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L R Frank

Publications and source records attributed to L R Frank.

At least 19 recordsLinked to original sources

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Fertility of broiler breeders following categorization by the OptiBreed sperm quality index when hens are inseminated with a constant number of sperm.

If semen quality was known prior to insemination, sperm doses could possibly be decreased, maximizing the number of hens inseminated. The sperm quality index (SQI), an indicator of overall semen quality, is determined by the number of deflections in a light path due to sperm movement inside a capillary tube. The objectives of this study were 1) to determine the age at which the SQI becomes a static predictor of semen quality and 2) to determine if fertility of males with a higher SQI responds more favorably to insemination dose reduction than that of males with a lower SQI. Weekly from 23 to 32 wk of age, 144 Cobb males were tested for SQI. At 32 wk of age, males were placed into four groups that represented the SQI population quartiles as follows: poor, fair, good, and best. A fifth SQI group, uncategorized, was created to determine fertility of the original population by mixing equal amounts of semen from each of the four groups. Semen was collected weekly from 33 to 40 wk of age from 18 males in each of the four groups, pooled by group, and used to inseminate 30 hens per group with 50 or 100 million sperm. Eggs were collected daily, incubated, and broken out to determine fertility. Correlation coefficients between weekly SQI results and overall averages for individual males indicated that the SQI stabilized after the birds were 28 wk of age. The main effect for SQI selection revealed that the best SQI group had the highest fertility (88%), which did not differ from the good (83%) or fair group (82%) but was greater than the uncategorized group (80%). Fertilities of the top three groups and the uncategorized group were higher than the poor group (63%) (P < 0.0001, SEM 2.18). In addition, there was an interaction between SQI classification and insemination dose. Fertilities of the top three SQI groups were similar at the 50 and 100 million sperm doses. However, the poor and uncategorized SQI groups had lower fertility at the 50 million dose as compared to the 100 million dose. By categorizing males into SQI groups after 28 wk of age, insemination dose can be reduced, maximizing a male's fertilizing potential.

Animals↗

T(1) and T(2) selective method for improved SNR in CSF-attenuated imaging: T(2)-FLAIR.

We present here a method for improving SNR in CSF-attenuated imaging relative to the standard technique of using an inversion pulse and imaging at the null point of CSF. In this new method the inversion pulse is replaced with a 90(x)-180(y)-90(x) preparation sequence that provides T(1) and T(2) selectivity. This allows the tissue magnetization to recover more rapidly, allows for the use of shorter TR values, and reduces T(1) weighting. Magn Reson Med 45:529-532, 2001.

Blood Volume↗

Nonlinear temporal dynamics of the cerebral blood flow response.

The linearity of the cerebral perfusion response relative to stimulus duration is an important consideration in the characterization of the relationship between regional cerebral blood flow (CBF), cerebral metabolism, and the blood oxygenation level dependent (BOLD) signal. It is also a critical component in the design and analysis of functional neuroimaging studies. To study the linearity of the CBF response to different duration stimuli, the perfusion response in primary motor and visual cortices was measured during stimulation using an arterial spin labeling technique with magnetic resonance imaging (MRI) that allows simultaneous measurement of CBF and BOLD changes. In each study, the perfusion response was measured for stimuli lasting 2, 6, and 18 sec. The CBF response was found in general to be nonlinearly related to stimulus duration, although the strength of nonlinearity varied between the motor and visual cortices. In contrast, the BOLD response was found to be strongly nonlinear in both regions studied, in agreement with previous findings. The observed nonlinearities are consistent with a model with a nonlinear step from stimulus to neural activity, a linear step from neural activity to CBF change, and a nonlinear step from CBF change to BOLD signal change.

Cerebrovascular Circulation↗

Estimation of respiration-induced noise fluctuations from undersampled multislice fMRI data.

Functional MRI time series data are known to be contaminated by highly structured noise due to physiological fluctuations. Significant components of this noise are at frequencies greater than those critically sampled in standard multislice imaging protocols and are therefore aliased into the activation spectrum, compromising the estimation of functional activations and the determination of their significance. However, in this work it is demonstrated that unaliased noise information is available in multislice data, and can be used to estimate and reduce noise due to high-frequency respiratory-related fluctuations. Magn Reson Med 45:635-644, 2001. Published 2001 Wiley-Liss, Inc.

Heart↗

Anisotropy in high angular resolution diffusion-weighted MRI.

The diffusion in voxels with multidirectional fibers can be quite complicated and not necessarily well characterized by the standard diffusion tensor model. High angular resolution diffusion-weighted acquisitions have recently been proposed as a method to investigate such voxels, but the reconstruction methods proposed require sophisticated estimation schemes. We present here a simple algorithm for the identification of diffusion anisotropy based upon the variance of the estimated apparent diffusion coefficient (ADC) as a function of measurement direction. The rationale for this method is discussed, and results in normal human subjects acquired with a novel diffusion-weighted stimulated-echo spiral acquisition are presented which distinguish areas of anisotropy that are not apparent in the relative anisotropy maps derived from the standard diffusion tensor model. Published 2001 Wiley-Liss, Inc.

Algorithms↗

Detection power, estimation efficiency, and predictability in event-related fMRI.

Experimental designs for event-related functional magnetic resonance imaging can be characterized by both their detection power, a measure of the ability to detect an activation, and their estimation efficiency, a measure of the ability to estimate the shape of the hemodynamic response. Randomized designs offer maximum estimation efficiency but poor detection power, while block designs offer good detection power at the cost of minimum estimation efficiency. Periodic single-trial designs are poor by both criteria. We present here a theoretical model of the relation between estimation efficiency and detection power and show that the observed trade-off between efficiency and power is fundamental. Using the model, we explore the properties of semirandom designs that offer intermediate trade-offs between efficiency and power. These designs can simultaneously achieve the estimation efficiency of randomized designs and the detection power of block designs at the cost of increasing the length of an experiment by less than a factor of 2. Experimental designs can also be characterized by their predictability, a measure of the ability to circumvent confounds such as habituation and anticipation. We examine the relation between detection power, estimation efficiency, and predictability and show that small increases in predictability can offer significant gains in detection power with only a minor decrease in estimation efficiency.

Artifacts↗

Sleep deprivation, EEG, and functional MRI in depression: preliminary results.

One night of total or partial sleep deprivation (SD) produces temporary remissions in 40-60% of patients with major depression. Two unmedicated patients with major depression and a matched control received quantitative perfusion MR images at baseline and after one night of partial SD (PSD). A reduction > or =30% in the 17-item Hamilton Depression Rating Scale (omitting sleep and weight loss items) defined antidepressant response. Theory, techniques, strengths and weaknesses of quantitative perfusion MRI are described in detail. At baseline, the responder exhibited elevated perfusion covering ventral anterior cingulate/medial frontal cortex; the control's maximal perfusion area was markedly smaller. The nonresponder's perfusion was lowest of all, particularly ventrally. PSD decreased perfusion over much of the responder's hyperperfused area but did not change the nonresponder's scan. These preliminary findings are consistent with previous SD studies using PET and SPECT.

Depressive Disorder↗

Local perfusion and metabolic demand during exercise: a noninvasive MRI method of assessment.

A noninvasive magnetic resonance imaging (MRI) method to assess the distribution of perfusion and metabolic demand (Q/VO(2)) in exercising human skeletal muscle is described. This method combines two MRI techniques that can provide accurate multiple localized measurements of Q/VO(2) during steady-state plantar flexion exercise. The first technique, (31)P chemical shift imaging, permits the acquisition of comparable phosphorus spectra from multiple voxels simultaneously. Because phosphocreatine (PCr) depletion is directly proportional to ATP hydrolysis, its relative depletion can be used as an index of muscle O(2) uptake (VO(2)). The second MRI technique allows the measurement of both spatially and temporally resolved muscle perfusion in vivo by using arterial spin labeling. Promising validity and reliability data are presented for both MRI techniques. Initial results from the combined method provide evidence of a large variation in Q/VO(2), revealing areas of apparent under- and overperfusion for a given metabolic turnover. Analysis of these data in a similar fashion to that employed in the assessment of ventilation-to-perfusion matching in the lungs revealed a similar second moment of the perfusion distribution and PCr distribution on a log scale (log SD(Q) and log SD(PCr)) (0.47). Modeling the effect of variations in log SD(Q) and log SD(PCr) in terms of attainable VO(2), assuming no diffusion limits, indicates that the log SD(Q) and log SD(PCr) would allow only 92% of the target VO(2) to be achieved. This communication documents this novel, noninvasive method for assessing Q/VO(2), and initial data suggest that the mismatch in Q/VO(2) may play a significant role in determining O(2) transport and utilization during exercise.

Adult↗

fMRI measurement of brain dysfunction in alcohol-dependent young women.

BACKGROUND: Studies of brain functioning in alcohol-dependent adults have produced varied results but generally suggest that alcohol affects brain functioning and that relatively short durations of heavy drinking may adversely affect women. It remains unclear when in the course of alcohol dependency and at which developmental stage these brain changes emerge. Our neuropsychological studies have indicated that drinking-related neurocognitive effects occur as early as adolescence (Brown et al., 2000; Tapert & Brown, 1999). This study seeks to characterize brain regions that subserve the affected neurocognitive functions. METHODS: Alcohol-dependent young women (n = 10) were recruited from a longitudinal study of alcohol- and drug-abusing youth, all of whom met criteria for alcohol dependence. Control participants (n = 10) had no history of alcohol or drug problems and were comparable with alcohol-dependent participants on age (18-25 years), family history of alcohol use disorders, and education. After a minimum of 72 hr of abstinence, functional magnetic resonance imaging, neuropsychological, alcohol/drug involvement, and mood data were collected. Participants performed spatial working memory and vigilance tasks during functional magnetic resonance imaging acquisition to probe brain response. RESULTS: Alcohol-dependent women demonstrated significantly less blood oxygen level-dependent response than controls during the spatial working memory task in the right superior and inferior parietal, right middle frontal, right postcentral, and left superior frontal cortex, after controlling for the baseline vigilance response. CONCLUSIONS: Working memory produces a larger neuronal response in some cortical regions than vigilance. Alcohol-dependent women showed less differential response to working memory than controls in frontal and parietal regions, especially in the right hemisphere. Heavy, chronic drinking appears to produce adverse neural effects that are detectable by functional magnetic resonance imaging.

Adolescent↗

Cartilage imaging techniques: current clinical applications and state of the art imaging.

The high incidence of cartilage lesions, coupled with the recent advances for their surgical and nonsurgical treatment, have necessitated the development of techniques for accurate diagnosis and monitoring of these lesions. Although arthroscopy has been the standard for cartilage evaluation, magnetic resonance imaging has emerged as the imaging method of choice, allowing analysis of its infrastructure and surface abnormalities. The authors will focus on current clinical applications for articular cartilage analysis and advances and the future direction of the imaging of articular cartilage.

Cartilage, Articular↗

Characterization of the "red zone" of knee meniscus: MR imaging and histologic correlation.

PURPOSE: To determine the extent and vascularity of knee menisci with conventional and gadolinium-enhanced magnetic resonance (MR) imaging in cadaveric specimens, with histologic findings as the reference standard, and to investigate signal intensity changes in menisci and perimeniscal soft tissues in symptomatic patients. MATERIALS AND METHODS: Radial dimensions and enhancement patterns of menisci were recorded and compared in (a) 12 cadaveric menisci examined with conventional and gadolinium-enhanced intermediate-weighted and fat-suppressed T1-weighted spin-echo MR imaging, high-spatial-resolution T1-weighted and fast low-angle shot MR imaging, and gross anatomic and histologic specimens and (b) 18 patients examined with conventional and gadolinium-enhanced fat-suppressed T1-weighted spin-echo MR imaging. RESULTS: No differences in radial measurements of the meniscus were found for different MR techniques (P =.551). Despite the presence of vessels in the peripheral 10%-15% of the menisci, no enhancement of menisci was detected in specimens or patients. Perimeniscal soft-tissue enhancement adjacent to the posterior horn was greater than that adjacent to the anterior horn (P <.05), and enhancement of the lateral meniscal body was greater than that of the medial meniscal body (P <.05). CONCLUSION: The wedge-shaped low-signal-intensity structure seen on MR images represents the entire meniscus. Intravenous injection of contrast material does not appear to be useful for differentiation of the vascularized from the nonvascularized zone of the meniscus.

Aged↗

Is MAST in the past? The pros and cons of MAST usage in the field.

Initially, MAST was viewed as a panacea for hypovolemic trauma patients. Through decades of study, this has not panned out. However, MAST seems to stabilize and decrease bleeding in pelvic and long-bone fractures of the lower extremities. It also appears useful in anaphylaxis and in non-traumatic intra-abdominal hemorrhage. The suit has proven deleterious to trauma victims with moderate hypotension (systolic BP 50-90 mm Hg) who face only a short ride to a hospital, especially those with thoracic injuries. Its role in patients with severe hypotension or long prehospital transport times remains unclear. In severely hypotensive patients, the improvement in BP and oxygenation to the heart and brain may override any negative effects of continued hemorrhage. We must wait for further studies to resolve these issues.

Accidents, Traffic↗

Dynamic imaging of perfusion in human skeletal muscle during exercise with arterial spin labeling.

MR images acquired by using an arterial spin-labeling technique showed spatial and temporal variations of perfusion in the skeletal muscle of exercising humans. Perfusion measurements made during plantar flexion exercise in normal volunteers were consistent with those obtained by traditional techniques reported in the literature. Spatial heterogeneity of perfusion values clearly delineated the various muscle groups within the lower leg. These results are interpreted in terms of a quantitative model for the perfusion signal in muscle. This method can provide a useful tool in the study of muscle physiology. Magn Reson Med 42:258-267, 1999. Published 1999 Wiley-Liss, Inc.

Arteries↗

Involvement of striate and extrastriate visual cortical areas in spatial attention.

We investigated the cortical mechanisms of visual-spatial attention while subjects discriminated patterned targets within distractor arrays. Functional magnetic resonance imaging (fMRI) was used to map the boundaries of retinotopic visual areas and to localize attention-related changes in neural activity within several of those areas, including primary visual (striate) cortex. Event-related potentials (ERPs) and modeling of their neural sources, however, indicated that the initial sensory input to striate cortex at 50-55 milliseconds after the stimulus was not modulated by attention. The earliest facilitation of attended signals was observed in extrastriate visual areas, at 70-75 milliseconds. We hypothesize that the striate cortex modulation found with fMRI may represent a delayed, re-entrant feedback from higher visual areas or a sustained biasing of striate cortical neurons during attention. ERP recordings provide critical temporal information for analyzing the functional neuroanatomy of visual attention.

Adult↗

Mapping the physiological parameters of articular cartilage with magnetic resonance imaging.

The ability of magnetic resonance imaging (MRI) to visualize the spatial distribution of parameters related to the physiological and structural properties of tissues makes it an ideal tool for the study of articular cartilage. A variety of ingenious MRI methods have been devised to probe the complex composition and biochemistry of normal and degenerate articular cartilage. In this article we review the current status of this research and pose some questions concerning the future directions of articular cartilage research and clinical applications.

Cartilage Diseases↗

Articular cartilage in the knee: mapping of the physiologic parameters at MR imaging with a local gradient coil--preliminary results.

The authors designed and constructed a local gradient coil that produces large gradients and short rise times and connects to their clinical system. In a cadaveric patellar cartilage specimen, the coil was used to acquire images of the physiologic parameters T1, T2, proton density, and apparent diffusion coefficient. Variations in these parameters were evident in regions of normal and abnormal cartilage.

Cartilage, Articular↗