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Biomedical subjects

Atom Sarkar

Publications and source records attributed to Atom Sarkar.

7 recordsLinked to original sources

The mechanical fingerprint of a parallel polyprotein dimer.

We use the GCN4 oligomerization domain to engineer a covalently linked parallel polyprotein dimer based on the well-studied I27 domain of titin. We use single molecule atomic force microscopy techniques to stretch single polyprotein fibers and verify their mechanical properties. We find that the engineered polyprotein dimers extend in perfect register, doubling the unfolding force and halving the persistence length while keeping the contour length increase unchanged. These experiments directly confirm the mechanical scaling laws proposed for parallel bundles of modular proteins.

Biomechanical Phenomena↗

Brain tumor imaging and surgical management: the neurosurgeon's perspective.

Advances in imaging technologies have influenced neurosurgical techniques and decisions and have enabled previously impossible resections, and neurosurgeons rely on the various modalities to make surgery as safe as possible. We look at the different technologies that have developed and how they are used by neurosurgeons, in combination with the knowledge of anatomy, to evaluate brain and spinal tumors and make surgical decisions that improve treatment outcomes.

Angiography↗

The elasticity of individual titin PEVK exons measured by single molecule atomic force microscopy.

The I-band region of the giant muscle protein titin contains a large domain enriched for the amino acids proline, glutamate, valine, and lysine and is denoted the PEVK domain. The PEVK domain of titin encodes a random coil shown to be an important factor in the passive elasticity of titin. Muscle-specific splicing of 116 PEVK exons encodes this domain. It has been proposed that proline contents determine the elasticity of the PEVK polypeptide, where the individual exons code for "flexibility cassettes." To test this hypothesis, we have measured the elasticity of three distinct polypeptides encoded by individual PEVK exons (161, 120 and 184) that varied greatly in their proline contents (7, 14, and 37% respectively) and total PEVK contents (55, 70, and 87%). We used single molecule atomic force microscopy techniques to measure the persistence length, p, of the engineered PEVK proteins. Surprisingly, all three exons 161, 120, and 184 coded for proteins with similar values of persistence length, p = 0.92 +/- 0.38, 0.89 +/- 0.42, and 0.98 +/- 0.4 nm, respectively. We conclude that the PEVK exons encode polypeptides of similar elastic properties, unrelated to their total PEVK contents. Hence, alternative splicing solely adjusts the length of the PEVK domain of titin.

Alternative Splicing↗

Simultaneous atomic force microscope and fluorescence measurements of protein unfolding using a calibrated evanescent wave.

Fluorescence techniques for monitoring single-molecule dynamics in the vertical dimension currently do not exist. Here we use an atomic force microscope to calibrate the distance-dependent intensity decay of an evanescent wave. The measured evanescent wave transfer function was then used to convert the vertical motions of a fluorescent particle into displacement (SD = < 1 nm). We demonstrate the use of the calibrated evanescent wave to resolve the 20.1 +/- 0.5-nm step increases in the length of the small protein ubiquitin during forced unfolding. The experiments that we report here make an important contribution to fluorescence microscopy by demonstrating the unambiguous optical tracking of a single molecule with a resolution comparable to that of an atomic force microscope.

Biophysical Phenomena↗

Distal anterior inferior cerebellar artery aneurysm masquerading as a cerebellopontine angle tumor: case report and review of literature.

We present the case of a distal anterior inferior cerebellar artery (AICA) aneurysm masquerading as a cerebellopontine angle tumor in a 60-year-old right-handed man with previously undiagnosed polyarteritis nodosa (PAN). The patient presented with a 2-month history of progressive right-sided hearing loss, intermittent severe headache, and sudden onset of complete facial paralysis 3 weeks before admission. Magnetic resonance imaging, including post-gadolinium images, showed a 1.2-cm heterogeneously enhancing mass that slightly enlarged the right internal auditory canal. A right suboccipital craniotomy was performed, and a partially thrombosed fusiform AICA aneurysm was discovered just anterior to the VII/VIII nerve complex. The aneurysm was trapped and opened, and a thrombectomy was performed. Postoperatively, the patient experienced abdominal pain; liver function tests were abnormal. Investigation revealed a small retroperitoneal hemorrhage and aneurysms of the celiac axis and gastroduodenal arteries. Further investigation revealed an increased erythrocyte sedimentation rate, and a diagnosis of PAN was made. PAN is a well-identified factor in the genesis of peripheral vascular aneurysms. Aneurysms involving the hepatic, renal, coronary, pancreatic, and tibial arteries have been described. PAN is an extremely rare cause of intracranial aneurysm. Patients who present with aneurysms in unusual locations (e.g., distal AICA) should be investigated for vasculopathy and collagen vascular disorders.

Case Reports↗

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗