tbuckley/cabot-search huggingface dataset:
Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Carsten Denkert, Sibylle Loibl, Aurelia Noske, Marc Roller, Berit Maria Müller, Martina Komor, Jan Budczies, Silvia Darb-Esfahani, Ralf Kronenwett, Claus Hanusch, Christian von Törne, Wilko Weichert, Knut Engels, Christine Solbach, Iris Schrader, Manfred Dietel, Gunter von Minckwitz
Journal: Journal of Clinical Oncology (2009)

PURPOSE Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. CONCLUSION The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.
`Paraffinosis' Secondary to Bilateral Oleothorax
Authors: P. D. Lewis, A. D. Dayan
Journal: Thorax (1965)

From the end of the last century (Hutchison, 1899) liquid paraffin was for several decades con- sidered to be biologically inert, but such compli- cations of its administration as lipoid pneumonia (Laughlen, 1925) and granuloma formation in lungs (Ikeda, 1937) and subcutaneous tissues (Lenormant and Ravaut, 1926) have shown it to be capable of producing an inflammatory re- sponse.We report a case in which oleothorax, induced as collapse therapy for pulmonary tuber- culosis, gave rise to widespread lesions attribut- able to disseminated mineral oil. CASE REPORTThis patient was aged 29 at the time of her death in May 1964.In 1951, at the age of 16, a diagnosis of bilateral pulmonary tuberculosis had been made.An artificial pneumothorax was induced on each side, and, because of difficulty in maintaining them, both were eonverted into oleothoraces, using liquid paraffin with crystalline penicillin in suspension.In June 1954 a relapse occurred on the left side which was treated with bed rest, streptomycin, and isoniazid for six months (Fig. 1).She made a good recovery and by 1955 was feeling well and started work.Towards the end of 1956 she complained of morning nausea, malaise, and loss of weight, and in March 1957 she was referred for the first time to the London Hospital.Apart from the respiratory system, the most striking findings on physical examination were a palpable spleen three finger- breadths below the left costal margin and a slightly enlarged liver.The E.
Acquired pulmonary stenosis and pulmonary artery compression
Authors: J. H. Gough, R. G. Gold, R. V. Gibson
Journal: Thorax (1967)

Three patients suffering from acquired pulmonary stenosis are described resulting from compression of the main pulmonary artery by anterior mediastinal teratoma, Hodgkin9s disease, and aneurysm of the ascending aorta, respectively; also four others who had compression of the right or left primary branch of the pulmonary artery. The pulmonary artery compression was demonstrated angiographically in every case, and in the patient with right and left pulmonary artery compression the main pulmonary artery pressure tracing was characteristic of bilateral pulmonary artery stenosis. Cardiac catheterization and selective angiography are indicated in patients who have evidence of right ventricular outflow obstruction to determine the site and severity of the obstruction and to differentiate between extrinsic compression and intrinsic stenosis.
Psychiatric Practice and Public Policy
Authors: BERTRAM S. BROWN
Journal: American Journal of Psychiatry (1968)

As men seek the answers to the major public policy questions of our time, they increasingly turn to psychiatry. The author cites several major areas where he feels psychiatry has a potential contribution, including health economics, antisocial disorders, and family planning. The author asks psychiatrists to respond to today's challenges with a combination of responsibility and humility.
Resistin Promotes Smooth Muscle Cell Proliferation Through Activation of Extracellular Signal–Regulated Kinase 1/2 and Phosphatidylinositol 3-Kinase Pathways
Authors: Paolo Calabro, Ismael Samudio, James T. Willerson, Edward T.H. Yeh
Journal: Circulation (2004)

Resistin, a novel adipokine, is elevated in patients with type 2 diabetes and may play a role in the vascular complications of this disorder. One recent study has shown that resistin has a proinflammatory effect on endothelial cells. However, there is no information on whether resistin could also affect vascular smooth muscle cells (SMCs). Thus, the purpose of this study was to assess whether resistin could induce SMC proliferation and to study the mechanisms whereby resistin signals in SMCs.Human aortic smooth muscle cells (HASMCs) were stimulated with increasing concentrations of resistin for 48 hours. Cell proliferation was induced by resistin in a dose-dependent manner as assessed by direct cell counting. To gain more insights into the mechanism of action of resistin, we investigated the extracellular signal-regulated kinase (ERK) and/or phosphatidylinositol 3-kinase (PI3K) signaling pathways. Transient phosphorylation of the p42/44 mitogen-activated protein kinase (ERK 1/2) occurred after addition of resistin to HASMCs. U0126, a specific inhibitor of ERK phosphorylation, significantly inhibited ERK 1/2 phosphorylation and reduced resistin-simulated proliferation of HASMCs. LY294002, a specific PI3K inhibitor, also significantly inhibited HASMC proliferation after resistin stimulation.Our results demonstrate that resistin induces HASMC proliferation through both ERK 1/2 and Akt signaling pathways. The proliferative action exerted by resistin on HASMCs may account in part for the increased incidence of restenosis in diabetes patients.
Dynamic Behavior during Noninvasive Ventilation
Authors: JOHN R. HOTCHKISS, ALEXANDER B. ADAMS, DAVID J. DRIES, JOHN J. MARINI, PHILIP S. CROOKE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Acute noninvasive ventilation is generally applied via face mask, with modified pressure support used as the initial mode to assist ventilation. Although an adequate seal can usually be obtained, leaks frequently develop between the mask and the patient's face. This leakage presents a theoretical problem, since the inspiratory phase of pressure support terminates when flow falls to a predetermined fraction of peak inspiratory flow. To explore the issue of mask leakage and machine performance, we used a mathematical model to investigate the dynamic behavior of pressure-supported noninvasive ventilation, and confirmed the predicted behavior through use of a test lung. Our mathematical and laboratory analyses indicate that even when subject effort is unvarying, pressure-support ventilation applied in the presence of an inspiratory leak proximal to the airway opening can be accompanied by marked variations in duration of the inspiratory phase and in autoPEEP. The unstable behavior was observed in the simplest plausible mathematical models, and occurred at impedance values and ventilator settings that are clinically realistic.
Effectiveness of Collaborative Stepped Care for Anxiety Disorders in Primary Care: A Pragmatic Cluster Randomised Controlled Trial
Authors: Anna Muntingh, Christina van der Feltz-Cornelis, Harm van Marwijk, Philip Spinhoven, Willem Assendelft, Margot de Waal, Herman Adèr, Anton van Balkom
Journal: Psychotherapy and Psychosomatics (2013)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Collaborative stepped care (CSC) may be an appropriate model to provide evidence-based treatment for anxiety disorders in primary care. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In a&lt;b&gt; &lt;/b&gt;cluster randomised controlled trial, the effectiveness of CSC compared to care as usual (CAU) for adults with panic disorder (PD) or generalised anxiety disorder (GAD) in primary care was evaluated. Thirty-one psychiatric nurses who provided their services to 43 primary care practices in the Netherlands were randomised to deliver CSC (16 psychiatric nurses, 23 practices) or CAU (15 psychiatric nurses, 20 practices). CSC was provided by the psychiatric nurses (care managers) in collaboration with the general practitioner and a consultant psychiatrist. The intervention consisted of 3 steps, namely guided self-help, cognitive behavioural therapy and antidepressants. Anxiety symptoms were measured with the Beck Anxiety Inventory (BAI) at baseline and after 3, 6, 9 and 12 months. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; We recruited 180 patients with a DSM-IV diagnosis of PD or GAD, of whom 114 received CSC and 66 received usual primary care. On the BAI, CSC was&lt;b&gt; &lt;/b&gt;superior to CAU [difference in gain scores from baseline to 3 months: -5.11, 95% confidence interval (CI) -8.28 to -1.94; 6 months: -4.65, 95% CI -7.93 to -1.38; 9 months: -5.67, 95% CI -8.97 to -2.36; 12 months: -6.84, 95% CI -10.13 to -3.55]. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; CSC, with guided self-help as a first step, was more effective than CAU for primary care patients with PD or GAD.
Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis
Authors: Devi Rani Sagar, Sadaf Ashraf, Luting Xu, James J Burston, Matthew R Menhinick, Caroline L Poulter, Andrew J Bennett, David A Walsh, Victoria Chapman
Journal: Annals of the Rheumatic Diseases (2013)

Background Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). Objectives To investigate the analgesic potential of a modified version of osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) in the monosodium iodoacetate (MIA) model of OA pain. Methods Male Sprague Dawley rats (140–260 g) were treated with either OPG-Fc (3 mg/kg, subcutaneously) or vehicle (phosphate-buffered saline) between days 1 and 27 (pre-emptive treatment) or days 21 and 27 (therapeutic treatment) after an intra-articular injection of MIA (1 mg/50 µl) or saline. A separate cohort of rats received the bisphosphonate zoledronate (100 µg/kg, subcutaneously) between days 1 and 25 post-MIA injection. Incapacitance testing and von Frey (1–15 g) hind paw withdrawal thresholds were used to assess pain behaviour. At the end of the study, rats were killed and the knee joints and spinal cord removed for analysis. Immunohistochemical studies using Iba-1 and GFAP quantified levels of activation of spinal microglia and astrocytes, respectively. Joint sections were stained with haematoxylin and eosin or Safranin-O fast green and scored for matrix proteoglycan and overall joint morphology. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts were quantified. N=10 rats/group. Results Pre-emptive treatment with OPG-Fc significantly attenuated the development of MIA-induced changes in weightbearing, but not allodynia. OPG-Fc decreased osteoclast number, inhibited the formation of osteophytes and improved structural pathology within the joint similarly to the decrease seen after pretreatment with the bisphosphonate, zoledronate. Therapeutic treatment with OPG-Fc decreased pain behaviour, but did not improve pathology in rats with established joint damage. Conclusions Our data suggest that early targeting of osteoclasts may reduce pain associated with OA.
Fibrinolytic Activity in Human Atherosclerotic Coronary Arteries
Authors: HAU C. KWAAN, TAGE ASTRUP
Journal: Circulation Research (1967)

The localization of fibrinolytic areas in normal and atheromatous human coronary arteries was studied by the histochemical fibrin slide technique. Fibrinolytic activity was caused by a plasminogen activator. The activator, occasionally observed at sites in the normal endothelial lining, was abundantly present in relation to vessels in the normal adventitia. The pathological adventitia contained an increased number of active sites and endothelium covering an atherosclerotic plaque was richer in fibrinolytic sites than the normal endothelium. Within the vascularized plaque, fibrinolytically active capillaries could be traced from their origin in the vasa vasorum or, occasionally, in the endothelium. The results confirm and extend previous observations obtained in assays after extraction. They present patterns similar to those observed in normal tissue repair.
Improved Therapeutic Effectiveness by Combining Recombinant CXC Chemokine Ligand 10 with Cisplatin in Solid Tumors
Authors: Gang Li, Ling Tian, Jian-mei Hou, Zhen-yu Ding, Qiu-ming He, Ping Feng, Yan-jun Wen, Fei Xiao, Bing Yao, Ru Zhang, Feng Peng, Yu Jiang, Feng Luo, Xia Zhao, Lin Zhang, Qiao Zhou, Yu-quan Wei
Journal: Clinical Cancer Research (2005)

Abstract Purpose: CXC chemokine ligand 10 (CXCL10) is a potent inhibitor of angiogenesis. We wonder whether the combination of CXCL10 with cisplatin would improve the therapeutic antitumor efficacy. Experiment Design: We evaluated the antitumor activity of the combination therapy in the immunocompetent C57BL/6 and BALB/c mice bearing LL/2 Lewis lung cancer and CT26 colon adenocarcinoma, respectively. Mice were treated with either CXCL10 s.c. at 25 μg per kg per day once daily for 30 days, cisplatin cycled twice (5 mg/kg i.p. on days 14 and 21 after the initiation of CXCL10), or both agents together. Tumor volume and survival time were observed. Antiangiogenesis of CXCL10 in vivo were determined by alginate capsule models and CD31 immunohistochemistry. Histologic analysis and assessment of apoptotic cells were also conducted in tumor tissues. Results: CXCL10 + cisplatin reduced tumor growth in LL/2 and CT26 tumor model, respectively, more effectively, although cisplatin or CXCL10 individually resulted in suppression of tumor growth and improved survival time of tumor-bearing mice. CXCL10 successfully inhibited angiogenesis as assessed by alginate model and CD31 (P &amp;lt; 0.05). Histologic analysis of tumors exhibited that CXCL10 in combination with cisplatin led to the increased rate of apoptosis, tumor necrosis, and elevated lymphocyte infiltration. Conclusions: Our data suggest that the combination of CXCL10, a well-tolerated angiogenesis inhibitor, with cisplatin can enhance the antitumor activity. The present findings may be of importance to the further exploration of the potential application of this combined approach in the treatment of lung and colon carcinoma.
Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease
Authors: Philip WL Ho, Jessica WM Ho, Hui-Fang Liu, Danny HF So, Zero HM Tse, Koon-Ho Chan, David B Ramsden, Shu-Leong Ho
Journal: Translational Neurodegeneration (2012)

This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson's disease (PD). Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation, but as an integral part of this process, superoxides and other reactive oxygen species are also produced. Excessive free radical production contributes to oxidative stress. Cells have evolved to handle such stress via various endogenous anti-oxidant proteins. One such family of proteins is the mitochondrial uncoupling proteins (UCPs), which are anion carriers located in the mitochondrial inner membrane. There are five known homologues (UCP1 to 5), of which UCP4 and 5 are predominantly expressed in neural cells. In a series of previous publications, we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium (MPP+; toxic metabolite of MPTP) and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential, and reducing oxidative stress. We also showed how their expression can be influenced by nuclear factor kappa-B (NF-κB) signaling pathway specifically in UCP4. Furthermore, we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin (hormone produced by adipocytes) acting via UCP2 against MPP+-induced toxicity. There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD. Their expression, which can be induced, may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.
<i>In vitro</i> diagnosis of farmers' IgE‐mediated allergy by Phadiatop® and three new multiallergen RAST analyses
Authors: M. van Hage‐Hamsten, S. G. O. Johansson
Journal: Allergy (1993)

Identification of persons with atopic allergy in a population is difficult if the pattern of sensitizing allergens is unique. Three new multiallergen tests, Professional Allergy Mixes (PAX) 1–3 (Pharmacia Diagnostics, Uppsala, Sweden), have recently been inttoduced to screen IgE‐mediated allergy among farmers. PAX 1 contains animal danders and feathers, PAX 2 mites and insects, and PAX 3 pollens and molds. The value of these new tests for the determination of IgE‐mediated allergy among fanners was compared with that of Phadiatop®, a test for general atopy. Of 440 farmers, 91 were positive to Phadiatop and 97 to any of PAX 1–3. None of the farmers were positive in all tests. Only 70/97 sera positive in RAST to PAX 1–3 had a positive Phadiatop, whereas of 91 sera positive in Phadiatop, 70 had specific IgE antibodies to PAX 1–3. The value of using either Phadiatop or PAX 1–3 is limited (sensitivity 74–79%), but, together, these four tests will detect almost all (95.9%) farmers with IgE‐mediated sensitization and all (100%) with symptoms. We have also shown that the grain weevil Sitophilus grcmarius and the botfly Gaslerophihts intestinalis are important sources of allergens in rural environments.
Bilateral Carotid Sinus Control of Ventricular Performance in the Dog
Authors: PAUL J. MARTIN, MATTHEW N. LEVY, HARRISON ZIESKE
Journal: Circulation Research (1969)

Left and right carotid sinus pressures were independently varied while the left ventricular systolic pressure was recorded in an anesthetized canine preparation with an isolated, isovolumetric left heart. Intrasinus pressures were changed in steps of 50 mm Hg to produce either an increase or decrease in pressure from a mean level of 150 mm Hg. The response to eight combinations of increases and decreases in left- and right-sided pressures was examined. Blockade of the sympathetic impulses to the heart produced a loss of response of left ventricular systolic pressure when the intrasinus pressure was decreased from 150 to 100 mm Hg. Parasympathetic blockade produced a loss of response to an increase in pressure from 150 to 200 mm Hg. Left ventricular systolic pressure was more sensitive to a decrease in pressure from 150 to 100 mm Hg in the right sinus than in the left, but there was no difference in sensitivity between left and right sides when intrasinus pressure was raised from 150 to 200 mm Hg. The summation pattern of the response to simultaneous steps in left and right pressure was mutually facilitative for steps from 150 to 100 mm Hg and mutually inhibitory for steps from 150 to 200 mm Hg. The entire system was simulated with a hybrid computer model consisting of separate functional relations used to represent the baroreceptors, central nervous system, and left ventricle. Due to the baroreceptor characteristics and other nonlinearities, the simulation results suggest that a careful distinction should be drawn between transient and steady-state responses when assessing the relative role of each autonomic division in any baroreceptor reflex.
Sertraline in the Treatment of Panic Disorder: A Double-Blind Multicenter Trial
Authors: R B Pohl, R M Wolkow, C M Clary
Journal: American Journal of Psychiatry (1998)

Objective: This study determined the efficacy and safety of sertraline in the treatment of patients with panic disorder. Method: The study was a randomized, double-blind, parallel-group, flexible-dose comparison of sertraline and placebo in outpatients with a DSM-III-R diagnosis of panic disorder with or without agoraphobia. After a 2-week single-blind placebo lead-in, 168 patients entered a 10-week double-blind phase in which they were randomly assigned to treatment with either sertraline or placebo.Results: Sertraline was significantly more effective than placebo in decreasing the number of full and limited-symptom panic attacks. Among patients who completed the study, the mean number of panic attacks per week dropped by 88% in the sertraline-treated patients and 53% in the placebo-treated patients. Sertraline-treated patients also had significantly more improvement than placebo-treated patients in scores on the Quality of Life Enjoyment and Satisfaction Questionnaire, patient global evaluation, and Clinical Global Impression severity of illness and global improvement scales. Overall, patients tolerated sertraline well, and only 9% terminated treatment because of side effects.Conclusions: Sertraline is an effective and well-tolerated treatment for patients with panic disorder. Am J Psychiatry 1998; 155: 1189-1195
Lives on the line? Ethics and practicalities of duty of care in pandemics and disasters
Authors: A. K. Simonds, D. K. Sokol
Journal: European Respiratory Journal (2009)

Pandemics and acute emergencies raise pressing medical, ethical and organisational challenges. These include global governance, priority setting, triaging of patients, allocation of scarce resources and restricting individual liberty in the interests of public health. We will focus particularly on an issue of direct relevance to all respiratory team members, i.e. what is the duty of the healthcare worker to continue working in the face of personal risk, and draw lessons from guidelines, ethical considerations, past pandemics and evolving experience with H1N1 swine influenza.
The epigenetic promotion of osteogenic differentiation of human adipose-derived stem cells by the genetic and chemical blockade of histone demethylase LSD1
Authors: Wenshu Ge, Yunsong Liu, Tong Chen, Xiao Zhang, Longwei Lv, Chanyuan Jin, Yong Jiang, Lei Shi, Yongsheng Zhou
Journal: Biomaterials (2014)