tbuckley/cabot-search huggingface dataset:
Abstract 18611: Increased Absorption and Decreased Synthesis of Cholesterol in Cardiac Sarcoidosis
Authors: Piia Simonen, Jukka Lehtonen, Helena Gylling, Markku Kupari
Journal: Circulation (2014)

Introduction: Sarcoidosis is a multisystem inflammatory disease characterised by the formation of granulomas in many tissues. Some reports suggest that the disease is associated with altered lipoprotein cholesterol profiles, but there is no deeper knowledge of cholesterol metabolism in these patients. Hypothesis: We tested the hypothesis that cholesterol metabolism is abnormal in cardiac sarcoidosis (CS). Methods: The study population consisted of 39 patients with histologically verified CS (31 women and 8 men, mean age 53 years) and 124 healthy controls of similar age and gender. 31 of the CS patients were on immunosuppressive treatment. Serum lipids were determined and cholesterol metabolism was evaluated by measuring serum markers of cholesterol absorption (cholestanol, campesterol and sitosterol) and synthesis (desmosterol and lathosterol) as ratios to cholesterol with gas-liquid chromatography. Results: CS was inactive in all patients based on clinical evaluation, cardiac ultrasound, and stable levels of serum TnT and proBNP. Serum total, LDL and HDL cholesterol concentrations (mean±SE) were 5.6±0.2, 3.3±0.1 and 1.5±0.1 mmol/l, respectively, and serum triglyceride averaged 1.7±0.7 mmol/l. These values did not differ from those of controls. Cholesterol absorption markers were higher in CS patients than in controls (eg. serum campesterol level 245±17 vs 190±17 10 2 μmol/mmol of cholesterol, p&lt;0.05). Cholesterol synthesis markers were lower in CS patients than in controls (eg. serum lathosterol level102±8 vs 195±17 10 2 μmol/mmol of cholesterol, p&lt;0.001). Concentrations of serum lipids and non-cholesterol sterols did not associate with the use of immunosuppressive drugs. Markers of cholesterol absorption and synthesis did not correlate with serum TnT levels, but there was a significant positive correlation between proBNP and cholesterol absorption markers (r=0.351, p&lt;0.05). Conclusions: We conclude that, in CS, cholesterol absorption is increased and its synthesis is decreased. The underlying mechanisms remain obscure and deserve further study. This is the first time that abnormal cholesterol metabolism has been described in CS.
Real time monitoring of cytotoxicity in selection of agents for treatment of refractory malignancy
Authors: Philip M. Grimley, William I. Smith, Donna Williams, Zhang Li, W. David Hankins
Journal: Clinical Cancer Research (2006)

B47  Real time monitoring of the cytotoxic effects of cancer chemotherapeutic agents offers an attractive alternative to conventional end-point analyses in the selection of agent combinations for treatment of refractory malignancies. Personalized oncology treatment can be critical, since the genetic instability and continuous evolution of progressive malignant neoplasms, including many common cancers and AIDS-associated lymphomas, presents a major chemotherapeutic challenge. While the cellular mechanisms of therapeutic resistance are manifold, evolution of molecular changes that impair terminal differentiation or subvert apoptosis pathways frequently are implicated. One rational counterstrategy is to induce fatal checkpoint conflicts during the process of cell division cycling. In particular, malignant cells with p53 malfunction can become susceptible to S phase perturbation by relatively low concentrations of metabolic inhibitors or cytotoxic agents that would normally evoke a protective block in G1/ S phase transit. Accordingly, we have been analyzing effects of classical DNA metabolic or polymerase inhibitors, platinum coordination compounds, and indolocarbazole protein kinase inhibitors (K252a or staurosporine homologs) which can produce significant cytotoxic synergies using minimal agent concentrations. When DNA inhibition is just sufficient to slow the passage of malignant cells through S phase (dynamic retardation), dysregulation of the G2 or M phase transits by a complementary agent can be facilitated. We compared a real time method of kinetic optical response (KOR) to conventional end-point methods of flow cytometry, MTT assay, caspase cleavages, or stress kinase activation as a preclinical means to quantify apoptosis and optimize dosage. Continuous KOR spectrophotometry (24-48 hours) in 96-well cultures of malignant cells, generated unique parabolic graphs with slope shifts reflecting changes in cellular shapes and concomitant growth inhibition or apoptosis in response to the individual test agents or combinations. Preliminary results with established and primary ovarian cancer cells indicated that a KOR assay could offer practical guidance in agent selection and individualization of chemotherapies.
A fairy story that I now understand: There's nothing really new
Authors: T. Treasure
Journal: BMJ (1999)

Once upon a time a King had a little daughter for whom he would do anything. She wanted an apple made of pure gold, and because he was rich he had one made for her. The princess wanted a pony with a coat of the purest white and because he was powerful, he had the land searched and the best one sent to the palace for her. One night she looked into the dark sky from her bed chamber and asked for the moon.

The King sent for the court astronomer and said, “Tell me about the moon.” “The moon, sire,” he said, “is three miles above the earth and made of green cheese.” The King sent for his engineer, and said, “My daughter wants the moon. Please get it down …
Elimination of cancer stem-like “side population” cells existed in hepatoma cell lines by human urine extract (HUE)
Authors: Gi-Ming Lai, Chih-Jung Yao, Shuang-En Chuang, Chih-Kai Chang, Chuan-Feng Yeh
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C20 

Recently, the concept of cancer stem cell may renew the notion of the designing of cancer therapy. The existence of cancer stem cells was proposed and demonstrated by many studies. The progression and relapse of tumor may be initiated by the cancer stem cells, which could escape from current anticancer agents. Thus, we attempt to search for the drugs targeting the therapeutically challenging cancer stem cells. By UV laser equipped flow cytometry and cell-permeable DNA binding dye Hoechst 33342, a distinct side population (SP) cells that expressed stem cell-like properties, such as high-level expression of the ATP-binding cassette transporter protein ABCG2/Bcrp1, could be detected and sorted. We used this SP cells as a model to evaluate the capability of drugs that are able to eliminate cancer stem cells and found that HUE could dose-dependently decreased the percentages of SP cells in hepatoma cell lines including HepG2, Hep3B, Huh7, PLC/PRF/5 and Sk-Hep 1, while this decrease could not be seen by cytotoxic chemotherapy agents. The sorted SP cells had self-renewal property and expressed much higher mRNA levels of stem cell-related genes, such as ABCG2, SMO, beta-catenin and CD133 than non-SP cells. Treatment with HUE dramatically decreased the above stem cell-related mRNA levels as well as the clonogenesity of SP cells. The SP cells were more sensitive to HUE than the non-SP cells, while the SP cells were more resistant to cytotoxic chemotherapy agents than the non-SP cells. Our finding indicates the capability of HUE to eliminate the cancer stem cells and drug resistant population, which might interpret that how HUE was able to improve chemotherapy response in phase III clinical trials.
Evaluation of Bowen disease by in vivo reflectance confocal microscopy
Authors: M. Ulrich, J. Kanitakis, S. González, S. Lange-Asschenfeldt, E. Stockfleth, J. Roewert-Huber
Journal: British Journal of Dermatology (2011)

Funding sources: none. Conflicts of interest: none declared. Madam, Bowen disease (BD) is a form of epidermal carcinoma in situ, characterized histologically by proliferation of atypical, pleomorphic keratinocytes involving the whole epidermis. Dyskeratotic, mitotic and multinucleated cells frequently occur.1 Clinically, BD should be differentiated from other nonmelanoma skin cancers (NMSC) and from inflammatory dermatoses such as eczema or psoriasis. Although BD develops as an in situ carcinoma, it may progress into invasive squamous cell carcinoma (SCC) in 3–5% of cases,2 with a potential risk for metastasis of up to 10%.3 Dermatoscopy has been applied as an adjunct imaging technique for the diagnosis of pigmented and nonpigmented BD, showing a peculiar dermatoscopic pattern characterized by glomerular vessels and a scaly surface in 100% and 90% of cases, respectively.4 However, the diagnosis of BD is usually based on histological examination of a skin biopsy. In vivo reflectance confocal microscopy (RCM) is a novel noninvasive diagnostic tool that has recently been applied for the evaluation of various skin diseases, including actinic keratosis, basal cell carcinoma and psoriasis. Here we report the RCM features of BD and correlate them to the corresponding histological features.
The Neurology Professor Retires
Authors: Ronald Pies
Journal: JAMA (2000)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fate of Circulating Tumor Cells: III. Comparison of Metastatic Growth Produced by Tumor Cell Emboli in Veins and Lymphatics
Authors: Irving Zeidman
Journal: Cancer Research (1965)

Experiments were designed to determine the relative ability of tumor cell emboli in blood and lymph to produce metastases. The transplantable V2 carcinoma was used in domestic rabbits. Equal volumes of the same suspension were injected into veins of some rabbits and into lymphatics of others. The rabbits were sacrificed later and the incidence of metastasis was determined. Under these circumstances, metastases occurred with significantly greater frequency in rabbits receiving the injection I.V. than in those which received the tumor into lymphatics. The experimental results suggest that some tumor cell emboli are destroyed in the lymph node.
Histories of childhood trauma in adult hypochondriacal patients
Authors: A J Barsky, C Wool, M C Barnett, P D Cleary
Journal: American Journal of Psychiatry (1994)

This study examined the childhood histories of trauma, parental attitudes toward health, and physical illness in hypochondriacal adults.Sixty outpatients with DSM-III-R hypochondriasis and 60 nonhypochondriacal outpatients from the same general medical clinic were compared. All patients completed the Childhood Traumatic Events Scale and an eight-item questionnaire about childhood illness and health. Medical morbidity was assessed with a medical record audit.Significantly more hypochondriacal than nonhypochondriacal patients reported traumatic sexual contact (28.6% versus 7.3%), physical violence (32.1% versus 7.3%), and major parental upheaval (28.6% versus 9.1%) before the age of 17. These differences remained statistically significant after sociodemographic differences between the groups were controlled for with multivariate regression analysis. The two groups did not differ in the age at which these traumas occurred or in the degree of trauma experienced. Significantly more hypochondriacal patients reported being sick as children and missing school for health reasons, but they did not differ in other measures of childhood illness and parental attitudes toward illness. The two groups had similar levels of aggregate medical morbidity.Hypochondriacal adults recall more childhood trauma than do nonhypochondriacal patients, even after sociodemographic differences are controlled for. They also recall more childhood illness, although they are not currently more medically sick.
Chlamydia pneumoniae in HIV-infected patients and controls assessed by a novel whole blood interferon-γ assay, serology and PCR
Authors: I.J. Woolley, M. Larsen, S. Jones, M.E. Gahan, I. Jasenko, S.P. Johnsen, S. Wesselingh, A. Fuller, L. Ostergaard
Journal: Clinical Microbiology and Infection (2004)
Identification of women at risk for unwanted pregnancy
Authors: V Abernethy, D Robbins, G L Abernethy, H Grunebaum, J L Weiss
Journal: American Journal of Psychiatry (1975)

Concern about increasing rates of unwanted pregnancy, particularly among adolescents, has led to consideration of steps necessary to develop effective intervention programs. In order to reach a young woman for counseling and contraceptive assistance before she places herself at risk for unintended pregnancy, it seems necessary to develop the capability for identifying high-risk individuals without reference to sexual history. The authors describe a preliminary attempt to predict contraceptively unprotected coitus from responses to projective test stimuli, noting that the problem is so urgent that even early and necessarily incomplete work in this area may have merit in stimulating further research in identification of women at risk for unwanted pregnancy.A trial series with a projective instrument was used with a sample of 85 women, aged 15-45, in an effort to stimulate other experimental and clinical efforts toward early identification of women at high risk for unwanted pregnancy. The overall strategy was to compare scores on the projective materia with a computerized behavioral measure of risking unwanted pregnancy in order to evaluate the discriminatory power of the projective test. The behavioral measure is a composite, machine-made variable that summarizes self-reported sexual behavior and feelings, and data for the behavioral measure were collected by a research assistance with no connection with the projective test scoring. I 2 of the 3 analyses, there was a statistically significant relationship between the projective test score and the behavioral measure of risk for unwanted pregnancy. On the basis of 1 modest trial, it seems that the role-redefinition criteria tap dimensions that are independent of usually described clinical syndromes. This research is not sufficiently advanced to be of general clinical value. There are problems with generalizability of the sample to the female population at large and standardization of scoring procedures.
397. Transduction of Primary Human CD34+ Cells by Self-Inactivating FIV Vectors
Authors: Charlene F. Barroga, Mehdi Gasmi, Olivera Marjanovic, Laura Innis, David J. Looney
Journal: Molecular Therapy (2004)

Minimal vectors derived from the feline immunodeficiency virus (FIV) were constructed which retained only 259 bp of gag cds, the FIV RRE, and incorporated the woodchuck posttranscriptional regulatory element (wPRE), human immunodeficiency virus (HIV) or FIV cPPT/CTS elements, and a variety of eGFP reporter gene promoters (including CMV IE, EF1a, PGK, MSCV, and MPSV). A packaging plasmid (pC34N) deleted of 1569 bp in the env gene and the principal packaging site was used to generate vectors pseudotyped with the VSV-G protein after transfection into 293FT cells. These second generation FIV vectors generated high titers of 106 TU/ml (up to 109 TU/ml upon concentration), and transduced primary human cord blood CD34+ cells at efficiencies of 50–75% (moi 20-40). Expression persisted at the level of 15–20% after 12 days in culture. Vectors containing the EF1a promoter and cPPT /CTS elements transduced CD34+ cells most efficiently. While the FIV LTR is relatively quiescent in human cells (no LTR-driven expression detected in transduced cells expression by RT PCR), self-inactivating 3rd generation FIV vectors were constructed by progressive deletion of the U3 in the 3'LTR, encompassing TATA boxes and binding sites for NF-kB, AP1 and C/EBP, in an attempt to increase expression. One FIV SIN vector had 2–3 fold increase in titer, higher mean fluorescence intensity and improved transduction efficiency of CD34+ cells. FIV vector transduced CD34+ cells expressed eGFP upon differentiation into myeloid cells. FIV SIN transduced CD34+ cells gave rise to GFP+ colonies which persisted for more than 3 weeks when plated onto methylcellulose for hematopoietic progenitor cell assays. Integration assay (two -step Alu PCR) demonstrated that these vectors were integrated into the genome. FIV SIN vectors have potential as an alternative to HIV-1 based vectors for stem cell gene therapy.
Abstract 8: Modulation of Cytochrome c Oxidase Activity with Specific Infrared Light Wave Lengths: Noninvasive Therapy for Reperfusion Injury
Authors: Thomas H Sanderson, Joseph M Wider, Christian A Reynolds, Brad D Lepore, Karin Przyklenk, Maik Huttemann
Journal: Circulation (2014)

Reperfusion injury plays a major role in multiple pathologies by inducing generation of reactive oxygen species (ROS) at high mitochondrial membrane potentials (ΔΨ m ). Traditional attempts to scavenge ROS have failed, due to inherent difficulties in sub-cellular delivery within the early minutes of reflow. Accordingly, we developed a non-pharmacologic therapy that targets cytochrome c oxidase (CcO) using infrared light (IRL), and discovered 4 specific IRL wavelengths that reversibly reduce the activity of CcO. We propose that these wavelengths will stabilize ΔΨ m  during reperfusion and, thus, provide a non-invasive strategy to attenuate cerebral ischemia-reperfusion injury.   Methods and Results:  In  Protocol 1 , we tested this hypothesis in cell culture. All 4 IRL wavelengths that reduce CcO activity: i) decreased mitochondrial respiratory rate (n=5; p m  in a switch-like manner (n=3; p in situ  (n=5; p Protocol 2 , we evaluated the neuroprotective effect of the 4 candidate wavelengths in the  in vivo  rat model of global brain ischemia. All possible wavelength combinations were evaluated using a randomized and blinded study design (15 treatments; n = 8-12/group; total n=153,). At 14 days post-reperfusion, untreated controls demonstrated an 88% loss of neurons in the CA1 hippocampus. Strikingly, all 15 IRL combinations were protective, with neuronal loss ranging from only 11% (best treatment) to 58%: all p-values  vs  control. The neurologic protection in IRL treated rats was accompanied by preservation of neurologic function, as demonstrated by a 40% improvement in spatial learning deficits (n = 10/group, p Protocol 3 ) we developed a prototype capable of delivering the 4 candidate IRL wavelengths to deep structures of the pig brain with no detectable increase in scalp or brain temperature (ΔT   Conclusion:  Non-invasive reduction of CcO activity with specific IRL wavelengths is profoundly neuroprotective.
Abstract 10957: Association of Insulin Resistance and Dysglycemia With Components of Blood Pressure: A Study From the Hispanic Community Health Study/Study of Latinos
Authors: Natalie A Bello, Brian Claggett, Fatima Rodriguez, Jianwen Cai, Ashley Moncrieft, Karin Garcia, Marina Del Rios Rivera, Robert C Kaplan, Martha L Daviglus, Scott D Solomon, Susan Cheng
Journal: Circulation (2014)

Background: Data are conflicting regarding the extent to which insulin resistance or dysglycemia contribute to the development of elevated blood pressure (BP). Therefore, we examined whether these metabolic abnormalities are associated with distinct BP components, including measures of pulsatile versus steady state load (surrogates for large and small artery disease) in a large community-based cohort. Methods: We studied 10,720 non-diabetic participants from 4 U.S. sites in the Hispanic Community Health Study / Study of Latinos who were free of cardiovascular disease and not on any anti-hypertensive medications. We used linear regression for complex survey sampling and non-parametric spline models to examine the relation of insulin resistance (HOMA-IR) and dysglycemia (HbA1c) with components of BP (systolic, diastolic, pulse pressure [PP, reflecting pulsatile load], and mean arterial pressure [MAP, reflecting steady state load]) while adjusting for established clinical correlates of BP. Results: The target population mean age was 38 years (s.e. 0.22) and included 52% women, 38% with pre-diabetes, 35% obese, and 9% with untreated hypertension. All BP component measures were higher in pre-diabetes than non-diabetes. In multivariable analyses, HOMA-IR was significantly associated with increase in all BP components (P&lt;0.01 for all), including both PP and MAP, in the setting of both pre-diabetes and particularly non-diabetes (Figure). By contrast, HbA1c was not significantly associated with increase in any BP component. Conclusion: In a large population of non-diabetic Hispanic/Latino adults, insulin resistance (rather than dysglycemia per se) is related to increase in all BP components including measures of both pulsatile load (representing large artery disease) and steady state load (representing small artery disease). These findings may have implications for interventions aimed at preventing large and small vessel disease in the community.