tbuckley/cabot-search huggingface dataset:
Chemiluminescence of phagocytic cells caused by N-formylmethionyl peptides
Authors: GE Hatch, DE Gardner, DB Menzel
Journal: The Journal of Experimental Medicine (1978)

N-formylmethionyl (F-Met) peptides, when added alone to macrophages or polymorphonuclear leukocytes (PMN), were found to induce a chemiluminescent response of shorter duration than that produced by the commonly employed particulate stimulant, zymosan. The cellular nature of F-Met peptide-induced chemiluminescence was indicated by its dependence on cell concentration, and by its inhibition by cell disruption, heat inactivation, or previous maximal stimulation by the peptides. Comparison of PMN and macrophages from different species showed that the maximal chemiluminescent response seen in the dose-response curve of F-Met- Phe was different in different cell types. Chemiluminescence reached highest values in human PMN, it was intermediate in guinea pig macrophages and PMN, and in rabbit PMN; but it was nonexistent in rabbit alveolar macrophages and very low in rabbit peritoneal macrophages. A definite relationship was observed between peptide structure and chemiluminescent activity. Met-Phe, F- Met and Phe were inactive even at millimolar concentrations, while F-Met-Phe caused chemiluminescence at micromolar concentrations. Four active peptides were tested in guinea pig, rabbit, and human PMN, and in guinea pig alveolar and peritoneal macrophages. The relative activity of these peptides was the same in all cells studied, e.g. F-Met-Leu-Phe &amp;gt;&amp;gt; F-Met-Phe &amp;gt; F-Met-Val &amp;gt; F- Met-Ala. The values of ED50 for each peptide were also comparable to previously reported ED50 values of these peptides in inducing lysosomal enzyme release. These results were seen both in the presence and absence ofthe chemiluminescent oxidant indicator, luminol. Low concentrations of superoxide dismutase (10 μg/ml) completely inhibited chemiluminescence caused by the F-Met peptides, suggesting the involvement of 0(2)(-) or O(2)(-)-derived compounds in this response. Sodium azide, an inhibitor of peroxidase reactions, had either no effect or a slight inhibitory effect on chemiluminescence. However, when the extracellular release of lysosomal enzymes was induced by cytochalasin B, an azide- inhibitable enhancement of chemiluminescence was seen in PMN, but not in macrophages. This effect appears to be correlated with the presence of granule-associated myeloperoxidase. Although azide-inhibitable peroxidases could be a potential source of light, they did not appear to be a significant contributor in these experiments. Based on these results and on those of previous investigators, we postulate that the F-Met-peptides stimulate 0(2)(-) production in addition to stimulating lysosomal enzyme release and chemotaxis. The similar structure- activity relationship which appears to exist for these processes may indicate that they are all initiated by a single receptor mechanism. Since F-Met peptides are formed in bacteria it is likely that their actions represent an important physiologic response.
Predicting the Overuse of PCSK-9 Inhibitors
Authors: Rene Rodriguez-Gutierrez, Nilay D. Shah, Victor M. Montori
Journal: JAMA (2015)

This Viewpoint anticipates widespread premature use of proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitors in response to the challenges some patients experience taking statins and urges caution until trials and experience demonstrate the new drugs are safe.
Ascitic fluid cholesterol level in the diagnosis of postsinusoidal portal hypertension
Authors: K. Demir, S. Kaymakoǧlu, S. Özdil, D. Dinçer, Z. Durakoǧlu, C. Karaca, F. Beşişik, G. Boztaş, Z. Mungan, Y. Çakaloǧlu, A. Ökten
Journal: Journal of Hepatology (2001)
MRI findings predict radiographic progression and development of erosions in hand osteoarthritis
Authors: Ida K Haugen, Barbara Slatkowsky-Christensen, Pernille Bøyesen, Sølve Sesseng, Désirée van der Heijde, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To examine whether MRI features predict radiographic progression including erosive evolution in patients from the Oslo hand osteoarthritis (OA) cohort, which is the first longitudinal hand OA study with available MRI. <h3>Methods</h3> We included 74 patients (91% female, mean (SD) age of 67.9 (5.3) years) with MRI of the dominant hand and conventional radiographs taken at baseline and 5-year follow-up. Baseline MRIs were read according to the Oslo hand OA MRI score. We used three definitions of radiographic progression: Progression of joint space narrowing (JSN, grades 0–3), increased Kellgren–Lawrence score (grades 0–4) or incident erosions (absent/present). For each definition, we examined whether MRI features predicted radiographic progression in the same joint using Generalised Estimating Equations. We adjusted for age, sex, Body Mass Index, follow-up time and other erosive joints (the latter for analyses on incident erosions only). <h3>Results</h3> MRI-defined moderate/severe synovitis (OR=3.52, 95% CI 1.29 to 9.59), bone marrow lesions (BML) (OR=2.73, 95% CI 1.29 to 5.78) and JSN (severe JSN: OR=11.05, 95% CI 3.22 to 37.90) at baseline predicted progression of radiographic JSN. Similar results were found for increasing Kellgren–Lawrence score, except for weaker association for JSN. Baseline synovitis, BMLs, JSN, bone damage, osteophytes and malalignment were significantly associated with development of radiographic erosions, of which malalignment showed the strongest association (OR=10.18, 95% CI 2.01 to 51.64). <h3>Conclusions</h3> BMLs, synovitis and JSN were the strongest predictors for radiographic progression. Malalignment was associated with incident erosions only. Future studies should explore whether reducing BMLs and inflammation can decrease the risk of structural progression.
Overall survival with cisplatin–gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL)
Authors: M. Reck, J Von Pawel, P. Zatloukal, R. Ramlau, V. Gorbounova, V. Hirsh, N B Leighl, J. Mezger, V. Archer, N C Moore, C. Manegold
Journal: Annals of Oncology (2010)
Efficacy and Safety of Lapatinib As First-Line Therapy for ErbB2-Amplified Locally Advanced or Metastatic Breast Cancer
Authors: Henry L. Gomez, Dinesh C. Doval, Miguel A. Chavez, Peter C.-S. Ang, Zeba Aziz, Shona Nag, Christina Ng, Sandra X. Franco, Louis W.C. Chow, Michael C. Arbushites, Michelle A. Casey, Mark S. Berger, Steven H. Stein, George W. Sledge
Journal: Journal of Clinical Oncology (2008)

This study (EGF20009) assessed the efficacy and tolerability of two lapatinib administration schedules as first-line monotherapy in women with ErbB2-amplified locally advanced or metastatic breast cancer.Patients with ErbB2-amplified, locally advanced or metastatic breast cancer previously untreated in the metastatic setting were randomly assigned to one of two lapatinib dose cohorts and received either 1,500 mg once daily or 500 mg twice daily. Clinical response was assessed at weeks 8 and 12 and every 12 weeks thereafter.A total of 138 patients were treated with lapatinib for a median of 17.6 weeks. The overall response rate (complete response [CR] plus partial response [PR]) was 24% in the intent-to-treat population, and 31% of patients derived clinical benefit (CR, PR, or stable disease for >or= 24 weeks). The median time to response was 7.9 weeks, and the progression-free survival rates at 4 and 6 months were 63% and 43%, respectively. The most common lapatinib-related adverse events (AEs) were diarrhea, rash, pruritus, and nausea, and these events were primarily grade 1 or 2. There were no significant differences in clinical activity or the AE profile between the dosing schedules.Lapatinib demonstrated clinical activity and was well tolerated as first-line therapy in ErbB2-amplified locally advanced or metastatic breast cancer. This study supports further evaluation of lapatinib in first-line and early-stage ErbB2-overexpressing breast cancer.
IL-13 R130Q, a common variant associated with allergy and asthma, enhances effector mechanisms essential for human allergic inflammation
Authors: Frank D. Vladich, Susan M. Brazille, Debra Stern, Michael L. Peck, Raffaella Ghittoni, Donata Vercelli
Journal: Journal of Clinical Investigation (2005)

Genetic factors are known to strongly influence susceptibility to allergic inflammation. The Th2 cytokine IL-13 is a central mediator of allergy and asthma, and common single-nucleotide polymorphisms in IL13 are associated with allergic phenotypes in several ethnically diverse populations. In particular, IL13+2044G→A is expected to result in the nonconservative replacement of arginine 130 (R130) with glutamine (Q). We examined the impact of IL13+2044G→A on the functional properties of IL-13 by directly comparing the activity of WT IL-13 and IL-13 R130Q on primary human cells involved in the effector mechanisms of allergic inflammation. Our results show that IL-13 R130Q was significantly more active than WT IL-13 in inducing STAT6 phosphorylation and CD23 expression in monocytes and hydrocortisone-dependent IgE switching in B cells. Notably, IL-13 R130Q was neutralized less effectively than WT IL-13 by an IL-13Rα2 decoy. Decreased neutralization of the minor variant could contribute to its enhanced in vivo activity. Neither IL-13 variant was able to engage T cells, which suggests that increased allergic inflammation in carriers of IL13+2044A depends on enhanced IL-13–mediated Th2 effector functions rather than increased Th2 differentiation. Collectively, our data indicate that natural variation in the coding region of IL13 may be an important genetic determinant of susceptibility to allergy.
Hypertension: a case of the gratuitous rider
Authors: K. T. Weber
Journal: Cardiovascular Research (1996)

Life in the thirteen colonies seemed constrained by another country's laws.In Boston and elsewhere, this at first was a small price to pay in return for greater personal freedoms.Why only Puritans were granted privileges to vote and hold public office, however, was a contradiction.But the rallying cry for all of Beantown was 'taxation without representation'.Duties imposed on imported goods caused frustrated patriots to dispatch cargoes of tea into their Harbor in the winter of 1773.Thanksgiving in South Boston, Thursday, November 25, 1993, was shared with family.It also served as remembrance when native Americans and European immigrants would break bread together.For Dr. Nick O'Donnell, resident in internal medicine, it was a time to reflect on patients seen during his tenure with the hypertension (HT) service.Ms. F., a 26-year-old, had presented with weakness, polyuria, BP lSO/lOO, a high-pitched bruit in the right epigastrium, hypokalemia and metabolic alkalosis.Nick suspected renovascular hypertension.Right renal artery stenosis, likely due to fibromuscular dysplasia, together with suppressed renin production from the left kidney, was found.Angioplasty relieved the obstruction; BP improved but only normalized months later.Nick knew HT was secondary to an activation of the circulating renin-angiotensin-aldosterone system @AAS), initiated by the 'endocrine' kidney.However, once renal perfusion was restored, why didn't arterial pressure normalize immediately?This must be related to arteriolar remodeling.Was this created by I-IT or RAAS?Insights might arise from Mr. R., a 25year-old with aortic coarctation (coarc).His upper extremity/thoracic development and arterial pulses
A promising therapeutic approach to spinal cord repair
Authors: G. Raisman
Journal: Journal of the Royal Society of Medicine (2003)

Every year 30 000 neuroscientists meet in the USA. Few cities have the facilities to accommodate them all. Their proceedings fill the equivalent of more than three London telephone directories. A patient with spinal cord injury may wonder if he is living on the same planet. How come he is still confined to a wheelchair? Is it simply the magnitude of the problem? Or is there some inbuilt pessimism that is retarding advance?
Sexually transmitted diseases continue to rise
Authors: Caroline White
Journal: BMJ (2004)

The overall numbers of sexually transmitted infections in England, Wales, and Northern Ireland continued to increase during 2003, the Health Protection Agency announced at the launch of its first annual report. But although there are some signs that the steady rises since 1995 may be starting to level out slightly, the figures hide huge variations in the diagnoses of individual infections. And they show that rates of infection are consistently higher in homosexual men than in heterosexual men for almost every infection reported by genitourinary medicine clinics.
Treatment modalities in lung cancer patients with brain metastasis
Authors: Evica BudiÅ¡in, Nikola Budisin, Nensi Lalic, Danica Sazdanic, Aleksandra Andelkovic
Journal: European Respiratory Journal (2012)

Forty lung cancer patients with diagnosed brain metastasis were evaluated at the Institute of Lung diseases at Sremska Kamenica in the period of three years. Duration of survival in such patients was evaluated and compared according to the treatment employed as well as to the histology, number of metastasis and presence/absence of synchronous other visceral metastasis. Treatment modalities included: irradiation, surgery, and chemotherapy for chest tumor, and for the brain metastasis, and symptomatic treatment. There were 34 male (85%) and 6 female (15%). 72.5% have had solitary metastases, while 27.5 % presented with multiple metastasis. Mean survival was 3.2 months from the diagnosis of brain metastasis (range 0-14 months). Irradiation of thorax underwent 57.5%, chest operation 15% and chemotherapy 22.5%. Irradiation of brain metastasis underwent 42.5% of patients, chemotherapy 7.5% patients, while 12.5% were operated for brain metastasis. 37.5% were treated only symptomatically. Sixty percent were without other visceral metastasis. Statistical significance in terms of longer survival was found in patients who had solitary compared to multiple metastasis p  Although prognosis of patients with lung cancer and brain metastasis is gloomy, our investigation suggests longer survival with employed brain surgery or brain irradiation.  Key words: lung cancer, brain, metastases.
Redox-dependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria
Authors: Chad R. Frasier, Fatiha Moukdar, Hetal D. Patel, Ruben C. Sloan, Luke M. Stewart, Rick J. Alleman, Justin D. La Favor, David A. Brown
Journal: Cardiovascular Research (2013)

We have previously shown that exercise leads to sustainable cardioprotection through a mechanism involving improved glutathione replenishment. This study was conducted to determine if redox-dependent modifications in glutathione reductase (GR) were involved in exercise cardioprotection. Furthermore, we sought to determine if reactive oxygen species generated by NADPH oxidase and/or mitochondria during exercise were triggering events for GR modulations.Rats were exercised for 10 consecutive days, after which isolated hearts were exposed to ischaemia/reperfusion (25 min/120 min). Exercise protected against infarction and arrhythmia, and preserved coronary flow. The GR inhibitor BCNU abolished the beneficial effects. GR activity was increased following exercise in a redox-dependent manner, with no change in GR protein levels. Because fluorescent labelling of GR protein thiols showed lower amounts of reduced thiols after exercise, we sought to determine the source of intracellular reactive oxygen species that may be activating GR. Subsets of animals were exercised immediately after treatment with either NADPH-oxidase inhibitors apocynin or Vas2870, or with mitoTEMPO or Bendavia, which reduce mitochondrial reactive oxygen species levels. The cardioprotective effects of exercise were abolished if animals exercised in the presence of NADPH oxidase inhibitors, in clear contrast to the mitochondrial reagents. These changes correlated with thiol-dependent modifications of GR.Adaptive cardioprotective signalling is triggered by reactive oxygen species from NADPH oxidase, and leads to improved glutathione replenishment through redox-dependent modifications in GR.
Adjuvant Clodronate Treatment Does Not Reduce the Frequency of Skeletal Metastases in Node-Positive Breast Cancer Patients: 5-Year Results of a Randomized Controlled Trial
Authors: Tiina Saarto, Carl Blomqvist, Pekka Virkkunen, Inkeri Elomaa
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Bisphosphonates have effectively reduced the development and progression of bone metastases in advanced breast cancer. The aim of this study was to determine whether bone metastases could be prevented by adjuvant clodronate treatment in patients with primary breast cancer. PATIENTS AND METHODS: Between 1990 and 1993, 299 women with primary node-positive breast cancer were randomized to clodronate (n = 149) or control groups (n = 150). Clodronate 1,600 mg daily was given orally for 3 years. All patients received adjuvant therapy: premenopausal six cycles of CMF chemotherapy and postmenopausal antiestrogens (randomized to tamoxifen 20 mg or toremifene 60 mg/d for 3 years). Seventeen patients were excluded from the analyses because of major protocol violations. The final population was 282 patients. Intent-to-treat analyses were also performed for all major end points. The follow-up time was 5 years for all patients. RESULTS: Bone metastases were detected equally often in the clodronate and control groups: 29 patients (21%) versus 24 patients (17%) (P = .27). The development of nonskeletal recurrence was significantly higher in the clodronate group compared with controls: 60 patients (43%) versus 36 patients (25%) (P = .0007). The overall survival (OS) and disease-free survival (DFS) rates were also significantly lower in the clodronate group than in the controls (OS, 70% v 83%, P = .009; DFS, 56% v 71%, P = .007, respectively). In multivariate analyses, clodronate remained significantly associated with DFS (P = .009). CONCLUSION: Adjuvant clodronate treatment does not prevent the development of bone metastases in node-positive breast cancer patients. However, clodronate seems to have a negative effect on DFS by increasing the development of nonskeletal metastases.
Effects of high-altitude exercise training on contractile function of rat skinned cardiomyocyte
Authors: O CAZORLA, Y AITMOU, L GORET, G VASSORT, M DAUZAT, A LACAMPAGNE, S TANGUY, P OBERT
Journal: Cardiovascular Research (2006)

Previous studies have questioned whether there is an improved cardiac function after high-altitude training. Accordingly, the present study was designed specifically to test whether this apparent blunted response of the whole heart to training can be accounted for by altered mechanical properties at the cellular level.Adult rats were trained for 5 weeks under normoxic (N, NT for sedentary and trained animals, respectively) or hypobaric hypoxic (H, HT) conditions. Cardiac morphology and function were evaluated by echocardiography. Calcium Ca2+ sensitivity of the contractile machinery was estimated in skinned cardiomyocytes isolated from the left ventricular (LV) sub-epicardium (Epi) and sub-endocardium (Endo) at short and long sarcomere lengths (SL).Cardiac remodelling was harmonious (increase in wall thickness with chamber dilatation) in NT rats and disharmonious (hypertrophy without chamber dilatation) in HT rats. Contrary to NT rats, HT rats did not exhibit enhancement in global cardiac performance evaluated by echocardiography. Stretch- dependent Ca2+ sensitization of the myofilaments (cellular index of the Frank-Starling mechanism) increased from Epi to Endo in N rats. Training in normoxic conditions further increased this stretch-dependent Ca2+ sensitization. Chronic hypoxia did not significantly affect myofibrilar Ca2+ sensitivity. In contrast, high-altitude training decreased Ca2+ sensitivity of the myofilaments at both SL, mostly in Endo cells, resulting in a loss of the transmural gradient of the stretch-dependent Ca2+ sensitization. Expression of myosin heavy chain isoforms was affected both by training and chronic hypoxia but did not correlate with mechanical data.Training at sea level increased the transmural gradient of stretch-dependent Ca2+ sensitization of the myofilaments, accounting for an improved Frank-Starling mechanism. High-altitude training depressed myofilament response to Ca2+, especially in the Endo layer. This led to a reduction in this transmural gradient that may contribute to the lack of improvement in LV function via the Frank-Starling mechanism.
Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood
Authors: R. T. Stein, C. J. Holberg, W. J. Morgan, A. L. Wright, E. Lombardi, L. Taussig, F. D. Martinez
Journal: Thorax (1997)

BACKGROUND: There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood. METHOD: In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined. RESULTS: Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p &lt; 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity). CONCLUSIONS: Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.
An unexpected cause of chronic diarrhoea
Authors: C-M Tai, C-H Tu, H-B Wu, D-S Perng, T-C Lee, C-T Shun, H-P Wang
Journal: Gut (2008)

A 41-year-old man suffered from chronic diarrhoea of 3 years’ duration, accompanied by weight loss of 20 kg. He was referred to our hospital for double-balloon enteroscopy (DBE). …
Cord Colitis Syndrome in Cord-Blood Stem-Cell Transplantation
Authors: Alex F. Herrera, Gabriela Soriano, Andrew M. Bellizzi, Jason L. Hornick, Vincent T. Ho, Karen K. Ballen, Lindsey R. Baden, Corey S. Cutler, Joseph H. Antin, Robert J. Soiffer, Francisco M. Marty
Journal: New England Journal of Medicine (2011)

Diarrhea is a frequent complication of hematopoietic stem-cell transplantation (HSCT). Important causes of diarrhea after HSCT include acute graft-versus-host disease (GVHD), infections, and medications. After the transplantation and engraftment of hematopoietic stem cells from umbilical-cord blood, we observed a new syndrome of culture-negative, antibiotic-responsive diarrhea not attributable to any known cause.