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981.
Shuman C Smith AC Steele L Ray PN Clericuzio C Zackai E Parisi MA Meadows AT Kelly T Tichauer D Squire JA Sadowski P Weksberg R 《American journal of medical genetics. Part A》2006,140(14):1497-1503
Isolated hemihyperplasia (IH) refers to a distinct diagnosis involving asymmetric overgrowth of single or multiple organs or regions of the body and can result from various genomic changes including molecular alterations of 11p15; these are paternal uniparental disomy (UPD), and alterations of methylation at two imprinting centers at 11p15: IC1 (H19) and IC2 (KCNQ1OT1). As little information is available on the molecular basis of tumor development in IH, or on the frequency of tumors in children with different molecular subtypes of IH, molecular testing was undertaken on 51 patients with IH and revealed: 8 (16%) with UPD, 3 (6%) with hypomethylation at KCNQ1OT1, and 0 with hypermethylation at H19. Of the 8 patients with UPD, 4 had tumors (3 hepatoblastomas, 1 Wilms tumor); 0/3 patients with hypomethylation at KCNQ1OT1 had a tumor; of the remaining 40 with no molecular alterations, 6 had tumors (3 Wilms tumors, 2 neuroblastomas, 1 adrenocortical adenoma). The 50% tumor frequency in patients with IH and UPD was statistically significantly higher than the 15% tumor frequency in those with IH and no molecular alteration detected (Fisher's exact test P = 0.047, OR 5.67). This is the first demonstration that UPD at 11p15 in patients with IH confers a higher tumor risk than in patients with IH without this molecular change. Of note, two of the eight patients with UPD and IH were conceived using assisted reproductive technologies (ART), thus raising the question whether ART might impact the rate of somatic recombination during embryonic development. 相似文献
982.
983.
984.
Alex F. Manini Lewis S. Nelson Adam H. Skolnick William Slater Robert S. Hoffman 《Journal of medical toxicology》2010,6(2):106-115
Poisoning is the second leading cause of injury-related fatality in the USA and the leading cause of cardiac arrest in victims under 40 years of age. The study objective was to define the electrocardiographic (ECG) predictors of adverse cardiovascular events (ACVE) complicating suspected acute poisoning (SAP). This was a case-control study in adults at three tertiary-care hospitals and one regional Poison Control Center. We compared 34 cases of SAP complicated by ACVE to 101 consecutive control patients with uncomplicated SAP. The initial ECG was analyzed for rhythm, intervals, QT dispersion, ischemia, and infarction. ECGs were interpreted by a cardiologist, blinded to study hypothesis and case data. Subjects were 48% male, with mean age 42?±?19 years. In addition to clinical suspicion of poisoning in 100% of patients, routine toxicology screens were positive in 77%, most commonly for benzodiazepines, opioids, and/or acetaminophen. Neither the ventricular rate, the QRS duration, nor the presence of infarction predicted the risk of ACVE. However, the rhythm, QTc, QT dispersion, and presence of ischemia correlated with the risk of ACVE. Independent predictors of ACVE based on multivariable logistic regression were prolonged QTc, any non-sinus rhythm, ventricular ectopy, and ischemia. Recursive partitioning analysis identified very low risk criteria (94.1% sensitivity, 96.2% NPV) and high risk criteria (95% specificity). Among patients with SAP, the presence of QTc prolongation, QT dispersion, ventricular ectopy, any non-sinus rhythm, and evidence of ischemia on the initial ECG are strongly associated with ACVE. 相似文献
985.
Adam J. Sellers Dolaana Khovalyg Wouter van Marken Lichtenbelt 《American journal of human biology》2023,35(10):e23933
Objectives
This study compared the metabolic and vascular responses, to whole-body and finger cold exposure, of a traditional population lifelong exposed to extreme cold winters with Western Europeans.Methods
Thirteen cold acclimatized Tuvan pastoralist adults (45 ± 9 years; 24.1 ± 3.2 kg/m2) and 13 matched Western European controls (43 ± 15 years; 22.6 ± 1.4 kg/m2) completed a whole-body cold (10°C) air exposure test and a cold-induced vasodilation (CIVD) test, which involved the immersion of the middle finger into ice-water for 30 min.Results
During the whole-body cold exposure, the durations until the onset of shivering for three monitored skeletal muscles were similar for both groups. Cold exposure increased the Tuvans' energy expenditure by (mean ± SD) 0.9 ± 0.7 kJ min−1 and the Europeans' by 1.3 ± 1.54 kJ min−1; these changes were not significantly different. The forearm-fingertip skin temperature gradient of the Tuvans was lower, indicating less vasoconstriction, than the Europeans during the cold exposure (0 ± 4.5°C vs. 8.8 ± 2.7°C). A CIVD response occurred in 92% of the Tuvans and 36% of the Europeans. In line, finger temperature during the CIVD test was higher in the Tuvans than the Europeans (13.4 ± 3.4°C vs. 3.9 ± 2.3°C).Conclusion
Cold-induced thermogenesis and the onset of shivering were similar in both populations. However, vasoconstriction at the extremities was reduced in the Tuvans compared to the Europeans. The enhanced blood flow to the extremities could be beneficial for living in an extreme cold environment by improving dexterity, comfort, and reducing the risk of cold-injuries. 相似文献986.
Maria Carolina Rodriguez Benavente Harrison B. Hughes Paul G. Kremer Ganesh P. Subedi Adam W. Barb 《Immunology》2023,170(2):202-213
Novel approaches are required to improve the efficacy of immunotherapies and increase the proportion of patients who experience a benefit. Antibody-dependent cell-mediated cytotoxicity (ADCC) contributes to the efficacy of many monoclonal antibodies therapies. Natural killer (NK) cells mediate ADCC, though responses are highly variable and depend on prior treatment as well as other factors. Thus, strategies to increase NK cell activity are expected to improve multiple therapies. Both cytokine treatment and NK cell receptor engineering are being explored to increase ADCC. Post-translational modifications, including glycosylation, are widely recognized as mediators of cellular processes but minimally explored as an alternative strategy to increase ADCC. We evaluated the impact of treatment with kifunensine, an inhibitor of asparagine-linked (N-)glycan processing, on ADCC using primary and cultured human NK cells. We also probed affinity using binding assays and CD16a structure with nuclear magnetic resonance spectroscopy. Treating primary human NK cells and cultured YTS-CD16a cells with kifunensine doubled ADCC in a CD16a-dependent manner. Kifunensine treatment also increased the antibody-binding affinity of CD16a on the NK cell surface. Structural interrogation identified a single CD16a region, proximal to the N162 glycan and the antibody-binding interface, perturbed by the N-glycan composition. The observed increase in NK cell activity following kifunensine treatment synergized with afucosylated antibodies, further increasing ADCC by an additional 33%. These results demonstrate native N-glycan processing is an important factor that limits NK cell ADCC. Furthermore, optimal antibody and CD16a glycoforms are defined that provide the greatest ADCC activity. 相似文献
987.
There is great diversity in in vitro fertilization (IVF) funding and reimbursement policies and practice throughout Europe and the rest of the world. While many existing reimbursement and regulatory frameworks address safety and legal concerns, economic factors also assume a central role. However, there are several problems with the evidence that is available on the economics of IVF. This suggests there is a need for more robust cost-effectiveness studies. It also indicates the need for alternative rationales to justify the reimbursement of IVF, which might more fully account for the social, political, ethical, and philosophical considerations embedded in notions of infertility and technology-driven reproductive treatments. The merits and limitations of five alternative rationales are discussed. The review suggests that while no existing single rationale provides a complete framework with which to support funding decisions, taken together they provide guideposts which signal important issues for consideration and highlight where further research, action, and debate are needed. 相似文献
988.
Zusammenfassung Die Markierung von Thrombozyten mit Na2
51CrO4 wurde in vitro unter verschiedenen Bedingungen untersucht. Dabei zeigte sich, daß Thrombozyten ein Vielfaches der Chromatmenge aufnehmen können, die üblicherweise verwendet wird. Die Inkorporationsrate steigt mit der Thrombozytenkonzentration, der Inkubationstemperatur und Inkubationszeit und ist außerdem vom Inkubationsmedium abhängig. Ein Teil des Chromats wird nur locker gebunden und läßt sich sehr rasch aus den markierten Plättchen eluieren. Die Bedeutung dieser Befunde in Hinsicht auf die optimalen Markierungsbedingungen für die Thrombozytenlebenszeitbestimmung und die Interpretation der dabei erhaltenen Kurven wird besprochen.
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
Summary The labelling of platelets with Na2 51CrO4 was investigated under different conditions in vitro. Platelets are able to incorporate a much greater amount of chormium as usually is used in survival studies. The incorporation rate of platelets is dependent mainly from the concentration of platelets, the incubation medium, further more from the time and temperature of incubation. It is higher in proteinfree solutions as Ringer or ACD than in plasma and only a certain amount of chromium is firmly bound by the cells. Under the present conditions 25% of the label can rapidly be eluted in vitro. The importance of those findings for optimal labelling conditions of platelets and for the interpretation of platelets survival curves is discussed.
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
989.
990.
Adam R. Cassidy Jane Holmes Bernstein David C. Bellinger Jane W. Newburger David R. DeMaso 《The Clinical neuropsychologist》2019,33(4):760-778
Objective: To determine whether visual-spatial processing style is associated with psychopathology in a large sample of adolescents with critical congenital heart disease (CHD). Local (part-oriented) style was hypothesized to increase risk for internalizing (but not externalizing) forms of psychopathology.Method: Participants included 278 adolescents with critical CHD (dextro-transposition of the great arteries?=?134, tetralogy of Fallot?=?58, single-ventricle cardiac anatomy requiring the Fontan procedure?=?86). Visual-spatial processing style was indexed using Copy Style Ratings from the Rey-Osterrieth Complex Figure-Developmental Scoring System. The Schedule for Affective Disorders and Schizophrenia for School-Aged Children–Present & Lifetime Version was used to determine presence/absence of diagnosable DSM-IV psychiatric disorder(s). Processing style and psychopathology were assessed concurrently.Results: Thirty-three percent of the sample had a part-oriented processing style. In multivariable binary logistic regression models, part-orientation was associated with more than twice the odds of having an anxiety disorder (lifetime: OR?=?2.2, p?=?.02, 95% CI?=?1.1–4.1; current: OR?=?2.7, p?=?.03, 95% CI?=?1.1–6.5) but was not associated with an increased risk for ADHD, disruptive behavior, or mood disorders (ps?>?.05).Conclusions: Adolescents with critical CHD who approach complex visual-spatial materials in a local, part-oriented fashion are more likely to meet criteria for an anxiety disorder than those who approach complexity more holistically. Part-orientation may make it more difficult for individuals to judge the relative importance of isolated details and engage in more adaptive perspective-taking. 相似文献