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Biomedical subjects

S Raghavan

Publications and source records attributed to S Raghavan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Benchmark test cases for evaluation of computer-based methods for detection of setup errors: realistic digitally reconstructed electronic portal images with known setup errors.

PURPOSE: The purpose of this investigation was to develop methods and software for computing realistic digitally reconstructed electronic portal images with known setup errors for use as benchmark test cases for evaluation and intercomparison of computer-based methods for image matching and detecting setup errors in electronic portal images. METHODS AND MATERIALS: An existing software tool for computing digitally reconstructed radiographs was modified to compute simulated megavoltage images. An interface was added to allow the user to specify which setup parameter(s) will contain computer-induced random and systematic errors in a reference beam created during virtual simulation. Other software features include options for adding random and structured noise, Gaussian blurring to simulate geometric unsharpness, histogram matching with a "typical" electronic portal image, specifying individual preferences for the appearance of the "gold standard" image, and specifying the number of images generated. The visible male computed tomography data set from the National Library of Medicine was used as the planning image. RESULTS: Digitally reconstructed electronic portal images with known setup errors have been generated and used to evaluate our methods for automatic image matching and error detection. Any number of different sets of test cases can be generated to investigate setup errors involving selected setup parameters and anatomic volumes. This approach has proved to be invaluable for determination of error detection sensitivity under ideal (rigid body) conditions and for guiding further development of image matching and error detection methods. Example images have been successfully exported for similar use at other sites. CONCLUSIONS: Because absolute truth is known, digitally reconstructed electronic portal images with known setup errors are well suited for evaluation of computer-aided image matching and error detection methods. High-quality planning images, such as the visible human CT scans from the National Library of Medicine, are essential for producing realistic images. Sets of test cases with systematic and random errors in selected setup parameters and anatomic volumes are suitable for use as standard benchmarks by the radiotherapy community. In addition to serving as an aid to research and development, benchmark images may also be useful for evaluation of commercial systems and as part of a quality assurance program for clinical systems. Test cases and software are available upon request.

Computer Simulation↗
PubMed1997

Positional preferences of polypurine/polypyrimidine tracts in Saccharomyces cerevisiae genome: implications for cis regulation of gene expression.

The complete genome of the baker's yeast S. cerevisiae was analyzed for the presence of polypurine/polypyrimidine (poly[pu/py]) repeats and their occurrences were classified on the basis of their location within and outside open reading frames (ORFs). The analysis reveals that such sequence motifs are present abundantly both in coding as well as noncoding regions. Clear positional preferences are seen when these tracts occur in noncoding regions. These motifs appear to occur predominantly at a unit nucleosomal length both upstream and downstream of ORFs. Moreover, there is a biased distribution of polypurines in the coding strands when these motifs occur within open reading frames. The significance of the biased distribution is discussed with reference to the occurrence of these motifs in other known mRNA sequences and expressed sequence tags. A model for cis regulation of gene expression is proposed based on the ability of these motifs to form an intermolecular triple helix structure when present within the coding region and/or to modulate nucleosome positioning via enhanced histone affinity when present outside coding regions.

Chromosome Mapping↗
PubMed1997

Pseudotumor cerebri in an infant after L-thyroxine therapy for transient neonatal hypothyroidism.

Pseudotumor cerebri is generally a benign disorder. It has been reported to occur in hypothyroidism, particularly after the initiation of L-thyroxine replacement therapy. Previous case reports have involved children primarily in the peripubertal age range (approximately 8 to 13 years). We report here the development of pseudotumor cerebri in an infant who required treatment with L-thyroxine for transient neonatal hypothyroidism as a result of maternal thyroid-stimulating hormone receptor-blocking antibodies.

Congenital Hypothyroidism↗
PubMed1997

Connectin mediates adhesion in Drosophila.

The Drosophila cell-surface molecule connectin mediates cell-cell adhesion in vitro, and its expression pattern in vivo fits well with an adhesion role in the embryonic neuromuscular system. However, connectin mutants do not show dramatic neuromuscular defects, and ectopic expression studies so far have not supported an adhesion role. Here, we demonstrate that connectin mutants do have a phenotype; the normally connectin-positive pleural muscles fail to adhere closely together. An in vivo adhesion role is supported by misexpression studies, which result in excessive adhesion of normally connectin-negative muscles. Misexpression also causes defects in axon pathfinding. While a previous study interpreted similar defects as indicating a repulsion role for connectin, we argue that the phenotypes are consistent with connectin's adhesion role.

Animals↗
PubMed1997

Intracellular pathways of insulin-mediated glucose uptake before and after puberty in conscious rats.

Studies in humans and animals indicate that peripheral insulin sensitivity is decreased after puberty. Although glucose, after its uptake and phosphorylation, will be diverted to either the glycolytic or glycogen synthesis pathway, these pathways have not been characterized after the transition to puberty. Thus, we examined the changes in the pathways of glucose utilization in conscious (n = 22) prepuberty (81 +/- 3 g), and postpuberty (258 +/- 9 g) Sprague-Dawley rats. Insulin stimulated (by insulin clamp 18 mU/kg/min) glucose uptake [rate of glucose disappearance (Rd)] was decreased by approximately 30% postpuberty (from 339 +/- 22 to 239 +/- 28 mumol/kg/min; p < 0.001). Although glycolysis (estimated by the rate of conversion of [3H]glucose to 3H2O) decreased by approximately 15% (p < 0.05), glycogen synthesis decreased by approximately 40% (from 200 +/- 17 prepuberty to 122 +/- 22 mumol/kg/min postpuberty; p < 0.001), and accounted for approximately 80% of the decrease in Rd postpuberty. Decrease in the capacity to store glycogen in response to insulin was also confirmed by approximately 40% decrease in both glycogen levels, and in 3H accumulation into glycogen (from 3H-glucose) at the end of the clamp study. This occurred in the absence of any changes in either the K(m) or the Vmax of glycogen synthase nor in the activity of glycogen phosphorylase. We conclude that the postpubertal decrease in insulin responsiveness is characterized by decreased ability to store muscle glycogen. We propose that high capacity for muscle glycogen synthesis may be required to sustain the increased metabolic requirements during peripubertal growth.

Adipose Tissue↗
PubMed1996

Intrathecal synthesis of anti-sulfatide IgG is associated with peripheral nerve disease in acquired immunodeficiency syndrome.

Peripheral nervous system involvement in the acquired immunodeficiency syndrome (AIDS) can take the form of an acute or chronic inflammatory demyelinating polyneuropathy, polyradiculopathy, mononeuropathy multiplex, or autonomic neuropathy. There is no widely held consensus on the etiology of PNS or other neurological complications associated with HIV infection. We report here that PNS disease in HIV-infected individuals is associated with intrathecal synthesis of an antibody directed against sulfatide, a major component of myelin. The anti-sulfatide antibody is also present nonspecifically in serum. The antibody requires the presence of the 3-O-sulfogalactosyl residue for binding and recognizes preferentially the hydroxy fatty acid-containing form of sulfatide. Anti-sulfatide antibodies are therefore one of the humoral factors responsible for demyelinating diseases in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene.

Late-onset GM2 gangliosidosis is a variant form of Tay-Sachs disease characterized by onset of symptoms and signs in adolescence or in early adult life. The deficiency of beta-hexosaminidase A (Hex A) in this form of GM2 gangliosidosis has been invariably associated with the presence of the Gly269-->Ser substitution in the alpha-chain. We found two siblings of Ashkenazi Jewish descent diagnosed with late-onset GM2 gangliosidosis who were negative for the Gly269-->Ser mutation. Analysis of the HEXA gene showed that they were compound heterozygotes for the functionally silent 4-bp insertion in exon 11, typical of the infantile form of the disease and for a novel mutation, T538-->C, resulting in the missense Tyr180-->His. Expression studies in COS-7 cells suggested that the effect of this mutation was to decrease the stability of the alpha-chain at physiologic temperatures and therefore to indirectly affect the formation of mature Hex A.

Adult↗
PubMed1995

Core-based portal image registration for automatic radiotherapy treatment verification.

PURPOSE: Portal imaging is the most important quality assurance procedure for monitoring the reproducibility of setup geometry in radiation therapy. The role of portal imaging has become even more critical in recent years due to the migration of three-dimensional (3D) treatment planning technology, including high-precision conformal therapy, from the research setting to routine clinical practice. Unfortunately, traditional methods for acquiring and interpreting portal images suffer from a number of deficiencies that contribute to the well-documented observation that many setup errors go undetected, and some persist for a clinically significant portion of the prescribed dose. Significant improvements in both accuracy and efficiency of detecting setup errors can, in principle, be achieved by using automatic image registration for on-line screening of images obtained from electronic portal imaging devices (EPIDs). METHODS AND MATERIALS: This article presents recent developments in a method called core-based image analysis that shows great promise for achieving the desired improvements in error detection. Core-based image analysis is a fundamental computer vision method that is capable of exploiting the full power of EPIDs by providing for on-line detection of setup errors via automatic registration of user-selected anatomical structures. We describe a robust method for automatic portal image registration based on core analysis and demonstrate an approach for assessing both accuracy and precision of registration methods using realistic, digitally reconstructed portal radiographs (DRPRs) where truth is known. RESULTS: Automatic core-based analysis of a set of 20 DRPRs containing known, random field positioning errors was performed for a patient undergoing treatment for prostate cancer. In all cases, the reported translation was within 1 mm of the actual translation with mean absolute errors of 0.3 mm and standard deviations of 0.3 mm. In all cases, the reported rotation was within 0.6 degree of the actual rotation with a mean absolute error of 0.18 degree and a standard deviation of 0.23 degree. CONCLUSION: Our results, using digitally reconstructed portal radiographs that closely resemble clinical portal images, suggest that automatic core-based registration is suitable as an on-line screening tool for detecting and quantifying patient setup errors.

Humans↗
PubMed1995

Simple repetitive sequences in the genome: structure and functional significance.

The current explosion of DNA sequence information has generated increasing evidence for the claim that noncoding repetitive DNA sequences present within and around different genes could play an important role in genetic control processes, although the precise role and mechanism by which these sequences function are poorly understood. Several of the simple repetitive sequences which occur in a large number of loci throughout the human and other eukaryotic genomes satisfy the sequence criteria for forming non-B DNA structures in vitro. We have summarized some of the features of three different types of simple repeats that highlight the importance of repetitive DNA in the control of gene expression and chromatin organization. (i) (TG/CA)n repeats are widespread and conserved in many loci. These sequences are associated with nucleosomes of varying linker length and may play a role in chromatin organization. These Z-potential sequences can help absorb superhelical stress during transcription and aid in recombination. (ii) Human telomeric repeat (TTAGGG)n adopts a novel quadruplex structure and exhibits unusual chromatin organization. This unusual structural motif could explain chromosome pairing and stability. (iii) Intragenic amplification of (CTG)n/(CAG)n trinucleotide repeat, which is now known to be associated with several genetic disorders, could down-regulate gene expression in vivo. The overall implications of these findings vis-à-vis repetitive sequences in the genome are summarized.

Animals↗
PubMed1994

Ciprofloxacin attachment to porous-coated titanium surfaces.

A simple and effective method for attaching ciprofloxacin HCl salt to the surface of porous-coated titanium based orthopedic materials was developed. The method utilizes the electrophoretic migration of both fine ciprofloxacin HCl particles and ciprofloxacin ions to deposit the antibiotic salt on a positively biased surface. The quantity of antibiotic deposited can be easily and effectively controlled by varying the time of deposition and applied voltage. In vitro tests have indicated that the antimicrobial activity of the treated surfaces is retained for a period of 5 days. The method allows a significant amount of antibiotic to be deposited and could theoretically be used to deliver antibiotics to the tissues surrounding prosthetic devices in order to prevent postoperative infections.

Biocompatible Materials↗
PubMed1994

Pathogenesis of Shigella diarrhea: XVII. A mammalian cell membrane glycolipid, Gb3, is required but not sufficient to confer sensitivity to Shiga toxin.

Shiga toxin recognizes a galactose-alpha 1-->4-galactose terminal glycolipid, globotriaosylceramide (Gb3), in sensitive mammalian cells and is translocated by endocytosis to the cytoplasm, where it blocks protein synthesis. To determine if Gb3 is both required and sufficient for toxicity, Gb3 content in cells was altered by blocking key biosynthetic or degradative path enzymes with specific inhibitors. The resulting decrease or increase in cellular Gb3 was associated with a decrease or increase in binding of and response to Shiga toxin. Toxin-resistant Gb3-deficient variants of sensitive cells fused with liposomes containing Gb3 but not globotetraosylceramide (Gb4) became susceptible, whereas fusion of Gb3 liposomes to naturally resistant Gb3-deficient CHO cells increased toxin binding but not cytotoxicity. These data demonstrate that Gb3 is required, but not sufficient, for the action of Shiga toxin and suggest the existence of a toxin translocation mechanism linked to surface glycolipids that is not expressed in CHO cells.

Animals↗