tbuckley/cabot-search huggingface dataset:
In vivo effect of methylene blue on endothelium-dependent and endothelium-independent dilations of brain microvessels in mice.
Authors: M Watanabe, W I Rosenblum, G H Nelson
Journal: Circulation Research (1988)

Arterioles on the surface of the mouse brain were observed by in vivo TV microscopy. Four dilators were topically applied to relax the vessels in vivo. Two of the dilators were acetylcholine and bradykinin, whose action in this vascular bed is dependent upon production of endothelium-dependent relaxing factors. The other two dilators were sodium nitroprusside and 8-bromo-cGMP, whose action is not endothelium dependent. The dilations by acetylcholine, bradykinin, and nitroprusside were significantly depressed by 10(-4) M methylene blue applied topically for 7 minutes prior to application of the dilators. The inhibitory effect was reversible, was greatest against acetylcholine, and was least against nitroprusside. These data parallel reports of methylene blue's action against these dilators when applied to large blood vessels in vitro. Our data appear to be the first microvascular data and the first in vivo data showing this effect. The data thus suggest that the mechanisms underlying dilation of cerebral arterioles and large extracerebral vessels are similar. The literature accounts for the effect of methylene blue on the basis of its action as an inhibitor of guanylate cyclase. Our data, including the failure of methylene blue to alter dilation by 8-bromo-cGMP, are in keeping with this hypothesis and with current beliefs that guanylate cyclase and cGMP have a central role in vasodilation. The data do not rule out the possibility that methylene blue has an additional action in the case of acetylcholine and inactivates the endothelium-dependent relaxing factor for that dilator.
Abstract 2479: Accurate Detection of Coronary Artery Disease by Echocardiography using Perflubutane Polymer Microspheres, a Novel Contrast Agent: Comparison with Nuclear Perfusion Imaging in Two Phase Three Multicenter Clinical Trials
Authors: Roxy Senior, Miguel Zabalgoitia, Mark Monaghan, Michael Main, Jose L Zamorano, Klaus Tiemann, Luciano Agati, Neil J Weissman, Allan L Klein, Thomas H Marwick, Masood Ahmad, Anthony N DeMaria, Harald Becher, Sanjiv Kaul, James E Udelson, Frans J Wackers, Richard C Walovitch, Michael H Picard
Journal: Circulation (2007)
Abstract 2883: Vimentin downregulation modulates p53 levels and apoptosis in cancer cells
Authors: Anne-Marie Fortier, Monique Cadrin, Eric Asselin
Journal: Cancer Research (2011)

Abstract Vimentin, a mesenchymal-specific intermediate filament (IF) protein, is often express in epithelial cancers exhibiting a de-differentiated phenotype. Vimentin is associated with increased chemoresistance and metastatic potential. Chemoresistance is a multifactorial phenomenon which is a major cause of treatment failure in human cancer. Some IF proteins are known to promote resistance to stress-induced apoptosis, but the role of vimentin in this process is still unknown. In the present study, we investigate the role of vimentin in response to apoptosis-induced chemotherapeutic drugs in different epithelial carcinoma cell lines. Surprisingly, using siRNA, our results show that vimentin downregulation decreases caspase-3 and PARP cleavage induced by cisplatin, doxorubicin and TNFalpha. This unexpected result could be explained by the decrease of p53 protein levels in vimentin-downregulated cells. Indeed, we observed that vimentin knockdown decreases p53 levels in a proteasome-dependent manner and also modulates p53 ubiquitination. PI3K/Akt pathway is well known to promote chemoresistant phenotype in different cancers and Akt can also regulate p53 function. Our results show that vimentin-induced p53 decrease is associated with an increase of Akt phosphorylation. We propose that vimentin knockdown results in an increase of Akt activity which in turn regulates ubiquitination and proteasomal degradation of p53. We have recently showed that Akt isoforms regulates vimentin and keratins IF expression in epithelial cancer cells, suggesting that IF proteins are directly involved in PI3K/Akt signaling pathway. To our knowledge, these results represent the first indication that vimentin could regulate Akt activity and p53 levels in response to apoptosis-induced chemotherapeutic drugs. These results support the hypothesis that modulation of IF expression plays an active role in cancer progression and that vimentin could be a possible target for cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2883. doi:10.1158/1538-7445.AM2011-2883
US asthma guidelines stress early steroid use
Authors: J. Bryan
Journal: BMJ (1997)

Newly updated guidelines on the management of asthma, released this week by the United States National Institutes of Health, emphasise the need for early use of anti-inflammatory drugs–in line with recommendations in the revised British Thoracic Society's guidelines (1 February, p 315-6).

The US version, however, uses a four step classification for asthma severity–mild intermittent, mild persistent, moderate persistent, and severe persistent–and recommends starting inhaled corticosteroids, cromoglycate, or nedocromil at the mild persistent stage.

“Inhaled …
Patient partnership is not a magic formula
Authors: A. Mariotto
Journal: BMJ (1999)

EDITOR—Partnership with patients in sharing medical decisions is an idea of paramount civil importance for modern health systems, as raised in correspondence in the eBMJ .1 Partnership stems, on the one hand, from the reasons underlying the right to informed consent to medical practices and the humanisation of the approach to patients and, on the other, from the development of advocacy in health promotion and self determination of civil rights. Such a profound innovation increases …
The association between objectively measured physical activity and knee structural change using MRI
Authors: Dawn A Doré, Tania Maree Winzenberg, Changhai Ding, Petr Otahal, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Flavia M Cicuttini, Graeme Jones
Journal: Annals of the Rheumatic Diseases (2012)

Objectives This study describes the longitudinal association between objectively assessed physical activity (PA) and knee structural change measured using MRI. Methods 405 community-dwelling adults aged 51–81 years were measured at baseline and approximately 2.7 years later. MRI of the right knee at baseline and follow-up was performed to evaluate bone marrow lesions (BMLs), meniscal pathology, cartilage defects, and cartilage volume. PA was assessed at baseline by pedometer (steps/day). Results Doing ≥10 000 steps/day was associated with BML increases (RR 1.97, 95% CI 1.19 to 3.27, p=0.009). Participants doing ≥10 000 steps/day had a 1.52 times (95% CI 1.05 to 2.20, p=0.027) greater risk of increasing meniscal pathology score, which increased to 2.49 (95% CI 1.05 to 3.93, p=0.002) in those with adverse meniscal pathology at baseline. Doing ≥10 000 steps/day was associated with a greater risk of increasing cartilage defect score in those with prevalent BMLs at baseline (RR 1.36, 95% CI 1.03 to 1.69, p=0.013). Steps/day was protective against volume loss in those with more baseline cartilage volume but led to increased cartilage loss in those with less baseline cartilage volume. (p=0.046 for interaction). Conclusions PA was deleteriously associated with knee structural change, especially in those with pre-existing knee structural abnormalities. This suggests individuals with knee abnormalities should avoid doing ≥10 000 steps/day. Alternatives to weight-bearing activity may be needed in order to maintain PA levels required for other aspects of health.
Renal Failure After Angiography
Authors: Charles P. Taliercio, Peter C. Hanley, John C. Burnett
Journal: JAMA (1985)

To the Editor.—  Dr Mason et al1conclude in their report concerning renal dysfunction following arteriography that patients with preexisting renal insufficiency are not at a higher risk for sustaining a fall in creatinine clearance when compared with patients with normal renal function. Their data demonstrate a 31% overall incidence of a 25% or greater fall in creatinine clearance following arteriography. The incidence is not significantly different in 22 patients with preexisting renal insufficiency defined by a baseline serum creatinine level of more than 1.5 mg/dL. The mean dose of radiocontrast material administered at arteriography is also noted to be similar in patients who had a 25% or greater fall in creatinine clearance and those who did not. Important data not presented are whether the patients with preexisting renal insufficiency received the same amount of radiocontrast material as the entire patient group. If these patients received a significantly lower
Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966–2001) on the mode of early feeding in infancy and its impact on later atopic manifestations
Authors: J. van Odijk, I. Kull, M. P. Borres, P. Brandtzaeg, U. Edberg, L. Å. Hanson, A. Høst, M. Kuitunen, S. F. Olsen, S. Skerfving, J. Sundell, S. Wille
Journal: Allergy (2003)

Background: Strategies to prevent children from developing allergy have been elaborated on the basis of state‐of‐the‐art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers. Methods: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group. Results: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design. Conclusions: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.
Abstract 1978: Demonstrating a role for nuclear Adenomatous polyposis coli in intestinal cell differentiation.
Authors: Matthew A. Miller, Maged Zeineldin, Kristi L. Neufeld
Journal: Cancer Research (2013)

Abstract Colon cancer is the second leading cause of cancer-related mortality in the United States, resulting in over 50,000 deaths annually. Approximately 80% of colon cancers begin with a mutation in the gene coding for the tumor suppressor protein Adenomatous Polyposis Coli, APC. APC protein can shuttle between the cytoplasm and the nucleus of cells, facilitated by two nuclear localization signals (NLS) and multiple nuclear export signals. To better understand functions of nuclear APC, our lab generated a “knock-in” mouse model with mutations introduced that inactivate both Apc NLS. These ApcmNLS/mNLS mice show a dramatic decrease in nuclear Apc. We previously showed increased proliferation and Wnt target gene expression in intestinal epithelial cells from ApcmNLS/mNLS mice, suggesting a role for nuclear APC in inhibition of proliferation and Wnt signaling. We also showed increased tumor number and size in ApcMin mice if they also harbor the ApcmNLS allele. Here we examine the role of nuclear Apc in intestinal epithelial differentiation and stem cell homeostasis. Paraffin-embedded tissue from the intestines of Apc+/+ and ApcmNLS/mNLS mice was sectioned and stained for markers of enterocytes (alkaline phosphatase) and goblet cells (alcian blue). Quantification of the positive cells indicated that ApcmNLS/mNLS mice had fewer differentiated enterocytes and goblet cells than their wild-type littermates. Intestines from ApcmNLS/mNLS mice were also stained for markers of quiescent and active stem cells, DCAMKL-1 and Lgr5 respectively. Quantification of the various stem cell populations will be described. Together, our data supports a role for nuclear Apc in promoting enterocyte and goblet cell differentiation, in suppression of tumors, and in inhibiting intestinal cell proliferation and Wnt signaling. Information gathered from analysis of ApcmNLS/mNLS mice will contribute to our understanding of the functions of nuclear APC in tumor suppression and ultimately the mechanism of intestinal tumorigenesis. Citation Format: Matthew A. Miller, Maged Zeineldin, Kristi L. Neufeld. Demonstrating a role for nuclear Adenomatous polyposis coli in intestinal cell differentiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1978. doi:10.1158/1538-7445.AM2013-1978
AIDS transmission: what about the hepatitis B vaccine?
Authors: Catherine Macek
Journal: JAMA (1983)

In An the Nov 13, 1981, issue of<i>JAMA</i>, MEDICAL NEWS ran a story on the as yet unapproved hepatitis B vaccine that carried the headline, "Looks Like Smooth Sailing for Experimental Hepatitis B Vaccine." Now the waters have gotten a little choppy. Although almost a million doses of the vaccine have been distributed since Food and Drug Administration approval was given last July, a number of health care workers has chosen not to be vaccinated. The reason: Some of the plasma used to produce the vaccine is harvested from hepatitis B-positive male homosexuals, and male homosexuals are still the primary victims of acquired immunodeficiency syndrome (AIDS). The plasma, therefore, may contain some as-yet-unidentified causative agent of AIDS, and that agent may not be destroyed during the preparation of the vaccine. Some investigators, however, strongly refute this view. And Arlene McLean, MD, from Merck Sharp &amp; Dohme in West Point,
Patterns of Calcification in Coronary Artery Disease
Authors: Gary S. Mintz, Jeffrey J. Popma, Augusto D. Pichard, Kenneth M. Kent, Lowell F. Satler, Ya Chien Chuang, Christine J. Ditrano, Martin B. Leon
Journal: Circulation (1995)

Background Target lesion calcium is a marker for significant coronary artery disease and a determinant of the success of transcatheter therapy. Methods and Results Eleven hundred fifty-five native vessel target lesions in 1117 patients were studied by intravascular ultrasound (IVUS) and coronary angiography. The presence, magnitude, location, and distribution of IVUS calcium were analyzed and compared with the detection and classification (none/mild, moderate, and severe) by angiography. Angiography detected calcium in 440 of 1155 lesions (38%): 306 (26%) moderate calcium and 134 (12%) severe. IVUS detected lesion calcium in 841 of 1155 (73%, P &lt;.0001 versus angiography). The mean arc of lesion calcium measured 115±110°; the mean length measured 3.5±3.7 mm. Target lesion calcium was only superficial in 48%, only deep in 28%, and both superficial and deep in 24%. The mean arc of superficial calcium measured 85±108°; the mean length measured 2.4±3.4 mm. Three hundred seventy-three of 1155 reference segments (32%) contained calcium ( P &lt;.0001 compared with lesion site). The mean arc of reference calcium measured 42±80°; the mean length measured 1.7±3.6 mm. Only 44 (4%) had reference calcium in the absence of lesion calcium. Angiographic detection and classification of calcium depended on arcs, lengths, location, and distribution of lesion and reference segment calcium. By discriminant analysis, the classification function for predicting angiographic calcium included the arc of target lesion calcium, the arc of superficial calcium, the length of reference segment calcium, and the location of calcium within the lesion. This model correctly predicted the angiographic detection of calcification in 74.4% of lesions and the angiographic classification (none/moderate/severe) of calcium in 62.8% of lesions. Conclusions IVUS detected calcium in &gt;70% of lesions, significantly more often than standard angiography. Although angiography is moderately sensitive for the detection of extensive lesion calcium (sensitivity, 60% and 85% for three- and four-quadrant calcium, respectively), it is less sensitive for the presence of milder degrees.
Influence of Amniotic Fluid Volume on Lecithin Estimation in Prediction of Respiratory Distress
Authors: G. F. Falconer, J. S. Hodge, R. L. Gadd
Journal: BMJ (1973)

One hundred samples of amniotic fluid were obtained by amniocentesis from 82 patients at different stages of normal and abnormal pregnancies. The concentration of lecithin was estimated together with the volume of the amniotic fluid, using the dilution technique. Thus the total quantity of lecithin in any amniotic sac could be calculated. While confirming the findings of others that concentrations of lecithin below 3.5 mg/100 ml in the liquor immediately before delivery suggested that the baby was likely to develop respiratory distress syndrome, we found that in borderline cases the total amount of lecithin in the sac was of greater prognostic significance than the lecithin concentration.
Diagnosis of Acute Inflammatory Conditions in Children and Adolescents Using ln-111 Oxine White Blood Cells
Authors: MARGARET A. GAINEY, I ROSS McDOUGALL
Journal: Clinical Nuclear Medicine (1984)

In-111 oxine labeled white cells were used to diagnose acute inflammatory conditions in 42 children and adolescents, aged 6 weeks to 19 years. In 43 scans where a clinical correlation could be made, the test had a sensitivity of 81% and a specificity of 94%. There were no adverse reactions. For children the dose of In-111 recommended is 10-12 mu Ci/kg body weight to a maximum of 500 mu Ci.
Noncoding RNAs: key molecules in understanding and treating pain
Authors: Kiran Kumar Bali, Rohini Kuner
Journal: Trends in Molecular Medicine (2014)

Although noncoding RNAs (ncRNAs) were initially considered to be transcriptional byproducts, recent technological advances have led to a steady increase in our understanding of their importance in gene regulation and disease pathogenesis. In keeping with these developments, pain research is also experiencing rapid growth in the investigation of links between ncRNAs and pathological pain. Although the initial focus was on analyzing expression and dysregulation of candidate miRNAs, elucidation of other ncRNAs and ncRNA-mediated functional mechanisms in pain modulation has just commenced. Here we review the major ncRNA literature available to date with respect to pain modulation and discuss tools and opportunities available for testing the impact of other types of ncRNA on pain.
Hepatitis B Virus Markers in Diabetes Mellitus
Authors: Khalil G Khuri, Munir H Shamma'a, Nicolas Abourizk
Journal: Diabetes Care (1985)

Serum markers for hepatitis B virus (HBV) were studied in 395 healthy control subjects and in 100 diabetic patients. Of the patients, 28 had type I diabetes, 31 had type II diabetes requiring insulin, and 41 had type II diabetes treated with oral agents or diet alone. None gave history of previous icterus or other signs of hepatitis, had received blood transfusions, or had been on hemodialysis. There was a significant difference in the prevalence of HBV markers (mainly HB surface antibody) between the diabetic group and the controls (51% versus 25%, P &amp;lt; 0.001). The control subjects included hospital personnel and, hence, their risk of HBV exposure was already relatively high. The increased occurrence of HBV markers did not seem to be related to diabetes duration, patient age, intake of insulin injections, or presence of microvascular complications. This study reveals a high degree of exposure to HBV in a moderately controlled diabetic group and possibly a high degree of proneness to subclinical hepatitis B.
Future of Transfer Programs
Authors: Terrence T. Kuske
Journal: JAMA (1981)

To the Editor.—  The Graduate Medical Education National Advisory Committee has recommended that entering medical school classes be decreased by 10% and that transfer programs from foreign medical schools be abolished. Implementation of this recommendation would mean that 10% of the students who are currently qualified for entry into US medical schools suddenly become not good enough. Admissions committees, while dedicated and sincere, recognize that they are also fallible. Many students rejected, then later accepted as transfers from foreign medical schools, perform as well as or better than their peers who were accepted initially into a US medical school. More rigorous admissions criteria tend to penalize the person who makes a late decision on a career in medicine or is a late maturer whose grade-point average is lower. Thus, many highly motivated and competent persons must seek an education abroad if they are to enter medicine. While the transfer programs
“Asthma,” “Rhinitis” and “Atopy” Reconsidered
Authors: Francis C. Lowell
Journal: New England Journal of Medicine (1979)

Airways obstruction has been considered to be the sine qua non of asthma. The obstruction may disappear spontaneously or may be relieved by administration of a bronchodilator or one of the corticosteroid drugs. There is also hyperactivity of the airways to bronchial challenge with drugs pharmacologically related to acetylcholine as evidenced by a transient obstructive response. I, with some others, would add eosinophilia as another consistent feature of asthma. Even though tradition has it that symptoms of asthma occur, as indeed they may, when an allergen encounters an antibody in the asthmatic patient, abundant clinical observation indicates that much ongoing . . .
Expression of Snail in Epidermal Keratinocytes Promotes Cutaneous Inflammation and Hyperplasia Conducive to Tumor Formation
Authors: Fei Du, Yoshikazu Nakamura, Tuan-Lin Tan, Pedro Lee, Robert Lee, Benjamin Yu, Colin Jamora
Journal: Cancer Research (2010)

Abstract Although metastasis is the most lethal consequence of tumor progression, comparatively little is known regarding the molecular machinery governing this process. In many carcinomas, there is a robust correlation between the expression of the transcription factor Snail and a poor prognosis, but the contribution of this protein to the metastatic process remains unresolved. Interestingly, the prolonged expression of Snail in epidermal keratinocytes is sufficient to recapitulate early features of metastasis. However, it does so without inducing a complete epithelial-mesenchymal transition (EMT), a developmental phenomenon mediated by Snail that is extensively invoked as the mechanism fueling tumorigenesis. Instead, we found that the local invasiveness of keratinocytes is the consequence of the recruitment and activity of macrophages. Moreover, keratinocyte proliferation is the product of an IL-17/IL-6/Stat3 signaling module initiated by activated resident γδT cells in the transgenic skin. Together, these phenotypes prime the transgenic skin for the formation and metastasis of tumors in response to chemically induced carcinogenesis. Thus, the contribution of Snail to the progression of carcinomas is largely through the creation of a hyperproliferative and inflammatory niche that facilitates tumor development and dissemination. Cancer Res; 70(24); 10080–9. ©2010 AACR.