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Biomedical subjects

R Acharya

Publications and source records attributed to R Acharya.

At least 19 recordsLinked to original sources
PubMed1998

Spatial and temporal dynamics of DNA replication sites in mammalian cells.

Fluorescence microscopic analysis of newly replicated DNA has revealed discrete granular sites of replication (RS). The average size and number of replication sites from early to mid S-phase suggest that each RS contains numerous replicons clustered together. We are using fluorescence laser scanning confocal microscopy in conjunction with multidimensional image analysis to gain more precise information about RS and their spatial-temporal dynamics. Using a newly improved imaging segmentation program, we report an average of approximately 1,100 RS after a 5-min pulse labeling of 3T3 mouse fibroblast cells in early S-phase. Pulse-chase-pulse double labeling experiments reveal that RS take approximately 45 min to complete replication. Appropriate calculations suggest that each RS contains an average of 1 mbp of DNA or approximately 6 average-sized replicons. Double pulse-double chase experiments demonstrate that the DNA sequences replicated at individual RS are precisely maintained temporally and spatially as the cell progresses through the cell cycle and into subsequent generations. By labeling replicated DNA at the G1/S borders for two consecutive cell generations, we show that the DNA synthesized at early S-phase is replicated at the same time and sites in the next round of replication.

3T3 Cells↗
PubMed1998

Segregation of transcription and replication sites into higher order domains.

Microscopy shows that individual sites of DNA replication and transcription of mammalian nuclei segregate into sets of roughly 22 and 16 higher order domains, respectively. Each domain set displayed a distinct network-like appearance, including regions of individual domains and interdigitation of domains between the two networks. These data support a dynamic mosaic model for the higher order arrangement of genomic function inside the cell nuclei.

3T3 Cells↗
PubMed1997

Corpectomy for multi-level cervical spondylosis and ossification of the posterior longitudinal ligament.

The choice of a surgical approach for multi-level cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) is still a controversial issue. While most of the surgeons are still performing decompression by laminectomy, some are doing multi-level anterior decompression. Few neurosurgeons are performing decompression by corpectomy. We have treated 26 patients by median cervical corpectomy during the last 4 years. These patients were followed up for a mean period of 25 months. Twenty one (80%) patients had a good outcome, 2 patients remained unchanged and 3 expired. Review of the literature and our experience indicates that patients with CSM and OPLL should be operated by median cervical corpectomy (anterior approach).

Adult↗
PubMed1996

A patient-specific in vivo tumor model.

A significant body of research, spanning approximately the last 25 years, has focused upon the task of developing a better understanding of tumor growth through the use of in vitro mathematical models. Although such models are useful for simulation, in vivo growth differs in significant ways due to the variety of competing biological, biochemical, and mechanical factors present in a living biological system. An in vivo, macroscopic, primary brain tumor growth model is developed, incorporating previous in vitro growth pattern research as well as scientific investigations into the biological and biochemical factors that affect in vivo neoplastic growth. The tumor growth potential model presents an integrated, universal framework that can be employed to predict the direction and extent of spread of a primary brain tumor with respect to time for a specific patient. This framework may be extended as necessary to include the results of current and future research into parameters affecting neoplastic proliferation. The patient-specific primary brain tumor growth model is expected to have multiple clinical uses, including: predictive modeling, tumor boundary delineation, growth pattern research, improved radiation surgery planning, and expert diagnostic assistance.

Biomechanical Phenomena↗
PubMed1996

Pilot study of controlled-release pilocarpine in normal subjects.

OBJECTIVES: Current systemic treatments with sialogogues for patients with xerostomia are limited because of minimal efficacy, short duration of activity, or problems with side effects. The purpose of this pilot study was an initial assessment of safety, efficacy, duration of action, multiple dose tolerance, and side effects of a controlled-release formulation of pilocarpine hydrochloride. STUDY DESIGN: Eight healthy hospitalized subjects were given 15 mg of a controlled-release pilocarpine formulation every 12 hours for three doses. Saliva and blood samples were collected at assigned intervals. Repeated measures analysis and paired t tests were used for statistical analyses. RESULTS: A significant (p < 0.05) increase in both parotid and whole saliva output followed all three doses beginning within 1 hour of dosing and lasting over 10 hours. Mean plasma pilocarpine concentration reached a maximum of 8.2 ng/ml at approximately 1 hour after the first dose, 11.5 ng/ml after the third dose, and declined to near baseline (0.06 ng/ml) 24 hours after the final dose. None of the participants showed evidence of adverse effects including complaints of sweating or gastrointestinal discomfort. CONCLUSIONS: A controlled-release formulation of pilocarpine may overcome the therapeutic weaknesses of current pilocarpine preparations by prolonging salivary secretion and reducing undesirable side effects.

Adult↗
PubMed1996

Posterior occipitoaxial fusion for atlantoaxial dislocation associated with occipitalized atlas.

Between 1989 and 1994, 50 patients suffering from congenital atlantoaxial dislocation with either an assimilated atlas or a thin or deficient posterior arch of the atlas were treated with occipitocervical fusion using the technique described by Jain and colleagues in 1993 with a few modifications. An artificial bridge created from the occipital bone along the margin of the foramen magnum was fused to the axis using sublaminar wiring and interposed strut and lateral onlay bone grafts. Ten patients (20%) also underwent atlantoaxial lateral joint fusion by intraarticular instillation of bone chips. In 22 patients (44%) with irreducible dislocation, posterior fusion was preceded by transoral odontoidectomy. In seven patients (14%) with ventral compression, who showed marked clinical improvement on traction despite radiological evidence of persisting atlantoaxial dislocation, occipitocervical fusion was performed without ventral decompression. Seven patients (14%) underwent a single-stage transoral odontoidectomy and posterior fusion. There was no perioperative mortality and the osseous fusion rate was 88%. Of the 43 patients available at follow-up examination (range 3-12 months), 31 patients (72.09%) improved, seven (16.28%) remained the same, and five (11.6%) deteriorated in comparison with their preoperative status. Hence, this technique achieves a stable occipitocervical arthrodesis without supplemental external orthoses and facilitates early postoperative mobilization.

Adolescent↗
PubMed1994

Algorithm for the automated alignment of radiographs for image subtraction.

The results of this study indicate that automated alignment of pairs of radiographs produces subtractions that are indistinguishable in quality from subtractions aligned manually by an experienced aligner. In developing the algorithm for automated alignment, care was taken that the criteria used for establishing a window appropriate for testing the quality of alignment were the same for both alignment techniques.

Algorithms↗
PubMed1993

Methods used in the structure determination of foot-and-mouth disease virus.

The structure of foot-and-mouth disease virus (FMDV) strain O1 BFS 1860 has been determined to 2.9 A resolution using the molecular-replacement method [Acharya, Fry, Stuart, Fox, Rowlands & Brown (1989). Nature (London), 337, 709-716]. Crystals of the virus with average dimensions 0.12 x 0.06 x 0.12 mm belong to space group I23, a = 345 A with 1/12 of the icosahedral particle per asymmetric unit giving fivefold noncrystallographic redundancy. Oscillation diffraction photographs were collected at the SERC Synchrotron Radiation Source at Daresbury in accordance with strict disease security regulations. The ambiguity in particle orientation was resolved using a self-rotation function and starting estimates of the phases to 8 A were derived from the known structures of two picornaviruses similarly oriented in the I23 unit cell. The phases were refined and extended using iterative averaging and solvent flattening with the implementation of a simple automatic envelope-determination procedure to increase the phasing power available.

Aphthovirus↗
PubMed1990

Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus.

Changes resulting in altered antigenic properties of viruses nearly always occur on their surface and have been attributed to the substitution of residues directly involved in binding antibody. To investigate the mechanism of antigenic variation in foot-and-mouth disease virus (FMDV), variants that escape neutralization by a monoclonal antibody have been compared crystallographically and serologically with parental virus. FMDVs form one of the four genera of the Picornaviridae. The unenveloped icosahedral shell comprises 60 copies each of four structural proteins VP1-4. Representatives from each of the genera have similar overall structure, but differences in the external features. For example, human rhinovirus has a pronounced 'canyon' that is proposed to contain the cell attachment site, whereas elements of the attachment site for FMDV, which involves the G-H loop (residues 134-160) and C-terminus (200-213) of VP1, are exposed on the surface. Moreover, this G-H loop, which is a major antigenic site of FMDV, forms a prominent, highly accessible protrusion, a feature not seen in other picornaviruses. It is this loop that is perturbed in the variant viruses that we have studied. The amino acid mutations characterizing the variants are not at positions directly involved in antibody binding, but result in far-reaching perturbations of the surface structure of the virus. Thus, this virus seems to use a novel escape mechanism whereby an induced conformational change in a major antigenic loop destroys the integrity of the epitope.

Antibodies, Monoclonal↗
PubMed1990

The structure of foot-and-mouth disease virus: implications for its physical and biological properties.

The structure of foot-and-mouth disease virus has been solved at a resolution of 2.9 A by X-ray diffraction techniques. The overall structural organisation of the particle is similar to that seen in other picornaviruses but there are several unique features. Many of these help to explain its characteristic physical and biological properties. In particular the canyon or pit found at the surface of other picornaviruses is lacking, which has important implications for cell attachment and the process of infection. Also there are 60 large disordered protrusions at the surface corresponding to the major antigenic site. This disorder is of particular interest in relation to the striking ability of linear synthetic peptides to induce protective immunity against foot-and-mouth disease.

Animals↗
PubMed1989

The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution.

The structure of foot-and-mouth disease virus has been determined at close to atomic resolution by X-ray diffraction without experimental phase information. The virus shows similarities with other picornaviruses but also several unique features. The canyon or pit found in other picornaviruses is absent; this has important implications for cell attachment. The most immunogenic portion of the capsid, which acts as a potent peptide vaccine, forms a disordered protrusion on the virus surface.

Algorithms↗
PubMedDate not supplied

Visualization and interactive exploration of multidimensional confocal images.

A confocal image analysis system is developed for automatic extraction of surface representation of biological structures. A visualization system is also developed to manipulate these surface representations and to obtain morphometrical parameters and provides a powerful tool for biomedical research such as microstructural characterization, morphogenesis, cell differentiation, tissue organization, and embryo development.

3T3 Cells↗