tbuckley/cabot-search huggingface dataset:
Ambient Air Pollution Exaggerates Adipose Inflammation and Insulin Resistance in a Mouse Model of Diet-Induced Obesity
Authors: Qinghua Sun, Peibin Yue, Jeffrey A. Deiuliis, Carey N. Lumeng, Thomas Kampfrath, Michael B. Mikolaj, Ying Cai, Michael C. Ostrowski, Bo Lu, Sampath Parthasarathy, Robert D. Brook, Susan D. Moffatt-Bruce, Lung Chi Chen, Sanjay Rajagopalan
Journal: Circulation (2009)

Background— There is a strong link between urbanization and type 2 diabetes mellitus. Although a multitude of mechanisms have been proposed, there are no studies evaluating the impact of ambient air pollutants and the propensity to develop type 2 diabetes mellitus. We hypothesized that exposure to ambient fine particulate matter (&lt;2.5 μm; PM 2.5 ) exaggerates diet-induced insulin resistance, adipose inflammation, and visceral adiposity. Methods and Results— Male C57BL/6 mice were fed high-fat chow for 10 weeks and randomly assigned to concentrated ambient PM 2.5 or filtered air (n=14 per group) for 24 weeks. PM 2.5 -exposed C57BL/6 mice exhibited marked whole-body insulin resistance, systemic inflammation, and an increase in visceral adiposity. PM 2.5 exposure induced signaling abnormalities characteristic of insulin resistance, including decreased Akt and endothelial nitric oxide synthase phosphorylation in the endothelium and increased protein kinase C expression. These abnormalilties were associated with abnormalities in vascular relaxation to insulin and acetylcholine. PM 2.5 increased adipose tissue macrophages (F4/80 + cells) in visceral fat expressing higher levels of tumor necrosis factor-α/interleukin-6 and lower interleukin-10/ N -acetyl-galactosamine specific lectin 1. To test the impact of PM 2.5 in eliciting direct monocyte infiltration into fat, we rendered FVBN mice expressing yellow fluorescent protein (YFP) under control of a monocyte-specific promoter (c- fms , c- fms YFP ) diabetic over 10 weeks and then exposed these mice to PM 2.5 or saline intratracheally. PM 2.5 induced YFP cell accumulation in visceral fat and potentiated YFP cell adhesion in the microcirculation. Conclusion— PM 2.5 exposure exaggerates insulin resistance and visceral inflammation/adiposity. These findings provide a new link between air pollution and type 2 diabetes mellitus.
Protriptyline in the treatment of sleep apnoea.
Authors: W A Conway, F Zorick, P Piccione, T Roth
Journal: Thorax (1982)

Nine patients with obstructive sleep apnoea were treated with 5 to 20 mg of protriptyline each night for two to 18 months. In four patients, there was dramatic, sustained improvement in symptoms and measured sleep quality and apnoea frequency and duration. There was no improvement in two patients and three developed intolerable side-effects preventing adequate treatment. Apnoea frequency was the only apparent predictor of responsiveness. Those with fewer than 30 episodes of apnoea per hour consistently improved. Only two of four patients with more than 60 episodes per hour improved. These results provide additional evidence that a carefully monitored trial of protriptyline may benefit selected patients with mild to moderate obstructive sleep apnoea.
Prognostic Model for Relapse After High-Dose Chemotherapy With Autologous Stem-Cell Transplantation for Stage IV Oligometastatic Breast Cancer
Authors: Yago Nieto, Samia Nawaz, Roy B. Jones, Elizabeth J. Shpall, Pablo J. Cagnoni, Peter A. McSweeney, Anna Barón, Carrington Razook, Steve Matthes, Scott I. Bearman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To study prognostic factors after high-dose chemotherapy (HDC) for patients with stage IV oligometastatic breast cancer. PATIENTS AND METHODS: Sixty patients with minimal metastatic disease amenable to local therapy enrolled onto a prospective HDC trial were analyzed for potential prognostic factors. Tumor blocks were retrospectively collected from referring institutions. RESULTS: Median follow-up was 62 months (range, 4 to 120 months). Median relapse-free survival (RFS) and overall survival (OS) times were 52 and 80 months, respectively. Five-year RFS and OS rates were 52% (95% confidence interval [CI], 39% to 64%) and 62% (95% CI, 49% to 74%), respectively. HER-2 expression, number of tumor sites, primary axillary nodal ratio (number of positive nodes divided by number of sampled nodes), number of positive axillary nodes, and delivery or omission of radiotherapy to metastases correlated with RFS. HER-2 overexpression and more than one site were independent adverse risk factors for RFS. HER-2 and the axillary nodal ratio were independent predictors of OS. The following prognostic categories for RFS were established (RFS rate, median RFS): good risk, no factors (77%, 80 months); intermediate risk, one factor (41%, 28 months); and poor risk, both factors (10%, 10 months). CONCLUSION: Long-term results in patients with oligometastatic breast cancer are encouraging but need validation in prospective randomized studies. HER-2 expression, number of sites, and primary nodal ratio are independent outcome predictors. Confirmation of these observations in this selected population would imply the need for reevaluation of the current tenet that early detection of metastatic breast cancer recurrence is of no benefit.
Prenatal care discriminates against black women in US
Authors: J Roberts
Journal: BMJ (1994)

Black pregnant women in the US get less advice on the effects of smoking and drinking alcohol in pregnancy than white women, says a paper published jointly by the National Center for Health Statistics, the University of North Carolina, and the University of Minnesota. The US ranks 25th among nations in its infant mortality, with almost 40 000 infants dying before their 1st birthday. The infants of black women are 2.4 times more …
Ethnicity influences breast cancer risk, diagnosis, and treatment but not survival, study finds
Authors: R. Dobson
Journal: BMJ (2009)

A woman’s risk of getting breast cancer, the stage at which it is diagnosed, and the treatment she gets all vary with ethnic background, a new UK study has found. 

But the researchers found, after adjusting fully for age, level of socioeconomic deprivation, stage of disease, and treatment received, that survival from breast cancer did not vary significantly ( British Journal of Cancer doi:10.1038/sj.bjc.6604852).

The researchers, from King’s College London, analysed data on 35 631 women who received a diagnosis of breast cancer in southeast England between 1998 and 2003. The ethnic groups they looked at were white, …
In Vivo Transduction of Cerebellar Purkinje Cells Using Adeno-Associated Virus Vectors
Authors: William F. Kaemmerer, Rukmini G. Reddy, Christopher A. Warlick, Seth D. Hartung, R. Scott McIvor, Walter C. Low
Journal: Molecular Therapy (2000)

We investigated whether adenovirus or adeno-associated virus vectors can transduce cerebellar Purkinje cells (PCs) in vivo. Mice were injected in the deep cerebellar nuclei (DCN) with lacZ-transducing adenovirus (Ad.RSV-βgal) or a recombinant AAV serotype 2 (rAAV2) vector (vTR-CMVβ) mixed with wild-type adenovirus type 5 (Ad5). One week later, Ad.RSV-βgal transduced cells were found throughout the cerebellar white matter in a dose-dependent manner, but few transduced PCs were evident. In contrast, vTR-CMVβ with Ad5 transduced several hundred PCs throughout the injected hemisphere. Using an rAAV2 vector transducing a CMV-regulated green fluorescent protein gene, we again found PC transduction, but only with Ad5 coinjection. To assess the effect of injection site and to determine whether the apparent requirement for Ad5 coinfection is observed with other promoters, a β-actin-regulated vector was injected with or without Ad5 to DCN or cerebellar cortical sites. Thousands of transduced PCs were observed under each condition. Cortical injection yielded greater numbers of transduced cells. Injection of rAAV2 without Ad5 led to greater specificity for PC transduction. We conclude that injection of rAAV2 vectors into the cerebellum is an effective means for transferring genes into substantial numbers of Purkinje cells in vivo. We investigated whether adenovirus or adeno-associated virus vectors can transduce cerebellar Purkinje cells (PCs) in vivo. Mice were injected in the deep cerebellar nuclei (DCN) with lacZ-transducing adenovirus (Ad.RSV-βgal) or a recombinant AAV serotype 2 (rAAV2) vector (vTR-CMVβ) mixed with wild-type adenovirus type 5 (Ad5). One week later, Ad.RSV-βgal transduced cells were found throughout the cerebellar white matter in a dose-dependent manner, but few transduced PCs were evident. In contrast, vTR-CMVβ with Ad5 transduced several hundred PCs throughout the injected hemisphere. Using an rAAV2 vector transducing a CMV-regulated green fluorescent protein gene, we again found PC transduction, but only with Ad5 coinjection. To assess the effect of injection site and to determine whether the apparent requirement for Ad5 coinfection is observed with other promoters, a β-actin-regulated vector was injected with or without Ad5 to DCN or cerebellar cortical sites. Thousands of transduced PCs were observed under each condition. Cortical injection yielded greater numbers of transduced cells. Injection of rAAV2 without Ad5 led to greater specificity for PC transduction. We conclude that injection of rAAV2 vectors into the cerebellum is an effective means for transferring genes into substantial numbers of Purkinje cells in vivo.
Epigenetic Up-regulation of C-C Chemokine Receptor 7 and C-X-C Chemokine Receptor 4 Expression in Melanoma Cells
Authors: Takuji Mori, Joseph Kim, Tomoki Yamano, Hiroya Takeuchi, Sharon Huang, Naoyuki Umetani, Kazuo Koyanagi, Dave S.B. Hoon
Journal: Cancer Research (2005)

Abstract Histone deacetylation and DNA methylation establish epigenetic modifications, which through chromatin remodeling may result in gene silencing. We hypothesized that chemokine receptors C-C chemokine receptor 7 (CCR7) and C-X-C chemokine receptor 4 (CXCR4) on melanoma cells undergo epigenetic regulation. We investigated whether a histone deacetylase inhibitor and a demethylating agent influence CCR7 and CXCR4 expression on melanoma cells. Initially, microarray analysis was done to screen changes in chemokine receptor expression on melanoma cells after treatment with trichostatin A (TSA) and 5-Aza-2-deoxycytidine (5-Aza). CCR7 and CXCR4 mRNA expression were uniformly altered and selected for further investigation. Quantitative real-time reverse transcription-PCR assay, immunohistochemistry, and Western blot analysis were used to assess changes in mRNA and protein expression induced by TSA and 5-Aza in melanoma lines. Cell migration assays were conducted to assess the effects of altered CCR7 and CXCR4 expression on cell function. Treatment with TSA or 5-Aza increased gene expression of both CCR7 and CXCR4 in melanoma lines. TSA was the strongest enhancer. With combined treatment, CCR7 and CXCR4 mRNA expression was also up-regulated. Immunohistochemistry after combined treatment showed enhanced staining of both CCR7 and CXCR4 compared with control cells. Melanoma cell migration in TSA- and 5-Aza-treated cells was 7- and 2-fold higher than control cells for CCR7 and CXCR4, respectively. In summary, a histone deacetylase inhibitor and a demethylating agent up-regulated CCR7 and CXCR4 expression on melanoma cells. This increase in chemokine receptor expression correlated with functional activity. Most importantly, we have identified an epigenetic mechanism that may endogenously regulate chemokine receptor expression on melanoma cells.
Memorial Service Remarks
Authors: VITTORIO PUDDU
Journal: Circulation (1974)

Dr. Vittorio Puddu was closely associated with Dr. White for over twenty-five years, beginning when they both were elected members of the First International Council of Cardiology, later to become the International Society of Cardiology, of which Dr. Puddu is the current president. He also serves as director of the Cardiac Department of the Hospitals of Rome, Italy. The following are his remembrances of Dr. White presented at the Memorial Service.
Pulse Methotrexate Therapy in Rheumatoid Arthritis
Authors: DAVID M. NORDSTROM
Journal: Annals of Internal Medicine (1987)

Study Objective: To assess whether weekly pulse methotrexate therapy alters radiographic progression of joint disease in patients with rheumatoid arthritis. Design: Prospective, controlled study. Hand, wrist and foot roentgenograms obtained before, at the onset of, and during methotrexate treatment were scored for degree of joint-space narrowing and erosions by three rheumatologists using a standard method. Patients: Sequential sample of 24 patients with active definite or classical rheumatoid arthritis and previous unsuccessful treatment; of these, 3 were excluded due to drug ineffectiveness; 2, due to side effects; and 1, due to refusal to take methotrexate. Interventions: Treatment with nonsteroidal anti-inflammatory drugs and prednisone was continued. Methotrexate was given weekly to control clinical evidence of disease in patients. Measurements and Main Results: After having had an average of 30 months of therapy, the 18 patients who continued to receive methotrexate therapy showed significant (p < 0.05) clinical improvement, as evidenced by their decreased joint counts and joint scores, duration of morning stiffness, pain scales, and sedimentation rates. Despite patients' prolonged clinical improvement, the mean rate of development of erosions and joint-space narrowing during methotrexate therapy was not significantly different from the rate of radiographic progression before methotrexate therapy (0.043 compared with 0.041; p > 0.05). Conclusions: Weekly pulse methotrexate is effective for the long-term management of clinical disease activity in patients with refractory rheumatoid arthritis but may not be a disease-modifying agent by roentgenographic criteria.
The role of cardiovascular magnetic resonance in the evaluation of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy
Authors: Mohammad S. Hamid, Asifa Quraishi, Juan R. Gimeno, Rajesh Thaman, Anna Johns, Sami Firoozi, Perry M. Elliott, William J. McKenna, Dudley Pennell
Journal: Journal of the American College of Cardiology (2003)
PRIMARY SARCOMA OF THE GALLBLADDER
Authors: Alexander Brunschwig
Journal: JAMA (1931)

Primary sarcoma of the gallbladder is rare. Kaufmann1states that there are only thirteen cases on record. Landsteiner,2in 1904, was the first to summarize the literature on the subject and to that date was able to collect only six alleged cases. Three of these, he stated, could not be definitely considered primary sarcomas of the gallbladder and in the other three the diagnosis was not finally accepted by him because the original descriptions were not available. Landsteiner's own case was a myosarcoma. At a later date he described another gallbladder exhibiting a spindle cell sarcoma and a squamous cell carcinoma.3Bayer4reported a case of myxochondro-osteosarcoma with adenomatous hyperplasia of Luschka's ducts. Parlavecchio,5Hotes,6Bayer,4Griffon and Segal,7Iwasaki,8and Jaffe9have each recorded a case of spindle cell sarcoma of the gallbladder; in some of these, giant cells
Endoscopic mucosal resection of a gastric bronchogenic cyst that was mimicking a solid tumor
Authors: S.-H. Lee, D. Park, J. Park, H.-S. Kim, S.-H. Park, S.-J. Kim, M.-H. Oh
Journal: Endoscopy (2006)

Gastric bronchogenic cysts are extremely rare congenital cystic lesions that originate from the ventral foregut during the 3rd to 7th weeks of embryonic development [1]. These lesions can be identified by computed tomography (CT) and magnetic resonance imaging but they are quite often misclassifed as solid tumors [2]. Although endoscopic ultrasound (EUS) is the most valuable diagnostic modality for distinguishing between cystic and noncystic lesions, the similarity of an intramurally located bronchogenic cyst to a smooth muscle tumor or gastrointestinal stromal tumor on EUS makes the diagnosis difficult [2]. We describe here a patient with an intramural bronchogenic cyst that mimicked a solid tumor and which was diagnosed and treated by endoscopic mucosal resection (EMR).
ANGIONEUROTIC EDEMA OF PENIS AND SCROTUM
Authors: William J. Ezickson
Journal: JAMA (1926)

A man, aged 34, white, married, with one child, suddenly developed itching of the penis and scrotum, June 20, 1926, followed by a burning sensation of the skin in that area. In about six hours he noticed a swelling of the scrotal sac and edema of the penis, which rapidly increased. In twelve hours there was a very marked edema of the entire penis and scrotum. There was no pain present, the only symptoms being an itching and heavy feeling of the scrotum. Examination revealed a very distorted, edematous penis, and a greatly thickened, edematous scrotum. There was no history of extramarital exposure, and the last intercourse had taken place about four weeks previously. There was no history of exposure to any poisonous plants, weeds or chemicals. No sore was present on penis or scrotum. There was no urethral discharge. The prostate and seminal vesicles were normal, as were the testes and epididymides. There was no enlargement of the inguinal glands.
A NEW RISK PREDICTION TOOL TO ASSESS LONG-TERM PROGNOSIS IN PATIENTS WITH STABLE ISCHEMIC HEART DISEASE (SIHD): THE “COURAGE RISK SCORE”
Authors: William E. Boden, Pamela M. Hartigan, Koon K. Teo, David J. Maron, Steven P. Sedlis, Eric R. Bates, Bernard R. Chaitman, John A. Spertus, William J. Kostuk, Marcin R. Dada, Gilbert Gosselin, Daniel S. Berman, Leslee Shaw, Merril Knudtson, Alvin S. Blaustein, David C. Booth, G.B. John Mancini, Robert A. O'Rourke, William S. Weintraub
Journal: Journal of the American College of Cardiology (2011)
Lessons from international experience in controlling pharmaceutical expenditure III: regulating industry
Authors: K. Bloor, A. Maynard, N. Freemantle
Journal: BMJ (1996)

This is the third of three papers that review international policies to control spending on drugs and to improve the efficiency of drug use. This paper reviews policies regulating the supply of drugs, particularly licensing and reimbursement controls, price and profit regulation. Price and profit controls contain few incentives for improving cost effective use of drugs, and focus on cost containment and profitability of domestic industry. Carefully monitored economic evaluation could lead to improvements in efficiency and benefits to patients and the health care system.
Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo.
Authors: B Sharma, M Handler, I Eichstetter, J M Whitelock, M A Nugent, R V Iozzo
Journal: Journal of Clinical Investigation (1998)

Perlecan, a ubiquitous heparan sulfate proteoglycan, possesses angiogenic and growth-promoting attributes primarily by acting as a coreceptor for basic fibroblast growth factor (FGF-2). In this report we blocked perlecan expression by using either constitutive CMV-driven or doxycycline- inducible antisense constructs. Growth of colon carcinoma cells was markedly attenuated upon obliteration of perlecan gene expression and these effects correlated with reduced responsiveness to and affinity for mitogenic keratinocyte growth factor (FGF-7). Exogenous perlecan effectively reconstituted the activity of FGF-7 in the perlecan-deficient cells. Moreover, soluble FGF-7 specifically bound immobilized perlecan in a heparan sulfate-independent manner. In both tumor xenografts induced by human colon carcinoma cells and tumor allografts induced by highly invasive mouse melanoma cells, perlecan suppression caused substantial inhibition of tumor growth and neovascularization. Thus, perlecan is a potent inducer of tumor growth and angiogenesis in vivo and therapeutic interventions targeting this key modulator of tumor progression may improve cancer treatment.
Hypertension and Lead Exposure-Reply
Authors: Howard Hu
Journal: JAMA (1996)

<h3>In Reply.</h3> —In response to Mr Glaser's comments, we repeated our multivariate analysis, controlling for 5 levels of education (reflecting socioeconomic status) and 3 levels of occupational status (lifetime blue collar, lifetime white collar, mixed blue collar and white collar). The effect estimate for tibia bone lead remained unchanged from that reported in Table 4 in our article, suggesting that these factors cannot explain the link between bone lead and hypertension. To address the first point of Dr Staessen and colleagues, lower blood pressure cutoff values (&gt;140 mm Hg systolic and/or 90 mm Hg diastolic) were used to define hypertension. Tibia bone lead continued to contribute to the prediction of hypertension, and the magnitude of the effect was even higher as shown in Table 4. Our analysis of bone lead in relation to blood pressure as a continuous variable is still in progress. In the second point, Staessen et al raise the
Response to Letter: Melloni et al., “Transient Induced Gamma-Band Response in EEG as a Manifestation of Miniature Saccades.” Neuron 58, 429–441
Authors: Shlomit Yuval-Greenberg, Alon S. Keren, Orr Tomer, Israel Nelken, Leon Y. Deouell
Journal: Neuron (2009)
Leucocyte integrin and CR1 expression on peripheral blood leucocytes of patients with rheumatoid arthritis.
Authors: D McCarthy, M.J Taylor, J Bernhagen, J.D Perry, A.S Hamblin
Journal: Annals of the Rheumatic Diseases (1992)

Expression of the leucocyte integrins (CD11a, b, c/CD18) and of CD35 (CR1) on leucocytes from the peripheral blood of patients with rheumatoid arthritis (RA) (n = 14) and control subjects (n = 12) was measured by flow cytometry using a rapid fixation and leucocyte preparation procedure. The mean (SE) percentages of lymphocytes expressing CD11a (RA 93.4 (1.7)%; controls 97.2 (1.8)%) and CD18 (RA 91.3 (2.3)%; controls 97.0 (2.6)%) were lower and the percentage of monocytes expressing CD11b (RA 86.9 (11.4)%; controls 78.4 (11.9)%) and CR1 (RA 62.6 (15.5)%; controls 36.6 (17.6)%) were higher in patients with RA than in controls. In addition, the mean fluorescence intensity of CD18 (RA 22.1 (2.3); controls 30.7 (2.5)) on lymphocytes was decreased and that of CD11b (RA 4.5 (0.8); controls 2.9 (0.9)) and CR1 (RA 2.4 (0.4); controls 1.5 (0.5)) on monocytes was increased in patients with RA compared with controls. The functional importance (if any) of the altered expression of the antigens on lymphocytes is not yet known. Altered expression on monocytes is consistent with activation within the circulation.
Primary Care Team of the Year: Primary care that makes a difference
Authors: H. Macdonald, D. MacAuley
Journal: BMJ (2011)

Outstanding teams develop innovative ideas beyond their normal remit. When the judges were discussing the shortlist for the primary care team of the year, the emphasis was on seeking out those who had gone beyond what would normally be expected in general practice. Each of the three shortlisted practices—from Bristol, Cambridgeshire, and Nottingham—identified a particular clinical need in their patient population and went out of their way to make a difference by, respectively, improving access to primary care for young people in temporary hostel accommodation, managing alcoholism in rural areas, and providing additional mental health services for university students.

Young people in temporary accommodation are often not registered with a general practice. With high levels of risk from drug and alcohol misuse, as well as sexual behaviour, they often present late to emergency services. The …