tbuckley/cabot-search huggingface dataset:
Interleukin-7 Mediates Selective Expansion of Tumor-redirected Cytotoxic T Lymphocytes (CTLs) without Enhancement of Regulatory T-cell Inhibition
Authors: Serena K. Perna, Daria Pagliara, Aruna Mahendravada, Hao Liu, Malcolm K. Brenner, Barbara Savoldo, Gianpietro Dotti
Journal: Clinical Cancer Research (2013)

The antitumor activity of chimeric antigen receptor (CAR)-redirected CTLs should be enhanced if it were possible to increase their proliferation and function after adoptive transfer without concomitantly increasing the proliferation and function of regulatory T cells (Treg). Here, we explored whether the lack of IL-7Rα in Treg can be exploited by the targeted manipulation of the interleukin-7 (IL-7) cytokine-cytokine receptor axis in CAR-engrafted Epstein-Barr Virus-specific CTLs (EBV-CTLs) to selectively augment their growth and antitumor activity even in the presence of Treg.We generated a bicistronic retroviral vector encoding a GD2-specific CAR and the IL-7Rα subunit, expressed the genes in EBV-CTLs, and assessed their capacity to control tumor growth in the presence of Treg in vitro and in vivo when exposed to either interleukin-2 (IL-2) or IL-7 in a neuroblastoma xenograft.We found that IL-7, in sharp contrast with IL-2, supports the proliferation and antitumor activity of IL-7Rα.CAR-GD2(+) EBV-CTLs both in vitro and in vivo even in the presence of fully functional Treg.IL-7 selectively favors the survival, proliferation, and effector function of IL-7Rα-transgenic/CAR-redirected EBV-CTLs in the presence of Treg both in vitro and in vivo. Thus, IL-7 can have a significant impact in sustaining expansion and persistence of adoptively CAR-redirected CTLs.
Confidentiality versus public duty
Authors: A. Savage
Journal: Journal of the Royal Society of Medicine (2006)

In 1963 I joined a long established practice in London. About half our patients came from the top of the hill, the rest from Inner London; a good mix. In those days we did our own emergencies and had a flourishing domiciliary midwifery practice, so we were welcomed into peoples' homes at all times of the day and night. In addition, I was Medical Officer to an Infant Welfare Clinic and to an Assessment Home; appointments that caused me to realize that my conventional middle class way of life was not necessarily the norm. Now, looking back on my experiences from the tranquillity of retirement I am bothered by doubts. Ought I, ought anyone with the same sort of experience, to have spoken out more openly. If we had would some of the violence we increasingly see in our homes and on our streets have been prevented. Where does confidentiality end and public duty begin? This is, I suggest, a subject for debate.
Use of mobile phones and risk of brain tumours: update of Danish cohort study
Authors: P. Frei, A. H. Poulsen, C. Johansen, J. H. Olsen, M. Steding-Jessen, J. Schuz
Journal: BMJ (2011)

To investigate the risk of tumours in the central nervous system among Danish mobile phone subscribers.Nationwide cohort study.Denmark.All Danes aged ≥ 30 and born in Denmark after 1925, subdivided into subscribers and non-subscribers of mobile phones before 1995.Risk of tumours of the central nervous system, identified from the complete Danish Cancer Register. Sex specific incidence rate ratios estimated with log linear Poisson regression models adjusted for age, calendar period, education, and disposable income.358,403 subscription holders accrued 3.8 million person years. In the follow-up period 1990-2007, there were 10,729 cases of tumours of the central nervous system. The risk of such tumours was close to unity for both men and women. When restricted to individuals with the longest mobile phone use--that is, ≥ 13 years of subscription--the incidence rate ratio was 1.03 (95% confidence interval 0.83 to 1.27) in men and 0.91 (0.41 to 2.04) in women. Among those with subscriptions of ≥ 10 years, ratios were 1.04 (0.85 to 1.26) in men and 1.04 (0.56 to 1.95) in women for glioma and 0.90 (0.57 to 1.42) in men and 0.93 (0.46 to 1.87) in women for meningioma. There was no indication of dose-response relation either by years since first subscription for a mobile phone or by anatomical location of the tumour--that is, in regions of the brain closest to where the handset is usually held to the head.In this update of a large nationwide cohort study of mobile phone use, there were no increased risks of tumours of the central nervous system, providing little evidence for a causal association.
Mortality in cases of asbestosis diagnosed by a pneumoconiosis medical panel.
Authors: I I Coutts, J C Gilson, I H Kerr, W R Parkes, M Turner-Warwick
Journal: Thorax (1987)

One hundred and fifty five male cases of asbestosis certified by the London Pneumoconiosis Medical Panel during 1968-74 were followed up during 1978-9, 4-11 (mean 7.5) years after certification. Fifty nine patients had died, 23 (39%) from lung cancer, 6 (10%) from mesothelioma, and 11 (19%) from other respiratory causes. The number of observed deaths was 2.25 times greater than expected and 7.4 times greater than expected for lung cancer. Adenocarcinoma was the commonest histological type but other cell types were also increased. Finger clubbing (p less than 0.01) and percentage of predicted FEV1 (p less than 0.01) were of value in predicting death, but increasing profusion of small opacities greater than 1/0 (ILO/U-C international classification of radiographs of pneumoconiosis, 1971), duration of exposure to asbestos, time from first exposure to asbestos, and percentage of predicted vital capacity and transfer factor did not predict death.
535 FXR-MEDIATED REGULATION OF THE HUMAN HEPATIC BILE ACID UDP-GLUCURONOSYLTRANSFERASE (UGT) 1A3 GENE IN CHOLESTASIS
Authors: T.J. Erichsen, A. Aehlen, U. Ehmer, T.O. Lankisch, M.P. Manns, C.P. Strassburg
Journal: Journal of Hepatology (2008)
Gene Amplification and Overexpression of <i>PRDM14</i> in Breast Cancers
Authors: Noriko Nishikawa, Minoru Toyota, Hiromu Suzuki, Toshio Honma, Tomoko Fujikane, Tousei Ohmura, Toshihiko Nishidate, Mutsumi Ohe-Toyota, Reo Maruyama, Tomoko Sonoda, Yasushi Sasaki, Takeshi Urano, Kohzoh Imai, Koichi Hirata, Takashi Tokino
Journal: Cancer Research (2007)

Abstract Several genes that encode PR (PRDI-BF1 and RIZ) domain proteins (PRDM) have been linked to human cancers. To explore the role of the PR domain family genes in breast carcinogenesis, we examined the expression profiles of 16 members of the PRDM gene family in a panel of breast cancer cell lines and primary breast cancer specimens using semiquantitative real-time PCR. We found that PRDM14 mRNA is overexpressed in about two thirds of breast cancers; moreover, immunohistochemical analysis showed that expression of PRDM14 protein is also up-regulated. Analysis of the gene copy number revealed that PRDM14 is a target of gene amplification on chromosome 8q13, which is a region where gene amplification has frequently been detected in various human tumors. Introduction of PRDM14 into cancer cells enhanced cell growth and reduced their sensitivity to chemotherapeutic drugs. Conversely, knockdown of PRDM14 by siRNA induced apoptosis in breast cancer cells and increased their sensitivity to chemotherapeutic drugs, suggesting that up-regulated expression of PRDM14 may play an important role in the proliferation of breast cancer cells. That little or no expression of PRDM14 is seen in noncancerous tissues suggests that PRDM14 could be an ideal therapeutic target for the treatment of breast cancer. [Cancer Res 2007;67(20):9649–57]
Response to Flumazenil in Women With Premenstrual Dysphoric Disorder
Authors: Jean-Michel Le Mellédo, Michelle Van Driel, Nicholas John Coupland, Paula Lott, Gian S. Jhangri
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors sought to determine whether the administration of flumazenil would induce marked panic symptoms in women suffering from premenstrual dysphoric disorder.METHOD: Ten women with premenstrual dysphoric disorder and 11 comparison subjects were injected with flumazenil or placebo in a double-blind, randomized, balanced crossover design in a single session in the luteal phase of their menstrual cycles.RESULTS: Flumazenil induced a much greater panic response in the women with premenstrual dysphoric disorder than in the comparison subjects.CONCLUSIONS: These preliminary results are consistent with a dysregulation of the g-aminobutyric acid A/benzodiazepine receptor complex during the premenstruum of women suffering from premenstrual dysphoric disorder.
Neuropsychiatric lupus erythematosus, cerebral infarctions, and anticardiolipin antibodies.
Authors: R A Fields, W L Sibbitt, H Toubbeh, A D Bankhurst
Journal: Annals of the Rheumatic Diseases (1990)

Anticardiolipin antibody (aCL) has been associated with thromboembolic phenomena, including stroke, in certain patients with systemic lupus erythematosus (SLE); however, the relation between this antibody and the central nervous system manifestations of SLE is unknown. Serum samples and cerebrospinal fluid from five patients with SLE and acute central nervous system manifestations were assayed for the presence of aCL. Anticardiolipin antibody was identified in sera from four of the five patients but in none of the cerebrospinal fluid samples. Nuclear magnetic resonance imaging showed 9infarct-like9 lesions in these four patients. This preliminary study suggests that a correlation between serum aCL and cerebral infarcts in central nervous system lupus may potentially exist. From this limited study it seems unlikely that aCL has a direct pathogenic role in the diffuse encephalopathy of acute central nervous system lupus.
Effects of controlled blood cooling on hemodynamic stability and urea kinetics during high-efficiency hemodialysis.
Authors: A M Kaufman, A T Morris, V A Lavarias, Y Wang, J F Leung, M B Glabman, S A Yusuf, A L Levoci, H D Polaschegg, N W Levin
Journal: Journal of the American Society of Nephrology (1998)

Although the use of cooled dialysate during hemodialysis is associated with stabilization of intradialytic BP, the effects of blood cooling on hemodynamics and urea kinetics in high-efficiency hemodialysis have not been completely studied. In particular, the effects of blood cooling have not been elucidated in very short-time, high K/V dialysis treatments, in which postdialysis urea rebound is maximized. In theory, blood cooling could increase urea compartmentalization during treatment and decrease dialysis efficacy. Measurements of cardiovascular hemodynamics and urea kinetics were performed in 15 patients (56 studies) during dialysis, using a blood temperature monitor with control of dialysate temperature. Dialysate temperature was adjusted to either lower the core temperature or raise the core temperature by, respectively, producing negative heat-energy exchange (cooled dialysis) or keeping heat-energy exchange in the extracorporeal circuit neutral (thermoneutral dialysis) so that energy was not transferred to or from the patient. Each subject was studied on both protocols, thereby allowing each individual to act as his own control. In cooled dialysis, heat-energy exchange in the extracorporeal circuit was -266+/-15 kJ per treatment, and dialysate temperature averaged 35.7+/-0.02 degrees C. In thermoneutral dialysis, heat-energy exchange in the extracorporeal circuit averaged 5+/-31 kJ per treatment, and dialysate temperature averaged 37.1+/-0.02 degrees C. Dialysate cooling resulted in a reduction in mean body temperature compared with thermoneutral therapy (-0.22+/-0.04 versus +0.31+/-0.05 degrees C). Cooling resulted in a greater increase in peripheral vascular resistance index (+515+/-160 versus + 114+/-92 dyn.sec/cm5 per m2), an increase in mean arterial pressure (+4+/-3 versus -4+/-4 mmHg), a reduction in the maximum intradialytic fall in mean arterial pressure (-10+/-2 versus -18+/-3, mmHg), and a reduction in staff interventions for hypotension or dialytic symptoms (6 of 28 versus 12 of 28 studies). These differences occurred without differences in the change in blood volume (-14.3+/-1.8% versus -13.9+/-2.2%) or cardiac index (-0.4+/-0.1 versus -0.4+/-0.2, L/min per m2). Urea rebound (37+/-4% versus 38+/-3%) and effective Kt/V (1.29+/-0.05 versus 1.32+/-0.06) were not different between groups. Thus, body temperature cooling can be used to stabilize BP and reduce intradialytic events requiring staff intervention without compromising the efficacy of treatment in high-efficiency dialysis.
Alpine skiing injuries.
Authors: Y Sahlin
Journal: British Journal of Sports Medicine (1989)

Alpine skiing accidents admitted to the Trondheim Regional and University Hospital during one year were recorded. Of the 339 injured, 67 per cent were male and 33 per cent were female. Eighty-seven per cent were outpatients, and 13 per cent were hospitalized. Falling accidents (67 per cent), followed by collision accidents (17 per cent), were the most common cause of injury. The injuries in the lower extremities were caused by falling and the head injuries were mostly caused by collisions. Knee ligament strains were the most common injuries, and 17 per cent of these were hospitalized and required operative treatment. Of the minor knee strains, all 44 per cent were not fully recovered after two and a half years. Seventeen patients sustained tibial fractures, eleven of them spiral fractures and six transverse fractures. The patients with spiral fractures were younger than the patients with transverse fractures. Head injuries were the most severe injuries, with eleven concussions and two epidural haematomas.
Abstract 1768: Magnetic Resonance Imaging Reveals Novel Phenotypic Expression of Desmosomal Mutation in First-Degree Relatives of Patients with Arrhythmogenic Right Ventricular Dysplasia (ARVD). Prevalence and Clinical Significance in Patients Evaluated For ARVD.
Authors: Harikrishna Tandri, Darshan Dalal, Aditya Jain, Daniel P Judge, Theodore Abraham, Cynthia James, Samanthapudi K Daya, Crystal Tichnell, Stuart Russell, Hugh Calkins, David A Bluemke
Journal: Circulation (2007)

Background: In this report we present the prevalence and significance of a novel MRI abnormality that we identified in desmosomal mutation positive asymptomatic relatives of arrhythmogenic right ventricular dysplasia (ARVD) patients. Methods: MRI of 38 first-degree relatives was analyzed for abnormalities blinded to the mutation status. Focal crinkling of the right ventricle (accordion sign) was observed in 15/25 mutation positive vs. 0/13 mutation negative patients. The presence of this finding was sought in 207 patients evaluated for ARVD blinded to clinical history and was correlated with electrophysiologic findings. Results: Mean age of the population was 32±16, 61% had a family history of ARVD. Based on non-invasive testing the 207 patients were classified into 4 groups 1) 106 normal, 2) 57 Idiopathic ventricular tachycardia (VT), 3) 33 probable ARVD, 4) 11 definite ARVD. A family history of ARVD was present in 74%, 0%, 67% and 36% respectively. 43 patients had the “accordion sign” and the prevalence in the four groups was 10%, 5%, 70% and 100% respectively. The abnormality was seen in the sub-tricuspid region in 62%, outflow tract in 30% in both regions in 8%. After excluding group 4, 48% of patients with the accordion sign had T wave inversion’s beyond V1 compared with 7% of those without the sign (p&lt;0.001). During electrophysiologic testing, reentrant VT could be induced in 44% (7/16) of patients with accordion sign compared to 2% (1/48) without the sign (p&lt;0.01). Conclusion: Focal crinkling of the RV termed “Accordion sign” may represent an early manifestation of ARVD that correlates with mutation positive status and predicts inducibility of ventricular arrhythmias.
Cytomegalovirus is not specifically associated with immunoglobulin A nephropathy.
Authors: J S Park, J H Song, W S Yang, S B Kim, Y K Kim, C D Hong
Journal: Journal of the American Society of Nephrology (1994)

Cytomegalovirus (CMV) has been suspected to be involved in the pathogenesis of IgA nephropathy (IgAN). Whether CMV is present in renal tissue of IgAN, however, remains controversial. To determine the presence of CMV in IgAN, compared with other glomerulonephritis (GN) as disease control, polymerase chain reaction amplifying a 159-base-pair fragment of the immediate early gene of CMV and indirect immunofluorescence staining with anti-CMV monoclonal antibody were performed on 10 IgAN and 14 non-IgAN GN renal tissues. CMV DNA was detected in 6 of 10 IgAN tissues and 10 of 14 other GN by polymerase chain reaction, whereas no CMV antigen was detected in all renal tissues by immunofluorescence. This frequent observation of CMV DNA in various types of GN as well as in IgAN would suggest that CMV is not specifically associated with the pathogenesis of IgAN seen in endemic areas of CMV infection.
Association between C-reactive protein and unrecognised sleep-disordered breathing in the elderly
Authors: F. Roche, J-M. Gaspoz, V. Pichot, M. Picard-Kossovsky, D. Maudoux, A. Garcin, S. Celle, E. Sforza, J. C. Barthélémy
Journal: European Respiratory Journal (2009)

Elevated levels of C-reactive protein (CRP) have been reported in patients with sleep-disordered breathing (SDB) and may represent an inflammatory marker of cardiovascular risk. However, the association of CRP with SBD in presumed healthy elderly subjects is unknown. In total, 851 (58.5% females) 68-yr-old subjects, who were free of any known cardiac or sleep disorders, were prospectively examined. Subjects underwent unattended polygraphy, and the apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) were assessed. Elevated levels of CRP were found on the morning after the sleep study in patients with more severe SDB. A significant correlation was found between CRP levels, time spent at night with arterial oxygen saturation &lt;90% and ODI. No association was found between CRP levels and AHI. After adjustments for body mass index, smoking status, hypertension, diabetes and dyslipidaemia, a significant association remained between CRP levels and ODI &gt;10 events·h −1 . CRP levels were frequently increased in a large sample of elderly subjects free of major cardiovascular disease. CRP levels were not correlated with the AHI and the indices of sleep fragmentation; the ODI &gt;10 events·h −1 was the strongest predictor of raised CRP level. The present results suggest that, in the elderly, intermittent hypoxaemia may underlie inflammatory processes leading to cardiovascular morbidity.
Risk Factors for Proteinuria in a Large, Multiracial, Southeast Asian Population
Authors: Sylvia Paz B. Ramirez, William McClellan, Friedrich K. Port, Stephen I-Hong Hsu
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The factors associated with proteinuria were examined in a large multiracial Asian population participating in a screening program aimed at the early detection of renal disease. Of 213,873 adults who participated, 189,117 with complete data were included. Malay race, increasing age, both extremes of body mass index (BMI), self-reported family history of kidney disease (FKD), and higher systolic and diastolic BP measurements (even at levels classified as being within the normal range) were independently associated with dipstick-positive proteinuria. The odds ratios (OR) for proteinuria increased progressively with age. There was a J-shaped relationship between BMI and proteinuria (OR of 1.3, 1.00, 1.3, 1.6, and 2.5 for BMI of ≤18.00, 23.00 to 24.99, 25.00 to 27.49, 27.50 to 29.99, and ≥30.00 kg/m<sup>2</sup>, respectively, compared with BMI of 18.01 to 22.99 kg/m<sup>2</sup>). OR for proteinuria according to systolic and diastolic BP were significantly increased beginning at levels of 110 and 90 mmHg, respectively. In addition, the Malay race was associated with a significantly higher OR for proteinuria, compared with the Chinese race (OR of 1.3). Finally, FKD was significantly associated with proteinuria (OR of 1.7), whereas a family history of diabetes mellitus and a family history of hypertension were not. When family histories were analyzed by clustering, isolated FKD remained a significant determinant of proteinuria and the magnitude of the effect was not significantly different from that observed in the presence of a coexisting family history of diabetes mellitus or hypertension. This is the first study to evaluate factors associated with proteinuria in an Asian population. The epidemiologic study of renal disease in this population suggests that risk factors for renal disease might differ significantly among racial groups.
Detecting Disabilities in Older Patients With Cancer: Comparison Between Comprehensive Geriatric Assessment and Vulnerable Elders Survey-13
Authors: Andrea Luciani, Gilda Ascione, Cecilia Bertuzzi, Desirè Marussi, Carla Codecà, Giuseppe Di Maria, Sarah Elisabetta Caldiera, Irene Floriani, Sabrina Zonato, Daris Ferrari, Paolo Foa
Journal: Journal of Clinical Oncology (2010)

PURPOSE Comprehensive geriatric assessment (CGA) is a multidimensional method used by geriatricians and oncologists to detect and evaluate multiple age-related problems and to plan and coordinate interventions. Because its main drawback is the time required, efforts have been made to evaluate screening instruments suitable for preliminarily assessing elderly patients. The main aim of this study was to establish the accuracy of the Vulnerable Elders Survey-13 (VES-13) in predicting the presence of abnormalities revealed by CGA. PATIENTS AND METHODS Patients age > or = 70 years with a histologically or cytologically confirmed diagnosis of a solid or hematologic tumor underwent both CGA and a VES-13 assessment, and the reliability and validity of VES-13 were analyzed. Results Fifty-three percent of the 419 elderly patients with cancer (mean age, 76.8 years) were vulnerable on VES-13; the rates of disabilities on CGA and activities of daily living (ADLs)/instrumental activities of daily living (IADLs) scales were 30% and 25%, respectively. The sensitivity and specificity of VES-13 were 87% and 62%, respectively, versus CGA and 90% and 70%, respectively, versus ADL/IADL scales. CONCLUSIONS On the basis of our data, VES-13 is highly predictive of impaired functional status and can thus be considered a useful preliminary means of assessing older patients with cancer before undertaking a full CGA.