tbuckley/cabot-search huggingface dataset:
Angiogenesis and Pericytes in the Initiation of Ectopic Calcification
Authors: G.D.M. Collett, A.E. Canfield
Journal: Circulation Research (2005)

Ectopic calcification of blood vessels, heart valves, and skeletal muscle is a major clinical problem. There is now good evidence that angiogenesis is associated with ectopic calcification in these tissues and that it is necessary, but not sufficient, for calcification to occur. Angiogenesis may regulate ectopic calcification in several ways. First, many angiogenic factors are now known to exert both direct and indirect effects on bone and cartilage formation. Second, cytokines released by endothelial cells can induce the differentiation of osteoprogenitor cells. Third, the new blood vessels provide oxygen and nutrients to support the growing bone. Finally, the new blood vessels can serve as a conduit for osteoprogenitor cells. These osteoprogenitor cells may be derived from the circulation or from pericytes that are present in the neovessels themselves. Indeed, there is now compelling evidence that pericytes can differentiate into osteoblasts and chondrocytes both in vitro and in vivo. Other vascular cells, including adventitial myofibroblasts, calcifying vascular cells, smooth muscle cells, and valvular interstitial cells, have also been shown to exhibit multilineage potential in vitro. Although these cells share many properties with pericytes, the precise relationship between them is not known. Furthermore, it still remains to be determined whether all or some of these cells contribute to the ectopic calcification observed in vivo. A better understanding of the underlying mechanisms that link angiogenesis, pericytes, and ectopic calcification should provide a basis for development of therapeutic strategies to treat or arrest this clinically significant condition.
An unusual case of dyspnoea
Authors: E M Giddings, M V Holmes, D Lonsdale, J Rees, M J Gleeson
Journal: Thorax (2009)

A 66-year-old woman presented with progressive exertional dyspnoea, productive cough and dysphonia, particularly when singing; she also experienced a dry obstructed nose, sore mouth and mild dysphagia. She had previously been diagnosed with autoimmune disease affecting her eyes, nasal passages, oropharynx and …
Secular changes in incidence and mortality associated with Staphylococcus aureus bacteraemia in Quebec, Canada, 1991–2005.
Authors: C. Allard, A. Carignan, M. Bergevin, I. Boulais, V. Tremblay, P. Robichaud, R. Duperval, J. Pepin
Journal: Clinical Microbiology and Infection (2008)
World records in running and swimming--re-evaluation of data.
Authors: E. Jokl, P. Jokl
Journal: British Journal of Sports Medicine (1978)

A comparative analysis of rates of decline of velocities in running and swimming undertaken after the 1976 Olympic Games yielded the results summarised in Table I and Fig. 1.The then existing world records served as bases for the computations.Professor Astrand of Stockholm and Professor Schuster of Leipzig raised with us the question whether the time difference between the 100 m sprint record (9.9 seconds) and the 100 m free style swimming record (49.9 seconds) justifies the allocation to both the same 100% reference level.They suggested that the data be re-evaluated taking the 400 m running world record of 43.8 seconds instead of the 100 m sprint record as equivalent to the 100 m free style swimming record.We have complied with their proposal and present the results of the calculation in Fig. 2. The difference between the rates of decline of running and swimming speeds is smaller, but does not necessitate reformulation of the hypothesis presented in our original communication.
Two-colour flow-cytometric analysis of pulmonary alveolar macrophages from smokers
Authors: T. Umino, C.m Sköld, S.J. Pirruccello, J.R. Spurzem, S.I. Rennard
Journal: European Respiratory Journal (1999)

The study of alveolar macrophages (AM) from smokers by flow cytometry (FCM) has been limited by strong autofluorescence and the lack of reliable markers to identify macrophages. Crystal violet quenching was reported to be effective in reducing autofluorescence of AM. CD68 is a marker for macrophages in immunohistochemistry, but has been less useful in FCM because of poor surface expression. This study evaluated the effectiveness of a method for two-colour FCM analysis of AM combined with membrane permeabilization and crystal violet quenching. Bronchoalveolar lavage cells, fixed in 4% paraformaldehyde and permeabilized using 0.5% Triton X100, were incubated with fluorescent-labelled antibodies for 30 min and quenched with a saturated crystal violet solution. Two-colour FCM was then performed using forward/side scatter gating to select AM. Autofluorescence at 525 nm (fluorescein isothiocyanate) and 575 nm (phycoerythrin) markedly decreased after quenching. After permeabilization, 97.1+/-2.8% of the gated cells were CD68+, while 53.9+/-18.6% of the AM were positive without permeabilization. CD68+ cells were sorted and proved to be AM morphologically. Analysis of CD71 (transferrin receptor) expression by FCM correlated with immunocytochemistry (r=0.77, p&lt;0.05). The permeabilization/quenching technique, therefore, represents a satisfactory means to evaluate alveolar macrophages by flow cytometry.
Neutrality of Foreign Complex Subunits in an Experimental Model of Lateral Gene Transfer
Authors: A. Wellner, U. Gophna
Journal: Molecular Biology and Evolution (2008)

Lateral gene transfer (LGT) is a powerful force in microbial evolution. However, the barriers that restrict this evolutionary phenomenon are not fully understood. It has long been observed that genes that encode subunits of complexes exhibit relatively compatible phylogenies, implying mostly vertical evolution. This may be explained by the failure of a new gene product to effectively interact with preexisting protein subunits, making its acquisition neutral—a theory termed the "complexity hypothesis." On the other hand, such genes may reduce the fitness of the host by disturbing the stoichiometric balance between complex subunits, resulting in purifying selection against gene retention. To examine these 2 alternative scenarios, we designed an experimental system that mimics the transfer of genes encoding homologs of essential complex subunits into the model bacterium Escherichia coli. In addition, we overexpressed the native E. coli gene in order to examine the contribution of gene dosage effects. We show that accumulation of native or foreign complex subunits in the cell does not result in loss of fitness, except for a minor fitness reduction observed for a single foreign homolog. Indeed, a series of genetic and biochemical assays failed to detect any interaction between the foreign subunits and the native polypeptides of the complex, implying an inability of such transfer events to generate positive selection for gene retention. We conclude that LGT of complex subunits may be mostly neutral and that forces operating against gene retention appear to be moderate.
Impact of a nurse-led home management training programme in children admitted to hospital with acute asthma: a randomised controlled study
Authors: P. Madge, J. McColl, J. Paton
Journal: Thorax (1997)

BACKGROUND: Re-admissions to hospital in childhood asthma are common with studies reporting that 25% or more of children will be re-admitted within a year. There is a need for strategies to reduce re-admissions. METHODS: A prospective randomised control study of an asthma home management training programme was performed in children aged two years or over admitted with acute asthma. Two hundred and one children were randomised at admission to either an intervention group (n = 96) which received the teaching programme or a control group (n = 105). A nurse-led teaching programme used the current attack as a model for the management of future attacks and included discussion, written information, subsequent follow up and telephone advice aimed at developing and reinforcing individualised asthma management plans. Parents were also provided with a course of oral steroids and guidance on when to start them. RESULTS: The groups were similar in degree of social deprivation, length of stay, number of previous admissions, acute asthma treatment, and asthma treatment at discharge. Subsequent re-admissions were significantly reduced in the intervention group from 25% to 8% in individual follow up periods that ranged from two to 14 months (chi 2 = 9.63; p = 0.002). This reduction was not accompanied by any increase in subsequent emergency room attendances nor, in the short term, by any increase in urgent community asthma treatment. The intervention group also showed significant reductions in day and night morbidity 3-4 weeks after admission to hospital. CONCLUSIONS: A nurse-led asthma home management training programme administered during a hospital admission can significantly reduce subsequent admissions to hospital for asthma. Acute hospitalisation may be a particularly effective time to deliver home management training.
Emerging clinical picture of lymphangioleiomyomatosis
Authors: M M Cohen
Journal: Thorax (2005)

<b>Objective:</b> To provide a comprehensive update of the clinical picture of lymphangioleiomyomatosis (LAM) using two large patient registries. <b>Methods:</b> A cross sectional questionnaire survey which included questions on 14 LAM symptoms, pneumothorax, tuberous sclerosis complex (TSC), date of diagnosis, and pulmonary function tests (PFTs). <b>Results:</b> The response rate was 70.5% (n = 328). The mean age at the time of the survey was 46.7 years. The mean age at diagnosis was 42.7 years for women diagnosed 1 year before the survey and 35.8 years for women diagnosed 10 years previously. The main symptoms were dyspnoea (74%), fatigue (72%), cough (47%) and chest pain (44%); younger patients (&lt;40 years) were less likely to report dyspnoea (p = 0.02). Patients with TSC (n = 51) were less likely to report dyspnoea (p = 0.05) and 76.5% reported angiomyolipoma (p&lt;0.0001) compared with patients with sporadic LAM. Patients with pneumothorax (63.0%) were less likely to report dyspnoea or fatigue (p⩽0.05) than patients without pneumothorax. PFT results showed that low forced expiratory volume in 1 second and carbon monoxide transfer factor were highly associated with dyspnoea (p&lt;0.0001), but not with fatigue or history of pneumothorax. <b>Conclusion:</b> Previously considered a condition of women of childbearing age, more older women (50% without pneumothorax) are now being diagnosed with LAM. LAM should be considered in women over 40 with unexplained dyspnoea. LAM patients with pneumothorax have less fatigue and less dyspnoea than those without pneumothorax. Fatigue has been overlooked as a symptom of LAM and appears across the spectrum of pulmonary function.
Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial
Authors: Silke Walter, Panagiotis Kostopoulos, Anton Haass, Isabel Keller, Martin Lesmeister, Thomas Schlechtriemen, Christian Roth, Panagiotis Papanagiotou, Iris Grunwald, Helmut Schumacher, Stephan Helwig, Julio Viera, Heiko Körner, Maria Alexandrou, Umut Yilmaz, Karin Ziegler, Kathrin Schmidt, Rainer Dabew, Darius Kubulus, Yang Liu, Thomas Volk, Kai Kronfeld, Christian Ruckes, Thomas Bertsch, Wolfgang Reith, Klaus Fassbender
Journal: The Lancet Neurology (2012)
Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome
Authors: Satish R. Raj, Bonnie K. Black, Italo Biaggioni, Paul A. Harris, David Robertson
Journal: Circulation (2005)

Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance notable for an excessive increase in heart rate that occurs on standing. Many current therapeutic strategies focus on sympatholysis, but the alternative strategy of enhancing cardiovagal tone has not been studied. The objective of this study was to test the hypothesis that acetylcholinesterase inhibitors will attenuate the tachycardia and improve symptom burden in patients with POTS.Seventeen patients with POTS underwent acute drug trials of pyridostigmine 30 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressures, heart rate, and symptoms were assessed while patients were seated and after they had been standing for up to 10 minutes both before the study drug was given and at 2 and 4 hours after study drug. The heart rate was significantly lower at 2 hours after pyridostigmine than after placebo (100+/-16 versus 111+/-14 bpm, P=0.001). Pyridostigmine significantly decreased the standing heart rate from baseline (119+/-16 bpm) at 2 hours (104+/-16 bpm, P<0.001) and 4 hours (100+/-16 bpm, P<0.001) after administration. There was no significant change in blood pressure. The decrease in symptom burden within 4 hours after study drug was significantly greater with pyridostigmine than placebo (-10.4+/-14.0 AU versus 0.6+/-7.5 AU, P<0.025).Acute acetylcholinesterase inhibition significantly attenuated tachycardia in POTS. There was also an improvement in symptom burden with this promising therapy.
Separation of Viable Tumor Cells From Nonviable Tumor Cells by Flotation on Bovine Serum Albumin. A Short Communication
Authors: H T Wepsic
Journal: JNCI Journal of the National Cancer Institute (1970)

A method is described for obtaining tumor cell suspensions that are 95% viable. This method does not require the use of enzymes. The yield of this procedure is approximately 50%.
Immunosurveillance of<i>Erbb2</i>Carcinogenesis in Transgenic Mice Is Concealed by a Dominant Regulatory T-Cell Self-Tolerance
Authors: Elena Ambrosino, Michela Spadaro, Manuela Iezzi, Claudia Curcio, Guido Forni, Piero Musiani, Wei-Zen Wei, Federica Cavallo
Journal: Cancer Research (2006)

To assess the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in overcoming immunosurveillance of Erbb2 (HER-2/neu) mammary lesions, we studied the effects of their sustained removal in BALB/c female mice made transgenic for the rat Erbb2 (r-Erbb2) oncogene (BALB-neuT mice), which develop multiple mammary carcinomas. During the progression of these lesions, Treg cells expand in the spleen, tumor draining lymph nodes, and tumors. Repeated administration of anti-CD25 antibodies extends tumor-free survival, reduces carcinoma multiplicity, and leads to the manifestation of a natural antibody and CTL-mediated reactivity against r-Erbb2. Loss of Foxp3(+) Treg cells during anti-CD25 treatment remarkably caused the disappearance of Gr1(+) immature myeloid cells, suggesting a cross-talk between these two inhibitory immune cell types. Treg cell expansion associated with r-Erbb2 overexpression may be seen as a physiologic response to dampen the immune reaction elicited by local anomalous overexpression of a self-antigen.
Islet Cell Tumors of the Pancreas
Authors: WILLIAM P. LONGMIRE
Journal: Annals of Internal Medicine (1968)

The features of the three types of functioning islet cell tumors of the pancreas are illustrated in the cases presented. Hypoglycemia caused by the classical insulin-producing islet cell adenoma must be distinguished from reactive or functional hypoglycemia before surgery is recommended. The hypoglycemia of the insuloma occurs after fasting and produces elevated blood insulin in two thirds of the patients. Surgical practice has favored the "blind" distal pancreatectomy when islet cell adenoma seems certain but cannot be located at laparotomy. Because of the increased complications resulting from a secondary total pancreatectomy and because of the frequency with which the tumor has been found in the head of the gland on pathologic examination, it is possible that resection of the head and uncinate process should be the initial procedure in these cases. More accurate localization of these tumors by angiography may make such considerations unnecessary. The typical diagnostic features of the Zollinger-Ellison tumor are gastric hypersecretion and fulminating ulcer diathesis refractory to conventional therapy. In addition, the Zollinger-Ellison tumor (and its metastasis) yields an extract with the physiologic properties of the hormone gastrin, a stimulator of gastric secretion 1,000 times more powerful than histamine. Best results in surgical therapy of the Zollinger-Ellison tumor have followed total gastrectomy combined with resection of the tumor (85% satisfactory results). A test is under evaluation by Zollinger and his associates to detect gastrin remaining in the circulation after tumor resection. Proof of complete eradication of the tumor could obviate gastrectomy. The rarest type of functioning islet cell tumor is recognized by a debilitating severe diarrhea and hypokalemia unaccompanied by gastric hypersecretion or peptic ulceration. Although secretion of a hormone by the tumor is probable, none has been extracted. A few patients may manifest both this syndrome and the Zollinger-Ellison syndrome, just as some have manifested a Zollinger-Ellison syndrome accompanied by the hypoglycemia of the classical insuloma. Chemotherapeutic treatment of functioning and nonfunctioning islet cell tumors has been under way for many years. Recently some responses have been achieved in cases of malignant tumors with 5-fluorouracil and a new drug, Tubercidin®. Successful chemotherapeutic treatment of islet cell tumors will depend upon finding a way to control the drug toxicity or to allow the drug to be excreted by the body so that severe bone marrow depression need not dictate cessation of treatment.
MicroRNA-21 in Glomerular Injury
Authors: Jennifer Y. Lai, Jinghui Luo, Christopher O’Connor, Xiaohong Jing, Viji Nair, Wenjun Ju, Ann Randolph, Iddo Z. Ben-Dov, Regina N. Matar, Daniel Briskin, Jiri Zavadil, Robert G. Nelson, Thomas Tuschl, Frank C. Brosius, Matthias Kretzler, Markus Bitzer
Journal: Journal of the American Society of Nephrology (2014)

TGF-β1 is a pleotropic growth factor that mediates glomerulosclerosis and podocyte apoptosis, hallmarks of glomerular diseases. The expression of microRNA-21 (miR-21) is regulated by TGF-β1, and miR-21 inhibits apoptosis in cancer cells. TGF-β1–transgenic mice exhibit accelerated podocyte loss and glomerulosclerosis. We determined that miR-21 expression increases rapidly in cultured murine podocytes after exposure to TGF-β1 and is higher in kidneys of TGF-β1–transgenic mice than wild-type mice. miR-21–deficient TGF-β1–transgenic mice showed increased proteinuria and glomerular extracellular matrix deposition and fewer podocytes per glomerular tuft compared with miR-21 wild-type TGF-β1–transgenic littermates. Similarly, miR-21 expression was increased in streptozotocin-induced diabetic mice, and loss of miR-21 in these mice was associated with increased albuminuria, podocyte depletion, and mesangial expansion. In cultured podocytes, inhibition of miR-21 was accompanied by increases in the rate of cell death, TGF-β/Smad3-signaling activity, and expression of known proapoptotic miR-21 target genes p53, Pdcd4, Smad7, Tgfbr2, and Timp3. In American-Indian patients with diabetic nephropathy (n=48), albumin-to-creatinine ratio was positively associated with miR-21 expression in glomerular fractions (r=0.6; P<0.001) but not tubulointerstitial fractions (P=0.80). These findings suggest that miR-21 ameliorates TGF-β1 and hyperglycemia-induced glomerular injury through repression of proapoptotic signals, thereby inhibiting podocyte loss. This finding is in contrast to observations in murine models of tubulointerstitial kidney injury but consistent with findings in cancer models. The aggravation of glomerular disease in miR-21–deficient mice and the positive association with albumin-to-creatinine ratio in patients with diabetic nephropathy support miR-21 as a feedback inhibitor of TGF-β signaling and functions.
Effect of Exemestane on Tamoxifen Pharmacokinetics in Postmenopausal Women Treated for Breast Cancer
Authors: Paul R. Hutson, Richard R. Love, Thomas C. Havighurst, Eric Rogers, James F. Cleary
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Rodent models of human breast cancer suggest that the combination of the steroidal aromatase inhibitor exemestane with tamoxifen may have additive activity. Clinical trials combining tamoxifen with letrozole or anastrazole have shown minor pharmacokinetic drug interactions. We did an open-label crossover clinical trial of the effect of exemestane on tamoxifen pharmacokinetics. Design: Thirty-two postmenopausal women who were clinically disease-free following primary treatments for breast cancer receiving tamoxifen for at least 3 months were studied. Blood was collected for pharmacokinetic analysis after at least 4 months of receiving 20 mg tamoxifen daily. Subjects then began 8 weeks of oral exemestane (25 mg daily), followed by another set of blood samples. Results: There were no serious toxicities noted when the two drugs were combined. There was no significant effect of exemestane on the area under the plasma concentration versus time curve (AUC) of tamoxifen at steady state before [3.04 mg h/L; 90% confidence interval (90% CI), 2.71-3.44] and during exemestane treatment (3.05 mg h/L; 90% CI, 2.72-3.41). There were no significant changes in the formation of primary tamoxifen metabolites. Oral clearance of exemestane averaged 602 L/h based on an average plasma exemestane AUC of 41.5 μg h/L (90% CI, 36.7-62.6). Plasma concentrations of estradiol, estrone, and estrone sulfate decreased when exemestane was begun; estradiol concentrations consistently decreased below the limit of quantitation. Conclusions: There is no pharmacokinetic interaction between tamoxifen and exemestane. No modification in the standard regimen of either drug seems to be indicated if they are used in combination. The combination of the two drugs was well tolerated during the 8-week evaluation period.
Sympathetic neuronal regulation of the heart in aging and heart failure
Authors: D KAYE, M ESLER
Journal: Cardiovascular Research (2005)

The documentation of preferential activation of the cardiac sympathetic outflow in patients with heart failure swept aside an entrenched notion that there was a functional sympathetic denervation of the failing heart and provided a theoretical basis for the clinical evaluation of β-adrenergic blocker therapy in this condition. The demonstration that heightened sympathetic nervous system activity is central to the pathogenesis and progression of congestive heart failure (CHF) has now led to the rational use of β-adrenoceptor blockade in CHF. More recently, it has also emerged that the aging heart exhibits some of the characteristic changes in autonomic control which are seen in CHF. Accordingly, alterations in cardiac sympathetic nerve function are now thought to contribute also to the pathophysiology of the aging heart. Furthermore, there is evidence that in humans, sympathoexcitatory rostral projections of brainstem noradrenergic neurons to the forebrain are important in the sympathetic nervous activation of both heart failure and aging. Given these similarities, in this review we compare and contrast the neurobiology of the sympathetic nervous system in the failing heart and the healthy, aging heart, and consider whether the sympathetic activation accompanying aging may, perhaps, underlie and contribute to the neural pathophysiology of heart failure. Our conclusion is, on balance, that this proposition is not supported by the available evidence.