tbuckley/cabot-search huggingface dataset:
Low Level of Brain Dopamine D<sub>2</sub> Receptors in Methamphetamine Abusers: Association With Metabolism in the Orbitofrontal Cortex
Authors: Nora D. Volkow, Linda Chang, Gene-Jack Wang, Joanna S. Fowler, Yu-Sin Ding, Mark Sedler, Jean Logan, Dinko Franceschi, John Gatley, Robert Hitzemann, Andrew Gifford, Christopher Wong, Naomi Pappas
Journal: American Journal of Psychiatry (2001)

The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers.Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function.Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects.Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.
Ethnicity, GORD, Barrett’s oesophagus and Helicobacter pylori infection
Authors: S Rajendra, I K Robertson
Journal: Gut (2008)

The community study of Helicobacter pylori infection and the risk of Barrett’s oesophagus of Corley et al ( Gut 2008; 57 :727–33) produced similar and contrasting results to our hospital-based endoscopic study on the same theme involving a multiethnic Asian patient population.1 Unfortunately, our study1 was not cited by the authors. We prospectively examined 188 consecutive patients with gastro-oesophageal reflux disease (GORD), short- and long-segment Barrett’s oesophagus (SSBO and LSBO) and controls. Malay, Chinese and Indian patients underwent gastroscopy with gastric biopsies to assess H pylori , …
Endothelial cells as regulators of cytokine storms during influenza infection
Authors: M Gautam
Journal: Thorax (2011)

The morbidity and mortality of severe influenza infections has been attributed to excessive inflammatory cytokine production and early innate immune cell recruitment. This study highlights the pulmonary endothelium as a central regulator of the cytokine storm, in particular demonstrating the role of the sphingosine-1-phosphate (S1P1) signalling system.

S1P1 receptor specific agonists were shown to significantly reduce …
Gallium nitrate inhibits accelerated bone turnover in patients with bone metastases.
Authors: R P Warrell, N W Alcock, R S Bockman
Journal: Journal of Clinical Oncology (1987)

Bone metastases are a major source of morbidity in patients with cancer. Previously, we found that gallium nitrate was a highly effective treatment for cancer-related hypercalcemia. Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We evaluated the clinical effects of gallium nitrate on biochemical parameters of increased bone turnover in 22 patients with bone metastases. Treatment with gallium nitrate for five to seven days caused a median reduction in 24-hour urinary calcium excretion of 66% relative to baseline measurements (P less than .01). Hydroxyproline (OHP) excretion was also significantly reduced (P less than .01). The greatest reduction in hydroxyprolinuria occurred in patients with high baseline excretion. Ionized serum calcium and serum phosphorous declined significantly after treatment (P less than .01 for each). Serum immunoreactive parathyroid hormone (PTH) increased significantly (P less than .01), as did serum levels of 1,25 (OH)2-vitamin D3 (P less than .05). Urinary phosphorous excretion and serum levels of 25-OH-vitamin D3 were not significantly changed. No major toxic reactions occurred as a result of this treatment. These results indicate that gallium nitrate significantly reduces biochemical parameters associated with accelerated bone turnover and that this agent may be useful for preventing pathologic conditions associated with bone metastases.
Contemporary genetic technologies and female reproduction
Authors: B. C. J. M. Fauser, K. Diedrich, P. Bouchard, F. Dominguez, M. Matzuk, S. Franks, S. Hamamah, C. Simon, P. Devroey, D. Ezcurra, C. M. Howles
Journal: Human Reproduction Update (2011)

BACKGROUNDThe Fifth Evian Annual Reproduction (EVAR) Workshop Meeting discussed knowledge regarding contemporary genetics in female reproduction.
Ser1369Ala Variant in Sulfonylurea Receptor Gene <i>ABCC8</i> Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients
Authors: Yan Feng, Guangyun Mao, Xiaowei Ren, Houxun Xing, Genfu Tang, Qiang Li, Xueqi Li, Lirong Sun, Jinqui Yang, Weiqing Ma, Xiaobin Wang, Xiping Xu
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates. RESULTS—After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P &amp;lt; 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide. CONCLUSIONS—In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.
Stevens-Johnson syndrome and toxic epidermal necrolysis: follow-up of pulmonary function after remission
Authors: T.A. Duong, N. de Prost, S. Ingen-Housz-Oro, A.-S. Carrié, F. Zerah, L. Valeyrie-Allanore, M. Bagot, O. Chosidow, J.-C. Roujeau, P. Wolkenstein, B. Maitre
Journal: British Journal of Dermatology (2014)

Background Acute-stage specific bronchial epithelial detachment has been described in 27% of patients with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Objectives To assess the pulmonary function of patients with SJS/TEN after remission. Methods Analysis of pulmonary function tests (PFTs) performed during the usual follow-up of patients with SJS/TEN managed in a referral centre from April 2007 to January 2010. Results Of 58 patients admitted, 32 underwent PFTs (17 male, 15 female). The median time from the acute stage to PFTs was 3 months (interquartile range 1–18). Three patients had grade 2 dyspnoea. Eighteen patients (56%) had abnormal PFTs, including 13 patients (41%) with moderately altered diffusion capacity for carbon monoxide (DLCO) normalized by the alveolar volume (VA) (giving the ratio KCO, which equals DLCO/VA) and five patients with decreased total lung capacity. No airway obstruction was observed. Patients with decreased KCO had higher initial detached body surface area than others (30% vs. 10%, P = 0·006), as did those with decreased DLCO (25% vs. 10%; P = 0·054). There were correlations between detached body surface area and both KCO (r = −0·41, P = 0·026) and DLCO (r = −0·47, P = 0·011). Among 10 patients with decreased KCO on the first PFT, eight patients had a sustained decrease in KCO on a second PFT. Conclusions More than half of patients with SJS/TEN displayed abnormalities on PFTs, mainly diffusion impairment, which was associated with higher initial skin surface detachment. These abnormalities were mostly asymptomatic and remained stable over time.
Analysis of survival by tumor response.
Authors: J R Anderson, R B Davis
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.1.115 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3510277 Analysis of survival by tumor response. J R AndersonxJ R AndersonSearch for articles by this author , R B DavisxR B DavisSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.1.115 First Page PDF © 1986 by American Society of Clinical Oncology
Use of Bisphosphonates and Risk of Postmenopausal Breast Cancer
Authors: Gad Rennert, Mila Pinchev, Hedy S. Rennert
Journal: Journal of Clinical Oncology (2010)

Bisphosphonates are commonly used for the treatment of osteoporosis and for prevention and treatment of skeletal lesions due to malignancy. However, the association between the use of bisphosphonates and the risk of developing breast cancer has not been reported.The Breast Cancer in Northern Israel Study is a population-based case-control study in northern Israel of patients with breast cancer and age-, clinic-, and ethnic-group matched controls. Use of bisphosphonates was assessed in 4,039 postmenopausal patients and controls, members of Clalit Health Services, using pharmacy records.The use of bisphosphonates for longer than 1 year before diagnosis, but not for shorter than 1 year, was associated with a significantly reduced relative risk of breast cancer (odds ratio [OR], 0.61; 95% CI, 0.50 to 0.76). This association remained significant after adjustment for age, fruit, and vegetable consumption, sports activity, family history of breast cancer, ethnic group, body mass index, use of calcium supplements, hormone replacement therapy use, number of pregnancies, months of breast feeding, and age at first pregnancy (OR, 0.72; 95% CI, 0.57 to 0.90). Breast cancer risk did not change further if bisphosphonates were used for more years. Breast tumors identified in bisphosphonates users were more often estrogen receptor positive and less often poorly differentiated.The use of bisphosphonates for longer than 1 year was associated with a 28% relative reduction in the risk of postmenopausal breast cancer. Tumors developing under bisphosphonates treatment tended to have a favorable prognostic factors profile.
Preimplantation Diagnosis for Early-Onset Alzheimer Disease Caused by V717L Mutation
Authors: Yury Verlinsky
Journal: JAMA (2002)

ContextIndications for preimplantation genetic diagnosis (PGD) have recently been expanded to include disorders with genetic predisposition to allow only embryos free of predisposing genes to be preselected for transfer back to patients, with no potential for pregnancy termination.ObjectiveTo perform PGD for early-onset Alzheimer disease (AD), determined by nearly completely penetrant autosomal dominant mutation in the amyloid precursor protein (APP) gene.DesignAnalysis undertaken in 1999-2000 of DNA for the V717L mutation (valine to leucine substitution at codon 717) in the APP gene in the first and second polar bodies, obtained by sequential sampling of oocytes following in vitro fertilization, to preselect and transfer back to the patient only the embryos that resulted from mutation-free oocytes.SettingAn in vitro fertilization center in Chicago, Ill.PatientsA 30-year-old AD-asymptomatic woman with a V717L mutation that was identified by predictive testing of a family with a history of early-onset AD.Main Outcome MeasuresResults of mutation analysis; pregnancy outcome.ResultsFour of 15 embryos tested for maternal mutation in 2 PGD cycles, originating from V717L mutation–free oocytes, were preselected for embryo transfer, yielding a clinical pregnancy and birth of a healthy child free of predisposing gene mutation according to chorionic villus sampling and testing of the neonate's blood.ConclusionThis is the first known PGD procedure for inherited early-onset AD resulting in a clinical pregnancy and birth of a child free of inherited predisposition to early-onset AD.
Generation and phenotyping of <i>mCd59a</i> and <i>mCd59b</i> double‐knockout mice
Authors: Xuebin Qin, Weiguo Hu, Wenping Song, Luciano Grubissich, Xuemei Hu, Gongxiong Wu, Sean Ferris, Martin Dobarro, Jose A. Halperin
Journal: American Journal of Hematology (2008)

CD59 is a membrane protein inhibitor of the membrane attack complex (MAC) of complement. Humans express only one, whereas mice express two CD59 genes. We previously reported the targeted deletion of the mCd59b gene in which absence of mCd59b together with an unintended down regulation of mCd59a caused hemolytic anemia with spontaneous platelet activation. To confirm the complement role in the hemolytic anemia caused by abrogation of mCd59 function, we have developed a mCd59a and mCd59b double knock out mice and analyzed its phenotype in complement sufficient and deficient (C3(-/-)). We report here that total abrogation of mCd59 function in mCd59ab(-/-) mice results in complement-mediated hemolytic anemia that is rescued by the deficiency of C3 in compound mCd59ab(-/-)/C3(-/-) mice.
Endoscopic sphincterotomy for common bile duct calculi in patients with gall bladder in situ considered unfit for surgery.
Authors: B R Davidson, J P Neoptolemos, D L Carr-Locke
Journal: Gut (1988)

Endoscopic sphincterotomy (ES) was attempted in 106 patients with common bile duct (CBD) calculi and gall bladders present, who were considered unfit for surgery on the grounds of age and frailty alone (35%) and/or the presence of major medical problems (65%). Endoscopic sphincterotomy was successful in 105 patients (99%). Early ES related complications occurred in 21 patients (19.8%). Twelve hospital deaths occurred (11.3%), although this was due to biliary causes in only five (4.7%) and one of these was moribund on admission. Complications were more frequent in those in whom initial ES did not clear the common bile duct (30.4%) compared with those in whom this was (11.7%; p = 0.0164). The mortality was also greater in patients in whom there was no ERCP proof of CBD clearance (p = 0.01) unless operated upon. Twelve patients developed gall bladder complications (11.3%) including five with empyema (4.7%). Analysis of clinical, haematological, and biochemical factors together with ERCP findings showed that the only factor which had any value in predicting gall bladder complications was pre-existing cholangitis. The present series was compared with another using ES as a definitive procedure, and with a surgical series. Although there were significant differences in outcome, differences with respect to medical risk factors and the incidence of complications of CBD stones (jaundice, cholangitis, and acute pancreatitis) were striking. Further analysis of these factors may allow a clearer definition of patients most likely to benefit from either ES or surgery.
Calreticulin, a Molecular Chaperone in the Endoplasmic Reticulum, Modulates Radiosensitivity of Human Glioblastoma U251MG Cells
Authors: Tomohiro Okunaga, Yoshishige Urata, Shinji Goto, Takayuki Matsuo, Shingo Mizota, Keisuke Tsutsumi, Izumi Nagata, Takahito Kondo, Yoshito Ihara
Journal: Cancer Research (2006)

Abstract Radiotherapy is the primary and most important adjuvant therapy for malignant gliomas. Although the mechanism of radiation resistance in gliomas has been studied for decades, it is still not clear how the resistance is related with functions of molecular chaperones in the endoplasmic reticulum. Calreticulin (CRT) is a Ca2+-binding molecular chaperone in the endoplasmic reticulum. Recently, it was reported that changes in intracellular Ca2+ homeostasis play a role in the modulation of apoptosis. In the present study, we found that the level of CRT was higher in neuroglioma H4 cells than in glioblastoma cells (U251MG and T98G), and was well correlated with the sensitivity to γ-irradiation. To examine the role of CRT in the radiosensitivity of malignant gliomas, the CRT gene was introduced into U251MG cells, which express low levels of CRT, and the effect of overexpression of CRT on the radiosensitivity was examined. The cells transfected with the CRT gene exhibited enhanced radiation-induced apoptosis compared with untransfected control cells. In CRT-overexpressing cells, cell survival signaling via Akt was markedly suppressed. Furthermore, the gene expression of protein phosphatase 2Acα (PP2Acα), which is responsible for the dephosphorylation and inactivation of Akt, was up-regulated in CRT-overexpressing cells, and the regulation was dependent on Ca2+. Thus, overexpression of CRT modulates radiation-induced apoptosis by suppressing Akt signaling through the up-regulation of PP2Acα expression via altered Ca2+ homeostasis. These results show the novel mechanism by which CRT is involved in the regulation of radiosensitivity and radiation-induced apoptosis in malignant glioma cells. (Cancer Res 2006; 66(17): 8662-71)
SMAD6 Contributes to Patient Survival in Non–Small Cell Lung Cancer and Its Knockdown Reestablishes TGF-β Homeostasis in Lung Cancer Cells
Authors: Hyo-Sung Jeon, Tatiana Dracheva, Sei-Hoon Yang, Daoud Meerzaman, Junya Fukuoka, Abbas Shakoori, Konstantin Shilo, William D. Travis, Jin Jen
Journal: Cancer Research (2008)

Abstract The malignant transformation in several types of cancer, including lung cancer, results in a loss of growth inhibition by transforming growth factor-β (TGF-β). Here, we show that SMAD6 expression is associated with a reduced survival in lung cancer patients. Short hairpin RNA (shRNA)–mediated knockdown of SMAD6 in lung cancer cell lines resulted in reduced cell viability and increased apoptosis as well as inhibition of cell cycle progression. However, these results were not seen in Beas2B, a normal bronchial epithelial cell line. To better understand the mechanism underlying the association of SMAD6 with poor patient survival, we used a lentivirus construct carrying shRNA for SMAD6 to knock down expression of the targeted gene. Through gene expression analysis, we observed that knockdown of SMAD6 led to the activation of TGF-β signaling through up-regulation of plasminogen activator inhibitor-1 and phosphorylation of SMAD2/3. Furthermore, SMAD6 knockdown activated the c-Jun NH2-terminal kinase pathway and reduced phosphorylation of Rb-1, resulting in increased G0-G1 cell arrest and apoptosis in the lung cancer cell line H1299. These results jointly suggest that SMAD6 plays a critical role in supporting lung cancer cell growth and survival. Targeted inactivation of SMAD6 may provide a novel therapeutic strategy for lung cancers expressing this gene. [Cancer Res 2008;68(23):9686–92]
Efficacy of Continuation ECT and Antidepressant Drugs Compared to Long-Term Antidepressants Alone in Depressed Patients
Authors: Gerard G. Gagné, Martin J. Furman, Linda L. Carpenter, Lawrence H. Price
Journal: American Journal of Psychiatry (2000)

The purpose of this study was to evaluate the efficacy of continuation ECT in depression.The authors used retrospective chart review to identify 29 patients who received continuation ECT plus long-term antidepressant treatment after a positive response to acute treatment with ECT for a depressive episode (continuation ECT group). A retrospective case-controlled approach was used to ascertain a matching group of 29 patients who received long-term antidepressant treatment alone after responding positively to acute ECT (antidepressant-alone group). All 58 patients (46 with unipolar depression, 12 with bipolar disorder) had been chronically depressed before receiving acute ECT. Data from medical records were analyzed by using survival analysis and proportional hazards regression to determine outcome and risk factors.The mean duration of the follow-up period for all patients was 3.9 years (5.4 years for the continuation ECT patients and 2.4 years for the antidepressant-alone patients). Outcome was significantly better in the continuation ECT group. The cumulative probability of surviving without relapse or recurrence at 2 years was 93% for continuation ECT patients and 52% for antidepressant-alone patients. At 5 years, survival declined to 73% for continuation ECT patients, but fell to 18% for antidepressant-alone patients. Mean survival times were 6.9 years for the continuation ECT patients and 2.7 years for the antidepressant-alone patients.The findings provide strong support for the efficacy of continuation ECT plus long-term antidepressant treatment in preventing relapse and recurrence in chronically depressed patients who have responded to acute treatment with ECT.
An assessment of adalimumab efficacy in three Phase III clinical trials using the European Consensus Programme criteria for psoriasis treatment goals
Authors: U. Mrowietz, K. Kragballe, K. Reich, C.E.M. Griffiths, Y. Gu, Y. Wang, S.J. Rozzo
Journal: British Journal of Dermatology (2012)

The European Consensus Programme (ECP) established pan-European consensus definitions of psoriasis disease severity and treatment goals among 19 psoriasis experts from European nations.To use the ECP treatment goals to retrospectively assess adalimumab efficacy in patients who participated in Phase III clinical trials and met ECP criteria for moderate to severe psoriasis.Three trials were analysed: CHAMPION (n = 108), REVEAL (n = 814) and BELIEVE (n = 364). Moderate to severe psoriasis was defined as Dermatology Life Quality Index (DLQI) score > 10, with either > 10% body surface area involvement or Psoriasis Area and Severity Index (PASI) score > 10. Treatment goals were achieved with either treatment success (≥ 75% PASI score reduction) or intermediate response (PASI response ≥ 50% and < 75%) with DLQI ≤ 5.The percentages of patients who achieved treatment goals at week 16 in CHAMPION, REVEAL and BELIEVE were, respectively, (i) treatment success, 79·3%, 72·1% and 68·2%; (ii) intermediate response, 1·7%, 5·0% and 5·0%; or (iii) either goal, 81·0%, 77·1% and 73·2%. DLQI ≤ 5 at week 16 was achieved by 70·7%, 70·1% and 67·4% of patients, respectively. Differences between the percentages of adalimumab- vs. placebo-treated patients achieving treatment success were statistically significant (P < 0·001) from week 4 and week 8 of REVEAL and CHAMPION, respectively.Treatment success was achieved by > 93% of patients who attained treatment goals. At week 16 > 70% of patients achieved ECP treatment goals and met ECP criteria for continued treatment without modification. These results support the utility of ECP treatment goals for the assessment of therapeutic efficacy in moderate to severe psoriasis.