tbuckley/cabot-search huggingface dataset:
Histamine‐Dependent Allergy Blood Test
Authors: B. A. Faraj, V. M. Camp, P. Lolies
Journal: Allergy (1986)

Allergen-mediated histamine release from human leukocytes represents an important model for in vitro studies of allergic reactions. The purpose of this study was to determine whether the measurement of histamine released in allergic patients by radioenzymatic assay following mixing of their blood with common allergens represents a reliable index for diagnosis of atopic allergy. Three categories of allergens were used: 1) house dust and mite; 2) cat and dog dander; 3) trees, grasses and ragweed mixture. The presence of allergy was established by clinical history and intradermal skin testing in the study group of 150 patients. A significant allergen-mediated histamine release ranging from 4 to 65% of the total blood histamine content was observed in 96% of the patients with skin test sensitivity of greater than or equal to 3+. There was a significant correlation between skin testing and histamine release in terms of the allergens causing the response. Thus, the measurement of histamine by radioenzymatic technique following its release in blood in response to allergen challenge represents a clinically useful in vitro test for the diagnosis of atopic disease.
An integrated tool to measure the burden of COPD, the assessment of burden of COPD (ABC)-scale: Development and validity
Authors: Annerika Slok, Hans In 't Veen, Niels Chavannes, Onno van Schayck
Journal: European Respiratory Journal (2014)

Background 

Burden of Chronic Obstructive Pulmonary Disease (COPD), as experienced by patients, is an important element in the treatment of COPD. It is important for daily practice to develop and validate a scale that can both assess the burden of COPD and facilitate communication with patients.

Methods 

Six consecutive steps were taken to develop and validate this scale. 1) Defining the burden of COPD, 2) Checking the definitions' compatibility with the experiences of patients and health care providers, 3) Formulating requirements an instrument should meet, 4) Conducting a systematic review, 5) Developing a scale, 6) Validation.

Results 

A definition of the burden of COPD was formulated by a Dutch expert team. Interviews with patients and health care providers showed agreement on this definition. The systematic review did not recover an instrument that fully measures our pre-defined burden of disease. However, the Clinical COPD Questionnaire met most requirements, and was therefore used and adapted into the Assessment of Burden of COPD (ABC) scale. Test-retest reliability of the scale was determined in 133 subjects in a 2-week interval (Intra Class Coefficient=0.92 (CI: 0.89-0.95)). A significant correlation was found between the ABC-scale and the Saint George Respiratory Questionnaire (r=0.72 (CI:0.61,0.83)).

Conclusions 

The ABC-scale was developed to assess and visualize the burden of COPD. The reliability and validity of the ABC-scale is excellent.

Implications 

The ABC scale will be used as the subjective part of our newly developed ABC-tool, a computer program with an algorithm that visualizes the outcomes and provides treatment advice.
Metabolic enzymatic activities in the intercostal and serratus muscles and in the latissimus dorsi of middle-aged normal men and patients with moderate obstructive pulmonary disease
Authors: J Sanchez, A Brunet, G Medrano, B Debesse, JP Derenne
Journal: European Respiratory Journal (1988)

The glycolytic and oxidative enzyme activities (lactate dehydrogenase (LDH), hexokinase (HK), citrate synthase (CS) and 3-hydroxyacyl-CoA-dehydrogenase (HAD] were measured in the fifth internal and external intercostal muscles, in the vertical and horizontal parts of the serratus, an accessory inspiratory muscle, and in a non-respiratory muscle, the latissimus dorsi (LD) of twenty middle-aged men: nine subjects with normal lung function and eleven patients with moderate chronic obstructive pulmonary disease (COPD). In the normal subjects the enzyme activities of the respiratory muscles were similar to those of the LD, and there were no differences between the internal and the external intercostal muscles. In the COPD patients the metabolic activities of HK, CS and HAD were higher in both intercostals than in LD. Furthermore, there was a significant increase in these enzymatic activities as compared to the intercostals of the normal subjects. These data support the hypothesis that the internal and external intercostal muscles play a more important role in COPD patients than in normal subjects. They are consistent with the hypothesis that COPD has an endurance training effect on both intercostal muscles which could compensate for diaphragmatic disuse.
The Hypocretin/Orexin System: An Increasingly Important Role in Neuropsychiatry
Authors: Quanhui Chen, Luis de Lecea, Zhian Hu, Dong Gao
Journal: Medicinal Research Reviews (2014)

Abstract Hypocretins, also named as orexins, are excitatory neuropeptides secreted by neurons specifically located in lateral hypothalamus and perifornical areas. Orexinergic fibers are extensively distributed in various brain regions and involved in a number of physiological functions, such as arousal, cognition, stress, appetite, and metabolism. Arousal is the most important function of orexin system as dysfunction of orexin signaling leads to narcolepsy. In addition to narcolepsy, orexin dysfunction is associated with serious neural disorders, including addiction, depression, and anxiety. However, some results linking orexin with these disorders are still contradictory, which may result from differences of detection methods or the precision of tools used in measurements; strategies targeted to orexin system (e.g., antagonists to orexin receptors, gene delivery, and cell transplantation) are promising new tools for treatment of neuropsychiatric disorders, though studies are still in a stage of preclinical or clinical research.
Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9
Authors: Parwiz Abrahimi, William G. Chang, Martin S. Kluger, Yibing Qyang, George Tellides, W. Mark Saltzman, Jordan S. Pober
Journal: Circulation Research (2015)

Rationale: The participation of endothelial cells (EC) in many physiological and pathological processes is widely modeled using human EC cultures, but genetic manipulation of these untransformed cells has been technically challenging. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) technology offers a promising new approach. However, mutagenized cultured cells require cloning to yield homogeneous populations, and the limited replicative lifespan of well-differentiated human EC presents a barrier for doing so. Objective: To create a simple but highly efficient method using CRISPR/Cas9 to generate biallelic gene disruption in untransformed human EC. Methods and Results: To demonstrate proof-of-principle, we used CRISPR/Cas9 to disrupt the gene for the class II transactivator. We used endothelial colony forming cell–derived EC and lentiviral vectors to deliver CRISPR/Cas9 elements to ablate EC expression of class II major histocompatibility complex molecules and with it, the capacity to activate allogeneic CD4 + T cells. We show the observed loss-of-function arises from biallelic gene disruption in class II transactivator that leaves other essential properties of the cells intact, including self-assembly into blood vessels in vivo, and that the altered phenotype can be rescued by reintroduction of class II transactivator expression. Conclusions: CRISPR/Cas9-modified human EC provides a powerful platform for vascular research and for regenerative medicine/tissue engineering.
DYPD genotyping to predict toxicity in patients with stage III colon cancer treated with 5-fluorouracil-based adjuvant chemotherapy in the PETACC-8 phase III trial.
Authors: Valérie Boige, Marc Vincent, Philippe Alexandre, Jan Stoehlmacher, Sabine Tejpar, Stefania Landolfi, Karine Le Malicot, Richard Greil, Pieter-Jan AR Cuyle, Mette K. N. Yilmaz, Roger Faroux, Axel Matzdorff, Ramon Salazar, Evaristo Sanches, Laurent Mineur, Come Lepage, Julien Taïeb, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2015)

3584 Background: Previous pharmacogenetic studies have shown the prognostic impact of several rare dihydropyrimidine dehydrogenase gene (DPYD) variants on 5-FU-related toxicity. However, conflicting results highlight the need for prospective validation in large homogeneous patient populations uniformly treated with current standard combination therapies used in colon cancer (CC). Methods: We genotyped 1545 patients with resected stage III CC treated in the PETACC-8 randomized phase III trial with adjuvant FOLFOX-4 alone or combined with cetuximab, and tested the individual associations between 25 DPYD variants and 5FU-related adverse events (5FUAEs). Logistic regressions were used to assess univariate and multivariable associations. Results: The incidence of grade ≥ 3 5FUAEs in D949V and V732I (DPYD*6) carriers were 18/21 (85.7%) and 121/199 (60.8%), respectively. After adjusting for multiple variables, statistically significant associations were identified between grade ≥ 3 5FU-AEs and both D949V (OR = 6.3; 95% CI = 0.037-0.49; p = 0.0007) and V732I variants (OR = 6.3; 95% CI = 0.037-0.49; p = 0.0004). Both SNPs were significantly associated with grade ≥ 3 overall hematologic toxicity (p = 0.0006 and 0.00002, respectively), and V732I with grade ≥ 3 neutropenia (0.0002). The association for D949V and V732I with the occurrence of grade ≥ 3 hematologic toxicity was validated in an independent cohort of 339 patients with metastatic colorectal cancer receiving FOLFOX in the FFCD2000-05 phase III trial (p = 0.02 and p = 0.001, respectively). Conclusions: In this large phase III study, statistically significant associations were found between DPYD variants (D949V and V732I) and increased incidence of grade 3 or greater 5FU-AEs in patients treated with adjuvant 5-FU-based combination chemotherapy.
Adaptation of muscle to exercise
Authors: P. A. Molé, L. B. Oscai, J. O. Holloszy
Journal: Journal of Clinical Investigation (1971)

The capacity of gastrocnemius and quadriceps muscles to oxidize palmitate, oleate, linoleate, palmityl CoA, and palmityl carnitine doubled in rats subjected to a program of treadmill running. The rate of palmitate oxdation by whole homogenates of, or the mitochondrial fraction from, leg muscles was twice as great per gram wet weight of muscle in the trained as in the sedentary animals over a wide range (0.125-1.5 mM) of palmitate concentrations. The levels of activity of carnitine palmityltransferase, palmityl CoA dehydrogenase, and mitochondrial ATP-dependent palmityl CoA synthetase expressed per gram of muscle doubled in gastrocnemius and quadriceps muscles in response to the running program. The protein content of the mitochondrial fraction from these muscles was increased approximately 60%.
Therapeutic potential of chimeric amyloid-reactive monoclonal antibody 11-1F4.
Authors: Alan Solomon, Deborah T. Weiss, Jonathan S. Wall
Journal: Clinical Cancer Research (2003)

Purpose:  We had previously reported that certain of our murine (m) antihuman light chain monoclonal antibodies (mAbs) recognized an epitope common to AL and other types of amyloid fibrils. On the basis of this evidence, one such antibody, 11-1F4, was administered to mice bearing AL amyloidomas induced by s.c. injection of human AL extracts. The mAb bound to the amyloid and initiated an Fc-mediated cellular inflammatory response that led to rapid reduction in the tumor masses. To develop this reagent for clinical use, the 11-1F4 mAb was chimerized and its activity compared with that of the unmodified antibody.   Experimental Design:  The chimeric (c) 11-1F4 mAb was produced in CHO dhfr -stable mammalian cell lines that had been transfected with a supervector DNA encoding the mouse 11-1F4 heavy and light chain variable regions (V H , V L ) and human heavy and light chain constant regions (C H , C L ). The antibody products were analyzed for their fibril binding activity and ability to effect amyloidolysis in two  in vivo  experimental models.   Results:  The capability of the c11-1F4 mAb to interact with amyloid was demonstrated  in vitro . Administration of this reagent into mice bearing human AL tumors or those with systemic AA deposits resulted in marked reduction in amyloid burden with no evidence of toxicity in the animals.   Conclusions:  These results have led to the decision to produce GMP-grade c11-1F4 for a Phase I/II clinical trial in patients with primary (AL) amyloidosis where the effectiveness of the reagent could be determined. The use of amyloid-reactive antibodies would represent a novel approach in the treatment of individuals with this invariably fatal disorder.
Gender differences in sleep apnea severity are diminished during REM sleep
Authors: Maria Pallayova, Igor Peregrim, Zoltan Tomori, Viliam Donic
Journal: European Respiratory Journal (2011)

Background: It has been shown previously that sleep apnea (SA) is substantially more common and more severe in men than women. Yet, the precise pathophysiological mechanisms accounting for gender differences in SA remain less well understood.

Method: A retrospective chart review was performed on patients who underwent in-lab polysomnography between January 2009 and December 2010 to examine the influence of gender on the polysomnographic features of SA. From 227 consecutive adults who met inclusion criteria, we identified 46 male-female pairs matched individually for age (mean±SD 52±9 years) and BMI (31±6 kg/m2).

Results: Despite similarities in age, BMI, sleep efficiency, and Epworth Sleepiness Scale score, men had higher total apnea-hypopnea index (AHI) [median (interquartile range) 21.3 (8.6-43.4) vs. 8.8 (1.7-26) events/h; P <0.001] and the level of the AHI during NREM sleep [21.6 (8.5-43.7) vs. 7.4 (0.7-23.2) events/h; P<0.001] than did women. Men also had higher oxygen desaturation index [24 (10-53.1) vs. 14.8 (3.1-29.9) events/h; P <0.001] and lower mean nocturnal oxyhemoglobin saturation [93 (91-94) vs. 94 (92-95)%; P =0.007]. Surprisingly, there was no statistical difference in AHI during REM sleep between men and women [21.3 (7-46.7) vs. 14.3 (2.1-45.8) events/h; P =0.662]. In addition, compared to men, women had a significantly higher difference between REM-AHI and NREM-AHI ( P =0.023).

Conclusions: To conclude, SA is less severe in women than men because of milder SA during NREM sleep, which is independent of age and BMI. Our findings indicated that severity of SA is similar in men and women during REM sleep, suggesting differences between the sexes in upper airway function during sleep in adults with SA.
ARMY PSYCHIATRY IN KOREA FOLLOWING THE CEASE FIRE AGREEMENT
Authors: GEORGE H. KLUMPNER
Journal: American Journal of Psychiatry (1955)

Follow-up findings of 149 psychiatric patients of the 3rd Infantry Division who were evaluated between September 1953 and February 1954 revealed that 77% of patients not in the process of separation at the time of consultation performed duty adequately or better after consultation. Almost half of the patients given medical clearance for discharge for unfitness (AR 615-368) performed duty adequately or better. Apparently many commanders use this regulation rather effectively as a deterrent to acting out. One infantry regiment and one specialist battalion had unusually high rates of psychiatric referrals. Other evidence including incidence of sick call visits, new AWOL's, delinquency reports, courts martial, and discussions with officers, patients, and battalion surgeons of these units suggested that they suffered from poor morale which appeared to be directly related to the personality of the commanding officers. Approximately half of the patients with severe schizoid personalities performed good duty in spite of their defective ego structures. Most patients with psychogenic somatic complaints functioned adequately or better when returned to duty after a single diagnostic evaluation. While psychiatrists are often tempted to make predictions regarding a man's potential adjustment, in the present study predictions were highly unsuccessful. The findings in this paper should serve as a control in any study that reports a high degree of success resulting from a specific treatment program in the realm of military psychiatry.
A loading dose/continuous infusion schedule of fludarabine phosphate in chronic lymphocytic leukemia.
Authors: C A Puccio, A Mittelman, S M Lichtman, R T Silver, D R Budman, T Ahmed, E J Feldman, M Coleman, P M Arnold, Z A Arlin
Journal: Journal of Clinical Oncology (1991)

Using a loading dose/continuous infusion schedule, fludarabine phosphate was administered to 51 patients with previously treated chronic lymphocytic leukemia (CLL). All patients had evidence of active disease, and the majority had advanced Rai stages. Of the 42 patients assessable for response, 22 (52%) achieved a partial response, five (12%) had stable disease, and 15 (36%) progressed. Thirteen of the 22 responders improved their Rai stages with fludarabine therapy, including six patients who achieved stage 0. Response rates for pretreatment stages III and IV were 60% and 53%, respectively. Patients with final Rai stages 0 to II had better survival than those with stages III and IV. Patients who had undergone splenectomy before starting therapy were more likely to respond. Myelosuppression was the primary toxicity and did not appear to be cumulative. Severe leukopenia and thrombocytopenia, although infrequent, were associated with several deaths in the early cycles of treatment. Nonhematologic toxicity was mild with no serious neurotoxicity noted. Infections were common with 22 minor, 18 major, and 10 fatal episodes. Fludarabine phosphate by this alternative dosing schedule is effective in refractory advanced CLL and is well tolerated by the majority of patients.
Evaluation and classification of RING-finger domains encoded by the Arabidopsis genome
Authors: Peter Kosarev, Klaus FX Mayer, Christian S Hardtke
Journal: Genome biology (2002)

In computational analysis, the RING-finger domain is one of the most frequently detected domains in the Arabidopsis proteome. In fact, it is more abundant in Arabidopsis than in other eukaryotic genomes. However, computational analysis might classify ambiguous domains of the closely related PHD and LIM motifs as RING domains by mistake. Thus, we set out to define an ordered set of Arabidopsis RING domains by evaluating predicted domains on the basis of recent structural data.Inspection of the proteome with a current InterPro release predicts 446 RING domains. We evaluated each detected domain and as a result eliminated 59 false positives. The remaining 387 domains were grouped by cluster analysis and according to their metal-ligand arrangement. We further defined novel patterns for additional computational analyses of the proteome. They were based on recent structural data that enable discrimination between the related RING, PHD and LIM domains. These patterns allow us to predict with different degrees of certainty whether a particular domain is indeed likely to form a RING finger.In summary, 387 domains have a significant potential to form a RING-type cross-brace structure. Many of these RING domains overlap with predicted PHD domains; however, the RING domain signature mostly prevails. Thus, the abundance of PHD domains in Arabidopsis has been significantly overestimated. Cluster analysis of the RING domains defines groups of proteins, which frequently show significant similarity outside the RING domain. These groups document a common evolutionary origin of their members and potentially represent genes of overlapping functionality.
Activation of respiratory muscles during respiratory muscle training
Authors: Stephan Walterspacher, Fabian Pietsch, David Walker, Kai Röcker, Hans-Joachim Kabitz
Journal: European Respiratory Journal (2013)

Introduction 

Respiratory muscle training (RMT) is applied by athletes and in patients with respiratory muscle dysfunction. Yet it is unknown which respiratory muscle groups are mainly activated by RMT.

Objective 

This study aimed at evaluating three RMT methods (Inspiratory Threshold Loading \[POWERbreathe\] (ITL), Targeted Resistive Breathing \[RespiFit S\] (TRB), Normocapnic Hyperpnoea \[SpiroTiger\] (NH)) with regard to their electromyographic (EMG) activation of three specific inspiratory muscle groups (M. sternocleidomastoideus (EMGsterno), 2nd intercostal parasternal muscles (EMGpara), Diaphragm (EMGdi)) in healthy subjects.

Methods 

EMG recordings were analyzed as their RootMeanSquare (RMS) at the end of each randomized training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax) and expressed as EMG%max.

Main Results 

41 subjects were included. Recordings for EMGsterno and EMGpara were higher in ITL and NH than for TRB (p<0.05). EMGdi was higher applying ITL compared to TRB or NH (p<0.05).

View this table:

Effects of respiratory muscle training on muscle activation





Conclusion 

ITL, TRB and NH differ in their activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominantly increased by ITL.
Phase II Trial of Liposome-Encapsulated Doxorubicin, Cyclophosphamide, and Fluorouracil as First-Line Therapy in Patients With Metastatic Breast Cancer
Authors: Vicente Valero, Aman U. Buzdar, Richard L. Theriault, Nozar Azarnia, Gustavo A. Fonseca, Jie Willey, Michael Ewer, Ronald S. Walters, Bruce Mackay, Donald Podoloff, Daniel Booser, Lily W. Lee, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluorouracil (5-FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D-99 60 mg/m 2 and cyclophosphamide 500 mg/m 2 on day 1 and 5-FU 500 mg/m 2 on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. RESULTS: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m 2 . Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m 2 . Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to ≤ 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. CONCLUSION: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of doxorubicin.