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J Shrager

Publications and source records attributed to J Shrager.

12 recordsLinked to original sources
PubMed2005

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.

Animals↗
PubMed2004

A small animal model of regional alveolar ventilation using HP 3He MRI1.

RATIONALE AND OBJECTIVES: The aim of this study was to establish a standardized procedure for the measurement of regional fractional ventilation in a healthy rat model as a baseline for further studies of pulmonary disorder models. MATERIALS AND METHODS: The lungs of five healthy male Sprague-Dawley rats were imaged using hyperpolarized helium-3 magnetic resonance imaging. From these images, regional fractional ventilation was calculated and maps generated detailing the distribution of fractional ventilation in the lung. The 1.56 mm x 1.56 mm x 4 mm regions of interest were assigned on 5 cm x 5 cm field of view lung maps. Histograms were also generated showing the frequency distribution of fractional ventilation values. To compare fractional ventilation values between animals, the ventilation procedure was standardized to results from individual pulmonary function tests. Each animal's spontaneous tidal volume, respiratory rate, and inspiration percentage (percent of total respiratory cycle in inspiration) were used in their mechanical ventilation settings. RESULTS: Results were similar among all five healthy rats based on examination of ventilation distribution maps and frequency distribution histograms. Mean (0.13) and standard deviation (0.07) were calculated for fractional ventilation in each animal. However, these values were determined to be influenced by slice selection, and therefore the maps and histograms were favored in analysis of results. CONCLUSION: This study shows consistent results in healthy rat lungs and will serve as a baseline study for future measurements in emphysematous rat lungs.

Animals↗
PubMed2004

Temporal aggregation bias and inference of causal regulatory networks.

Time course experiments with microarrays have begun to provide a glimpse into the dynamic behavior of gene expression. In a typical experiment, scientists use microarrays to measure the abundance of mRNA at discrete time points after the onset of a stimulus. Recently, there has been much work on using these data to infer causal regulatory networks that model how genes influence each other. However, microarray studies typically have slow sampling rates that can lead to temporal aggregation of the signal. That is, each successive sampling point represents the sum of all signal changes since the previous sample. In this paper, we show that temporal aggregation can bias algorithms for causal inference and lead them to discover spurious relations that would not be found if the signal were sampled at a much faster rate. We discuss the implications of temporal aggregation on inference, the problems it creates, and potential directions for solutions.

Computational Biology↗
PubMed2000

Developmental myosin heavy chains in the adult human diaphragm: coexpression patterns and effect of COPD.

In preliminary experiments we noted developmental (i.e., embryonic and neonatal) myosin heavy chains (MHCs) in the diaphragms of patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that this finding represented new fiber formation secondary to injury associated with the mechanical stress of COPD or previously undescribed MHCs in the human diaphragm. To distinguish between these possibilities, we analyzed diaphragmatic biopsies obtained from 9 patients with severe COPD (forced expiratory volume in 1 s = 21 +/- 2% predicted, residual volume = 283 +/- 22% predicted) and 10 age-matched controls. First, using immunocytochemistry with specific monoclonal antibodies, we noted that control diaphragms had greater proportions of fibers expressing embryonic (50 +/- 2 vs. 28 +/- 3%, P < 0.0001) and neonatal (52 +/- 2 vs. 32 +/- 3%, P < 0.001) MHCs than COPD diaphragms. Second, SDS-PAGE demonstrated that these developmental MHCs represented only a very small fraction of the diaphragmatic MHC content. Third, the RT-PCR demonstrated mRNA coding for embryonic and neonatal MHCs in COPD and control diaphragms. Last, COPD and control diaphragms exhibited normal histology on light microscopy. We conclude that the presence of developmental MHC isoforms does not indicate new fiber formation in diaphragms of patients with severe COPD. Although these results represent the first systematic description of embryonic and neonatal MHCs in normal adult human diaphragms, their function remains to be elucidated.

Adult↗
PubMed1997

Perforated villous adenoma of the cecum: report of a case.

Villous adenomas are common neoplasms of the colon, often causing anemia or hemoccult positive stools. Less typically, these lesions may result in abdominal pain, melena, obstruction, or change in bowel habits. Intussusception may occur, but this complication is unusual in adults. Spontaneous bowel perforation attributable to colonic polyps has not been previously reported. We present here the first reported case of an adenomatous polyp with bowel perforation and bladder involvement.

Adenoma, Villous↗
PubMed1997

Oral pigmentation representing Laugier-Hunziker syndrome.

Oral pigmentation is seen fairly commonly in dermatologic practice. Several conditions must be considered in the differential diagnosis. We present a patient whose condition highlights the clinical syndrome known as Laugier-Hunziker and provides the opportunity to review the clinical course, pathologic features, and literature of this uncommon syndrome.

Diagnosis, Differential↗
PubMed1996

The emergence of hierarchical clustered representations in a Hebbian neural network model that simulates aspects of development in the neocortex.

In this paper we show how clustered representations emerge within a simple neural network which simulates some aspects of the development of the mammalian neocortex. Synapse death and stabilization, postulated to occur in the real neocortex are modelled. The representations that emerge under certain conditions show a spatially hierarchical coarse- and fine-grain cluster structure. In two sets of simulations where the relative lengths of excitory and inhibitory links are different we show that the emergence of clustered representations depends upon changes to this parameter.

Journal Article↗
PubMed1988

A graph-dynamic model of the power law of practice and the problem-solving fan-effect.

Numerous human learning phenomena have been observed and captured by individual laws, but no unified theory of learning has succeeded in accounting for these observations. A theory and model are proposed that account for two of these phenomena: the power law of practice and the problem-solving fan-effect. The power law of practice states that the speed of performance of a task will improve as a power of the number of times that the task is performed. The power law resulting from two sorts of problem-solving changes, addition of operators to the problem-space graph and alterations in the decision procedure used to decide which operator to apply at a particular state, is empirically demonstrated. The model provides an analytic account for both of these sources of the power law. The model also predicts a problem-solving fan-effect, slowdown during practice caused by an increase in the difficulty of making useful decisions between possible paths, which is also found empirically.

Decision Making↗
PubMedDate not supplied

Revising regulatory networks: from expression data to linear causal models.

Discovering the complex regulatory networks that govern mRNA expression is an important but difficult problem. Many current approaches use only expression data from microarrays to infer the likely network structure. However, this ignores much existing knowledge because for a given organism and system under study, a biologist may already have a partial model of gene regulation. We propose a method for revising and improving these initial models, which may be incomplete or partially incorrect, with expression data. We demonstrate our approach by revising a model of photosynthesis regulation proposed by a biologist for Cyanobacteria. Applied to wild type expression data, our system suggested several modifications consistent with biological knowledge. Applied to a mutant strain, our system correctly modified the disabled gene. Power experiments with synthetic data that indicate that reliable revision is feasible even with a small number of samples.

Gene Expression Profiling↗