tbuckley/cabot-search huggingface dataset:
Is learning involved in plasticity in nociceptive regulation?
Authors: Kjell Hole, Frode Svendsen, Arne Tjølsen
Journal: Behavioral and Brain Sciences (1997)

Plastic changes in spinal cord function like neuronal wind-up and increased receptive field are too short-lived to explain chronic pain without structural changes. It is possible that learning could be a mechanism for longlasting changes in nociceptive regulation. A learning process localized to the spinal cord has been shown to be important for the development of tolerance to the analgetic effect of ethanol, suggesting that nociceptive control systems may be changed by learning. Long term potentiation (LTP) is regarded as a useful model of learning and memory. LTP-like changes have been observed in in vitro preparations from the spinal cord and in spinal cord field potentials. Recently a long term increase in spinal A-β and C-fibre evoked responses after painful stimulation has been observed. [coderre &amp; katz, dickenson, wiesenfeld-hallin et al.]
The Prognostic Significance of Serum β2 Microglobulin Levels in Acute Myeloid Leukemia and Prognostic Scores Predicting Survival: Analysis of 1,180 Patients
Authors: Apostolia-Maria Tsimberidou, Hagop M. Kantarjian, Sijin Wen, Susan O'Brien, Jorge Cortes, William G. Wierda, Charles Koller, Sherry Pierce, Mark Brandt, Emil J. Freireich, Michael J. Keating, Elihu H. Estey
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Serum β2 microglobulin (β2M) is prognostic in other hematologic malignancies; therefore, we evaluated its prognostic significance in acute myeloid leukemia (AML). Experimental Design: Multivariate analyses were used to examine the effect of pretreatment serum β2M levels on clinical outcomes in patients with AML. β2M was associated with poorer survival in older but not younger patients. We thus fit separate Cox survival models in patients above and below age 60 years treated with remission induction therapy containing high-dose cytarabine (n = 1,280). In each age group, 50% of the patients were used to develop the model, which was tested in the other 50%. Resampling methods were also used to validate the independent prognostic significance of covariates. Results: In patients 60 years or older (n = 591), poorer risk cytogenetics; poorer performance status; and higher levels of β2M, uric acid, and lactate dehydrogenase were each found to independently predict shorter survival and formed the basis of a scoring system. A similar approach was used in patients younger than 60 years (n = 589), with poorer risk cytogenetics, poorer performance status, older age, higher hemoglobin level, and higher leukocyte count predicting a shorter survival and forming the basis of the scoring system. Higher β2M levels were an adverse independent factor for response, survival, relapse-free survival, and event-free survival in older but not in younger patients. Conclusions: Serum β2M levels can help predict outcome in patients ≥60 years with untreated AML, and their use is strongly encouraged.
Lung Cancers with Concomitant <i>EGFR</i> Mutations and <i>ALK</i> Rearrangements: Diverse Responses to EGFR-TKI and Crizotinib in Relation to Diverse Receptors Phosphorylation
Authors: Jin-Ji Yang, Xu-Chao Zhang, Jian Su, Chong-Rui Xu, Qing Zhou, Hong-Xia Tian, Zhi Xie, Hua-Jun Chen, Yi-Sheng Huang, Ben-Yuan Jiang, Zhen Wang, Bin-Chao Wang, Xue-Ning Yang, Wen-Zhao Zhong, Qiang Nie, Ri-Qiang Liao, Tony S. Mok, Yi-Long Wu
Journal: Clinical Cancer Research (2014)

We investigated the incidence of concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in Chinese patients with non-small cell lung cancer (NSCLC), and assessed responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors.We screened 977 consecutive patients with NSCLC for the presence of concomitant EGFR mutations and ALK rearrangements by rapid amplification of cDNA ends-coupled PCR sequencing and FISH. Immunohistochemistry (IHC) and Western blotting were used to correlate the activation of EGFR, ALK, and downstream proteins with responses to EGFR-TKIs and crizotinib.The overall frequency of concomitant EGFR mutations and ALK rearrangements was 1.3% (13/977). EGFR/ALK co-alterations were found in 3.9% (13/336) EGFR-mutant and 18.6% (13/70) ALK-rearranged patients. Ten tumors were treated with first-line EGFR-TKIs, with a response rate of 80% (8/10). Two tumors with high phospho-ALK levels and low phospho-EGFR levels achieved stable and progressive disease, respectively. Median progression-free survival was 11.2 months. Coexpression of mutant EGFR and ALK fusion proteins in the same tumor cell populations was detected by IHC. Two cases with high phospho-ALK levels treated with crizotinib achieved partial responses; two cases with low phospho-ALK levels had progressive or stable disease.ALK rearrangements and EGFR mutations could coexist in a small subgroup of NSCLC. Advanced pulmonary adenocarcinomas with such co-alterations could have diverse responses to EGFR-TKIs and crizotinib. Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR-TKI and crizotinib.
Genetic Susceptibility to Cancer
Authors: Linda M. Dong, John D. Potter, Emily White, Cornelia M. Ulrich, Lon R. Cardon, Ulrike Peters
Journal: JAMA (2008)

Continuing advances in genotyping technologies and the inclusion of DNA collection in observational studies have resulted in an increasing number of genetic association studies.To evaluate the overall progress and contribution of candidate gene association studies to current understanding of the genetic susceptibility to cancer.We systematically examined the results of meta-analyses and pooled analyses for genetic polymorphisms and cancer risk published through March 2008.We identified 161 meta-analyses and pooled analyses, encompassing 18 cancer sites and 99 genes. Analyses had to meet the following criteria: include at least 500 cases, have cancer risk as outcome, not be focused on HLA antigen genetic markers, and be published in English.Information on cancer site, gene name, variant, point estimate and 95% confidence interval (CI), allelic frequency, number of studies and cases, tests of study heterogeneity, and publication bias were extracted by 1 investigator and reviewed by other investigators.These 161 analyses evaluated 344 gene-variant cancer associations and included on average 7.3 studies and 3551 cases (range, 508-19 729 cases) per investigated association. The summary odds ratio (OR) for 98 (28%) statistically significant associations (P value <.05) were further evaluated by estimating the false-positive report probability (FPRP) at a given prior probability and statistical power. At a prior probability level of 0.001 and statistical power to detect an OR of 1.5, 13 gene-variant cancer associations remained noteworthy (FPRP <0.2). Assuming a very low prior probability of 0.000001, similar to a probability assumed for a randomly selected single-nucleotide polymorphism in a genome-wide association study, and statistical power to detect an OR of 1.5, 4 associations were considered noteworthy as denoted by an FPRP value <0.2: GSTM1 null and bladder cancer (OR, 1.5; 95% CI, 1.3-1.6; P = 1.9 x 10(-14)), NAT2 slow acetylator and bladder cancer (OR, 1.46; 95% CI, 1.26-1.68; P = 2.5 x 10(-7)), MTHFR C677T and gastric cancer (OR, 1.52; 95% CI, 1.31-1.77; P = 4.9 x 10(-8)), and GSTM1 null and acute leukemia (OR, 1.20; 95% CI, 1.14-1.25; P = 8.6 x 10(-15)). When the OR used to determine statistical power was lowered to 1.2, 2 of the 4 noteworthy associations remained so: GSTM1 null with bladder cancer and acute leukemia.In this review of candidate gene association studies, nearly one-third of gene-variant cancer associations were statistically significant, with variants in genes encoding for metabolizing enzymes among the most consistent and highly significant associations.
Osteoblast-derived PTHrP is a physiological regulator of bone formation
Authors: T. J. Martin
Journal: Journal of Clinical Investigation (2005)

Parathyroid hormone–related protein (PTHrP) acts as a paracrine regulator in several tissues, and its physiological roles also extend to bone. In this issue of the JCI, Miao et al. demonstrate that osteoblast-specific ablation of Pthrp in mice results in osteoporosis and impaired bone formation both in vivo and ex vivo. These mice recapitulate the phenotype of mice with haploinsufficiency of Pthrp. The findings demonstrate that PTHrP plays a central role in the physiological regulation of bone formation, by promoting recruitment and survival of osteoblasts, and probably plays a role in the physiological regulation of bone resorption, by enhancing osteoclast formation. This has implications for both our understanding of the pathogenesis of osteoporosis and its treatment.
Low-Field Magnetic Stimulation in Bipolar Depression Using an MRI-Based Stimulator
Authors: Michael Rohan, Aimee Parow, Andrew L. Stoll, Christina Demopulos, Seth Friedman, Stephen Dager, John Hennen, Bruce M. Cohen, Perry F. Renshaw
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Anecdotal reports have suggested mood improvement in patients with bipolar disorder immediately after they underwent an echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) procedure that can be performed within clinical MR system limits. This study evaluated possible mood improvement associated with this procedure. METHOD: The mood states of subjects in an ongoing EP-MRSI study of bipolar disorder were assessed by using the Brief Affect Scale, a structured mood rating scale, immediately before and after an EP-MRSI session. Sham EP-MRSI was administered to a comparison group of subjects with bipolar disorder, and actual EP-MRSI was administered to a comparison group of healthy subjects. The characteristics of the electric fields generated by the EP-MRSI scan were analyzed. RESULTS: Mood improvement was reported by 23 of 30 bipolar disorder subjects who received the actual EP-MRSI examination, by three of 10 bipolar disorder subjects who received sham EP-MRSI, and by four of 14 healthy comparison subjects who received actual EP-MRSI. Significant differences in mood improvement were found between the bipolar disorder subjects who received actual EP-MRSI and those who received sham EP-MRSI, and, among subjects who received actual EP-MRSI, between the healthy subjects and the bipolar disorder subjects and to a lesser extent between the unmedicated bipolar disorder subjects and the bipolar disorder subjects who were taking medication. The electric fields generated by the EP-MRSI scan were smaller (0.7 V/m) than fields used in repetitive transcranial magnetic stimulation (rTMS) treatment of depression (1–500 V/m) and also extended uniformly throughout the head, unlike the highly nonuniform fields used in rTMS. The EP-MRSI waveform, a 1-kHz train of monophasic trapezoidal gradient pulses, differed from that used in rTMS. CONCLUSIONS: These preliminary data suggest that the EP-MRSI scan induces electric fields that are associated with reported mood improvement in subjects with bipolar disorder. The findings are similar to those for rTMS depression treatments, although the waveform used in EP-MRSI differs from that used in rTMS. Further investigation of the mechanism of EP-MRSI is warranted.
Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)
Authors: Alf Kastbom, Gunnar Strandberg, Annette Lindroos, Thomas Skogh
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To evaluate the diagnostic sensitivity of antibodies to cyclic citrullinated peptide (CCP) in recent onset rheumatoid arthritis (RA) at diagnosis and 3 years later, and to evaluate anti-CCP antibody as a predictor of the disease course during 3 years. <b>Methods:</b> 242 patients with recent onset (⩽1 year) RA were followed up regularly during 3 years after inclusion in the Swedish multicentre study “TIRA” 1996–98. Anti-CCP antibodies were analysed by an enzyme immunoassay (EIA). Rheumatoid factors (RFs) were analysed by latex agglutination and two isotype-specific (IgM and IgA) EIAs. Disease activity was assessed by plasma CRP, ESR, 28 joint disease activity score, and the physician’s global assessment of disease activity. Functional ability was evaluated by the Health Assessment Questionnaire. <b>Results:</b> Overall, the diagnostic sensitivity of anti-CCP antibodies was 64% and the proportion of positive tests increased with the number of fulfilled classification criteria according to the American College of Rheumatology. The anti-CCP antibody results correlated with RF, but were better than RF as predictor of a more aggressive disease course. After 3 years 5/97 patients had changed anti-CCP status: 2 from negative to positive and 3 from positive to negative. The mean level of anti-CCP antibodies declined by 131 U/ml during the 3 year follow up (95% CI 34 to 228 U/ml). <b>Conclusion:</b> The anti-CCP antibody assay has a similar diagnostic sensitivity to that of RF in early RA, but is better as a predictor of the disease course over 3 years. Although the mean serum level declines, anti-CCP antibody positivity remains essentially unaltered 3 years after diagnosis and start of antirheumatic treatment.
Regional Brain Volume Differences Associated With Hyperglycemia and Severe Hypoglycemia in Youth With Type 1 Diabetes
Authors: Dana C. Perantie, Jenny Wu, Jonathan M. Koller, Audrey Lim, Stacie L. Warren, Kevin J. Black, Michelle Sadler, Neil H. White, Tamara Hershey
Journal: Diabetes Care (2007)

OBJECTIVE—Despite interest in the effects of type 1 diabetes on the developing brain, structural brain volumes in youth with this disease have not previously been examined. This study is the first to quantify regional brain volume differences in a large sample of youth with diabetes. RESEARCH DESIGN AND METHODS—Magnetic resonance images (MRIs) were acquired from youth with diabetes (n = 108) and healthy sibling control subjects (n = 51) aged 7–17 years. History of severe hypoglycemia was assessed by parent interview and included seizure, loss of consciousness, or requiring assistance to treat. A1C values since diagnosis were obtained from medical records; median A1C was weighted by duration of disease. Voxel-based morphometry was used to determine the relationships of prior hypo- and hyperglycemia to regional grey and white matter volumes across the whole brain. RESULTS—No significant differences were found between diabetic and healthy control groups in grey or white matter. However, within the diabetic group, a history of severe hypoglycemia was associated with smaller grey matter volume in the left superior temporal region. Greater exposure to hyperglycemia was associated with smaller grey matter volume in the right cuneus and precuneus, smaller white matter volume in a right posterior parietal region, and larger grey matter volume in a right prefrontal region. CONCLUSIONS—Qualitatively different relationships were found between hypo- and hyperglycemia and regional brain volumes in youth with type 1 diabetes. Future studies should investigate whether these differences relate to cognitive function and how these regions are affected by further exposure.
Gene therapy for ?-fetoprotein-producing human hepatoma cells by adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene
Authors: F Kanai, Y Shiratori, Y Yoshida, H Wakimoto, H Hamada, Y Kanegae, I Saito, H Nakabayashi, T Tamaoki, T Tanaka, K Lan, N Kato, S Shiina, M Omata
Journal: Hepatology (1996)

We have developed a recombinant replication–defective adenovirus containing human α–fetoprotein (AFP) promoter/enhancer to direct cell type–specific expression of the herpes simplex virus thymidine kinase (HSV tk ) gene to AFP–producing hepatocellular carcinoma (HCC) cells. After an in vitro infection by a recombinant adenovirus carrying the lacZ gene under the control of human AFP promoter/enhancer (AdAFP lacZ ), an expression of the lacZ gene was demonstrated efficiently in AFP–producing HuH–7 and HepG2 cell lines, but not in AFP–nonproducing HLE and HLF cell lines, although lacZ gene expression was demonstrated in all these cell lines when infected with adenovirus vector carrying lacZ gene driven by the β–actin–based promoter. Expression of the HSV tk gene by adenovirus, from AFP promoter/enhancer (AdAFP tk ) induced the cells sensitive to ganciclovir (GCV) in the AFP–producing cell line efficiently, but not in AFP–nonproducing HLF hepatoma cells. An in vitro bystander effect was observed when only 10% of the cells were infected with AdAFP tk . These findings suggest that the AFP promoter/enhancer sequence can provide the tumor–specific activity for the therapeutic gene expression, and that the AdAFP tk vector induces the selective growth inhibition by GCV in the adenovirus–infected human hepatoma cells in vitro . Recombinant adenovirus transfer of the HSV tk gene under the control of tumor–specific promoter followed by GCV may have promise as a targeted in situ treatment for solid neoplasms.
Long-term impairment of endothelium-dependent relaxations to aggregating platelets after reperfusion injury in canine coronary arteries.
Authors: P J Pearson, H V Schaff, P M Vanhoutte
Journal: Circulation (1990)

Experiments were designed and performed to determine whether endothelial function remained chronically impaired after coronary artery reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (12 weeks). Rings (3-4 mm wide) of the reperfused artery and of normal left circumflex (control) coronary artery segments were suspended in organ chambers containing physiological saline solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurement. Endothelium-independent contractions to KCl or prostaglandin F2 alpha and endothelium-independent relaxations to nitric oxide or isoproterenol were comparable in control and chronically reperfused arteries. However, chronically reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to aggregating platelets. In addition, the reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to the platelet-derived compounds adenosine diphosphate, serotonin, and thrombin. However, the endothelium-dependent relaxations to acetylcholine were comparable between control and reperfused arteries. Thus, after 12 weeks of reperfusion, previously occluded coronary arteries exhibited a selective impairment of endothelium-dependent relaxation evoked by aggregating platelets. In vivo, this phenomenon could favor platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle and thus facilitate ischemic events such as vasospasm and coronary thrombosis.
Hypertension, Natriuresis, and the Renal Prostaglandins
Authors: JAMES B. LEE
Journal: Annals of Internal Medicine (1969)

Substantial evidence has accumulated that the prostaglandins A (PGA) compounds, potent naturally occurring renal antihypertensive agents, may function as circulating renal vasodilators and may be responsible at least in part for the antihypertensive function of the kidney. The concept that essential hypertension is not solely the result of increased renal pressure mechanisms but may be a deficiency disorder of renal vasodepressor agents has been reinforced with isolation from the kidney of the naturally occurring peripheral vasodilator, PGA2. Along with its possible role in essential hypertension, PGA2 might function as a natriuretic "hormone." All available data indicate that the renal response to prostaglandin infusion in animals and humans with essential hypertension is characterized by an increase in cortical blood flow, glomerular filtration rate, sodium and potassium excretion, urine flow, and free-water clearance. Of all the prostaglandins investigated thus far, the most promising compounds from a cardiovascular-renal perspective are the PGA class. From their highly desirable mechanism of antihypertension and natriuretic action, the greatest immediate potential for PGA1 and PGA2 is for pharmacological use in the treatment of such disorders as hypertension and edema.
Chromatography Studies of the Excretion Products after Meralluride Administration in Normal Subjects and Cardiac Patients
Authors: JOHN H. MOYER, RICHARD A. SEIBERT, CARROLL A. HANDLEY
Journal: Circulation Research (1957)

Separation of the urinary excretory products of the organomercurial diuretic, meralluride (Mercuhydrin) has been possible using adsorption chromatography. Practically all of the mercury is excreted in a form closely resembling the administered meralluride. Most of the excretion occurs within the first 6 hours in both cardiac patients and normal subjects. The amount of mercury excreted as degradation products is insufficient to produce diuresis. Therefore, it is concluded that the diuretic action of meralluride depends on the specific organic mercurial molecule.
Patient and Graft Survival in Older Kidney Transplant Recipients
Authors: Veronika Fabrizii, Wolfgang C. Winkelmayer, Renate Klauser, Josef Kletzmayr, Markus D. Säemann, Rudolf Steininger, Reinhard Kramar, Walter H. Hörl, Josef Kovarik
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. An increasing gap between supply and demand of donor kidneys for transplantation exists. There is concern regarding the allocation of scarce organs to elderly patients, because the benefit obtained by the transplant may be less in elderly compared with younger recipients. It was the objective of this study to determine differences in patient and organ survival between organ recipients >65 yr and 50 to 64 yr of age at transplantation. A retrospective cohort of 627 patients >50 yr who received a kidney transplant between 1993 and 2000 was assembled. Detailed information on patient demographics, comorbidities, and immunological and donor characteristics was ascertained before transplantation. Five-year patient and graft survival were evaluated by Kaplan-Meier survival curves and multivariate Cox proportional-hazard models. Five-year patient mortality was similar between patients aged >65 and 60 to 64 at transplantation (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.66 to 1.74). Patients aged 50 to 59 yr showed a clear trend toward lower 5-yr mortality (RR = 0.66; 95% CI, 0.43 to 1.03). Compared with patients >65 yr, 5-yr graft loss was not different in patients aged 60 to 64 (RR = 1.28; 95% CI, 0.82 to 2.02) or those aged 50 to 59 yr at transplantation (RR = 1.02; 95% CI, 0.68 to 1.53). After thorough control for confounding, 5-yr graft survival was not materially different by age group. Discrimination against older candidates for kidney transplantation on age-related grounds alone is not warranted.
Control of the larynx in patients with obstructive and restrictive pulmonary impairment
Authors: M Yanai, K Sekizawa, H Sasaki, T Takishima
Journal: European Respiratory Journal (1989)

To study changes in glottic movements associated with pulmonary functional abnormalities, we measured changes in glottic resistance (Rgl) during quiet tidal breathing in normal subjects (N), patients with chronic obstructive pulmonary disease (COPD) and patients with idiopathic pulmonary fibrosis (IPF). Changes in Rgl were measured with a non-invasive method using low frequency sound. Changes in Rgl were tightly coupled to changes in tidal volume and were reproducible in all subjects. Rgl was higher during expiration than during inspiration in N and COPD. COPD showed greater changes in Rgl between inspiration and expiration than did N. However, Rgl did not differ between inspiration and expiration in three of six IPF, and was lower during expiration than during inspiration in two of six IPF. We suggest that glottic movements during quiet tidal breathing change in association with the functional abnormalities of pulmonary diseases.