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S Sastry

Publications and source records attributed to S Sastry.

11 recordsLinked to original sources
PubMed1998

The native form of alpha-synuclein is not found in the cerebrospinal fluid of patients with Parkinson's disease or normal controls.

Alpha-synuclein has recently been shown to be a major constituent of Lewy bodies in Parkinson's disease (PD). This observation led us to investigate the possibility that its detection in the cerebrospinal fluid (CSF) could be used as a marker for Lewy bodies in the central nervous system. In this study we determined the pattern of expression of alpha-synuclein in patients with sporadic Parkinson's disease (PD) and normal controls, using western immunoblotting in conjunction with an antibody that recognizes the carboxyl terminal of alpha-synuclein protein. The native 19 kDa band normally seen in brain homogenates was not found in the CSF of either parkinsonian patients or control subjects. However, a novel band was observed, which migrated at a position in the range of 42 kDa in CSF from both patients and controls. We conclude that alpha-synuclein cannot be used as a biomarker for Lewy bodies during life. However, further characterization of the 42 kDa protein may be of interest.

Blotting, Western↗
PubMed1998

RNA-binding site in T7 RNA polymerase.

Recent models of RNA polymerase transcription complexes have invoked the idea that enzyme-nascent RNA contacts contribute to the stability of the complexes. Although much progress on this topic has been made with the multisubunit Escherichia coli RNA polymerase, there is a paucity of information regarding the structure of single-subunit phage RNA polymerase transcription complexes. Here, we photo-cross-linked the RNA in a T7 RNA polymerase transcription complex and mapped a major contact site between amino acid residues 144 and 168 and probably a minor contact between residues 1 and 93. These regions of the polymerase are proposed to interact with the emerging RNA during transcription because the 5' end of the RNA was cross-linked. The contacts are both ionic and nonionic (hydrophobic). The specific inhibitor of T7 transcription, T7 lysozyme, does not compete with T7 RNA polymerase for RNA cross-linking, implying that the RNA does not bind the lysozyme. However, lysozyme may act indirectly via a conformational change in the polymerase. In the current model, the DNA template lies in the polymerase cleft and the fingers subdomain may contact or maintain a template bubble, and a region in the N terminus forms a partly solvent-accessible binding channel for the emerging RNA.

Bacteriophage T7↗
PubMed1998

Renal cell carcinoma with X;1 translocation in a child with Klinefelter syndrome.

Klinefelter syndrome (KS) is a sex chromosome abnormality occurring in 1 in 1,000 males. An association with leukemia, germ cell tumor, and male breast cancer has been suggested in KS. Such information is important for professionals caring for KS patients as the condition is frequently not clinically recognizable until after puberty. We report on a renal cell carcinoma (RCC) in a 10-year-old boy with KS. He developed intermittent hematuria at age 10 years and was diagnosed with a right kidney mass, which on pathology was identified as RCC. In addition, he was known to have learning disabilities and language delays. Analysis of peripheral blood chromosomes showed a 47,XXY karyotype while analysis of tumor cells demonstrated clonal abnormalities including a translocation between chromosomes X and 1, designated 47,XXYc,t(X;1)(p11.2;q21)[6]/47,XXYc,t(X;1),r(Xp)[2]/46,X XYc,-X,t(X;1)[7]. Renal cell carcinoma is rare in childhood and is not previously reported in KS. The oncogenetic significance of the chromosomal regions involved in this translocation is discussed in relation to the congenital abnormality of the patient.

Carcinoma, Renal Cell↗
PubMed1998

Mechanisms for the processing of a frozen topoisomerase-DNA conjugate by human cell-free extracts.

The metabolic fate of covalently linked DNA-protein complexes (cross-links) is not clearly understood. Our aim was to investigate the processing of protein-DNA cross-links by cellular enzymes. As an example of a DNA-protein cross-link, we have constructed frozen topoisomerase-DNA conjugates and investigated their processing by human cell-free extracts. A suicide DNA substrate was constructed that upon reaction with vaccinia type I topoisomerase yielded a highly stable covalent DNA-protein cross-link. When this conjugate was treated with human nuclear or whole cell extracts, two sites of DNA breakpoints were detected: one set of double-stranded breaks occurred close to the 3' side of the topoisomerase (topo) conjugation site, and there was another set of nicks about 30 nucleotides 3' to the topo site. The double-stranded breaks were not made by extracts from xeroderma pigmentosum group A mutant cells, suggesting that the xeroderma pigmentosum group A damage recognition protein may be required for the occurrence of DNA breakage. In addition to these DNA breakage reactions, there was an activity that resulted in the delinking of the frozen topoisomerase (or proteolytic fragments thereof) from the DNA substrate, which was followed by a ligation step that restored the continuity of the broken DNA strand at the erstwhile topo attachment site. We suggest that frozen topoisomerase-DNA conjugates (and perhaps other types of covalent DNA-protein complexes) are processed by multiple pathways that may involve the cleavage of the DNA in the covalent protein-DNA complex and/or enzymatic delinking followed by ligation of the broken DNA ends. These processes may represent the "repair" of DNA-protein cross-links.

Base Sequence↗
PubMed1998

Novel alpha-synuclein-immunoreactive proteins in brain samples from the Contursi kindred, Parkinson's, and Alzheimer's disease.

A specific mutation (A53T) in the encoding region for alpha-synuclein has been identified in a large multigenerational family with an autosomal dominant parkinsonism known as the Contursi kindred. In this study, we used a monoclonal antibody directed against alpha-synuclein in order to identify novel proteins in the brain of an affected member of this kindred who had come to autopsy. Homogenates from the frontal cortex and caudate nucleus were examined using Western blot techniques and compared to matched autopsy specimens from control subjects and patients with various forms of parkinsonism. Western blots, using a 15-min exposure time, revealed the expected 19-kDa band representing alpha-synuclein in all brain samples examined. However, a novel band in the 36-kDa range was also present in the Contursi brain which was not seen in cortex or caudate from control brains or in frontal cortex from 14 cases of typical Parkinson's disease. With a 24-h exposure time, this band was faintly seen in the caudate nucleus of three of the Parkinson's disease cases. Surprisingly, the 36-kDa band (as well as other high-molecular-weight bands) was also present in frontal cortex and caudate nucleus in 3 additional cases that met diagnostic criteria for both Parkinson's disease and Alzheimer's disease. A preliminary analysis of samples from the frontal cortex of 10 Alzheimer's disease cases revealed a 36-kDa band in only one instance. The identification of novel alpha-synuclein-immunoreactive bands in these various forms of parkinsonism may open new research avenues for exploring the relationship between abnormal protein deposition in the brain and one or more neurodegenerative disorders, including the Contursi form of familial parkinsonism.

Adult↗
PubMed1997

Multimodality Bayesian algorithm for image reconstruction in positron emission tomography: a tissue composition model.

The use of anatomical information to improve the quality of reconstructed images in positron emission tomography (PET) has been extensively studied. A common strategy has been to include spatial smoothing within boundaries defined from the anatomical data. We present an alternative method for the incorporation of anatomical information into PET image reconstruction, in which we use segmented magnetic resonance (MR) images to assign tissue composition to PET image pixels. We model the image as a sum of activities for each tissue type, weighted by the assigned tissue composition. The reconstruction is performed as a maximum a posteriori (MAP) estimation of the activities of each tissue type. Two prior functions, defined for tissue-type activities, are considered. The algorithm is tested in realistic simulations employing a full physical model of the PET scanner.

Algorithms↗
PubMed1995

Time-dependent changes in iron levels and associated neuronal loss within the substantia nigra following lesions within the neostriatum/globus pallidus complex.

The substantia nigra and globus pallidus (two iron-rich brain areas) receive a substantial innervation from the neostriatum, a considerable amount of which is GABAergic. Because of this anatomic relationship and the finding that prevention of GABA degradation in these two areas decreases their histochemical levels of iron, GABAergic transmission/metabolism may be important in regulating brain iron levels. Therefore, the present study investigated the effects of denervation of striatal/pallidal inputs to globus pallidus/substantia nigra on iron levels and associated pathologic changes in globus pallidus/substantia nigra. Adult male Sprague-Dawley rats received unilateral ibotenic acid infusions resulting in comprehensive lesions of the entire neostriatum/globus pallidus complex, or of either the anterior neostriatum or the posterior neostriatum/globus pallidus. Animals were killed at one week or one month following surgery. Between one week and one month postlesioning, comprehensive neostriatum/globus pallidus lesions induced a progressive decrease in substantia nigra volume, as well as a progressive increase in both substantia nigra zona reticularis iron staining and substantia nigra iron concentration. By one month following neostriatum/globus pallidus lesions, a marked 73% loss of substantia nigra zona reticularis neurons occurred in association with a 65% increase in glial cell numbers within zona reticularis. Compared to comprehensive neostriatum/globus pallidus lesions at the one month postlesion time point, more restricted anterior neostriatum and posterior neostriatum/globus pallidus lesions induced a less severe atrophy of the substantia nigra, a small (anterior neostriatum lesions) to moderate (posterior neostriatum/globus pallidus lesions) increase in substantia nigra zona reticularis iron staining, and either no zona reticularis neuronal loss (anterior neostriatum lesions) or limited zona reticularis neuronal loss selectively within areas of increased iron staining. These results suggest that destruction of striatal/pallidal innervation to the substantia nigra's zona reticularis induces a disruption of zona reticularis iron homeostasis, resulting in a redistribution and/or accumulation of iron in the zona reticularis and consequent zona reticularis of the substantia nigra neurodegeneration. The results further suggest that loss or dysfunction of striatonigral/striatopallidal GABAergic neurons in several neurodegenerative diseases (including Hallervorden-Spatz syndrome, progressive supranuclear palsy, multiple system atrophy, and Parkinson's disease) may result in an increase or redistribution of nigral iron to cause loss of substantia nigra neurons.

Animals↗
PubMed1991

Removal of psoralen monoadducts and crosslinks by human cell free extracts.

Human cell free extracts are capable of carrying out damage-induced DNA synthesis in response to DNA damage by UV, psoralen, and cisplatin. We show that this damage-induced DNA synthesis is associated with removal of psoralen adducts and therefore is 'repair synthesis' and not an aberrant DNA synthesis reaction potentiated by DNA deformed by adducts. By comparing the denaturable fraction of psoralen adducted DNA which becomes labeled in the repair reaction to that of terminally labeled DNA (without repair) we have found that all DNA synthesis induced by psoralen monoadducts is the consequence of removal of these adducts. By the same approach we have obtained preliminary evidence that this in vitro system is capable of removing psoralen crosslinks as well.

Cell-Free System↗
PubMed1988

Primary mucinous adenocarcinoma developing in an ileostomy stoma.

We report a mucinous adenocarcinoma arising in an ileostomy stoma of a 60 year old woman after a subtotal colectomy done 28 years previously for ulcerative colitis. A study of the histochemical profiles of the mucin within the mucosa of the ileostomy and the carcinoma was undertaken. Previously documented cases are reviewed.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

Variation of sex chromatin percentage during menstrual cycle and menopause.

Buccal smears were obtained from 2 groups of women to study the percentage of Barr bodies. The first group comprised of normal women with regular menstrual cycle between the age group 18-22 years. The second group comprised of Menopausal women in the age group 47-55 years. A definite variation in percentage of barr bodies was observed in the first group whereas the percentage remained normal in the second group.

Adolescent↗