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Biomedical subjects

Jayashree Srinivasan

Publications and source records attributed to Jayashree Srinivasan.

5 recordsLinked to original sources
PubMed2002

Isolated dissections and dissecting aneurysms of the posterior inferior cerebellar artery: topic and literature review.

Isolated dissections of the posterior inferior cerebellar artery (PICA) are rare. Thus, no large series of cases have been reported in the literature. Due to limited knowledge regarding the natural history of these lesions and the lack of high-quality evidence supporting various treatment options, management is controversial and practice parameters are ill defined. In order to offer a comprehensive reference for the diagnosis and management of isolated PICA dissections, the authors reviewed the National Library of Medicine from 1966 to October 2001. Twenty-seven patients averaging 43.6 years of age and including 14 males and 13 females were reported. Subarachnoid hemorrhage occurred in 20 patients, and two died. Dissections were located in the proximal PICA in 22 patients and were three times more common on the left side (left:right=3:1). Six patients were managed conservatively, and four with endovascular techniques. Seventeen had open surgery: five underwent resection, two went through trapping, and two had proximal clipping. Wrapping with muscle was performed in two patients, encasement with Sundt clips in two, and four had occipital artery (OA)-PICA bypass surgery. A meticulous analysis of reported cases with regard to clinical and pathological features, management strategies, and outcomes is presented.

Adult↗
PubMed2002

Evaluation of a novel shape-based computational filter for lead evolution: application to thrombin inhibitors.

A novel shape-feature-based computational method is described and used to rapidly filter compound libraries. The computational model, built using three-dimensional conformations of active and inactive molecules, consists of a collection of whole molecule shapes and chemical feature positions that are ranked according to their correlation with activity. A small ensemble of these shapes and features is used to filter virtual compound libraries. The method is applied to two thrombin data sets and is shown to be efficient in identifying novel scaffolds with enhanced hit rates.

Combinatorial Chemistry Techniques↗
PubMed2002

Hemodynamic response changes in cerebrovascular disease: implications for functional MR imaging.

BACKGROUND AND PURPOSE: Patients with cerebrovascular occlusive disease may develop compensatory changes in local cerebral vasculature with a resultant loss of vascular reactivity. These alterations can affect the blood oxygen level-dependent (BOLD) signal that is the basis for functional MR imaging. We investigated the BOLD signal in patients with unilateral cerebrovascular disease to ascertain the clinical utility of functional MR imaging in these patients. METHODS: Five healthy volunteers and three patients with cerebro-occlusive disease were imaged with both a block and an event-related design of a visually cued bilateral motor task. Activation maps were calculated, and individual hemodynamic response curves were generated for left and right primary motor cortices. Vascular reserve was determined for the relevant vascular territory by using transcranial Doppler ultrasonography (US). RESULTS: In the event-related data, the amplitude of the BOLD response was significantly decreased in the motor cortex ipsilateral to the stenosis and showed significant delays in the timing of the hemodynamic response. In contrast, the longer duration stimulus and longer TR of the block design showed significant decreases in the BOLD amplitude but no significant interhemispheric temporal differences. Corroborating the hemodynamic status, transcranial Doppler US analysis showed diminished vascular reserve ipsilateral to the lesion. CONCLUSION: Differences in the results between the event-related and block paradigms reflect the sensitivity to alterations in autoregulation or vascular compliance. These changes in the vasculature directly affect the BOLD contrast underlying functional MR imaging. Thus, while this technique remains a useful clinical tool, caution is warranted when studying patients with cerebrovascular disease.

Adult↗
PubMedDate not supplied

Using pharmacophore models to gain insight into structural binding and virtual screening: an application study with CDK2 and human DHFR.

This study provides results from two case studies involving the application of the HypoGenRefine algorithm within Catalyst for the automated generation of excluded volume from ligand information alone. A limitation of pharmacophore feature hypothesis alone is that activity prediction is based purely on the presence and arrangement of pharmacophoric features; steric effects remained unaccounted. Recently reported studies have illustrated the usefulness of combining excluded volumes to the pharmacophore models. In general, these excluded volumes attempt to penalize molecules occupying steric regions that are not occupied by active molecules. The HypoGenRefine algorithm in Catalyst accounts for steric effects on activity, based on the targeted addition of excluded volume features to the pharmacophores. The automated inclusion of excluded volumes to pharmacophore models has been applied to two systems: CDK2 and human DHFR. These studies are used as examples to illustrate how ligands could bind in the protein active site with respect to allowed and disallowed binding regions. Additionally, automated refinement of the pharmacophore with these excluded volume features provides a more selective model to reduce false positives and a better enrichment rate in virtual screening.

Algorithms↗