm Erol
Journal: Annals of the Rheumatic Diseases (2013)

We appreciate that EULAR is preparing a specific recommendation on non-pharmacological treatment of knee osteoarthritis but we are also very surprised to discover that crenobalneotherapy was not even mentioned in the analysed treatments.

Crenobalneotherapy (also called balneotherapy or spa therapy) is a very common treatment for knee osteoarthritis …
Granulocyte-Macrophage Colony-Stimulating Factor Potentiates Rituximab in Patients With Relapsed Follicular Lymphoma: Results of a Phase II Study
Authors: Guillaume Cartron, Lu Zhao-Yang, Marion Baudard, Tarik Kanouni, Valérie Rouillé, Philippe Quittet, Bernard Klein, Jean-Francois Rossi
Journal: Journal of Clinical Oncology (2008)

Purpose We hypothesized that granulocyte-macrophage colony-stimulating factor (GM-CSF) could potentiate the clinical activity of rituximab given its individual and cooperative effects on FcγRIIa- and FcγRIIIa-expressing cells. A phase II clinical study combining GM-CSF and rituximab was initiated in patients with relapsed follicular lymphoma (FL) to determine the clinical and biologic responses, as well as safety of the combination. Patients and Methods Thirty three patients with relapsed FL were treated with GM-CSF 5 μg/kg/d on days 1 to 8 and rituximab 375 mg/m 2 on day 5 of each 21-day cycle for four cycles. Clinical response and tolerability were examined according to international criteria. Biologic monitoring included evaluation of immune cells involved in rituximab activity. Results Of 33 evaluated patients, a 70% overall response rate (complete response plus complete response unconfirmed, 45%) and a median progression-free survival (PFS) of 16.5 months were achieved. Outcome was influenced by the quality of response and the Follicular Lymphoma International Prognostic Index (FLIPI), where low- and intermediate-risk FLIPI groups were associated with significantly better PFS. After treatment there was a significant increase in granulocyte and monocyte counts. Examination of dendritic cell response showed an overall increase in plasmacytoid dendritic cells, especially in non-complete response patients, after treatment. Addition of GM-CSF did not impair tolerance to rituximab, and adverse events were rare and mild. Discussion GM-CSF plus rituximab results in high response rates, along with a tolerable safety profile in patients with relapsed or progressive FL. The improved efficacy over rituximab monotherapy may be due to increases seen in monocyte, granulocyte, and dendritic cell populations.
Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy
Authors: Ning Liu, Takahiko Ono, Katsuo Suyama, Fumiaki Nogaki, Kiichi Shirakawa, Mari Maeda, Takahide Kawamura, Tadashi Kamata, Atsushi Oyama, Eri Muso, Shigetake Sasayama
Journal: Kidney International (2000)
Isolation of Variant Cell Lines During Serial Transplantation of Hematopoietic Cells Derived From Fetal Liver&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. E. Till, E. A. McCulloch, L. Siminovitch
Journal: JNCI Journal of the National Cancer Institute (1964)

Serial transplantation, in irradiated hosts, of cells derived from mouse fetal liver was found in some cases to result in a loss of proliferative capacity by the hematopoietic cells in the graft, as detected by a decrease in their ability to form colonies in the spleens of irradiated mice. In other cases, variant cell types emerged, which exhibited an unusually high efficiency of colony formation. Two such variant cell strains have been isolated, which differ from each other in colony-forming efficiency and in their sensitivity to γ-radiation. Some of the properties of these variant strains have been studied; both differ from normal hematopoietic cells and resemble lymphoma cells in that serial transplantation of the variant strains does not result in a decrease in proliferative capacity. In addition, the variant strains form splenic colonies showing no clear evidence of differentiation, and they are able to proliferate in the livers of irradiated adult hosts. They differ from lymphoma cells in that unirradiated, isologous animals receiving grafts of cells of the variant type do not form splenic colonies, nor have they been observed to develop malignant disease. Such unirradiated animals do, however, appear to develop a resistance to subsequent transplants of cells of the variant type. The properties of the variant cells are such that they have a selective advantage over normal hematopoietic cells in the irradiated, but not in the unirradiated, host.
Thrombocytosis is associated with increased short and long term mortality after exacerbation of chronic obstructive pulmonary disease: a role for antiplatelet therapy?
Authors: Michelle T Harrison, Philip Short, Peter A Williamson, Aran Singanayagam, James D Chalmers, Stuart Schembri
Journal: Thorax (2014)

<h3>Introduction</h3> Evidence suggests that platelets play a significant role in inflammation in addition to their role in thrombosis. Systemic inflammation is linked to poor short and long term outcomes in COPD. Increased platelet activation has been reported in acute exacerbations of COPD (AECOPD). We investigated whether thrombocytosis is independently associated with poor outcomes following AECOPD. <h3>Methods</h3> An observational cohort study of patients hospitalised with AECOPD was performed. Patients were &gt;40 years with spirometry confirmed COPD admitted between 2009 and 2011. Platelet count was recorded on admission. The primary outcome was 1-year all-cause mortality. Secondary outcomes included inhospital mortality and cardiovascular events. Analyses were conducted using logistic regression after adjustment for confounding variables. <h3>Results</h3> 1343 patients (49% male) were included. Median age was 72 years (IQR 63–79 years). 157 (11.7%) had thrombocytosis. Thrombocytosis was associated with both 1-year mortality and inhospital mortality; OR 1.53 (95% CI 1.03 to 2.29, p=0.030) and OR 2.37 (95% CI 1.29 to 4.34, p=0.005), respectively. Cardiovascular hospitalisation was not significantly increased (OR 1.13 (95% CI 0.73 to 1.76, p=0.600)) in patients with thrombocytosis. Aspirin or clopidogrel treatment correlated with a reduction in 1-year mortality (OR 0.63 (95% CI 0.47 to 0.85, p=0.003)) but not inhospital mortality (OR 0.69 (95% CI 0.41 to 1.11, p=0.124)). <h3>Conclusions</h3> After adjustment for confounders thrombocytosis was associated with increased 1-year mortality after exacerbation of COPD. Antiplatelet therapy was associated with significantly lower 1-year mortality and may have a protective role to play in patients with AECOPD.
Chronic fatigue in developing countries: population based survey of women in India
Authors: Vikram Patel, Betty R Kirkwood, Helen Weiss, Sulochana Pednekar, Janice Fernandes, Bernadette Pereira, Medha Upadhye, David Mabey
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To describe the prevalence of and risk factors for chronic fatigue in a developing country; in particular, to determine the association of anaemia, mental health, and gender disadvantage factors with chronic fatigue. <b>Design</b> Community survey. <b>Setting</b> Primary health centre catchment area in Goa, India. <b>Participants</b> 3000 randomly sampled women aged 18 to 50 years. <b>Main outcome measures</b> Data on the primary outcome (reporting of fatigue for at least six months) and psychosocial exposures elicited by structured interview; presence of anaemia determined from a blood sample. <b>Results</b> 2494 (83%) women consented to participate; 12.1% (95% confidence interval 10.8 to 13.4%) complained of chronic fatigue. In multivariate analyses, older women (P = 0.03) and those experiencing socioeconomic deprivation—less education (P &lt; 0.001), families in debt (P = 0.09), or hunger in the past three months (P = 0.03)—were more likely to report chronic fatigue. After adjustment for these factors, factors indicating gender disadvantage (notably sexual violence by the husband; P &lt; 0.001) and poor mental health (P &lt; 0.001) were strongly associated with chronic fatigue. Although women with a high body mass index had a reduced risk, suggesting an influence of poor nutrition, no association was found between chronic fatigue and haemoglobin concentrations. <b>Conclusions</b> Chronic fatigue was commonly reported by women in this community study from India. The strongest associations with chronic fatigue were for psychosocial factors indicative of poor mental health and gender disadvantage.
Comparison of Pentazocine and Pethidine in Labour
Authors: J. Mowat, M. M. Garrey
Journal: BMJ (1970)

A double-blind between-patient study was carried out comparing pentazocine with pethidine in 94 women in labour. Similar analgesic and sedative effects were obtained with the two drugs, and Apgar scores were similar for babies of both drug groups. Fewer emetic sequelae were reported after pentazocine injections, though there was no statistically significant difference between the two drug groups in incidence of other side-effects.
Blisters and Erosions in a Neonate
Authors: Jake E. Turrentine, Olayemi Sokumbi, Nnenna G. Agim
Journal: JAMA Dermatology (2014)

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Nitric oxide generation ameliorates the tubulointerstitial fibrosis of obstructive nephropathy.
Authors: J J Morrissey, S Ishidoya, R McCracken, S Klahr
Journal: Journal of the American Society of Nephrology (1996)

Angiotensin-converting enzyme (ACE) inhibitors have been shown to minimize fibrosis of the kidney tubulointerstitium in several diseases. In addition to lowering angiotensin II levels, ACE inhibitors can increase kinin levels and subsequently increase nitric oxide formation. To determine whether nitric oxide generation is a component of the beneficial effect of ACE inhibitors on renal fibrosis, enalapril, enalapril plus NG-nitro-L-arginine methyl ester (L-NAME) or L-arginine was administered to rats that had undergone unilateral ureteral obstruction (UUO). Ureteral obstruction caused significant increases in interstitial volume, monocyte macrophage infiltration, interstitial collagen IV and alpha-smooth muscle actin expression, transforming growth factor-beta 1 mRNA, collagen IV mRNA, and tissue inhibitor of metalloproteinase-1 mRNA. Enalapril treatment significantly blunted the increase in all parameters during UUO. Cotreatment of the animals with enalapril and L-NAME reversed the beneficial effect of enalapril in the obstructed kidney for all parameters. Treatment of animals with UUO with L-arginine significantly blunted the increase in all parameters except for transforming growth factor-beta 1 mRNA expression. In the enalapril- plus-L-NAME-treated animals, there were modest but significant increases in monocyte/macrophage infiltration of the interstitium and glomerulus, and collagen IV and alpha-smooth muscle actin expression in the interstitium of the contralateral unobstructed kidney. The urine nitrite concentration was significantly increased by either enalapril or L-arginine treatment, whereas L-NAME significantly reduced urine nitrite concentration. These results suggest that treatment modalities that increase nitric oxide formation have a beneficial effect on the progression of cellular and molecular parameters of tubulointerstitial fibrosis caused by obstruction of the ureter.
Automated extraction of typing information for bacterial pathogens from whole genome sequence data: Neisseria meningitidis as an exemplar
Authors: K A Jolley, M C Maiden
Journal: Eurosurveillance (2013)

Whole genome sequence (WGS) data are increasingly used to characterise bacterial pathogens. These data provide detailed information on the genotypes and likely phenotypes of aetiological agents, enabling the relationships of samples from potential disease outbreaks to be established precisely. However, the generation of increasing quantities of sequence data does not, in itself, resolve the problems that many microbiological typing methods have addressed over the last 100 years or so; indeed, providing large volumes of unstructured data can confuse rather than resolve these issues. Here we review the nascent field of storage of WGS data for clinical application and show how curated sequence-based typing schemes on websites have generated an infrastructure that can exploit WGS for bacterial typing efficiently. We review the tools that have been implemented within the PubMLST website to extract clinically useful, strain-characterisation information that can be provided to physicians and public health professionals in a timely, concise and understandable way. These data can be used to inform medical decisions such as how to treat a patient, whether to instigate public health action, and what action might be appropriate. The information is compatible both with previous sequence-based typing data and also with data obtained in the absence of WGS, providing a flexible infrastructure for WGS-based clinical microbiology.