tbuckley/cabot-search huggingface dataset:
Differential Effects of Estrogen and Antiestrogen on In Vitro Clonogenic Growth of Human Breast Cancers in Soft Agar
Authors: Y. Nomura, H. Tashiro, K. Hisamatsu
Journal: JNCI Journal of the National Cancer Institute (1990)

Of 534 human primary breast cancers provided for clonogenic assay in vitro, 276 (51.7%) developed distinctive colony formation by the soft-agar method. Estrogen receptors (ERs) were assayed by dextran-coated charcoal methods. A total of 65 (23.7%) of 274 breast cancers responded to added 10 n M 17β-estra-diol (E2) by an increase in the number of colonies per dish of 150% or more of that in the controls treated with dextran-coated charcoal. The ER-positive and ER-negative tumors differed significantly in their response to E2: 55 (29.9%) of 184 ER-positive tumors responded versus 10 (11.1%) of 90 ER-negative tumors. The cancers in which the number of colonies increased to 150% or more of that of the controls were considered to be estrogen dependent; those in which the number of colonies increased to less than 150% of the control values were considered to be estrogen independent. When 1 μ M ta-moxifen (TMX) was added to the medium, 48 (21.3%) of 225 cancers showed a decrease in the number of colonies to 50% or less of that of the controls. Thus, we could separate breast cancers that were TMX sensitive (No. of colonies ≤50% of that of controls) from those that were TMX resistant (No. of colonies >50% of that of controls). The response to TMX of the ER-positive cancers was significantly higher than that of the ER-negative tumors: 39 (25.5%) of 153 ER-positive tumors responded versus nine (12.5%) of 72 ER-negative tumors. In 153 ER-positive and 71 ER-negative tumors, we evaluated the correlation between the response to E2 and the response to TMX. ER-positive and ER-negative tumors differed significantly in their sensitivities to the two drugs. The TMX sensitivity did not completely correlate with the E2 dependence. The discrepancy (i.e., estrogen dependent-TMX resistant and estrogen independent-TMX sensitive) was seen more frequently in the ER-positive tumors. These results suggest that this clonogenic assay can be used to predict the dependence of an individual breast cancer on a specific hormonal agent. Furthermore, they indicate the existence of different mechanism(s) of hormone dependence of breast cancer cells on E2 and TMX.
ANAPHYLAXIS IN CHOPPED GUINEA PIG LUNG
Authors: K. F. Austen, W. E. Brocklehurst
Journal: The Journal of Experimental Medicine (1961)

The quantitative release of histamine and slow reacting substance by specific antigen from perfused, chopped, sensitized guinea pig lung has been used to study the opposing effects of monobasic and certain dibasic fatty acids on the anaphylactic reaction. The anaphylactic release of histamine and slow reacting substance is doubled by the addition of 0.5 mM of succinic or maleic acid to the reaction mixture, and enhancement is definite with as little as 0.05 mM of succinic acid. Prolonged preincubation of the tissue with the dibasic acids is not required, for 60 to 90 per cent of maximal enhancement is apparent when the antigen is added to the tissue only 10 seconds after succinic or maleic acid. The increased histamine release is not due to a qualitative change in the time course of histamine release, is not the result of increased histamine formation, and cannot be attributed to an effect on the tricarboxylic acid cycle. The enhancement seems to be due to potentiation of some step activated by the antigen-antibody interaction and common to both the release of histamine and slow reacting substance. The structural configuration required for a dibasic acid to enhance the anaphylactic reaction in guinea pig lung is quite specific; the carboxyl groups should be separated by a two carbon chain, and must be free or fixed in the cis position. The monobasic fatty acids from valeric to dodecanoic inhibit the anaphylactic release of histamine, and the concentration needed to produce 50 per cent inhibition decreases with increasing chain length. The introduction of a polar group, amino or carboxyl, into the hydrocarbon residue diminishes or abolishes inhibitory capacity. The inhibition produced by the fatty acids is neither due to calcium binding nor due to prevention of effective antigen-antibody interaction; the fatty acids probably inhibit by acting on an antigen-antibody-activated step. The inhibition of the anaphylactic release of histamine and slow reacting substance produced by caproic or decanoic acid can be reversed by the enhancing effect of succinic acid, and vice versa. Thus, compounds normally present in mammalian tissue can greatly influence the intensity of the in vitro anaphylactic reaction in the guinea pig.
Localisation of hyaluronan in the human intestinal wall.
Authors: B Gerdin, R Hallgren
Journal: Gut (1991)

<h3>Abstract</h3> The scientific community has widely supported wastewater monitoring of SARS-CoV-2 due to the early and prolonged excretion of coronavirus in the faecal matter. In the present study, eighteen influent wastewater samples from different wastewater treatment plants and pumping stations (5 samples from Vadodara city, 4 from Gandhinagar, and nine from Ahmedabad city) were collected and analyzed for the occurrence of SARS-CoV-2 RNA in Gujarat province, India. The results showed the highest SARS-CoV-2 genome concentration in Vadodara (3078 copies/ L), followed by Ahmedabad (2968 copies/ L) and Gandhinagar (354 copies/ L). The comparison of genome concentration more or less corresponded to the number of confirmed and active cases in all three cities. The study confirms the potential of the Surveillance of Wastewater for Early Epidemic Prediction (SWEEP) that can be used at a large scale around the globe for better dealing with the pandemic situation. <h3>Graphical abstract</h3>
Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes
Authors: Elena N. Dedkova, Xiang Ji, Yong Gao Wang, Lothar A. Blatter, Stephen L. Lipsius
Journal: Circulation Research (2003)

Fluorescence microscopy and the NO-sensitive indicator 4,5-diaminofluorescein were used to determine the effects of acetylcholine (ACh) on intracellular NO (NO i ) in cat atrial myocytes. Field stimulation (1 Hz) of cells or exposure of quiescent cells to ACh (1 to 10 μmol/L) had no effect on NO i . However, in field-stimulated cells, ACh exposure increased NO i , and ACh withdrawal elicited an additional, prominent increase in NO i production. During ACh exposure, addition of 1 μmol/L atropine increased NO i production similar to ACh withdrawal. ACh-induced increases in NO i were reduced by prior exposure to 1 mmol/L extracellular Ca 2+ ([Ca 2+ ] o ) and prevented by 0.5 mmol/L [Ca 2+ ] o , 1 μmol/L verapamil, 1 μmol/L atropine, 10 μmol/L L- N 5 -(1-iminoethyl)ornithine, 10 μmol/L W-7, or incubating cells in pertussis toxin or 10 μmol/L LY294002 (inhibits phosphatidylinositol 3-kinase). Switching to 0.5 mmol/L [Ca 2+ ] o during ACh withdrawal prevented the additional increase in NO i . ACh exposure increased phosphorylation (Ser 473 ) of protein kinase B (Akt), and this effect was blocked by LY294002 and unaffected in low (0.5 mmol/L) [Ca 2+ ] o . Confocal microscopy revealed that ACh exposure increased NO i at local subsarcolemmal sites, and ACh withdrawal additionally increased NO i by recruiting additional subsarcolemmal release sites. Disruption of caveolae by 2 mmol/L methyl-β-cyclodextrin abolished ACh-induced NO i production. We conclude that in cat atrial myocytes, ACh stimulates NO i release from local subsarcolemmal sites. ACh-induced increases in NO i requires both muscarinic receptor–mediated G i protein/phosphatidylinositol 3-kinase/Akt signaling and voltage-activated Ca 2+ influx for stimulation of calmodulin-dependent endothelial NO synthase activity. Increases in NO i elicited by ACh withdrawal result from the recovery of Ca 2+ influx after ACh inhibition. NO signaling elicited by ACh withdrawal stimulates rapid recovery from cholinergic atrial inhibition.
Virtual Look AHEAD Program: Initial Support for a Partly Virtualized Intensive Lifestyle Intervention in Type 2 Diabetes
Authors: Geoffrey C. Williams, Christopher P. Niemiec, Ari J. Elliot, Jennifer G. LaGuardia, Amy A. Gorin, C. Scott Rigby
Journal: Diabetes Care (2014)

The Look AHEAD (Action for Health in Diabetes) program produces clinically significant weight loss and improvements in glycemic control, blood pressure, and quality of life in patients with type 2 diabetes (1,2), yet lifestyle interventions are time-intensive and less effective when delivered with lower intensity in primary care settings (2). Obesity guidelines endorse using technology to increase the reach of effective lifestyle interventions in the population (2), and therefore we conducted a pilot evaluation of a partly virtualized intervention that delivered content from the 16 initial group sessions of the Look AHEAD program along with 6 monthly visits with a registered dietitian.

The theoretical framework for this pilot evaluation was self-determination theory, which is an organismic approach to human motivation that has applications to health-behavior change and maintenance. We posited that perceptions of the virtual clinician (VC) as supportive of the basic …
Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury
Authors: M Bhatia
Journal: Gut (2000)

Lung injury manifest clinically as adult respiratory distress syndrome (ARDS) is a common cause of morbidity and mortality following acute pancreatitis (AP). Neutrophils play a critical role in the progression of AP to ARDS. C-x-C chemokines are potent neutrophil chemoattractants and activators and have been implicated in AP.To evaluate the effect of blocking the C-x-C chemokine, cytokine induced neutrophil chemoattractant (CINC), in AP on pancreatic inflammation and the associated lung injury in rats.AP was induced by hourly intraperitoneal injections of caerulein. Goat anti-CINC antibody was administered either before or after starting caerulein injections to evaluate the prophylactic and therapeutic effects, respectively. Severity of AP was determined by measuring plasma amylase, pancreatic water content, and pancreatic myeloperoxidase (MPO) activity as a measure of neutrophil sequestration in the pancreas. Lung injury was determined by measurement of pulmonary microvascular permeability and lung MPO activity.Treatment with anti-CINC antibody had little effect on caerulein induced pancreatic damage. However, it reduced the caerulein mediated increase in lung MPO activity as well as lung microvascular permeability when administered either prophylactically (lung MPO (fold increase over control): 1.53 (0.21) v. 3.30 (0.46), p<0.05; microvascular permeability (L/P%): 0.42 (0.07) v. 0.77 (0.11), p<0.05) or therapeutically (lung MPO (fold increase over control): 2.13 (0.10) v 4.42 (0.65), p<0.05; microvascular permeability (L/P%): 0.31 (0.05) v 0.79 (0.13), p<0.05).Treatment with anti-CINC antibody afforded significant protection against pancreatitis associated lung injury. These results suggest that CINC plays an important role in the systemic inflammatory response in AP.
Right Ventricular End-Diastolic Volume Combined With Peak Systolic Blood Pressure During Exercise Identifies Patients at Risk for Complications in Adults With a Systemic Right Ventricle
Authors: Teun van der Bom, Michiel M. Winter, Maarten Groenink, Hubert W. Vliegen, Petronella G. Pieper, Arie P.J. van Dijk, Gertjan T. Sieswerda, Jolien W. Roos-Hesselink, Aeilko H. Zwinderman, Barbara J.M. Mulder, Berto J. Bouma
Journal: Journal of the American College of Cardiology (2013)
Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial
Authors: Guillermo Torre-Amione, Stefan D Anker, Robert C Bourge, Wilson S Colucci, Barry H Greenberg, Per Hildebrandt, Andre Keren, Michael Motro, Lemuel A Moyé, Jan Erik Otterstad, Craig M Pratt, Piotr Ponikowski, Jean Lucien Rouleau, Francois Sestier, Bernhard R Winkelmann, James B Young
Journal: The Lancet (2008)
Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial
Authors: S. Moore
Journal: BMJ (2002)

<b>Objective</b>: To assess the effectiveness of nurse led follow up in the management of patients with lung cancer. <b>Design</b>:Randomised controlled trial. <b>Setting</b>:Specialist cancer hospital and three cancer units in southeastern England <b>Participants</b>: 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months. <b>Intervention</b>: Nurse led follow up of outpatients compared with conventional medical follow up. <b>Outcome measures</b>: Quality of life, patients9 satisfaction, general practitioners9 satisfaction, survival, symptom-free survival, progression-free survival, use of resources, and comparison of costs. <b>Results</b>: Patient acceptability of nurse led follow up was high: 75% (203/271) of eligible patients consented to participate. Patients who received the intervention had less severe dyspnoea at 3 months (P=0.03) and had better scores for emotional functioning (P=0.03) and less peripheral neuropathy (P=0.05) at 12 months. Intervention group patients scored significantly better in most satisfaction subscales at 3, 6, and 12 months (P&lt;0.01 for all subscales at 3 months). No significant differences in general practitioners9 overall satisfaction were seen between the two groups. No differences were seen in survival or rates of objective progression, although nurses recorded progression of symptoms sooner than doctors (P=0.01). Intervention patients were more likely to die at home rather than in a hospital or hospice (P=0.04), attended fewer consultations with a hospital doctor during the first 3 months (P=0.004), had fewer radiographs during the first 6 months (P=0.04), and had more radiotherapy within the first 3 months (P=0.01). No other differences were seen between the two groups in terms of the use of resources. <b>Conclusion</b>: Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes.
The association between public transport and active tuberculosis in Lima, Peru
Authors: N. W. Furukawa, A. Mendoza-Ticona, J. O. Alarcon-Villaverde, H. Montejo, M. A. Micek, J. R. Zunt
Journal: European Respiratory Journal (2013)

To the Editor: 

While there have been impressive gains in the global control of tuberculosis (TB) over the past two decades, TB remains a leading cause of death and efforts to decrease its burden have been limited by the rise of drug resistant strains [1]. As drug-resistant TB remains exceedingly difficult and costly to treat, more research is needed to identify areas for improving primary prevention of TB.

The risk of TB transmission is increased whenever there is overcrowding, poor ventilation and exposure to an infected individual, and public transport has been identified as a potential setting with increased risk for TB transmission [2]. Indeed, recent research demonstrates the fraction of rebreathed air on public transport is mathematically correlated with a higher risk of contracting TB [3].

Previous investigations using cross-sectional data in Lima, Peru, have demonstrated that community, rather than household, transmission may account for up to 70% of incident infections [4]. Studies conducted in Lima found an increased risk of TB infection among individuals who rode minibuses [5] and those who worked on public transport [6]. However, these studies were limited by misclassification of TB diagnosis, imprecise time variables and wide confidence intervals.

The objective of our study was to assess the association between use of public transportation and active TB using a detailed transportation questionnaire, multiple control groups and improved TB diagnostics.

We used a matched case–control design and enrolled treatment-naive individuals newly diagnosed with TB on the day of diagnosis from three peripheral health centres in the Lima metropolitan …
TRPC1 Associates With BK <sub>Ca</sub> Channel to Form a Signal Complex in Vascular Smooth Muscle Cells
Authors: Hiu-Yee Kwan, Bing Shen, Xin Ma, Yuk-Chi Kwok, Yu Huang, Yu-Bun Man, Shan Yu, Xiaoqiang Yao
Journal: Circulation Research (2009)

TRPC1 (transient receptor potential canonical 1) is a Ca(2+)-permeable cation channel involved in diverse physiological function. TRPC1 may associate with other proteins to form a signaling complex, which is crucial for channel function. In the present study, we investigated the interaction between TRPC1 and large conductance Ca(2+)-sensitive K(+) channel (BK(Ca)). With the use of potentiometric fluorescence dye DiBAC(4)(3), we found that store-operated Ca(2+) influx resulted in membrane hyperpolarization of vascular smooth muscle cells (VSMCs). The hyperpolarization was inhibited by an anti-TRPC1 blocking antibody T1E3 and 2 BK(Ca) channel blockers, charybdotoxin and iberiotoxin. These data were confirmed by sharp microelectrode measurement of membrane potential in VSMCs of intact arteries. Furthermore, T1E3 treatment markedly enhanced the membrane depolarization and contraction of VSMCs in response to several contractile agonists including phenylephrine, endothelin-1, and U-46619. In coimmunoprecipitation experiments, an antibody against BK(Ca) alpha-subunit [BK(Ca)(alpha)] could pull down TRPC1, and moreover an anti-TRPC1 antibody could reciprocally pull down BK(Ca)(alpha). Double-labeling immunocytochemistry showed that TRPC1 and BK(Ca) were colocalized in the same subcellular regions, mainly on the plasma membrane, in VSMCs. These data suggest that, TRPC1 physically associates with BK(Ca) in VSMCs and that Ca(2+) influx through TRPC1 activates BK(Ca) to induce membrane hyperpolarization. The hyperpolarizing effect of TRPC1-BK(Ca) coupling could serve to reduce agonist-induced membrane depolarization, thereby preventing excessive contraction of VSMCs to contractile agonists.
Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer
Authors: A.M. Hong, A. Martin, B.K. Armstrong, C.S. Lee, D. Jones, M.D. Chatfield, M. Zhang, G. Harnett, J. Clark, M. Elliott, C. Milross, R. Smee, J. Corry, C. Liu, S. Porceddu, K. Vaska, M. Veness, G. Morgan, G. Fogarty, D. Veivers, G. Rees, B. Rose
Journal: Annals of Oncology (2012)
NHS reforms pass final hurdle in House of Lords
Authors: A. O'Dowd
Journal: BMJ (2012)

The government’s proposals for the NHS in England looked almost certain to become law as the BMJ went to press this week, as the Health and Social Care Bill was passed in the House of Lords.

Peers voted in favour of the bill after debate over amendments, but on Tuesday 20 March Labour’s shadow health secretary, Andy Burnham, was granted an emergency 90 minute debate in the House of Commons to try to stop the bill gaining royal assent and becoming law.

In the House of Lords a motion proposed by the Labour peer Glenys Thornton had called for the bill to be dropped but was rejected by 269 to 174 votes. The cross bench peer David Owen called for a delay to the bill’s third reading until the publication of a risk register document that analyses the risks of the reforms, but this was also defeated, by 328 votes to 213.

Meanwhile around 240 doctors have announced that they plan to stand as MPs in the next general election against Conservative and Liberal Democrat candidates or to help …
PHASEII Study of S-1 with Irinotecan Combination Therapy for EGFR-Mutated NSCLC Resistant to EGFR-TKI: NJLCG0804
Authors: K. Nakano, S. Sugawara, M. Harada, T. Harada, M. Maemondo, A. Inoue, K. Kobayashi, O. Ishimoto, N. Matsubara, T. Nukiwa
Journal: Annals of Oncology (2013)
An Address System in the Vasculature of Normal Tissues and Tumors
Authors: E. Ruoslahti, D. Rajotte
Journal: Annual Review of Immunology (2000)

The vasculature of individual tissues is highly specialized. The endothelium in lymphoid tissues expresses tissue-specific receptors for lymphocyte homing, and recent work utilizing phage homing has revealed an unprecedented degree of specialization in the vasculature of other normal tissues. In vivo screening of libraries of phage that displace random peptide sequences on their surfaces has yielded specific homing peptides for a large number of normal tissues. The tissue-specific endothelial molecules to which the phage peptides home may serve as receptors for metastasizing malignant cells. Probing of tumor vasculature has yielded peptides that home to endothelial receptors expressed selectively in angiogenic neovasculature. These receptors, and those specific for the vasculature of individual normal tissues, are likely to be useful in targeting therapies to specific sites.
Oncolytic measles virus prolongs survival in a murine model of cerebral spinal fluid-disseminated medulloblastoma
Authors: A. W. Studebaker, B. Hutzen, C. R. Pierson, S. J. Russell, E. Galanis, C. Raffel
Journal: Neuro-Oncology (2012)

Medulloblastoma is the most common malignant brain tumor of childhood. Although the survival rate of afflicted children has improved considerably over the past several years, a subset of these patients will present with disseminated disease and face a much bleaker prognosis. In addition, patients may present with disseminated disease at recurrence. We previously demonstrated the efficacy of a recombinant oncolytic measles virus (MV) to treat localized medulloblastoma in a mouse xenograft model. In the present study, we sought to extend our findings to the treatment of disseminated disease. To this end, we developed and characterized a mouse xenograft model of disseminated medulloblastoma using serial bioluminescent imaging techniques in combination with histopathological examination. Mice injected with medulloblastoma cells into their right lateral ventricle showed tumor growth in their ventricles and in both intracranial and spinal subarachnoid spaces, closely recapitulating the human disease. Subsequent intraventricular administration of MV resulted in stabilization and shrinkage of the tumor, significantly prolonging the survival of the treated animals, compared with those treated with an inactivated virus. These data demonstrate that oncolytic MV may be of use in treating disseminated medulloblastoma. In addition, our protocol of intraventricular tumor cell injection, followed by bioluminescent imaging coupled with histopathological examination, provides a model for use in evaluating future recombinant oncolytic viruses and other preclinical therapeutic approaches for disseminated medulloblastoma.
Cetuximab plus cisplatin–5-fluorouracil versus cisplatin–5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie
Authors: S. Lorenzen, T. Schuster, R. Porschen, S.-E. Al-Batran, R. Hofheinz, P. Thuss-Patience, M. Moehler, P. Grabowski, D. Arnold, T. Greten, L. Müller, N. Röthling, C. Peschel, R. Langer, F. Lordick
Journal: Annals of Oncology (2009)