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Biomedical subjects

R Santhanam

Publications and source records attributed to R Santhanam.

11 recordsLinked to original sources
PubMed2006

Genetic modification of cerebral arterial wall: implications for prevention and treatment of cerebral vasospasm.

Genetic modification of cerebral vessels represents a promising and novel approach for prevention and/or treatment of various cerebral vascular disorders, including cerebral vasospasm. In this review, we focus on the current understanding of the use of gene transfer to the cerebral arteries for prevention and/or treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). We also discuss the recent developments in vascular therapeutics, involving the autologous use of progenitor cells for repair of damaged vessels, as well as a cell-based gene delivery approach for the prevention and treatment of cerebral vasospasm.

Animals↗
PubMed2002

Evaluation of the immunocontraceptive potential of Escherichia coli-expressed recombinant dog ZP2 and ZP3 in a homologous animal model.

Dog zona pellucida glycoprotein 2 (dZP2), excluding the N-terminal signal sequence and the C-terminal transmembrane-like domain, was cloned and expressed as a polyhistidine fusion protein in Escherichia coli to evaluate the immunocontraceptive efficacy of ZP glycoproteins. The recombinant dZP2 (rec-dZP2) revealed a 70 kDa band corresponding to the full length transcript, as well as several low molecular mass fragments in western blot analysis. In addition to rec-dZP2, E. coli expressed recombinant dog ZP glycoprotein 3 (rec-dZP3), which has also been evaluated for its efficacy to block fertility in a homologous system. Three groups of female dogs (n = 4 per group) were immunized with rec-dZP2 conjugated to diphtheria toxoid (rec-dZP2-DT), rec-dZP3 conjugated to DT (rec-dZP3-DT) and DT alone. Immunization of female dogs with rec-dZP2-DT and rec-dZP3-DT led to generation of antibodies against the respective ZP proteins as well as to DT. Subsequent to mating, the four female dogs immunized with rec-dZP2-DT all conceived, which is indicative of failure of the anti-rec-dZP2 antibodies to block fertility. In the group of dogs immunized with rec-dZP3-DT, three of four animals did not conceive when mated with males of proven fertility. The block in fertility was associated with anti-dZP3 antibody titres. Ovarian histopathology revealed that the block in fertility in the group immunized with rec-dZP3-DT is probably manifested by inhibition in the development of follicles and is due to atretic changes in the zona pellucida. These results, although preliminary, indicate that immunization with dZP3 may be a feasible proposition to control dog populations provided that adequate antibody titres are achieved.

Animals↗
PubMed2001

Novel human testis-specific cDNA: molecular cloning, expression and immunobiological effects of the recombinant protein.

A differential display-polymerase chain reaction was employed to obtain a testis-specific cDNA fragment. On screening the human testis-(lambda)gt10-cDNA library with testis-specific cDNA fragment, a novel cDNA encoding for a sperm antigen, designated TSA-1, was obtained. It has a novel open reading frame (ORF) of 471 base pairs encoding for 156 amino acids. The computer generated translated protein has a calculated molecular mass of 17.4 kDa and contains a potential N-glycosylation site at amino acids 122-124. The hydrophilicity analysis of the amino acid sequence suggested that this protein is a membrane-anchored peptide. Extensive analysis for tissue-specificity by Northern blots and RT-PCR-Southern blot procedures using various human tissues indicated that TSA-1 was specifically expressed only in the human testis. Based on the results of in vitro transcription and translation experiments, the TSA-1 (ORF) was subcloned into pGEX-6P-3 vector and expressed using the glutathione S-transferase gene fusion system. Antibodies (Ab) against the purified recombinant protein specifically recognized the approximately 17 kDa recombinant TSA-1, and a approximately 24 kDa band in human sperm extract in the Western blot procedure. The recombinant TSA-1 Ab recognized the acrosomal, equatorial, mid-piece, and tail regions of human sperm cell in indirect immunofluorescence, bound to live human sperm in the immunobeads binding technique (IBT) and caused a significant concentration-dependent inhibition of human sperm acrosome reaction. These findings indicate that the novel sperm-specific recombinant TSA-1 has a role in sperm function and may have applications in the development of a contraceptive vaccine, and in the specific diagnosis and treatment of male infertility.

Acrosome Reaction↗
PubMed2001

Artefactual skin disease in children and adolescents.

As in adults, artefactual skin disease in children and adolescents has heterogenous presentations with multifactorial aetiology. We report a series of 32 young patients aged 8-16 years. There were 24 females and 8 males. In over half of the cases the lesions were on the head and neck. The types of lesions encountered included physical injury producing grazing, erosions and deep ulcers, chemical and thermal burns, hair cutting and shaving and skin painting. We discuss the approach that we believe should be taken with these patients, emphasizing the role of dermatology-psychiatry liaison in their management. Of great importance is the avoidance of confrontation of the patient but the clear exposition of the nature of the problem to the parents. The major aim should be to have the family accept the need for expert psychiatric assistance.

Adolescent↗
PubMed1998

Molecular cloning and expression in Escherichia coli of cDNA encoding bonnet monkey (Macaca radiata) zona pellucida glycoprotein-ZP2.

Zona pellucida (ZP) glycoproteins have been proposed as candidate antigens for an immunocontraceptive vaccine. The efficacy of such a vaccine has to be evaluated in nonhuman primates, thus necessitating the characterization of their ZP glycoproteins. A bonnet monkey (Macaca radiata) ovarian cDNA lambda gt11 library was screened for ZP2 (bZP2) using full-length human ZP2 cDNA as a probe. Two identical full-length clones with an open reading frame of 2235 nt encoding a polypeptide of 745 aa residues were isolated. The deduced aa sequence of bZP2 revealed high sequence identity (94.2%) with human ZP2. The bZP2 cDNA (115-1914 nt, 1.8 kb), excluding sequences coding for N-terminal signal sequence and C-terminal transmembranelike domain, was PCR amplified and Sac1-Sal1 restricted fragment cloned in frame downstream of the T5 promoter under the lac operator control in a pQE-30 vector. Recombinant bZP2 (r-bZP2) was expressed as a polyhistidine fusion protein in Escherichia coli strain M15 [pREP4]. Immunoblot with rabbit polyclonal antibodies against bZP2 synthetic peptide (corresponding to aa residues 429-444; K434 replaced by R and 1436 by V) revealed a major band of 68 kDa. Immunization of male rabbits with the r-bZP2 protein purified on Ni-NTA resin under denaturing conditions generated antibodies reactive with r-bZP2 in ELISA as well as with native protein as revealed by positive fluorescence of ZP of bonnet monkey ovary. The availability of r-bZP2 and its aa sequence will help in the development and evaluation of a contraceptive vaccine based on ZP2.

Amino Acid Sequence↗
PubMed1998

Dog zona pellucida glycoprotein-3 (ZP3): expression in Escherichia coli and immunological characterization.

An internal fragment (978 bp) corresponding to the dog zona pellucida glycoprotein-3 (DZP3), excluding the N-terminal signal sequence and the C-terminal transmembrane-like domain, was amplified by polymerase chain reaction from a full-length cDNA clone. The amplified SacI and PstI restricted fragment was cloned in-frame downstream of the T5 promoter under lac operator control for expression in the pQE-30 vector. Recombinant DZP3 (rec-DZP3) was expressed as a polyhistidine fusion protein in Escherichia coli. Optimum expression of rec-DZP3 was observed at 1.0 mM isopropyl-beta-D-thiogalactopyronoside. Immunoblots with a murine monoclonal antibody, MA-451 (raised against porcine ZP3beta-a homologue of DZP3 and cross-reactive with dog zona pellucida), revealed a major band of 42 kDa. Localization studies revealed that the recombinant protein was present only in an insoluble intracellular fraction. Further optimization studies revealed that the level of expression of rec-DZP3 was significantly higher in Luria broth medium containing glycerol rather than glucose and maximum expression was observed when cultures were induced during the mid-log phase of growth. Batch fermentation with glycerol as the carbon source yielded 30 mg/L of rec-DZP3 compared to 4 mg/L from a shake flask culture. Immunization of two male rabbits with Ni-NTA-purified rec-DZP3 and two female dogs with the rec-DZP3 conjugated to diphtheria toxoid generated high antibody titers against rec-DZP3 as determined by enzyme-linked immunosorbent assay. Rabbit immune serum reacted with porcine ZP3beta but failed to react with porcine ZP3alpha in a Western blot. Moreover, antisera when tested by indirect immunofluorescence on dog ovarian sections showed positive fluorescence with zona pellucida. The availability of rec-DZP3 will help in evaluating its efficacy for fertility regulation in stray dogs.

Animals↗
PubMed1996

Cutting force measurements platform for quantitative assessment of surgical cutting instruments.

This paper describes the design and development of a Cutting Force Measurement Platform (CFMP) in the R&D department at Valleylab, Inc. for quantitative assessment of surgical instruments used for cutting tissue. This system controls various parameters including cutting speed, while measuring the force required as a function of time. The cutting force measurements are acquired and analyzed by a data acquisition program. The relevance of the cutting force measurements with regards to electrosurgery are discussed.

Animals↗
PubMed1992

Inhibition of the cation-induced reversible changes in excitation energy distribution in thylakoids of BASF 13.338-grown plants.

Measurements of relative quantum yields of Photosystem II and Photosystem I partial reactions and room-temperature chlorophyll a fluorescence of thylakoids in high- and low-salt media showed that the cation-induced changes in the excitation energy distribution were inhibited in the thylakoids isolated from pea plants grown in the presence of sublethal concentration of the pyridazinone herbicide BASF 13.338. Simultaneous measurement of Photosystem II and Photosystem I fluorescence emission kinetics at 77 K showed that the ability of cations to regulate excitation energy spillover from Photosystem II to Photosystem I was inhibited in thylakoids of the BASF-grown plants. Cation regulation of the absorption cross-section of the photosystems was not affected. Electron microscope data revealed that the proportion of stroma membranes relative to grana membranes was markedly less in the thylakoids of the BASF-grown plants. Furthermore, when the thylakoids were resuspended in low-salt medium, no unstacking of the grana was detected. The observed inhibition of cation-induced spillover change was presumably due to loss of ability of these photosynthetic membranes to undergo unstacking in low-salt medium.

Cations↗
PubMed1979

Delayed pacemaker erosion due to electrode seal defects.

Over a 7-year period, follow-up data were available on 163 patients who underwent 209 pacemaker-related operations for initial insertion or revision of previously implanted units. During the follow-up period, 16 pacemaker generator units were remoaved from 16 pacemaker generator units were removed from 12 patients solely because of the development of local skin erosion. This represents a 7.7% incidence of pacemaker generator erosion. Tree units were removed within a 3-month interval following pacemaker implantation and were associated with positive bacterial cultures, theraby indicating an infectious cause. Findings at removal of the remaining 13 pacemaker generators included extensive fibrosis with chronic inflammation, fibroblastic proliferation, and granulation tissue, which was most prominent at the site of insertion of the pacemaker lead into the pacemaker generator unit. Granulation tissue frequently led from this area to the area of skin attenuation and erythema. Inspection of the pacemaker generator units and electrodes demonstrated fluid ingress and tissue ingrowth toward the electrode due to inadequate seal mechanisms. Inadequate seal design of the pacemaker generator and electrode junction leads to tissue ingrowth with fibroblastic proliferatiog chronic inflammation, and eventual pacemaker erosion.

Aged↗
PubMedDate not supplied

Prospects of zona pellucida glycoproteins as immunogens for contraceptive vaccine.

The zona pellucida (ZP) surrounding a mammalian oocyte mediates the initial recognition and binding of spermatozoon to oocyte in a relatively species-specific manner and plays an important role in the subsequent activation events during the fertilization process. The ZP comprises three biochemically and immunologically distinct glycoproteins termed ZP1, ZP2 and ZP3. The critical role of ZP glycoproteins in reproduction together with their tissue-specific nature have led to their being considered as potential candidate antigens for immunocontraception. Immunization of females with ZP glycoproteins leads to a block of fertility in several animal models. However, it is invariably associated with either a transient or an irreversible alteration in the cyclicity, hormonal profile and follicular development in the ovary. To overcome these problems, attempts are being made to delineate relevant 'B' cell epitopes on ZP proteins so as to design immunocontraceptive vaccines based on synthetic peptides devoid of oophoritogenic 'T' cell epitopes. Monoclonal antibodies capable of inhibiting the gamete interaction are being employed to delineate such regions. Additionally, DNA-recombinant technology has made it feasible to obtain, in reasonably large quantities, the ZP glycoproteins from human and non-human primates. Availability of sequence information of these zona proteins and the availability of recombinant antigens (devoid of other ovarian-associated proteins) will further help in understanding more precisely their functions during fertilization and make it feasible to undertake immunization studies to determine their prospects as immunogens for fertility regulation.

Amino Acid Sequence↗