tbuckley/cabot-search huggingface dataset:
Allelic Imbalances in Human Bladder Cancer: Genome-Wide Detection With High-Density Single-Nucleotide Polymorphism Arrays
Authors: Hanne Primdahl, Friedrik P Wikman, Hans von der Maase, Xiao-ge Zhou, Hans Wolf, Torben F Orntoft
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Bladder cancer is characterized by genomic instability. In this study, we investigated whether genome-wide screening using single-nucleotide polymorphism (SNP) arrays could detect allelic imbalance (loss or gain of at least one allele) in bladder cancers. Methods: For microarray analysis, DNA was isolated from microdissected bladder tumors and leukocytes from 11 patients. The stage T1 tumor (connective tissue invasive) and the subsequent stage T2–4 tumor (muscle invasive) were available from eight of these patients, and only the first muscle-invasive stage T2–4 tumor was available from three of the 11 patients. The microarray contained 1494 biallelic polymorphic sequences. For microsatellite analyses, DNA was isolated from tumors and leukocytes of nine patients with primary T2–4 tumors and 13 patients with Ta (noninvasive) tumors. All statistical tests were two-sided. Results: We assigned a genotype to 1204 loci, 343 of which were heterozygous. Allelic imbalance was detected in known areas of imbalance on chromosomes 6, 8, 9, 11, and 17, and a new area of imbalance was detected on the p arm of chromosome 6. Microsatellite analysis of nine other T2–4 tumors and 13 Ta tumors showed that allelic imbalance was more frequent in T2–4 tumors than in Ta tumors (P<.001). We detected 8.5 allelic imbalances (median) in 348 informative loci in T1 tumors and 28 allelic imbalances (median) in 329 informative loci in T2–4 tumors. When pairs of T1 and T2–4 tumors were analyzed from eight patients, 68% of imbalances detected in T1 tumors (146 imbalances) occurred in the subsequent T2–4 tumors (99 imbalances). Homozygous TP53 mutations were more often associated (P = .005) with high allelic imbalance than with low allelic imbalance. Conclusion: SNP arrays are feasible for high-throughput, genome-wide scanning for allelic imbalances in bladder cancer.
Safety of general anaesthesia and surgery in acute hepatic porphyria.
Authors: S B Dover, L Plenderleith, M R Moore, K E McColl
Journal: Gut (1994)

Patients with acute hepatic porphyria are denied essential operations because of concern that general anaesthesia and surgery will precipitate a life threatening porphyric crisis. This study assessed the safety of surgery under general anaesthesia in these patients. A combined prospective and retrospective case note study, with a biochemical study, was conducted in 25 patients with acute hepatic porphyria undergoing 38 surgical operations. Clinical outcome measures were survival and occurrence of porphyric crisis after surgery. The biochemical activity of porphyria was assessed by measurement of the perioperative 24 hour excretion of the haem precursors delta amino-laevulinic acid (ALA) and porphobilinogen (PBG). There were no deaths or crises after 29 operations in 19 patients who were known to have porphyria before their surgery, and therefore given only appropriate drugs. These operations include such major procedures as mitral valve replacement, hip replacement, coronary artery grafting, cholecystectomies, and renal transplantation. In eight of these patients the urinary excretion of ALA and PBG were studied, and showed no sustained postoperative increase. Nine operations were performed in eight patients before the diagnosis of porphyria was known and who thus received routine anaesthetic agents. Seven of these patients developed a postoperative porphyric crisis. Two of them died. It is concluded therefore that even the most major surgery can be undertaken safely in patients with porphyria. The risk is for undiagnosed cases.
STUDIES ON THE CONTROL OF ANTIBODY SYNTHESIS
Authors: Gregory W. Siskind, Philip Dunn, J. Geoffrey Walker
Journal: The Journal of Experimental Medicine (1968)

The effect of antigen dose on the kinetics of circulating antibody synthesis and on antibody affinity was studied in a haptenic system. High doses of antigen resulted, early in immunization, in higher concentrations of antibody followed later in the immune response by decreased serum levels of antibody as compared with lower doses of antigen. The affinity of the initial antibody synthesized was very similar over a wide antigen dose range. Subsequently, however, a rapid rise in affinity was seen in animals immunized with low doses of antigen, while relatively little change in affinity was seen in animals immunized with higher antigen doses. Suppression of active antibody formation by passive antiserum led to an increase in antibody affinity. The results are discussed in terms of the mechanisms involved in the selection of a population of cells to participate in the immune response and the mechanisms whereby antigen dose and circulating antibody function to control antibody synthesis.
Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity
Authors: S. Kezic, G. M. O’Regan, N. Yau, A. Sandilands, H. Chen, L. E. Campbell, K. Kroboth, R. Watson, M. Rowland, W. H. Irwin McLean, A. D. Irvine
Journal: Allergy (2011)

Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity.The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population.The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease.Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique.
Anticipation of Age at Onset in Panic Disorder
Authors: Marco Battaglia, Silvana Bertella, Sonia Bajo, Flora Binaghi, Laura Bellodi
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Anticipation (i.e., the decrease in age at onset or the increase in severity of a disorder in successive generations) has recently been reappraised as a key to understanding the genetics of some familial illnesses. The purpose of this study was to search for possible anticipation in panic disorder. METHOD: Thirty-eight unilineal, multigenerational families with multiple directly interviewed members who had panic disorder were compared across two successive generations for 1) age at the first panic attack, 2) age at the onset of panic disorder, and 3) the highest degree of agoraphobia ever experienced, as a tentative index of severity of illness. Intergenerational pairwise comparisons were implemented according to four different sampling schemes: random pairs, random transmitting pairs, all possible pairs, and all possible transmitting pairs. RESULTS: Life table analyses showed a significant decrease in the time before the first episode of panic and onset of panic disorder from the older to the younger generation. Evidence for anticipation was found for both indexes of onset in all four sampling schemes. No evidence of a generational effect on the index of severity of agoraphobia was found. Corrections for possible biases suggested that these results are not likely to be simple artifacts. CONCLUSIONS: Anticipation is supported in this specific set of families and, if it is confirmed by other studies, a role for trinucleotide repeat sequences may be considered to account for the familial aggregation of panic disorder.
RNA interference targeting survivin exerts antitumoral effects in vitro and in established glioma xenografts in vivo
Authors: S. Hendruschk, R. Wiedemuth, A. Aigner, K. Topfer, M. Cartellieri, D. Martin, M. Kirsch, C. Ikonomidou, G. Schackert, A. Temme
Journal: Neuro-Oncology (2011)

Malignant glioma represents the most common primary adult brain tumor in Western industrialized countries. Despite aggressive treatment modalities, the median survival duration for patients with glioblastoma multiforme (GBM), the highest grade malignant glioma, has not improved significantly over past decades. One promising approach to deal with GBM is the inactivation of proteins essential for survival or progression of glioma cells by means of RNA interference (RNAi) techniques. A likely candidate for an RNAi therapy of gliomas is the inhibitor of apoptosis protein survivin. Survivin is involved in 2 main cellular processes–cell division and inhibition of apoptosis. We show here that stable RNAi of survivin induced polyploidy, apoptosis, and impaired proliferation of human U343-MG, U373-MG, H4, and U87-MG cells and of primary glioblastoma cells. Proteome profiler arrays using U373-MG cells identified a novel set of differentially expressed genes upon RNAi-mediated survivin knockdown. In particular, the death receptor TRAIL R2/DR5 was strongly upregulated in survivin-depleted glioma cells, inducing an enhanced cytotoxic response of allogeneic human NK cells. Moreover, an experimental in vivo therapy using polyethylenimine (PEI)/siRNA complexes for survivin knockdown efficiently blocked tumor growth of established subcutaneous U373-MG tumors and enhanced survival of NMRInu/nu mice orthopically transplanted with U87-MG cells. We conclude that survivin is functionally relevant in gliomas and that PEI-mediated exogenous delivery of siRNA targeting survivin is a promising strategy for glioblastoma therapy.
Erythrophagocytic Tγ Lymphoma
Authors: Marshall E. Kadin, Malek Kamoun, John Lamberg
Journal: New England Journal of Medicine (1981)

CLINICOPATHOLOGICAL studies suggest that the T-cell lymphomas are heterogeneous with respect to clinical presentation, course, and morphology. Mycosis fungoides and the Sézary syndrome affect the skin primarily, are slowly progressive, and are characterized by peripheral T cells with cerebriform nuclei that infiltrate the epidermis.1 T-cell lymphoblastic lymphoma often presents as a mediastinal mass, commonly spreads to the bone marrow and central nervous system, and is rapidly fatal.2 , 3 Other variants of T-cell lymphoma with distinctive clinical and pathologic features have been described.4 , 5 We report a unique T-cell lymphoma in two adult patients with clinical and pathological features resembling those of malignant . . .
Improved Prognosis of Thoracic Aortic Aneurysms
Authors: W D Clouse, J W Hallett, H V Schaff, M M Gayari, D M Ilstrup, L J Melton
Journal: JAMA (1998)

Context.—Managing thoracic aortic aneurysms identified incidentally by increased use of computed tomography, echocardiography, and magnetic resonance imaging is problematic, especially in the elderly.Objective.—To ascertain whether the previously reported poor prognosis for individuals with thoracic aortic aneurysms has changed with better medical therapies and improved surgical techniques that can now be applied to aneurysm management.Design.—Population-based cohort study.Setting and Patients.—All 133 patients with the diagnosis of degenerative thoracic aortic aneurysms among Olmsted County, Minnesota, residents between 1980 and 1994 compared with a previously reported cohort of similar patients between 1951 and 1980.Main Outcome Measures.—The primary clinical end points were incidence, cumulative rupture risk, rupture risk as a function of aneurysm size, and survival.Results.—In contrast to abdominal aortic aneurysms, for which men are affected predominately, 51% of thoracic aortic aneurysms were identified in women who were considerably older at recognition than men (mean age, 75.9 vs 62.8 years, respectively; P=.01). The overall incidence rate of 10.4 per 100,000 person-years (95% confidence interval [CI], 8.6-12.2) between 1980 and 1994 was more than 3-fold higher than the rate from 1951 to 1980. The cumulative risk of rupture was 20% after 5 years. Seventy-nine percent of ruptures occurred in women (P=.01). The 5-year risk of rupture as a function of aneurysm size at recognition was 0% for aneurysms less than 4 cm in diameter, 16% (95% CI, 4%-28%) for those 4 to 5.9 cm, and 31% (95% CI, 5%-56%) for aneurysms 6 cm or more. Overall 5-year survival improved to 56% (95% CI, 48%-66%) between 1980 and 1994 compared with only 19% between 1951 and 1980 (P&lt;.01).Conclusions.—In this population, elderly women represent an increasing portion of all patients with clinically recognized thoracic aortic aneurysms and constitute the majority of patients whose aneurysm eventually ruptures. Overall survival for thoracic aortic aneurysms has improved significantly in the past 15 years.
Duration of Short-Course Androgen Suppression Therapy and the Risk of Death As a Result of Prostate Cancer
Authors: Anthony V. D'Amico, Ming-Hui Chen, Juanita Crook, John G. Armstrong, Shawn Malone, Allison Steigler, Mary Dunne, Philip W. Kantoff, James W. Denham
Journal: Journal of Clinical Oncology (2011)

We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.Between February 2, 1996, and December 27, 2001, 761 men with unfavorable-risk PC were treated in Australia, New Zealand, Ireland, or the United States in a randomized trial with radiotherapy and 3, 4, or 6 months of AST (the study cohort). Competing risks regression was used to evaluate whether the duration of AST interacted with GS and was significantly associated with the risk of PCSM, adjusting for age, trial site, and PC prognostic factors.After a median follow-up of 10.9 years, 263 men died, 111 (42%) from PC. For all men, 6 versus 3 or 4 months of AST was associated with a reduced risk of PCSM (adjusted hazard ratio [AHR], 0.55; 95% CI, 0.36 to 0.82; P = .004). AHRs evaluating the impact of the duration of AST on the risk of PCSM were 0.67 (95% CI, 0.29 to 1.56; P = .35), 0.47 (95% CI, 0.25 to 0.85; P = .01), and 0.59 (95% CI, 0.30 to 1.19; P = .14) for men with GS ≤ 6, 7, and 8 to 10 PC, respectively. Therefore, the strongest evidence for this benefit was in men with GS 7 PC.AST durations of no less than 6 months should be considered when treating GS 7 PC with conventional dose RT.
Effects of vasopressin and bradykinin on anion transport by the rat cortical collecting duct. Evidence for an electroneutral sodium chloride transport pathway.
Authors: K Tomita, J J Pisano, M B Burg, M A Knepper
Journal: Journal of Clinical Investigation (1986)

Our previous studies in cortical collecting ducts isolated from rat kidneys have shown that vasopressin increases both sodium absorption and potassium secretion, while bradykinin inhibits sodium absorption without affecting potassium transport. To determine which anions are affected by these agents, we perfused cortical collecting ducts from rats treated with deoxycorticosterone and measured net chloride flux, net bicarbonate flux (measured as total CO2), transepithelial voltage, and the rate of fluid absorption. Arginine vasopressin (10(-10) M in the peritubular bath) caused a sustained sixfold increase in net chloride absorption and a two- to threefold increase in the magnitude of the lumen negative transepithelial voltage. Before addition of vasopressin, the tubules secreted bicarbonate. Vasopressin abolished the bicarbonate secretion, resulting in net bicarbonate absorption (presumably due to proton secretion) in many tubules. Bradykinin (10(-9) M added to the peritubular bath) caused a reversible 40% inhibition of net chloride absorption, but did not affect the transepithelial voltage or the bicarbonate flux. We concluded: (a) that arginine vasopressin stimulates absorption of chloride and inhibits bicarbonate secretion (or stimulates proton secretion) in the rat cortical collecting duct; and (b) that bradykinin inhibits net chloride absorption in the rat cortical collecting duct without affecting transepithelial voltage or bicarbonate flux. Combining these results with the previous observations on cation fluxes described above, we conclude that bradykinin inhibits electroneutral NaCl absorption (or stimulates electroneutral NaCl secretion) in the rat cortical collecting duct.
From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the french intergroup (IFCT) and the groupe d'Oncologie de langue française (GOLF)
Authors: S. Couraud, A.B. Cortot, L. Greillier, V. Gounant, B. Mennecier, N. Girard, B. Besse, L. Brouchet, O. Castelnau, P. Frappé, G.R. Ferretti, L. Guittet, A. Khalil, P. Lefebure, F. Laurent, S. Liebart, O. Molinier, E. Quoix, M.-P. Revel, B. Stach, P.-J. Souquet, P. Thomas, J. Trédaniel, E. Lemarié, G. Zalcman, F. Barlési, B. Milleron
Journal: Annals of Oncology (2012)

Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France.A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article.The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given.Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.
Differential Response to Neoadjuvant Chemotherapy Among 7 Triple-Negative Breast Cancer Molecular Subtypes
Authors: Hiroko Masuda, Keith A. Baggerly, Ying Wang, Ya Zhang, Ana Maria Gonzalez-Angulo, Funda Meric-Bernstam, Vicente Valero, Brian D. Lehmann, Jennifer A. Pietenpol, Gabriel N. Hortobagyi, W. Fraser Symmans, Naoto T. Ueno
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The clinical relevancy of the 7-subtype classification of triple-negative breast cancer (TNBC) reported by Lehmann and colleagues is unknown. We investigated the clinical relevancy of TNBC heterogeneity by determining pathologic complete response (pCR) rates after neoadjuvant chemotherapy, based on TNBC subtypes. Experimental Design: We revalidated the Lehmann and colleagues experiments using Affymetrix CEL files from public datasets. We applied these methods to 146 patients with TNBC with gene expression microarrays obtained from June 2000 to March 2010 at our institution. Of those, 130 had received standard neoadjuvant chemotherapy and had evaluable pathologic response data. We classified the TNBC samples by subtype and then correlated subtype and pCR status using Fisher exact test and a logistic regression model. We also assessed survival and compared the subtypes with PAM50 intrinsic subtypes and residual cancer burden (RCB) index. Results: TNBC subtype and pCR status were significantly associated (P = 0.04379). The basal-like 1 (BL1) subtype had the highest pCR rate (52%); basal-like 2 (BL2) and luminal androgen receptor had the lowest (0% and 10%, respectively). TNBC subtype was an independent predictor of pCR status (P = 0.022) by a likelihood ratio test. The subtypes better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like). Conclusions: Classifying TNBC by 7 subtypes predicts high versus low pCR rate. We confirm the clinical relevancy of the 7 subtypes of TNBC. We need to prospectively validate whether the pCR rate differences translate into long-term outcome differences. The 7-subtype classification may spur innovative personalized medicine strategies for patients with TNBC. Clin Cancer Res; 19(19); 5533–40. ©2013 AACR.
Infliximab in refractory psoriatic arthritis with severe psoriasis: a 2-year experience
Authors: P. V Voulgari, A. I Venetsanopoulou, E. K Epagelis, Y. Alamanos, I. Takalou, A. A Drosos
Journal: Annals of the Rheumatic Diseases (2006)

Infliximab was shown to be effective and safe in controlled trials of psoriatic arthritis (PsA).1–4 In an open-label study, we reported a notable clinical benefit accompanied by clearing and healing of psoriatic skin lesions.5 Thus, we conducted this study to evaluate the efficacy and safety of infliximab in patients with active PsA and recalcitrant psoriasis in whom treatment with disease-modifying antirheumatic drugs had failed. Thirty two patients who had a negative purified protein derivative skin test and normal chest radiographs were included. All had an active disease, defined as ⩾6 tender or swollen joints count, psoriasis area and severity index (PASI) score ⩾10,6 and erythrocyte sedimentation rate ⩾28 mm Hg/h or C reactive protein concentration ⩾10 …
Arginine-stimulated acute phase of insulin and glucagon secretion in diabetic subjects.
Authors: J P Palmer, J W Benson, R M Walter, J W Ensinck
Journal: Journal of Clinical Investigation (1976)

To determine if both phases of glucagon secretion are excessive in diabetes, arginine was admimistered intravenously as pulses and as infusions to normal subjects, insulin-dependent diabetics, and noninsulin-requiring diabetics. The acute phase of glucagon secretion, in response to arginine pulses at four different doses (submaximal to maximal alpha-cell stimulating), was indistinguishable in terms of timing, peak levels attained, and total increments comparing controls and diabetics. During the first half of the arginine infusion (500 mg/kg over 30 min) the glucagon rise in controls and diabetics was similar (P greater than 0.1), whereas during the last half of the infusion excessive glucagon levels were seen in the diabetics. No difference in the glucagon responses to arginine administered as either a pulse or an infusion was observed between the two types of diabetics. The acute phase responses of insulin to intravenous, maximal stimulating doses of glucose (20 g) and arginine (2.5 g) were measured in five insulin-independent diabetics. Although the acute insulin response to arginine was normal, there was marked attentuation of the early beta-cell response upon stimulation by glucose. From these results we conclude that although in diabetes excessive glucagon levels are observed with chronic arginine stimulation, the acute phase of glucagon secretion in response to arginine is normal. In addition, the beta-cell in noninsulin-requiring diabetics, although acutely hyporesponsive to glucose, remains normally responsive to another stimulus, arginine.