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21.
Frank A Middleton Marco G Trauzzi Antony E Shrimpton Karen L Gentile Christopher P Morley Helena Medeiros Michele T Pato Carlos N Pato 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(1):28-32
Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded. 相似文献
22.
23.
Frank G. Shellock Jerrold H. Mink Andrew L. Deutsch James Fox Todd Molnar Ronald Kvitne Richard Ferkel 《Journal of magnetic resonance imaging : JMRI》1994,4(4):590-594
The effect of a newly developed patellar realignment brace was evaluated in 21 patellofemoral joints (19 patients) with patellar subluxation (13 joints with lateral subluxation and eight with medial subluxation) by using active-movement, loaded kinematic magnetic resonance (MR) imaging. Sixteen patellofemoral joints (76%) demonstrated a qualitative correction of or improvement in patellar subluxation (ie, centralization of the patella or a decrease in the displacement of the patella) after application of the brace. Four of the five “failures” occurred in patellofemoral joints that had patella alta and/or dysplastic bone anatomy. These results indicate that the patellar realignment brace was able to counteract patellar subluxation in the majority of patellofemoral joints studied, as shown by active-movement, loaded kinematic MR imaging. This brace appears to be useful for conservative treatment of patients with patellofemoral joint pain secondary to patellar malalignment and maltracking. 相似文献
24.
Thomas Donohue Morton J. Kern Richard Bach Frank Aguirre Thomas Wolford 《Catheterization and cardiovascular interventions》1993,28(2):155-161
The vasomotor response of native human collateral vessels to pharmacologic or hemodynamic vasodilatory stimuli is not well known. We describe a case where retrograde collateral flow velocity was measured both at baseline and following selected hemodynamic and pharmacologic interventions. This index case represents the first in a series of potential human physiologic studies designed to address questions pertaining to control of collateral blood supply in humans. © 1993 Wiley-Liss, Inc. 相似文献
25.
Humoral and cellular immunity following severe head injury: review and current investigations. 总被引:9,自引:0,他引:9
Infection is a common and serious complication of severe head injury. Immunocompetence in 25 severely head injured patients was investigated by measuring: (1) delayed-type hypersensitivity (DTH) skin test responses to common antigens; (2) phytohaemagglutinin (PHA) stimulated peripheral blood lymphocyte (PBL): blastogenesis, phenotype expression, and lymphokine production; (3) lymphokine-activated killer (LAK) cytotoxicity, antibody dependent cellular cytotoxicity (ADCC) and natural killer (NK) cytotoxicity; and (4) immunoglobulin and complement levels. The incidence of anergy to DTH skin testing was 100%. There was a decrease in PHA stimulated: PBL blastogenesis (p = 0.002), T-cell expression (p = 0.018), helper T-cell expression (p less than 0.001), interleukin-2 receptor expression (p less than 0.001), interleukin-2 production (p = 0.035) and gamma-interferon production (p less than 0.001). LAK cytotoxicity was depressed following incubation with IL-2 (p less than 0.001). There was no significant decrease in immunoglobulin levels and all acute phase reactants tested increased. The results of this study indicate that the cellular arm of immune response, including lymphocyte activation and cytokine production, is suppressed following severe head injury. The lack of enhancement in LAK cytotoxicity following incubation of PBLs with interleukin-2 suggests that factors other than decreased interleukin-2 production, such as the inherent lymphocyte dysfunction, other soluble mediators or suppressor cells, may be responsible for the reduction in cellular immunity observed following severe head injury. 相似文献
26.
Frank Lindseth Thomas Lang? Jon Bang Toril A Nagelhus Hernes 《Computer aided surgery》2002,7(4):197-222
27.
Dnyanesh N Tipre James J Fox Daniel P Holt Gilbert Green Jianhua Yu Martin Pomper Robert F Dannals Frank M Bengel 《Journal of nuclear medicine》2008,49(7):1189-1195
The sympathetic nervous system of the heart plays a key role in the pathophysiology of various cardiac diseases. Small-animal models are valuable for obtaining further insight into mechanisms of cardiac disease and therapy. To determine the translational potential of cardiac neuronal imaging from rodents to humans, we characterized the rat sympathetic nervous system using 3 radiotracers that reflect different subcellular mechanisms: (11)C-meta-hydroxyephedrine (HED), a tracer of neuronal transport showing stable uptake and no washout in healthy humans; (11)C-phenylephrine (PHEN), a tracer of vesicular leakage and intraneuronal metabolic degradation with initial uptake and subsequent washout in humans; and (11)C-epinephrine (EPI), a tracer of vesicular storage with stable uptake and no washout in humans. METHODS: We used a small-animal PET system to study healthy male Wistar rats at baseline, after desipramine (DMI) pretreatment (DMI block), and with DMI injection 15 min after tracer delivery (DMI chase). The rats were kept under general isoflurane anesthesia while dynamic emission scans of the heart were recorded for 60 min after radiotracer injection. A myocardial retention index was determined by normalizing uptake at 40 min to the integral under the arterial input curve. Washout rates were determined by monoexponential fitting of myocardial time-activity curves. RESULTS: At baseline, HED showed high myocardial uptake and sustained retention, EPI showed moderate uptake and significant biphasic washout, and PHEN showed moderate uptake and monoexponential washout. The average (+/- SD) left ventricular retention index for HED, PHEN, and EPI was 7.38% +/- 0.82%/min, 3.43% +/- 0.45%/min, and 4.24% +/- 0.59%/min, respectively; the washout rate for HED, PHEN, and EPI was 0.13% +/- 0.23%/min, 1.13% +/- 0.35%/min, and 0.50% +/- 0.24%/min, respectively. The DMI chase resulted in increased washout only for HED. DMI block decreased myocardial uptake of all tracers by less than 90%. CONCLUSION: Kinetic profiles of HED in the rat myocardium were similar to those of HED in humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN were encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover, and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology in humans. 相似文献
28.
Harold C. Lyon Jr. James C. Healy James R. Bell Joseph F. O'Donnell Edward K. Shultz Robert S. Wigton Frank Hirai J. Robert Beck 《Journal of medical systems》1991,15(2):117-132
Richard E. Clark in his widely published comprehensive studies and meta-analyses of the literature on computer assisted instruction (CAI) has decried the lack of carefully controlled research, challenging almost every study which shows the computer-based intervention to result in significant post-test proficiency gains over a non-computer-based intervention. We report on a randomized study in a medical school setting where the usual confounders found by Clark to plague most research, were carefully controlled. PlanAlyzer is a microcomputer-based, self-paced, case-based, event-driven system for medical education which was developed and used in carefully controlled trials in a second year medical school curriculum to test the hypothesis that students with access to the interactive programs could integrate their didactic knowledge more effectively and/or efficiently than with access only to traditional textual “nonintelligent” materials. PlanAlyzer presents cases, elicits and critiques a student's approach to the diagnosis of two common medical disorders: anemias and chest pain. PlanAlyzer uses text, hypertext, images and critiquing theory. Students were randomized, one half becoming the experimental group who received the interactive PlanAlyzer cases in anemia, the other half becoming the controls who received the exact same content material in a text format. Later in each year there was a crossover, the controls becoming the experimentals for a similar intervention with the cardiology PlanAlyzer cases. Preliminary results at the end of the first two full trials shows that the programs have achieved most of the proposed instructional objectives, plus some significant efficiency and economy gains. 96 faculty hours of classroom time were saved by using PlanAlyzer in their place, while maintaining high student achievement. In terms of student proficiency and efficiency, the 328 students in the trials over two years were able to accomplish the project's instructional objectives, and the experimentals accomplished this in 43% less time than the controls, achieving the same level of mastery. However, in spite of these significant efficiency findings, there have been no significant proficiency differences (as measured by current factual and higher order multiple choice post-tests) between the experimental and control groups. Very careful controls were used to avoid what Clark has found to be the most common confounders of CAI research. Accordingly, this research proved Clark's rival hypothesis, that the computer, in itself, does not appear to contribute to proficiency gains, at least as measured by our limited post-testing. Clark's position is that the computer is primarily a vehicle—as is either a pill or a hypodermic needle for delivering a drug. The hypodermic needle can deliver the drug more efficiently than can the pill, (as can the computer deliver the subject matter content more efficiently, as our research indicates), but the same content is delivered. At the same time, we proved our own hypothesis, as far as efficiency gains resulting from the computer are concerned. However, going beyond Clark's research, we may be teaching processes both more effectively and efficiently with the computer (experience in problem-solving or clinical reasoning and pattern recognition) which our current post-tests do not adequately measure. Our on-going research suggests additional inquiry in several areas: better evaluation instruments to measure the clinical reasoning skills PlanAlyzer was designed to teach; the addition of more advanced cases to determine if this might transform efficiency gains of the computer group into proficiency gains; the addition of enhanced graphic decision support tools and other pedagogical enhancements including cognitive feedback to strengthen PlanAlyzer's power to teach complex concepts of medical decision-making. 相似文献
29.
Reactive oxygen species: a breath of life or death? 总被引:7,自引:0,他引:7
New insights into cancer cell-specific biological pathways are urgently needed to promote development of rationally targeted therapeutics. Reactive oxygen species (ROS) and their role in cancer cell response to growth factor signaling and hypoxia are emerging as verdant areas of exploration on the road to discovering cancer's Achilles heel. One of the distinguishing and near-universal hallmarks of cancer growth is hypoxia. Unregulated cellular proliferation leads to formation of cellular masses that extend beyond the resting vasculature, resulting in oxygen and nutrient deprivation. The resulting hypoxia triggers a number of critical adaptations that enable cancer cell survival, including apoptosis suppression, altered glucose metabolism, and an angiogenic phenotype. Ironically, recent investigations suggest that oxygen depletion stimulates mitochondria to elaborate increased ROS, with subsequent activation of signaling pathways, such as hypoxia inducible factor 1alpha, that promote cancer cell survival and tumor growth. Because mitochondria are key organelles involved in chemotherapy-induced apoptosis induction, the relationship between mitochondria, ROS signaling, and activation of survival pathways under hypoxic conditions has been the subject of increased study. Insights into mechanisms involved in ROS signaling may offer novel avenues to facilitate discovery of cancer-specific therapies. Preclinical and clinical evaluation of agents that modify ROS signaling in cancer offers a novel avenue for intervention. This review will cover recent work in ROS-mediated signaling in cancer cells and its potential as a target for developmental therapeutics. 相似文献
30.
An Analysis of the Buy-Vs-Lease Decision 总被引:1,自引:0,他引:1