tbuckley/cabot-search huggingface dataset:
Abstract 5585: Generation of novel cell lines for analyzing the role of TLR4 in breast cancer
Authors: Mike Korte, Sandeep Rajput, Sophia Ran
Journal: Cancer Research (2011)

Abstract Background: Toll like receptor 4 (TLR4) is a transmembrane receptor expressed in macrophages that plays a major role in pathogen recognition and activation of innate immunity. TLR4 signaling has been linked to tumorigenesis and promotion of metastasis in ovarian, lung, prostate and head-neck cancers through up-regulation of the expression of inflammatory cytokines (e.g., IL-6, IL-8 and TNF-alpha). These factors increase cancer cell survival and resistance to chemotherapy through up-regulation of anti-apoptotic and down-regulation of apoptotic proteins, respectively. The goal of this study was to generate new isogenic cell lines that would allow analysis of the TLR4 role in paclitaxel resistance in breast cancer. To this end, we used TLR4-positive and negative lines (MDA-MB-231 and HCC1806, respectively) to generate stable TLR4 knockdown and over-expressing line derivatives. Methods: To generate a TLR4 knockdown line, MDA-MB-231 cells were transfected with pisiRNA-TLR4 plasmid and selected with zeocin (50μg/ml). To generate a TLR4 over-expressing line, HCC1806 cells were transfected with pKT2-TLR4-PURO plasmid and selected with puromycin (1μg/ml). Ten to 20 monoclonal colonies were selected from each line and characterized for TLR4 expression and TLR4-dependent cell activities by qRT-PCR and western blot. Results: TLR4 mRNA expression was reduced by &amp;gt;90% as compared with parental line in five out of 8 MDA-MB-231TLR4− clones examined. One clone had 60% reduction and two clones had no effect on TLR4 mRNA determined by qRT-PCR. TLR4 mRNA was up-regulated 1,000-12,000 fold in five (out of 11) clones derived from HCC1806 line. Two clones overexpressed TLR4 mRNA by 300-500 fold and four clones had increased TLR4 expression by 1-6 fold. All selected clones were analyzed for TLR4 functional signaling by exposure to LPS (1μg/ml), which was reduced by 50-70% in MDA-MB-231TLR4− clones and increased by 15-25 folds in HCC1806TLR4+ sub-lines, as compared with cells transfected with empty vectors. Conclusions: These data show that we successfully created sub-lines of MDA-MB-231 with stable knockdown of TLR4 and sub-lines of breast carcinoma HCC1806 line with stable over-expression of TLR4. Ectopically expressed human TLR4 as well as TLR4 downregulating sequence had significant functional effects on the TLR4 signaling as demonstrated by increase and decrease of LPS-activated targets (IL-6, IL-8 and TNF-alpha) in MDA-MB-231TLR4− and HCC1806TLR4+ sub-lines, respectively. These new sub-lines will serve as excellent tools for analyzing the role of the TLR4 pathway signaling in breast cancer progression, metastasis and resistance to therapy. * These authors contributed equally in this work. 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 5585. doi:10.1158/1538-7445.AM2011-5585
Occurrence of Goitre during Lithium Treatment
Authors: M. Schou, A. Amdisen, S. E. Jensen, T. Olsen
Journal: BMJ (1968)

Of 330 patients given lithium for recurrent manic-depressive disorder 12 developed goitre after treatment periods of five months to two years. All the patients remained clinically euthyroid. Pressure symptoms necessitated subtotal thyroidectomy in two patients. In 9 out of 10 patients with goitre, and in two out of seven without goitre study with radioactive iodine showed abnormal findings in iodine metabolism. Discontinuance of lithium led to disappearance of goitres, while thyroid metabolism returned to normal. Thyroxine or desiccated thyroid produced shrinkage of the gland in spite of continued lithium medication.
Recent advances: hiv infection I
Authors: J. A. Cohn
Journal: BMJ (1997)

Impressive advances in the understanding of the virology and immunology of HIV infection have led to new treatments, new methods to monitor treatment, and new optimism regarding the treatment of early HIV infection.Although controversial, the possibility of curing HIV infection in selected patients by using existing technology was discussed at the 1996 international AIDS conference in Vancouver, Canada.However, the substantial expense, toxicity, and inconvenience of the new treatments make many clinicians and patients more cautious than are the investigators regarding the potential effectiveness of these new approaches.Further, 90% of the 22 million people with HIV infection worldwide live in societies without the financial resources to pay the current price for these treatments, and others in developed nations may lack access due to a lack of, or limitations on, health insurance.In industrialised nations, we can work with our patients to take advantage of the lessons learnt in the past year.
Notes on the Gradation of the Intensity of Cardiac Murmurs
Authors: Samuel A. Levine
Journal: JAMA (1961)

SIMPLE numerical expressions are often used in medical practice to indicate the severity or degree of various features under consideration. A patient is said to have "1-plus" or "4-plus" jaundice. Another shows a "1-plus" or "4-plus" trace of albumin in the urine. One might readily dismiss a "slightest possible trace" as inconsequential, whereas a very large trace of albumin is practically never inconsequential, and makes one think of nephrosis. It was with these general thoughts in mind that in 1933 I suggested designating the intensity of systolic murmurs in 6 gradations.<sup>1,2</sup>It seemed useful and desirable to do this, although it depended entirely upon the subjective auditory sensations of the observer, without any other accurate acoustic apparatus than an ordinary stethoscope. At first it appeared to many that there was no real value in this and, to others, that it was not feasible. Six gradations were recommended, i.e., 1
Crystalluria and Urinary Tract Abnormalities Associated with Indinavir
Authors: Jeffrey B. Kopp
Journal: Annals of Internal Medicine (1997)

Background: Indinavir, a protease inhibitor widely used to treat patients with HIV infection, has been associated with nephrolithiasis. Distinctive urinary crystals and a spectrum of urologic disorders were noted in patients receiving indinavir. Objective: To determine the composition of urinary crystals and the frequency of asymptomatic crystalluria and urinary tract symptoms in patients receiving indinavir. Patients: Patients with HIV infection who were enrolled in studies conducted at the National Institutes of Health. Measurements: Microscopic urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry of urinary crystals and stones, and clinical evaluation of patients with urologic symptoms. Results: Of 240 patients receiving indinavir, 142 provided urine specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir. Of 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7 (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed syndromes: crystalluria associated with dysuria and crystalluria associated with back or flank pain. Four of the patients with the latter syndrome had radiographic evidence of intrarenal sludging. Conclusions: Indinavir forms characteristic crystals in the urine. This crystalluria may be associated with dysuria and urinary frequency, with flank or back pain associated with intrarenal sludging, and with the classic syndrome of renal colic.
A CASE OF CONGENITAL HOUR-GLASS STOMACH WITH ACCESSORY PANCREAS.
Authors: JOHN PATERSON GARDINER
Journal: JAMA (1907)

This case of congenital hour-glass stomach with accessory pancreas, occurring in a three months' old child, is worth recording on account of the rarity of condition and the variety of opinions expressed in the literature concerning it. There are two recognized forms of hour-glass stomach, the acquired, resulting from ulcer, cicatrix or other pathologic change taking place after birth, the other variety, congenital hour-glass stomach, being of prenatal origin. Although the congenital anomaly has received comparatively little attention, yet from time to time descriptions have appeared and theories have been advanced to account for it. Some authorities believe that when there are no additional pathologic alterations besides the constriction, one is justified in assuming a congenital origin for the hour-glass malformation. Others maintain that an hour-glass stomach of congenital origin has never been found and that all reported cases can be accounted for by some change taking place after birth.
Who wants to be the flu doctor?
Authors: D. K Sokol
Journal: BMJ (2009)

<b><i>Article abstract</i></b> Increased amounts of CSF pyruvate and lactate were found in patients with AD and patients with vascular dementia (VaD). In the AD group, CSF pyruvate values did not show any overlap with those obtained in controls; within the VaD group, the highest values were observed in possible VaD cases. A significant correlation between the severity of dementia and these biochemical parameters was also observed in both AD and possible VaD. The similarities of CSF pyruvate patterns observed in AD and possible VaD patients implicate a neurodegenerative component in this VaD subgroup.
Topical retinoic acid for treatment of solar damage
Authors: L. LEVER, P. KUMAR, R. MARKS
Journal: British Journal of Dermatology (1990)

Twenty patients with chronic solar damage of the skin were entered in a double-blind, withinpatient trial to compare the effect of 0.05% tretinoin cream with a placebo applied once daily for 12 weeks. Sixteen completed the study. Clinical assessment of the individual signs of solar damage were recorded on separate visual analogue scales. After 12 weeks, there were significant improvements in fine wrinkling around the eyes, crease lines around the mouth and cheeks, wrinkling on the dorsum of the hands and yellow discoloration. Overall, 14 of the tretinointreated sides were judged to have improved compared to only two of the placebo-treated sides (P=0.011). Measurement of skin thickness by pulsed A-scan ultrasound revealed that the sides treated with tretinoin were significantly thicker than the placebo-treated sides (P=0.019). Skin biopsies taken before and after treatment showed an increase in mean epidermal thickness with tretinoin treatment (P=0.019). The clinical signs of improvement persisted at the follow-up assessment performed 4 weeks after cessation of therapy.
Markers of Autophagy Are Downregulated in Failing Human Heart After Mechanical Unloading
Authors: Christos Kassiotis, Kalpana Ballal, Kari Wellnitz, Deborah Vela, Mei Gong, Rebecca Salazar, O. Howard Frazier, Heinrich Taegtmeyer
Journal: Circulation (2009)

Autophagy is a molecular process that breaks down damaged cellular organelles and yields amino acids for de novo protein synthesis or energy provision. Mechanical unloading with a left ventricular assist device (LVAD) decreases the energy demand of the failing human heart. We tested the hypothesis that LVAD support reverses activation of autophagy.Paired biopsy samples of left ventricular myocardium were obtained from 9 patients with idiopathic dilated cardiomyopathy (mean duration of LVAD support, 214 days) at the time of implantation and explantation of the LVAD. Transcript and protein levels of markers and mediators of autophagy and apoptosis were measured by quantitative reverse-transcription polymerase chain reaction and Western blotting. TUNEL assays, C9 immunohistochemistry, and 20S proteasome activity assays were also performed. Mechanical unloading significantly decreased mRNA transcript levels of Beclin-1, autophagy-related gene 5 (Atg5), and microtubule-associated protein-1 light chain-3 (MAP1-LC3 or LC3; P<0.02). Protein levels of Beclin-1, Atg5-Atg12 conjugate, and LC3-II were also significantly reduced after LVAD support (P<0.05). A significant increase in 20S proteasome activity was observed with unloading, in parallel to the decrease in autophagic markers. Although BNIP3 and the ratio of activated caspase 3 to procaspase 3 increased after LVAD support, Bcl-2 and TUNEL-positive nuclei were not significantly different between samples.Mechanical unloading of the failing human heart decreases markers of autophagy. These findings suggest that autophagy may be an adaptive mechanism in the failing heart, and this phenomenon is attenuated by LVAD support.
Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma
Authors: Rebecca L. Morgan, Brittney Baack, Bryce D. Smith, Anthony Yartel, Marc Pitasi, Yngve Falck-Ytter
Journal: Annals of Internal Medicine (2013)

Background: Hepatitis C virus (HCV) is a leading cause of hepatocellular carcinoma (HCC). In the United States, this form of cancer occurs in approximately 15 000 persons annually. A systematic review of the evidence is needed to assess the benefits of treatment of HCV-infected persons on development of HCC. Purpose: To systematically review observational studies to determine the association between response to HCV therapy and development of HCC among persons at any stage of fibrosis and those with advanced liver disease. Data Sources: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science, and the Database of Abstracts of Reviews and Effectiveness from inception through February 2012. Study Selection: English-language observational studies that compared therapy-derived sustained virologic response (SVR) with no response to therapy among HCV-infected persons, targeted an adult population, and had an average follow-up of at least 2 years. Data Extraction: Two investigators independently extracted data into uniform relative risk measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence. Data Synthesis: Thirty studies fulfilled the inclusion criteria, and 18 provided adjusted effect estimates that were used to calculate pooled relative risks. Among HCV-infected persons, SVR was associated with reduced risk for HCC (relative risk for all persons, 0.24 [95% CI, 0.18 to 0.31], moderate-quality evidence; advanced liver disease hazard ratio, 0.23 [CI, 0.16 to 0.35], moderate-quality evidence). Limitation: In the meta-analyses, some variables could not be controlled for because of the observational design of the included studies. Conclusion: Sustained virologic response after treatment among HCV-infected persons at any stage of fibrosis is associated with reduced HCC. The evidence was determined to be of moderate quality. Primary Funding Source: Centers for Disease Control and Prevention.
The transnational study on oral contraceptives and the health of young women. Methods, results, new analyses and the healthy user effect
Authors: M. Lewis
Journal: Human Reproduction Update (1999)

The results of the Transnational study on Oral Contraceptives and the Health of Young Women studies are reviewed, potential biases shown, and new analyses are presented. The initial finding was a slight increase in the risk of venous thromboembolism (VTE) when users of third generation OC (containing the progestins desogestrel and gestodene) were compared with users of older (second generation) OC [odds ratio (OR) of 1.5; 95% confidence interval (CI) 1.0, 2.1]. In order to account for potential biases in the study, new analyses were performed. A quadratic spline technique comparing first users of OC with never-users found that risk of VTE is highest in the first year of OC use, but showed no difference between the two generations of OC upon adjustment. An analysis of new dataset which now included full information on the past exposure history of all study subjects with a Cox regression model with time-dependent covariates produced an OR of 0.8 (0.5, 1.3) for the comparison of current users of third generation OC with current users of second generation OC. The results of the new analyses with more refined techniques and with an enhanced dataset which includes data collected on the past exposures of all study subjects indicates that bias, particularly that introduced by healthy user cohorts, accounts for the results initially shown for VTE within the Transnational Study. Key words: case-control study/epidemiology/oral contraceptives/Transnational study/venous thromboembolism
Scintigraphic ‘Rim Sign’ in a Patient with Epididymitis Associated with Fluid Collection
Authors: SARA GIPS, YOEL MECZ, RUTH HARDOFF
Journal: Clinical Nuclear Medicine (1991)

The scintigraphic rim sign demonstrated in testicular imaging is considered to be characteristic of testicular missed torsion. However, a central cold area surrounded by increased activity has also been described in patients with testicular tumors and post-traumatic hematoma. An incomplete rim sign has been described in acute inflammatory processes such as epididymitis. The authors describe a patient with a complete rim sign on testicular scintigraphy consistent with missed torsion. At surgery, the patient was found to have epididymitis.
Abstract 3976: A novel violet-laser excitable ratiometric probe for the detection of membrane asymmetry breakdown during apoptosis
Authors: Justin Hicks, Jolene Bradford
Journal: Cancer Research (2010)

Abstract Apoptosis is carefully regulated and essential part of normal tissue development and homeostasis. Regulatory changes in the apoptotic pathway have been implicated in many diseases; most notable are many types of cancers and autoimmune disorders. Normal cells exhibit a remarkable asymmetry in lipid distribution between the outer and inner cell membranes characterized by phosphatidyl-serine (PS) and phosphatidylethanolamine (PE) normally located on the inner leaflet of the cell membrane. During apoptosis translocation of PE and PS to the external cellular environment facilitates recognition and elimination of these cells by macrophages. The Violet Ratiometric Membrane Asymmetry Probe, 4′-N, N-diethylamino-6-(N, N, N-dodecyl-methylamino-sulfopropyl)-methyl-3-hydroxyflavone (F2N12S), is a novel violet excitable dye for the detection of membrane asymmetry changes during apoptosis. The dye exhibits an excited-state intramolecular proton transfer (ESIPT) reaction resulting in a dual fluorescence with two emission bands corresponding to 530 nm and 585 nm, producing a two-color ratiometric response to variations in surface charge. This ratiometric probe is a self-calibrating absolute parameter of apoptotic transformation, which is independent of probe concentration, cell size, and instrument variation. The two-color ratiometric response of the F2N12S reagent will detect apoptotic cells in samples that vary in cell concentration by as much as 100 fold. The Violet Ratiometric Membrane Asymmetry Probe rapidly targets the plasma membrane requiring only a 5 minute room temperature incubation without additional buffers or wash steps reducing the chance of cell death that can occur from prolonged sample processing. The Violet Ratiometric Membrane Asymmetry Probe will work in both suspension and adherent cell lines and its efficacy is confirmed by caspase and mitochondrial apoptosis markers. Annexin V staining produced a larger population of apoptotic cells during early time points in both suspension and adherent cell lines that do not correlate with caspase and mitochondrial apoptosis markers. The violet 405 nm excitation of F2N12S expands the capability of multi-parameter apoptosis assays to study the apoptotic process while reducing or eliminating the need to create complex compensation controls by taking advantage of the time and spectral separation a violet-excitable reagent provides. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3976.
Psychiatry in the Practice of Medicine
Authors: Barry Liskow
Journal: JAMA (1984)

This book, according to its introduction, is intended to "convey practical information concerning psychiatric syndromes commonly seen in medical practice" to nonpsychiatric physicians and medical students. Considering an estimated 50% of general medical patients have a primary or concomitant psychiatric disorder, this is a necessary undertaking. However, many books of this type fail to achieve their good intentions for a variety of reasons, including lack of a coherent viewpoint, sloppy editing, and poor understanding of the needs of their intended audience. This book, fortunately, has none of these flaws. Although the book has the typical problem of multiple contributors to its four sections and 23 chapters, all are either currently or previously from Yale University's Department of Psychiatry and have the same basic approach to psychiatric problems. Each chapter is closely edited and follows the same format, emphasizing the recognition, evaluation, management, and indications for referral of common psychiatric problems.
Thoracoscopic Thermal Ablation Therapy for Hepatocellular Carcinoma Located Beneath the Diaphragm
Authors: T. Ishikawa, T. Kohno, T. Shibayama, Y. Fukushima, S. Obi, T. Teratani, S. Shiina, Y. Shiratori, M. Omata
Journal: Endoscopy (2001)

Background and Study Aims: Percutaneous interstitial thermal ablation therapy effectively treats hepatocellular carcinoma (HCC) that can be visualized on percutaneous ultrasonography. However, when the tumor is located just under the top of the diaphragm, visualization can be difficult with conventional ultrasonographic examination. There are also problems concerning complete tumor ablation. We performed thoracoscopic thermal ablation therapy for HCC located just beneath the diaphragm in nine patients with advanced liver cirrhosis.
The Effect of BCG Treatment on the Allergic Responses in a Murine Model of Chronic Asthma
Authors: S.S. Kwon, C.H. Kim, J.H. Ahn, S.Y. Lee, S.J. Kim, Y.K. Kim, K.H. Kim, H.S. Moon, J.S. Song, S.H. Park
Journal: Journal of Allergy and Clinical Immunology (2006)
The Eicosanoids of Asthma
Authors: Gerald Weissmann
Journal: New England Journal of Medicine (1983)

Nowadays, bronchial asthma is generally regarded as a disease of allergy. Its expression can be attributed to a constitutional predisposition which not only manifests itself as a hypersensitivity to various allergens, but also as an altered resistance of the airways.1 Fifty years after this formulation of asthma emerged from the school of Clemens von Pirquet, we are on the verge of understanding how chemically defined mediators produced by "hypersensitivity to various allergens" cause "altered resistance of the airways."Asthmatic attacks are triggered not only by extrinsic agents such as inhaled antigens but also by ill-defined "intrinsic" factors; both lead to . . .
HLA-linked genes and islet-cell antibodies in diabetes mellitus.
Authors: R Lendrum, G Walker, A G Cudworth, J C Woodrow, D R Gamble
Journal: BMJ (1976)

In a random series of 139 insulin-dependent diabetics aged 30 or under at the onset of disease islet-cell antibody (ICA) was detected in 33 cases (24%). In 27 patients who had had diabetes for less than one year 16 (59%) had ICA. Only one out of 51 patients with maturity onset diabetes who were not dependent on insulin were positive for ICA. Four out of 19 patients with late onset insulin-dependent diabetes had ICA. There was no association between the presence of ICA and any particular HLA phenotype. Within families containing two or more HLA haploidentical siblings with juvenile onset diabetes ICA was a variable finding both in its occurrence and in its relation to the duration of disease. A possible mode of action for the HLA-linked gene may be to permit a rapid immunological destructive process, possibly associated with viral infection.