tbuckley/cabot-search huggingface dataset:
Multiplexed in vivo fluorescence optical imaging of the therapeutic efficacy of photodynamic therapy
Authors: Katja Haedicke, Susanna Gräfe, Frank Lehmann, Ingrid Hilger
Journal: Biomaterials (2013)

In our study we wanted to elucidate a time frame for in vivo optical imaging of the therapeutic efficacy of photodynamic therapy (PDT) by using a multiplexed imaging approach for detecting apoptosis and vascularization. The internalization of the photosensitizer Foslip(®) into tongue-squamous epithelium carcinoma cells (CAL-27) was examined in vitro and in vivo. For detecting apoptosis, annexin V was covalently coupled to the near-infrared dye DY-734 and the spectroscopic properties and binding affinity to apoptotic CAL-27 cells were elucidated. CAL-27 tumor bearing mice were treated with PDT and injected 2 days and 2 weeks thereafter with DY-734-annexin V. PDT-induced changes in tumor vascularization were detected with the contrast agent IRDye(®) 800CW RGD up to 3 weeks after PDT. A perinuclear enrichment of Foslip(®) could be seen in vitro which was reflected in an accumulation in CAL-27 tumors in vivo. The DY-734-annexin V (coupling efficiency 30-50%) revealed a high binding affinity to apoptotic compared to non-apoptotic cells (17.2% vs. 1.2%) with a KD-value of 20 nm. After PDT-treatment, the probe showed a significantly higher (p <0.05) contrast in tumors at 2 days compared to 2 weeks after therapy (2-8 h post injection). A reduction of the vascularization could be detected after PDT especially in the central tumor areas. To detect the therapeutic efficacy of PDT, a multiplexed imaging approach is necessary. A detection of apoptotic cells is possible just shortly after therapy, whereas at later time points the efficacy can be verified by investigating the vascularization.
Differential expression of IL‐10 receptor by epithelial cells and alveolar macrophages
Authors: S. Lim, G. Caramori, K. Tomita, E. Jazrawi, T. Oates, K. F. Chung, P. J. Barnes, I. M. Adcock
Journal: Allergy (2004)

Background: Interleukin (IL)‐10 is a pleiotropic cytokine with a broad spectrum of immunosuppressive and anti‐inflammatory effects. IL‐10 secretion from alveolar macrophages is defective in patients with asthma and lower concentrations of IL‐10 are found in bronchoalveolar lavage (BAL) from asthmatic patients than in normal control subjects. Reduced IL‐10 may result in exaggerated and more prolonged inflammatory responses in asthmatic airways. IL‐10 acting through the IL‐10 receptor (IL‐10R) stimulates the transcription factors STAT1 and STAT3. Methods: We investigated IL‐10 and IL‐10R expression in normal and asthmatic bronchial epithelium and BAL macrophages using reverse transcription‐polymerase chain reaction, immunohistochemistry and Western blotting. The functional effect of IL‐10 was examined using granulocyte–macrophage‐colony stimulating factor, enzyme‐linked immunosorbent assay and Western blotting for phosphorylated STAT1 and STAT3. Results: IL‐10 was not expressed in epithelial cells; furthermore these cells did not express the IL‐10R and had no functional response to exogenous IL‐10. Bronchial epithelial cells expressed variable levels of phosphorylated STAT1 and STAT3 with no change in expression between normal subjects and asthmatics. IL‐10 protein and IL‐10R expression was detected in alveolar macrophages from all subjects. Conclusion: Our study suggests that the bronchial epithelium is not a source of IL‐10 and cannot respond to exogenous IL‐10 because of a lack of IL‐10R expression.
Effect of Disodium Cromoglycate on Exacerbations of Asthma Produced by Hyperventilation
Authors: P. S. Clarke
Journal: BMJ (1971)

The prophylactic inhalation of disodium cromoglycate lessens the exacerbations which occur in some asthmatic patients after voluntary hyperventilation. Reasons are given for considering this to be a possible mechanism for certain types of emotional exacerbation of the disease and for disodium cromoglycate giving sypmtomatic relief of asthma disproportionate to the improvement in routine measurements of ventilatory capacity. It is suggested that one clinical indication for giving disodium cromoglycate is to observe whether a fall in FEV(1) occurs after two minutes hyperventilation.
AAV9-mediated VEGF-B Gene Transfer Improves Systolic Function in Progressive Left Ventricular Hypertrophy
Authors: Jenni Huusko, Line Lottonen, Mari Merentie, Erika Gurzeler, Andrey Anisimov, Atsushi Miyanohara, Kari Alitalo, Pasi Tavi, Seppo Ylä-Herttuala
Journal: Molecular Therapy (2012)

Mechanisms of the transition from compensatory hypertrophy to heart failure are poorly understood and the roles of vascular endothelial growth factors (VEGFs) in this process have not been fully clarified. We determined the expression profile of VEGFs and relevant receptors during the progression of left ventricular hypertrophy (LVH). C57BL mice were exposed to transversal aortic constriction (TAC) and the outcome was studied at different time points (1 day, 2, 4, and 10 weeks). A clear compensatory phase (2 weeks after TAC) was seen with following heart failure (4 weeks after TAC). Interestingly, VEGF-C and VEGF-D as well as VEGF receptor-3 (VEGFR-3) were upregulated in the compensatory hypertrophy and VEGF-B was downregulated in the heart failure. After treatment with adeno-associated virus serotype 9 (AAV9)-VEGF-B(186) gene therapy in the compensatory phase for 4 weeks the function of the heart was preserved due to angiogenesis, inhibition of apoptosis, and promotion of cardiomyocyte proliferation. Also, the genetic programming towards fetal gene expression, a known phenomenon in heart failure, was partly reversed in AAV9-VEGF-B(186)-treated mice. We conclude that VEGF-C and VEGF-D are associated with the compensatory LVH and that AAV9-VEGF-B(186) gene transfer can rescue the function of the failing heart and postpone the transition towards heart failure.
ONE OF THE POSSIBLE FACTORS IN THE CAUSATION OF PELLAGRA
Authors: ALLAN H. JENNINGS
Journal: JAMA (1913)

Among the various phases of the problem presented by pellagra, of its symptomatology alone can we be said to have even moderately full knowledge. Its epidemiologic features and geographic distribution are as yet but imperfectly known, while in spite of the labors of many investigators whose researches have been directed toward the discovery of its etiology, the knowledge thus far gained leaves that important factor still largely within the realm of theory. Many hypotheses of causation, based on certain aspects of the disease or its environment, have been advanced, but none of these, perhaps, quite accounts for all the phenomena involved. It is not our purpose to discuss these theories in detail or to attempt to show the truth of any one of them, far less to propound a new one, but rather to point to facts which may have a bearing on the question. If it be admitted that
Learning from low income countries: what are the lessons?: Health is a dynamic process
Authors: P C Das
Journal: BMJ (2004)

EDITOR—In 1999 I joined as a haematologist the one medical school in Malawi, Africa. I was asked to see a young pregnant woman with fever, confusion, and oral thrush. The pinprick-like marks apparent on her abdomen were explained by the resident, my translator—she had already seen a traditional healer. History and the few available laboratory tests led to a tentative diagnosis of haemolytic uraemic syndrome related to AIDS. …
Abstract 2765: Combination strategies for management of ovarian cancer using doxorubicin and withaferin A
Authors: Sham S. Kakar, Ramesh C. Gupta, Miranda Y. Fong
Journal: Cancer Research (2012)

Abstract Ovarian cancer is the 5th cause of cancer death in women with a mortality rate of 70%. Main treatment options include cytoreductive surgery with platinum-based therapy. However, 70% of patients relapse due to the carcinomas becoming platinum-resistant. As an alternative method, doxorubicin (Dox) is used for the treatment of several cancers, including ovarian. However, due to severe side effects, Dox is used as a second-line treatment strategy despite better patient response rates. To overcome this problem, we developed a novel treatment strategy that combines Dox with Withaferin A (WFA). WFA has been used as an anti-inflammatory and anti-bacterial compound in traditional Indian medicine. More recently, it has gained attention as an anti-cancer compound to prevent tumor growth, angiogenesis, and metastasis. We propose that combination of Dox with WFA will enhance the therapeutic effect of Dox so a lower dose of Dox can be used and many side-effects avoided. We used epithelial ovarian cancer cell line A2780 as our in vitro model. Based on our results, combination of Dox with WFA increased cell death over Dox or WFA alone measured by MTT assays. In particular, combination of Dox 200nM with WFA 2μM resulted in 90-95% cell death after 48 hr of treatment. Early apoptosis marker Annexin V-FITC was used to confirm these results as well as TUNEL assay for DNA damage. In addition, we have studied the signaling mechanism responsible for cell death through the inactivation of pro-survival Akt pathway. We demonstrated that down regulation of mTOR/p70S6K leads to autophagy and confirmed this with transmission electron microscopy, autophagy marker LC3B, and cleaved caspase 3. We have also validated this combination therapy in vivo using a xenograft model of ovarian cancer and showed reduction in tumor growth and weight as well as reduced Ki67 and CD31 staining. Mice tolerated receiving low dose of Dox (1 mg/kg) and combination Dox (1mg/kg) + WFA (2 mg/kg), whereas mice receiving high dose of Dox (9 mg/kg) did not tolerate treatment and died within 6 six days of treatment. Three dimensional tumor growth studies showed that treatment of tumors with Dox and WFA suppressed tumors growth by 80% within 3 days of treatment compared to untreated tumors. This work was supported by a grant from NCI CA124630 (SSK).Three dimensional tumor growth studies were performed in association with Vivo Biosciences Inc., Birmingham, AL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2765. doi:1538-7445.AM2012-2765
Light blue crest (blue fringe): endoscopic diagnosis of pathology
Authors: N. Uedo
Journal: Endoscopy (2008)

I have been greatly interested in the meaningful data from Tahara et al. presented in response to our reported finding using magnifying narrow band imaging (NBI). The authors suggested that a finding of the light blue crest by magnifying NBI, especially in the gastric corpus, could be a good indicator of high risk for the development of gastric cancer. I think their data highlight two important points about endoscopic diagnosis of intestinal metaplasia in the stomach.
Think 'Trismus-Pseudocamptodactyly,' Say 'Dutch-Kentucky.' But 'Dutch-Kennedy'?
Authors: George X. Trimble
Journal: JAMA (1989)

<h3>To the Editor. —</h3> While reading the book review of<i>Anesthesia and Co-existing Disease</i>,<sup>1</sup>I was intrigued by the reference to "Dutch-Kentucky disease," especially because I could find no reference to such a disease entity in the medical dictionaries available to me or in my reprint files. However, my files did provide information about Dutch-Kennedy syndrome. Could this have been the condition the author of the book review really meant to name?
Lack of Association between Antibiotic Use in the First Year of Life and Asthma, Allergic Rhinitis, or Eczema at Age 5 Years
Authors: Juan C. Celedón, Augusto A. Litonjua, Louise Ryan, Scott T. Weiss, Diane R. Gold
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Five retrospective studies have reported an association between antibiotic use in early life and asthma in childhood. We studied the relationship between the use of oral antibiotics in the first year of life and asthma, allergic rhinitis, and eczema at age 5 years among 448 children with a parental history of atopy monitored from birth. After adjustment for potential confounders, we found no significant association between antibiotic use in the first year of life and asthma (odds ratio [OR] for one versus no courses of antibiotics, 0.5; 95% confidence interval [CI] for OR, 0.2 to 1.5; OR for two or more versus no courses of antibiotics, 1.0; 95% CI for OR, 0.5 to 2.2), recurrent wheezing, allergic rhinitis, or eczema at age 5 years. There was no significant association between antibiotic use in the first year of life and having at least one of three atopic diseases (asthma, allergic rhinitis, or eczema) at age 5 years (OR for one versus no courses of antibiotics, 0.7; 95% CI, 0.4 to 1.4; OR for two or more versus no courses of antibiotics, 0.9; 95% CI, 0.5 to 1.4). Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma and atopy in childhood.
Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127
Authors: Marion G. Peters, Janet Andersen, Patrick Lynch, Tun Liu, Beverly Alston-Smith, Carol L. Brosgart, Jeffrey M. Jacobson, Victoria A. Johnson, Richard B. Pollard, James F. Rooney, Kenneth E. Sherman, Susan Swindells, Bruce Polsky
Journal: Hepatology (2006)

Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in subjects coinfected with HIV. Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are licensed for the treatment of HIV-1 and HBV infection, respectively, but both have in vivo and in vitro activity against HBV. This study evaluated the anti-HBV activity of TDF compared to ADV in HIV/HBV-coinfected subjects. ACTG A5127 was a prospective randomized, double-blind, placebo-controlled trial of daily 10 mg of ADV versus 300 mg of TDF in subjects with HBV and HIV coinfection on stable ART, with serum HBV DNA ≥ 100,000 copies/mL, and plasma HIV-1 RNA ≤ 10,000 copies/mL. This study closed early based on results of a prespecified interim review, as the primary noninferiority end point had been met without safety issues. Fifty-two subjects were randomized. At baseline, 73% of subjects had a plasma HIV-1 RNA &lt; 50 copies/mL, 86% were HBeAg positive, 94% were 3TC resistant, median serum ALT was 52 IU/L, and 98% had compensated liver disease. The mean time-weighted average change in serum HBV DNA from baseline to week 48 (DAVG48) was −4.44 log10 copies/mL for TDF and −3.21 log10 copies/mL for ADV. There was no difference in toxicity between the 2 treatment arms, with 11 subjects (5 ADV and 6 TDF) experiencing elevations of serum ALT on treatment. In conclusion , over 48 weeks, treatment with either ADV or TDF resulted in clinically important suppression of serum HBV DNA. Both drugs are safe and efficacious for patients coinfected with HBV and HIV.
The Nostrum and the Public Health
Authors: ARTHUR J. CRAMP
Journal: New England Journal of Medicine (1929)

Broadly speaking, the nostrum belongs in one of two general classes; one class comprises those unscientific mixtures that are advertised primarily to the medical profession, and first reach the public by way of the prescription; the other class includes those mixtures that are sold direct to the public. Nostrums in the first class are sometimes spoken of as proprietaries; those in the second class are colloquially known as patent medicines. The public suffers from both classes, the only difference being that in the case of the former the physician has to share the responsibility with the nostrum exploiter. There is no clearly defined line of demarkation between these two classes. Many of the patent medicines of today were the proprietaries of yesterday. Shrewd manufacturers—or, more correctly, exploiters, for many of these products are not manufactured by those that sell them—discovered years ago that one of the least expensive methods of
Erythrocyte incorporation of ingested stable isotope of iron (58Fe)
Authors: Morteza Janghorbani, Bill T. G. Ting, Samuel J. Fomon
Journal: American Journal of Hematology (1986)

Abstract Because of a possible hazard from the use of radioisotopes to determine iron absorption by infants, the use of stable isotopes for this purpose has much appeal. We have applied the method of inductively coupled plasma mass spectrometry (ICP/MS) to determine the mass ratio, 58 Fe/ 57 Fe, in blood before and after oral administration of 58 Fe. From the increase in erythrocyte enrichment with 58 Fe, we have calculated percentage absorption of iron. We have shown that the coefficient of variation of measured mass isotope ratio is 0.1‐1.0%, depending on the conditions of the measurement. The method has been applied to a feasibility study involving four infants. Each infant was given 58 Fe either as a single dose or as one dose on each of two consecutive days. Each dose provided 1.945 mg iron and 1.440 mg 58 Fe. Samples of blood were obtained before isotope administration and at 14, 42, and 60 days thereafter. Isotopic analysis of the samples demonstrates that this approach results in a sufficiently large isotope enrichment to permit satisfactory measurement of iron availability. It is concluded that this new method is highly promising for studies of iron availability in infants and children.
Stress echocardiography with transesophageal atrial pacing: preliminary report of a new method for detection of ischemic wall motion abnormalities.
Authors: P D Chapman, T P Doyle, P J Troup, C M Gross, L S Wann
Journal: Circulation (1984)

We performed two-dimensional echocardiography in 19 patients with significant coronary artery disease and in six normal volunteers at rest and during transesophageal atrial pacing. Technically adequate resting echocardiograms were obtained in 18 of the 19 patients and in all six normal volunteers. In two subjects, atrial capture was not possible, and in one subject, discomfort from the pacing at the beginning of the study precluded its completion. In all subjects (n = 21) who completed the protocol satisfactory two-dimensional echocardiograms were obtained during pacing. Wall motion was normal at rest and during atrial pacing in five normal volunteers. New transient wall motion abnormalities developed in 13 of the 16 patients during pacing. Twelve of the 13 patients had significant coronary lesions in the coronary arteries supplying the abnormal wall segment. Only three of the patients developed significant ST segment depression during pacing. We conclude that stress echocardiography with transesophageal atrial pacing is safe and practical and can be used in patients who cannot perform dynamic exercise, this technique can detect ischemic segmental wall motion abnormalities corresponding to the distribution of coronary arterial obstruction, and the technique provides high-quality echocardiographic images during stress and thus may expand the usefulness of resting two-dimensional echocardiography in patients who have ischemic heart disease.
Which differences do elderly patients present in single-stage treatment for cholecysto-choledocholithiasis?
Authors: A. Bove, R.M. Di Renzo, G. Palone, V. D'Addetta, F. Caldararo, C. Antonopulos, P. Panaccio, S. Chiarini, G. Bongarzoni
Journal: International Journal of Surgery (2014)
Androgen Receptor Attenuation of Ad5 Replication: Implications for the Development of Conditionally Replication Competent Adenoviruses
Authors: Naseruddin Höti, Ying Li, Chien-Lun Chen, Wasim H Chowdhury, David C Johns, Qinghua Xia, Arup Kabul, Jer-Tsong Hsieh, Michael Berg, Gary Ketner, Shawn E Lupold, Ronald Rodriguez
Journal: Molecular Therapy (2007)

Conditionally replication competent adenoviruses (CRAds) represent one of the most intensely studied gene therapy strategies for a variety of malignancies, including prostate cancer. These viruses can be generated by placing a tissue or cancer-specific promoter upstream of one or more of the viral genes required for replication (e.g., E1A, E1B). We report here that E1A inhibits androgen receptor (AR) target gene induction and, correspondingly, activated AR inhibits adenoviral replication. This mutual inhibition appears to be an indirect effect, possibly through competition for shared transcriptional co-activators. The net effect is that the oncolytic effect of prostate-specific CRAds is attenuated by these interactions. Fusion of the E1A to AR ameliorates this inhibition, while enhancing specificity. These findings have significant implications in the development of prostate-specific CRAd therapies. Conditionally replication competent adenoviruses (CRAds) represent one of the most intensely studied gene therapy strategies for a variety of malignancies, including prostate cancer. These viruses can be generated by placing a tissue or cancer-specific promoter upstream of one or more of the viral genes required for replication (e.g., E1A, E1B). We report here that E1A inhibits androgen receptor (AR) target gene induction and, correspondingly, activated AR inhibits adenoviral replication. This mutual inhibition appears to be an indirect effect, possibly through competition for shared transcriptional co-activators. The net effect is that the oncolytic effect of prostate-specific CRAds is attenuated by these interactions. Fusion of the E1A to AR ameliorates this inhibition, while enhancing specificity. These findings have significant implications in the development of prostate-specific CRAd therapies.
Facing up to the prescription opioid crisis
Authors: I. A. Dhalla, N. Persaud, D. N. Juurlink
Journal: BMJ (2011)

Deaths resulting from prescription opioids tripled in the United States between 1999 and 2007 and are also increasing in many other countries, including the United Kingdom. <b>Irfan A Dhalla</b>, <b>Navindra Persaud</b>, and <b>David N Juurlink</b> describe how this situation developed and propose several ways to reduce morbidity and mortality from opioids
Intra- and Interspecific DNA Variation and Codon Bias of the Alcohol Dehydrogenase (Adh) Locus in Arabis and Arabidopsis Species
Authors: N. T. Miyashita, A. Kawabe, H. Innan, R. Terauchi
Journal: Molecular Biology and Evolution (1998)

Sequence variation at the alcohol dehydrogenase (Adh) locus was analyzed for six species each of the genera Arabis and Arabidopsis. Phylogenetic analysis showed that investigated species were grouped into three clusters, and the generic classification did not correspond to the clusterings. The results indicated that the genera could not be distinguished on the basis of the Adh variation. A significant difference in the ratio of silent to replacement sites was detected by MK test in two comparisons, with Arabidopsis thaliana polymorphism due to excess silent divergence. Silent changes were predominant in the evolution of the Adh locus in Arabis and Arabidopsis. To infer evolutionary significance of silent substitutions, codon bias was studied. The degree of codon bias of the Adh region was relatively constant over Arabis and Arabidopsis species. "Preferred" codons of A. thaliana were determined. No evidence of natural selection on codon change was detected in the Adh regions of A. thaliana and Arabis gemmifera.