tbuckley/cabot-search huggingface dataset:
Clonal Evolution in t(14;18)-Positive Follicular Lymphoma, Evidence for Multiple Common Pathways, and Frequent Parallel Clonal Evolution
Authors: Francesco d'Amore, Eric Chan, Javeed Iqbal, Huimin Geng, Ken Young, Li Xiao, Michelle M. Hess, Warren G. Sanger, Lynette Smith, Carsten Wiuf, Oskar Hagberg, Kai Fu, Wing C. Chan, Bhavana J. Dave
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Follicular lymphoma typically has acquired a t(14;18) translocation, but subsequent additional cytogenetic abnormalities contribute to disease progression. The main aims of the study are to (a) identify the frequency and temporal sequence of cytogenetic events in t(14;18)-positive follicular lymphoma, (b) determine if there are specific pathways in the evolution of follicular lymphoma, (c) determine the clonal divergence in cases with sequential biopsies or multiple clones from a single biopsy, and (d) determine the association of genetic imbalances with clinical outcome. Experimental Design: All cases with a histologically confirmed diagnosis of follicular lymphoma and cytogenetic analysis showing t(14;18)(q32;q21) were included. The karyotypes were reviewed and cytogenetic data were entered into a relational database for further computational analysis; 418 biopsies from 360 follicular lymphoma patients including 43 sequential biopsies were analyzed. Results: Of the cases with only one or two genomic imbalances, the most frequent chromosomal imbalances were +7, del(6q), +der(18)t(14;18), +18, and +X. These abnormalities were also among the most frequent ones encountered when all karyotypes were analyzed. Cytogenetically abnormal clones in the same (26%) and sequential biopsies (63%) often showed divergence of genetic alterations. Balanced translocations other than the t(14;18) were uncommon events, but chromosomal breaks involving 14q32, 18q21, 1p36, 1q21, 10q22, 10q24, and a large cluster at 6q occurred relatively frequently. del(6q), +5, +19, and +20 were associated with poorer overall survival, and del(17p) was associated with poorer event-free survival. Lower-grade tumors (1 and 2) were associated with fewer imbalances. Conclusion: Our analysis suggested that +der(18)t(14;18) may be an entry point to a distinct pathway of genetic evolution in follicular lymphoma. The other common early events appeared to provide multiple entry points, and they might cooperate in the pathogenesis and progression of the follicular lymphoma. Cytogenetically abnormal clones from same patients often showed divergence of genetic alterations, suggesting that parallel evolution from precursor clones are frequent events. This study provides the framework for further analysis of genetic pathways of tumor progression.
Genome-Wide Linkage Scan of a Large Family with IgA Nephropathy Localizes a Novel Susceptibility Locus to Chromosome 2q36
Authors: Andrew D. Paterson, Xiao-Qing Liu, Kairong Wang, Riccardo Magistroni, Xuewen Song, Joanne Kappel, Judith Klassen, Daniel Cattran, Peter St. George-Hyslop, York Pei
Journal: Journal of the American Society of Nephrology (2007)

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and an important cause of ESRD. Familial clustering of cases suggests genetic predisposition to this disease. Two recent genome-wide studies in IgAN have identified a major susceptibility locus on chromosome 6q22 (IGAN1) and two additional loci with suggestive linkage signals on chromosomes 4q26-31 and 17q12-22. A large four-generation family with 14 affected individuals has been clinically ascertained and excluded from linkage to these loci. A genome-wide linkage scan was performed on this family with GeneChip Mapping 10K 2.0 Arrays using an "affected-only" strategy. By nonparametric analysis, two regions of suggestive linkage (multipoint logarithm of odds [LOD] scores >2) were identified on chromosomes 2q36 and 13p12.3. By parametric analysis (assuming an autosomal dominant inheritance, a disease allele frequency of 0.001, phenocopy rate of 0.01, and penetrance of 75%), a significant linkage to chromosome 2q36 (maximum multipoint LOD score 3.47) was found. Nine simple sequence repeat markers then were genotyped in 21 members (included all of the affected individuals), and significant linkage to chromosome 2q36 over a region of 12.2 cM (maximum multipoint LOD score 3.46) was confirmed. Recombination events in two affected individuals, as detected by haplotype analysis, delineated a critical interval of approximately 9 cM (equivalent to approximately 7 Mb) between D2S1323 and D2S362. Taken together, these data provide strong evidence for a novel disease susceptibility locus for familial IgAN.
Decreased insulin binding to adipocytes and circulating monocytes from obese subjects.
Authors: J M Olefsky
Journal: Journal of Clinical Investigation (1976)

Insulin binding to isolated adipocytes from 16 normal and 14 obese patients was studied. The data indicated that, as a group, adipocytes from the obese patients bound significantly less insulin than normal. However, of the 14 obese patients, 5 were not hyperinsulinemic and 4 of these 5 subjects had normal insulin binding. These subjects were also younger, and had the onset of obesity in childhood. When these five patients were separated from the original 14 obese patients, enhanced differences in insulin binding to adipocytes were observed when normals and the remaining 9 obese subjects were compared. Similar findings were obtained with isolated circulating mononuclear cells from these same patients. Presumably the five normoinsulinemic obese patients were not insulin-resistant, and, thus, the data indicate that insulin binding to adipocytes was decreased only in insulin-resistant obese patients. This conclusion was strengthened by finding a highly significant correlation (r=-0.71, p less than 0.001) between insulin binding to adipocytes and fasting plasma insulin level, while a weaker correlation (r=-0.49,p less than 0.01) existed between insulin binding and degree of obesity. Finally, when insulin binding to adipocytes and mononuclear cells from the same individual was compared, a significant positive correlation was found (r=0.53,p less than 0.01). In conclusion: (a) insulin binding to adipocytes and mononuclear cells is decreased in cells from insulin-resistant obese patients; (b) a significant inverse relationship exists between fasting plasma insulin level and insulin binding to adipocytes; and (c) in obesity, events that affect insulin receptors on adipocytes similarly affect insulin receptors on mononuclear cells.
Presupplementary Motor Area Hyperactivity During Response Inhibition: A Candidate Endophenotype of Obsessive-Compulsive Disorder
Authors: Stella J. de Wit, Froukje E. de Vries, Ysbrand D. van der Werf, Danielle C. Cath, Dirk J. Heslenfeld, Eveline M. Veltman, Anton J.L.M. van Balkom, Dick J. Veltman, Odile A. van den Heuvel
Journal: American Journal of Psychiatry (2012)

Objective Endophenotype studies of obsessive-compulsive disorder (OCD) may uncover heritable traits that are related to genetic susceptibility to OCD. Deficient response inhibition is a promising endophenotype of OCD, although its functional neural correlates have not been extensively studied. The authors sought to determine the functional neural correlates of response inhibition in a large sample of medication-free OCD patients and their unaffected siblings. Method Forty-one OCD patients, 17 of their siblings, and 37 matched healthy comparison subjects performed a stop-signal task during 3-T functional MRI. The stop-signal reaction time provided a behavioral measure of response inhibition. The neural correlates of response inhibition were assessed in a region-of-interest analysis that included the presupplementary motor area, inferior frontal gyrus, subthalamic nucleus, and inferior parietal cortex. Results Patients with OCD had greater stop-signal reaction times relative to healthy comparison subjects. The numerical stop-signal reaction time difference between siblings and comparison subjects failed to reach significance. Both patients with OCD and their siblings showed greater activity in the left presupplementary motor area during successful inhibition relative to comparison subjects. Relative to both the comparison subjects and the siblings, patients with OCD showed decreased activity in the right inferior parietal cortex and inferior frontal gyrus. In patients and siblings, presupplementary motor area activity correlated negatively with stop-signal reaction time. Conclusions These findings suggest that presupplementary motor area hyperactivity is a neurocognitive endophenotype of OCD that is possibly related to inefficient neural processing within the presupplementary motor area itself. Patients with OCD further showed a state-dependent deficit in recruiting right inferior parietal cortex and inferior frontal gyrus, which may contribute to their inhibition deficit.
Transthoracic Ventricular Defibrillation with Square-wave Stimuli: One-Half Cycle, One Cycle, and Multicycle Waveforms
Authors: JOHN C. SCHUDER, HARRY STOECKLE, ALFRED M. DOLAN
Journal: Circulation Research (1964)

A very high powered amplifier for experimental transthoracic ventricular defibrillation has been described. The effectiveness of both one-half-cycle unidirectional and one-cycle bidirectional square waves in terminating ventricular fibrillation first increases, then reaches a maximum and finally decreases as the duration of the shock is increased. With 10- and 20-ampere unidirectional shocks and 10-ampere bidirectional shocks, a maximal effectiveness of substantially 100% was found under the chosen experimental conditions. Five-ampere unidirectional and bidirectional shocks yielded maximal effectiveness of 70%. The effectiveness of a 128-millisecond, 5-ampere, multicycle square-wave shock is a strong function of frequency and has a maximal value of approximately 70%.
Income inequality, mortality, and self rated health: meta-analysis of multilevel studies
Authors: N. Kondo, G. Sembajwe, I. Kawachi, R. M van Dam, S V Subramanian, Z. Yamagata
Journal: BMJ (2009)

<b>Objective</b> To provide quantitative evaluations on the association between income inequality and health. <b>Design</b> Random effects meta-analyses, calculating the overall relative risk for subsequent mortality among prospective cohort studies and the overall odds ratio for poor self rated health among cross sectional studies. <b>Data sources</b> PubMed, the ISI Web of Science, and the National Bureau for Economic Research database. <b>Review methods</b> Peer reviewed papers with multilevel data. <b>Results </b>The meta-analysis included 59 509 857 subjects in nine cohort studies and 1 280 211 subjects in 19 cross sectional studies. The overall cohort relative risk and cross sectional odds ratio (95% confidence intervals) per 0.05 unit increase in Gini coefficient, a measure of income inequality, was 1.08 (1.06 to 1.10) and 1.04 (1.02 to 1.06), respectively. Meta-regressions showed stronger associations between income inequality and the health outcomes among studies with higher Gini (≥0.3), conducted with data after 1990, with longer duration of follow-up (&gt;7 years), and incorporating time lags between income inequality and outcomes. By contrast, analyses accounting for unmeasured regional characteristics showed a weaker association between income inequality and health. <b>Conclusions </b>The results suggest a modest adverse effect of income inequality on health, although the population impact might be larger if the association is truly causal. The results also support the threshold effect hypothesis, which posits the existence of a threshold of income inequality beyond which adverse impacts on health begin to emerge. The findings need to be interpreted with caution given the heterogeneity between studies, as well as the attenuation of the risk estimates in analyses that attempted to control for the unmeasured characteristics of areas with high levels of income inequality.
Cytokines and allergy
Authors: Mathew Vadas, Angel Lopez, Jennifer Gamble, Yeesim Khew-Goodall, William Smith, Christophe Bernard, Gillian Cockerill, Peter Cockerill, Frances Shannon, Qiyu Sun, Eija Korpelainen, Cameron van den Heuvel, Timothy Hercus
Journal: Journal of Allergy and Clinical Immunology (1994)
Surgical ventricular restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation
Authors: Constantine L. Athanasuleas, Gerald D. Buckberg, Alfred W.H. Stanley, William Siler, Vincent Dor, Marisa Di Donato, Lorenzo Menicanti, Sergio Almeida de Oliveira, Friedhelm Beyersdorf, Irving L. Kron, Hisayoshi Suma, Nicholas T. Kouchoukos, Wistar Moore, Patrick M. McCarthy, Mehmet C. Oz, Francis Fontan, Meredith L. Scott, Kevin A. Accola
Journal: Journal of the American College of Cardiology (2004)
Hereditary angioedema with<i>F12</i>mutation: factors modifying the clinical phenotype
Authors: D. Charignon, A. Ghannam, F. Defendi, D. Ponard, N. Monnier, M. López Trascasa, D. Launay, T. Caballero, K. Djenouhat, O. Fain, S. Cichon, L. Martin, C. Drouet
Journal: Allergy (2014)

Hereditary angioedema (HAE) with normal C1 inhibitor (C1Inh) associated with the c.983C>A and c.983C>G mutations of the F12 gene (FXII-HAE) is a rare condition, and presents with highly variable clinical expression. On the basis of data gathered from a large carrier cohort, we assessed the modifiers affecting the clinical phenotype.We analyzed clinical and biological data recorded from 118 mutation carriers (80 symptomatic and 38 asymptomatic), 58 noncarrier relatives from 40 families, and 200 healthy donors. Disease severity was scored in relation to frequency and location of edema, as well as age at disease onset. To predict FXII-HAE disease severity, we analyzed the biological phenotype [C1Inh, C4, spontaneous amidase, angiotensin-I-converting enzyme (ACE), aminopeptidase P (APP), and carboxypeptidase N/M (CPN)] by means of logistic regression (Akaike information criterion) and odds ratio (OR).Meaningful variables contributed to FXII-HAE, with the kinin catabolism enzymes ACE and CPN exhibiting a significant inverse relationship with disease severity (OR = 0.36, 95% CI 0.23-0.59, P < 0.001; OR = 0.58, 95% CI 0.36-0.91, P < 0.05, respectively). CPN activities were 37.5 (28.5-41.3) nmol/ml/min and 38.5 (32.8-45.6) for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 37.9 (30.5-43.7) nmol/ml/min for noncarriers. Angiotensin-I-converting enzyme activities were 58 (44-76) and 49 (35-59) nmol/ml/min for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 56 (49-66) nmol/ml/min for noncarriers.The FXII-HAE is associated with modifiers, for example kinin catabolism enzymes, ACE and CPN, different from those recognized in HAE with C1Inh deficiency.
Greater loop chloride uptake contributes to blunted pressure natriuresis in Dahl salt sensitive rats.
Authors: K A Kirchner
Journal: Journal of the American Society of Nephrology (1990)

A blunted pressure natriuretic response is present in Dahl salt sensitive rats. To determine whether this results from tubular or glomerular mechanisms, late proximal, early distal, and late distal micropuncture were performed in salt resistant (R), salt sensitive (S), or salt sensitive rats with renal perfusion reduced to that of R rats (S-AC). Differences in neuro-endocrine background between groups were eliminated by renal denervation and by fixing plasma aldosterone, norepinephrine, and vasopressin levels by infusion. Renal perfusion pressure was greater (P less than 0.05) and inulin clearance less (P less than 0.05) in S than R rats. Urinary sodium excretion, however, was not different. S-AC had renal perfusion pressures that were similar to R rats and inulin clearance similar to S rats. Urinary NaCl excretion was less (P less than 0.05) than either group. Single nephron inulin clearance, fluid, and chloride delivery to late proximal sites were not different between groups. Absolute and fractional chloride delivery to early distal sites was less (P less than 0.05) in S-AC than R or S but not different between R and S. Late distal chloride delivery was not different between any group. Calculated loop chloride reabsorption was greater in S-AC than R or S. Thus, the lower urinary NaCl excretion in S-AC rats is in part due to increased loop chloride reabsorption. This effect is probably intrinsic to the S kidney as it occurs despite renal denervation when plasma levels of vasopressin, norepinephrine, and aldosterone are fixed. The increased loop chloride uptake is abolished when perfusion pressure increases.
Panel of Serum Biomarkers for the Diagnosis of Lung Cancer
Authors: Edward F. Patz, Michael J. Campa, Elizabeth B. Gottlin, Irina Kusmartseva, Xiang Rong Guan, James E. Herndon
Journal: Journal of Clinical Oncology (2007)

Currently, a blood test for lung cancer does not exist. Serum biomarkers that could aid clinicians in making case management decisions would be enormously valuable. We used two proteomic platforms and a literature search to select candidate serum markers for the diagnosis of lung cancer.We initially assayed six serum proteins, four discovered by proteomics and two previously known to be cancer associated, on a training set of sera from 100 patients (50 with a new diagnosis of lung cancer and 50 age- and sex-matched controls). Classification and Regression Tree (CART) analysis selected a panel of four markers that most efficiently predicted which patients had lung cancer. An independent, blinded validation set of sera from 97 patients (49 lung cancer patients and 48 matched controls) determined the accuracy of the four markers to predict which patients had lung cancer.Four serum proteins-carcinoembryonic antigen, retinol binding protein, alpha1-antitrypsin, and squamous cell carcinoma antigen-were collectively found to correctly classify the majority of lung cancer and control patients in the training set (sensitivity, 89.3%; specificity, 84.7%). These markers also accurately classified patients in the independent validation set (sensitivity, 77.8%; specificity, 75.4%). Remarkably, 90% of patients who fell into any one of three groupings in the CART analysis had lung cancer.This panel of four serum proteins is valuable in suggesting the diagnosis of lung cancer. These data may be useful for treating patients with an indeterminate pulmonary lesion, and potentially in predicting individuals at high risk for lung cancer.
Melody as a primordial legacy from early roots of language
Authors: Kathleen Wermke, Werner Mende
Journal: Behavioral and Brain Sciences (2006)

The stormy development of vocal production during the first postnatal weeks is generally underestimated. Our longitudinal studies revealed an amazingly fast unfolding and combinatorial complexification of pre-speech melodies. We argue that relying on “melody” could provide for the immature brain a kind of filter to extract life-relevant information from the complex speech stream.
Effect of Lifestyle Intervention on the Occurrence of Metabolic Syndrome and its Components in the Finnish Diabetes Prevention Study
Authors: Pirjo Ilanne-Parikka, Johan G. Eriksson, Jaana Lindström, Markku Peltonen, Sirkka Aunola, Helena Hämäläinen, Sirkka Keinänen-Kiukaanniemi, Mauri Laakso, Timo T. Valle, Jorma Lahtela, Matti Uusitupa, Jaakko Tuomilehto
Journal: Diabetes Care (2008)

The aim of this secondary analysis of the Finnish Diabetes Prevention Study was to assess the effects of lifestyle intervention on metabolic syndrome and its components.A total of 522 middle-aged overweight men and women with impaired glucose tolerance were randomized into an individualized lifestyle intervention group or a standard care control group. National Cholesterol Education Program criteria were used for the definition of metabolic syndrome.At the end of the study, with a mean follow-up of 3.9 years, we found a significant reduction in the prevalence of metabolic syndrome in the intervention group compared with the control group (odds ratio [OR] 0.62 [95% CI 0.40-0.95]) and in the prevalence of abdominal obesity (0.48 [0.28-0.81]).The results suggest that lifestyle intervention may also reduce risk of cardiovascular disease in the long run.
What we talk about when we talk about low-grade dysplasia
Authors: Patrick Yachimski
Journal: Gut (2014)

Nearly a decade has elapsed since initial publication of a multicentre randomised trial of porfimer sodium photodynamic therapy (psPDT) for the treatment of Barrett's oesophagus (BO) containing high-grade dysplasia (HGD).1 With the addition of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) to the therapeutic armamentarium, a seismic shift has now ensued in the treatment landscape of BO-associated mucosal neoplasia. An ever-increasing proportion of patients with BO HGD or T1 oesophageal adenocarcinoma (OAC), opt for endoscopic therapy rather than surgery.2 Durable disease remission is achievable for the majority of patients, with most instances of recurrence being amenable to further endoscopic management and with low rates of salvage oesophagectomy or oesophageal cancer-related mortality.3

Compared with a significant post-treatment stricture rate (>30% for PDT1) and prolonged duration of photosensitivity following psPDT, the relatively lower toxicity profile of newer-generation endoscopic therapies (<10% stricture rate for RFA4) has enabled consideration of whether prophylactic endoscopic therapy may be offered, in lieu of surveillance, to an expanded treatment pool of patients with pathology less advanced than HGD. Indeed, an endoscopic ablation strategy for BO has been envisioned as analogous to the widespread practice of screening colonoscopy and resection of adenomatous polyps for prevention of colorectal cancer.5

Yet at the same time, epidemiological investigation has prompted a recalibration of the risk of BO neoplastic progression. An annual progression rate from non-dysplastic BO to OAC of 0.12% was reported from a …
Copy-Neutral Loss of Heterozygosity at the <i>p53</i> Locus in Carcinogenesis of Esophageal Squamous Cell Carcinomas Associated with <i>p53</i> Mutations
Authors: Hiroshi Saeki, Hiroyuki Kitao, Keiji Yoshinaga, Tomonori Nakanoko, Nobuhide Kubo, Yoshihiro Kakeji, Masaru Morita, Yoshihiko Maehara
Journal: Clinical Cancer Research (2011)

LOH at the p53 locus has been reported to be associated with esophageal squamous cell carcinogenesis. The aim of this study is to identify potential mechanisms resulting in LOH around the p53 locus in its carcinogenesis.We investigated 10 esophageal cancer cell lines and 91 surgically resected specimens, examining them for LOH at the p53 locus on chromosome 17. We examined the p53 gene by using microsatellite analysis, comparative genomic hybridization (CGH), FISH, and single-nucleotide polymorphism-CGH (SNP-CGH).In an analysis of specimens by microsatellite markers, a close positive correlation was found between p53 mutations and LOH at the p53 locus (P < 0.01). Although four cell lines were found to be homozygous for p53 mutations, LOH at the p53 locus was not detected by CGH. Among two p53 mutant cancer cell lines and five p53 mutant/LOH cancer specimens analyzed by FISH, both the cell lines and four of the specimens exhibited no obvious copy number loss at the p53 locus. SNP-CGH analysis, which allows both determination of DNA copy number and detection of copy-neutral LOH, showed that LOHs without copy number change were caused by whole or large chromosomal alteration.LOH without copy number change at the p53 locus was observed in p53 mutant esophageal squamous cell carcinomas. Our data suggest that copy-neutral LOH occurring as a result of chromosomal instability might be the major mechanism for inactivation of the intact allele in esophageal squamous cell carcinogenesis associated with p53 mutation.