tbuckley/cabot-search huggingface dataset:
Hydroxychloroquine-Induced Pigmentation in Patients With Systemic Lupus Erythematosus
Authors: Moez Jallouli, Camille Francès, Jean-Charles Piette, Du Le Thi Huong, Philippe Moguelet, Cecile Factor, Noël Zahr, Makoto Miyara, David Saadoun, Alexis Mathian, Julien Haroche, Christian De Gennes, Gaelle Leroux, Catherine Chapelon, Bertrand Wechsler, Patrice Cacoub, Zahir Amoura, Nathalie Costedoat-Chalumeau
Journal: JAMA Dermatology (2013)

Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising.To describe the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE).In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ.The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses.Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration.Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.
Change in Physician Perspective on Cholesterol and Heart Disease
Authors: Beth Schucker
Journal: JAMA (1987)

The National Heart, Lung and Blood Institute, Bethesda, Md, and the Food and Drug Administration, Washington, DC, sponsored two national probability telephone surveys (N = 4000) of adults to assess attitudes and knowledge about heart disease risk from high blood cholesterol levels and the public's efforts to lower blood cholesterol levels. The first survey was conducted in 1983, before release of the results from the Lipid Research Clinics Coronary Primary Prevention Trial, which showed that a reduction in the blood cholesterol level reduced coronary heart disease; the second survey was conducted in 1986. The percentage of adults who believed that reducing high blood cholesterol levels would have a large effect on heart disease increased from 64% in 1983 to 72% in 1986, so that the importance attached to reducing high blood cholesterol levels approached that attributed to reducing smoking and high blood pressure. In 1983, 35% of adults reported that they had their cholesterol level checked vs 46% in 1986. In both years, diet changes were most frequently chosen (greater than 60%) as ways to control the blood cholesterol level; reducing dietary fat was believed to be as important as reducing dietary cholesterol. By 1986, 23% of adults reported that they made dietary changes specifically to lower their blood cholesterol level, up from 14% in 1983. These comparative data show gains in public awareness and action relating to high blood cholesterol level risk. The data can be used to develop education programs.
Seven new mutations in the nicotinamide adenine dinucleotide reduced–cytochrome b5 reductase gene leading to methemoglobinemia type I
Authors: Jan Dekker, Michel H. M. Eppink, Rob van Zwieten, Thea de Rijk, Angel F. Remacha, Lap Kay Law, Albert M. Li, Kam Lau Cheung, Willem J. H. van Berkel, Dirk Roos
Journal: Blood (2001)
Rational Design of the Microtubule-Targeting Anti–Breast Cancer Drug EM015
Authors: Ritu Aneja, Manu Lopus, Jun Zhou, Surya N. Vangapandu, Amr Ghaleb, Joyce Yao, James H. Nettles, Binfei Zhou, Meenakshi Gupta, Dulal Panda, Ramesh Chandra, Harish C. Joshi
Journal: Cancer Research (2006)

We studied in silico docking of noscapine onto tubulin, combined with calculations of surface charge, pi-pi, van der Waals, and hydrogen bonding interactions, to rationally design a new compound, EM015. This tubulin-binding semisynthetic compound is a selective and potent anti-breast cancer agent and displays a 20-fold lower IC(50) against many tumor cells compared with our founding compound, (S)-6,7-dimethoxy-3-((R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]-dioxolo-[4,5-g]isoquinolin-5-yl)isobenzo-furan-1(3H)-one (noscapine). Furthermore, EM015 is also effective against a variety of drug-resistant cells. Surprisingly, the cell cycle profile of nontumorigenic normal cells is not affected. Many antimicrotubule cancer drugs in clinic today, particularly taxanes and Vincas, face challenges including frequent visits to the hospital for prolonged i.v. infusions, toxicities, and tumor recurrences due to drug resistance. EM015, on the other hand, is orally available, regresses breast tumor xenografts in nude mice models, and increases longevity. Furthermore, we have failed to observe any detectable toxicity in tissues, such as liver, kidney, spleen, lung, heart, and brain, as well as neurons, which are common targets of antimicrotubule drug therapy. Thus, EM015 has a great promise in the clinic.
Cyclooxygenase-2 Is an Independent Prognostic Factor in Gastric Cancer and Its Expression Is Regulated by the Messenger RNA Stability Factor HuR
Authors: Johanna Mrena, Jan-Patrik Wiksten, Alexandra Thiel, Arto Kokkola, Leena Pohjola, Johan Lundin, Stig Nordling, Ari Ristimäki, Caj Haglund
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cyclooxygenase-2 (COX-2) promotes carcinogenesis and its expression associates with clinicopathologic characteristics in gastric cancer. HuR is an mRNA binding protein that controls the stability of certain transcripts including COX-2. We evaluated the prognostic significance of COX-2 and HuR expressions in gastric cancer and whether there exists a link between HuR and COX-2 expressions. Experimental Design: The study included 342 consecutive patients with histologically confirmed gastric adenocarcinoma, of whom 321 patients had tissue specimens available for COX-2 and 316 for HuR immunohistochemistry. Specimens were stained by COX-2– and HuR-specific monoclonal antibodies and scored by two independent observers. Correlation to clinical data and survival was assessed. TMK-1 gastric adenocarcinoma cells were treated with small interfering RNA against HuR and expressions of HuR and COX-2 were detected by immunofluorescence and Western blot analysis. Results: Patients with low COX-2 expression had a cumulative 5-year survival of 53% and those with high COX-2 expression had 16% (P &amp;lt; 0.0001). In multivariate analysis, COX-2 was an independent prognostic factor (P = 0.003). Cytoplasmic HuR expression was associated with high COX-2 expression (P &amp;lt; 0.0001) and with reduced survival (P = 0.004) whereas nuclear positivity for HuR was not. When TMK-1 cells were treated with HuR small interfering RNA, expressions of HuR and COX-2 were reduced. Conclusions: High COX-2 is an independent prognostic factor in gastric cancer. Cytoplasmic expression of HuR associates with high COX-2 expression and with reduced survival, and tissue culture experiments show that HuR can regulate expression of COX-2 in gastric cancer cells.
Contributions of Stromal Metalloproteinase-9 to Angiogenesis and Growth of Human Ovarian Carcinoma in Mice
Authors: S. Huang
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: The expression level of several matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, in ovarian cancer cells is directly associated with their invasive and metastatic potentials. MMP-9 is also expressed in stromal cells adjacent to the tumor. To investigate the contribution of MMP-9 expression in stromal cells to ovarian tumor growth, we examined angiogenesis and progressive growth of human ovarian cancer cells implanted into mice with and without the MMP-9 gene. Methods: Human ovarian cancer cells SKOV3.ip1 and HEY-A8 were implanted into the peritoneal cavities of nude mice that lacked the gene for MMP-9 (MMP-9−/−) or were wild type for MMP-9 (MMP-9+/+) (10 mice of each genotype per cell line). Tumor incidence, tumor size, and volume of ascites fluid were recorded for each mouse at 30 and 45 days after HEY-A8 and SKOV3.ip1 cell injections, respectively. Blood vessel density and macrophage infiltration into the lesions were analyzed in excised tumors by immunohistochemistry and double immunofluorescence. Tumor growth was also studied in MMP-9−/− nude mice that had been reconstituted with spleen cells collected from either MMP-9+/+ or MMP-9−/− nude mice. All statistical tests were two-sided. Results: HEY-A8 cells expressed high levels of MMP-9, and SKOV3.ip1 cells expressed low levels. Nevertheless, tumor incidence and growth were statistically significantly lower in MMP-9−/− mice than in MMP-9+/+ mice injected with cells from either line (for tumor size, P = .006 and .042 for HEY-A8 and SKOV3.ip1 cells, respectively). Compared with MMP-9+/+ mice injected with human ovarian cancer cells, MMP-9−/− mice injected with human ovarian cancer cells displayed decreased microvessel density and decreased macrophage infiltration into the lesions. Compared with MMP-9−/− mice that received spleen cells (a rich source of macrophages) from MMP-9−/− mice, those that received spleen cells from MMP-9+/+ mice before cancer cell injections displayed increased angiogenesis and tumorigenicity of the cancer cells. The growing tumors contained MMP-9-expressing macrophages. Conclusion: Host-derived MMP-9 expression, most likely in tumor-infiltrating macrophages, appears to play a critical role in angiogenesis and progressive growth of human ovarian tumors in mice.
Pathways to Recovery and Loss of Nephrons in Anti-Thy-1 Nephritis
Authors: Wilhelm Kriz, Bruni Ha[Combining Diaeresis]hnel, Hiltraud Hosser, Tammo Ostendorf, Soeren Gaertner, Bettina Kra[Combining Diaeresis]nzlin, Norbert Gretz, Fujio Shimizu, Ju[Combining Diaeresis]rgen Floege
Journal: Journal of the American Society of Nephrology (2003)

The present histopathologic study of anti-Thy-1.1 models of mesangioproliferative glomerulonephritis in rats provides a structural analysis of damage development and of pathways to recovery and to nephron loss. As long as the disease remains confined to the endocapillary compartment, the damage may be resolved or recover with a mesangial scar. Irreversible lesions with loss of nephrons emerge from extracapillary processes with crucial involvement of podocytes, leading to tuft adhesions to Bowman's capsule (BC) and subsequent crescent formation. Two mechanisms appeared to be responsible: (1) Epithelial cell proliferation at BC and the urinary orifice and (2) misdirected filtration and filtrate spreading on the outer aspect of the nephron. Both may lead to obstruction of the tubule, disconnection from the glomerulus, and subsequent degeneration of the entire nephron. No evidence emerged to suggest that the kind of focal interstitial proliferation associated with the degeneration of injured nephrons was harmful to a neighboring healthy nephron.
Prolonged Fever, Hepatosplenomegaly, and Pancytopenia in a 46-Year-Old Woman
Authors: Liran Levy, Abedelmajeed Nasereddin, Moshe Rav-Acha, Meirav Kedmi, Deborah Rund, Moshe E. Gatt
Journal: PLoS Medicine (2009)

A 46-year-old woman was hospitalized due to fever of up to 39uC of one week's duration.The patient complained of weakness, night sweats, and weight loss for two weeks prior to admission.The patient had no past medical history, and did not take any medications, supplements, or illicit drugs.She was born and lived all her life in a rural village.She was indirectly exposed to farm animals and pets, yet had no close contact with these, and her family was not engaged in agricultural work.She denied having been bitten by ticks or fleas.There was no history of recent foreign travel or eating raw meat or unpasteurized milk.She reported no rashes, arthralgia, dryness of eyes, mouth ulcers, or mucocutaneous bleeding.On examination she appeared pale and sweaty.The cardiorespiratory examination was unremarkable.A markedly tender and enlarged liver and spleen, 3 cm and 10 cm below the costal margins, respectively, were noted, with no palpable lymph nodes.Periorbital and peripheral extremity edema was also present.The Learning Forum discusses an important clinical problem of relevance to a general medical audience.
Early Variations of Circulating Interleukin-6 and Interleukin-10 Levels During Thoracic Radiotherapy Are Predictive for Radiation Pneumonitis
Authors: Dominique Arpin, David Perol, Jean-Yves Blay, Lionel Falchero, Line Claude, Sylvie Vuillermoz-Blas, Isabelle Martel-Lafay, Chantal Ginestet, Laurent Alberti, Dimitri Nosov, Bénédicte Etienne-Mastroianni, Vincent Cottin, Maurice Perol, Jean-Claude Guerin, Jean-François Cordier, Christian Carrie
Journal: Journal of Clinical Oncology (2005)

To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis.Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses.Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFalpha, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011).Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.
Induced sputum in children: feasibility, repeatability, and relation of findings to asthma severity
Authors: N. M Wilson
Journal: Thorax (2000)

<h3>BACKGROUND</h3> The collection of induced sputum provides a non-invasive method of investigating airway inflammation. Few studies have been performed in children, so a study was undertaken to determine the feasibility of sputum induction, the repeatability of eosinophil counts and sputum eosinophil cationic protein (ECP) levels, and the relation of these to current asthma severity. For comparison, serum ECP levels were also measured. <h3>METHODS</h3> In a cross sectional study of children aged 5–15 years, 27 healthy children and 60 with asthma underwent sputum induction using inhaled nebulised hypertonic saline. The whole sputum sample was used for analysis. Ten children with stable asthma repeated the procedure within 10 days. <h3>RESULTS</h3> A satisfactory sample (&gt;500 non-squamous cells) was obtained in 61% of children with asthma and in 60% of healthy controls. The limits of agreement within subjects ranged from a 0.68 to 2.8 fold difference for eosinophil differential counts and from 0.38 to 4.4 fold for sputum ECP. Despite a median of 42% squamous cells, significant differences were found between asthma and healthy controls for the eosinophil differential count (p = 0.0004), total eosinophil counts (p = 0.03), and sputum ECP level (p = 0.0001). Overall, there was no correlation between any marker of airway inflammation and asthma severity, however expressed, including lung function. <h3>CONCLUSIONS</h3> Sputum induction is only possible in a proportion of children. The repeatability of sputum cell counts and ECP levels, measured in a small number of children, was similar to that reported in adults. Sputum analysis revealed no evidence of airway inflammation in a number of highly symptomatic children with asthma.
THICK SKIN AND STIFF JOINTS IN INSULIN-DEPENDENT DIABETES MELLITUS
Authors: J.L. Burton
Journal: British Journal of Dermatology (1982)

Journal Article THICK SKIN AND STIFF JOINTS IN INSULIN‐DEPENDENT DIABETES MELLITUS Get access J.L. Burton J.L. Burton Department of Dermatology, Royal Infirmary, Bristol BS2 8HW Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 106, Issue 3, 1 March 1982, Pages 369–371, https://doi.org/10.1111/j.1365-2133.1982.tb01739.x Published: 01 March 1982
Clinical Utility of Proton Magnetic Resonance Spectroscopy in Characterizing Breast Lesions
Authors: Rachel Katz-Brull, Philip T. Lavin, Robert E. Lenkinski
Journal: JNCI Journal of the National Cancer Institute (2002)

Proton magnetic resonance spectroscopy (1H MRS) of the breast has been proposed as an adjunct to the magnetic resonance imaging (MRI) examination to improve the specificity of distinguishing malignant breast tumors from benign breast tumors. In this review, we carry out a pooled analysis of the clinical breast 1H MRS studies undertaken to date to determine the factors that influence the diagnostic performance of this method. In total, five studies of breast 1H MRS from four independent centers around the world have been published to date. Altogether, 153 tumors were examined, 100 of which were confirmed histologically to be malignant and 53 of which were benign. The lesions presenting a detectable composite choline signal in their corresponding 1H MR spectra were diagnosed as malignant, whereas the lesions with no choline signal were diagnosed as benign. The sensitivity and specificity of breast 1H MRS for detecting breast cancer were 83% (95% confidence interval [CI] = 73% to 89%) and 85% (95% CI = 71% to 93%), respectively, and both values could be as high as 92% after technical exclusions. In a subgroup of 20 young women, the sensitivity and the specificity of the method approached 100%. The factors limiting the sensitivity of the examination were mainly technical. The use of the composite choline signal as a marker for malignancy in breast 1H MRS is a robust method with highly reliable interpretation, because it is based on the appearance of a single peak. The method is likely to provide even better results with technologic advances in breast MRS that lead to the improved detection of the composite choline signal.
Two years of intensive glycemic control and left ventricular function in the Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM).
Authors: S U Pitale, C Abraira, N V Emanuele, M McCarren, W G Henderson, I Pacold, D Bushnell, J A Colwell, F Q Nuttall, S R Levin, C T Sawin, J P Comstock, C K Silbert
Journal: Diabetes Care (2000)

OBJECTIVE: The Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM) was a multicenter randomized prospective study of 153 male type 2 diabetic patients to assess the ability to sustain clinically significant glycemic separation between intensive and standard treatment arms. A trend toward an excess of combined cardiovascular events in the intensive treatment arm of this trial was reported earlier. The present analysis was done to evaluate the effect of 2 years of intensive glycemic control on the left ventricular (LV) function. RESEARCH DESIGN AND METHODS: The patients were randomized to intensive step treatment with insulin alone or with sulfonylurea (intensive treatment arm [INT], n = 75) or to standard once-daily insulin injection (standard treatment arm [STD], n = 78) treatment. A total of 136 patients (standard treatment arm [STD], n = 70; INT, n = 66) had radionuclide ventriculography at entry and at 24 months for the assessment of LV function. RESULTS: There was no difference in the mean LV ejection fraction (at entry: STD 57.1+/-9.51%; INT 58.1+/-8.7%; at 24 months: STD 57.3+/-10.8%, INT 59.5+/-10.7%), peak filling rate (at entry: STD 2.6+/-0.7 end diastolic volume per second, INT 2.4+/-0.8 end diastolic volume per second; at 24 months: STD 2.7+/-1.0 end diastolic volume per second, INT 2.5+/-0.7 end diastolic volume per second), or time to peak filling rate (at entry: STD 195.3+/-69.5 ms, INT 185.6 +/-62.4 ms; at 24 months: STD 182.6+/-64.8 ms, INT 179.2+/-61.2 ms) between the 2 treatment arms. A subgroup analysis of 104 patients (STD, n = 53; INT, n = 51) that omitted individuals with intervening cardiac events/revascularization or a change in cardioactive medications also showed no difference in the LV function at entry and at 24 months between the 2 groups. Abnormal LV ejection fraction at baseline predicted cardiac events (interval between cardiac beats [RR] = 2.5). CONCLUSIONS: Two years of intensive glycemic control does not affect the LV systolic or diastolic function in patients with type 2 diabetes.
Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival
Authors: Qian Li, Olindi Wijesekera, Sussan J. Salas, Joanna Y. Wang, Mingxin Zhu, Colette Aprhys, Kaisorn L. Chaichana, David A. Chesler, Hao Zhang, Christopher L. Smith, Hugo Guerrero-Cazares, Andre Levchenko, Alfredo Quinones-Hinojosa
Journal: Clinical Cancer Research (2014)

Glioblastoma is the most common adult primary malignant intracranial cancer. It is associated with poor outcomes because of its invasiveness and resistance to multimodal therapies. Human adipose-derived mesenchymal stem cells (hAMSC) are a potential treatment because of their tumor tropism, ease of isolation, and ability to be engineered. In addition, bone morphogenetic protein 4 (BMP4) has tumor-suppressive effects on glioblastoma and glioblastoma brain tumor-initiating cells (BTIC), but is difficult to deliver to brain tumors. We sought to engineer BMP4-secreting hAMSCs (hAMSCs-BMP4) and evaluate their therapeutic potential on glioblastoma.The reciprocal effects of hAMSCs on primary human BTIC proliferation, differentiation, and migration were evaluated in vitro. The safety of hAMSC use was evaluated in vivo by intracranial coinjections of hAMSCs and BTICs in nude mice. The therapeutic effects of hAMSCs and hAMSCs-BMP4 on the proliferation and migration of glioblastoma cells as well as the differentiation of BTICs, and survival of glioblastoma-bearing mice were evaluated by intracardiac injection of these cells into an in vivo intracranial glioblastoma murine model.hAMSCs-BMP4 targeted both the glioblastoma tumor bulk and migratory glioblastoma cells, as well as induced differentiation of BTICs, decreased proliferation, and reduced the migratory capacity of glioblastomas in vitro and in vivo. In addition, hAMSCs-BMP4 significantly prolonged survival in a murine model of glioblastoma. We also demonstrate that the use of hAMSCs in vivo is safe.Both unmodified and engineered hAMSCs are nononcogenic and effective against glioblastoma, and hAMSCs-BMP4 are a promising cell-based treatment option for glioblastoma.