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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 595 records · Page 33Linked to original sources

Prevention of hypercholesterolemia and atherosclerosis in rabbits after supplementation of Myristica fragrans seed extract.

Myristica seed extr. administration to hypercholesterolemic rabbits reduced serum cholesterol and LDL Cholesterol by 69.1% and 76.3% respectively and also lowered cholesterol/phospholipid ratio by 31.2% and elevated the decreased HDL-ratio significantly. Myristica seed extr. feeding also prevented the accumulation of cholesterol, phospholipids and triglycerides in liver, heart and aorta and dissolved atheromatous plaques of aorta by 70.9-76.5%. Fecal excretion of cholesterol and phospholipid were significantly increased in seed extract fed rabbits.

Animals↗

Speech-evoked cognitive P300 potentials in cochlear implant recipients.

The cognitive P300 evoked potential was elicited by speech stimuli in successful cochlear implant recipients, and the resulting P300 morphology was remarkably similar to that of normal-hearing individuals. The P300 was elicited by the synthesized speech pair/da/and/di/ presented using an oddball paradigm to nine "good" Nucleus cochlear implant users and nine age-matched normal-hearing subjects (34-81 yr old). There were no significant differences in P300 amplitude and latency between the two groups. Moreover, the N1 and P2 potentials occurred at similar latencies in the two groups, although the N1 amplitude was significantly smaller in the cochlear implant users. The P300 was absent in one "poor" cochlear implant user. The results suggest that the P300 may serve as a useful tool for evaluating the cognitive aspects of auditory processing in cochlear implant recipients, and that it may aid in assessing the success of cochlear implantation.

Acoustic Stimulation↗

Assessment of puberty growth spurt in boys and girls--a dental radiographic method.

The first radiographic appearance of adductor sesamoid bone of thumb is considered reliable and is the most commonly used indicator of puberty growth spurt. The purpose of this study was to find out whether the tooth mineralization stage/stages were as reliable an indicator of puberty growth spurt as the adductor sesamoid bone. Puberty assessment has its necessary application in diagnosis, treatment planning of various malocclusions and in medico legal cases. The results indicated that a close relationship existed between tooth mineralization Stage G and appearance of the sesamoid bone. Hence it can be used in dentistry as an indicator for onset of puberty growth spurt via periapical or panoramic radiographs. The result of this study were not applicable to boys as the apical closure of these teeth had already occurred at the time of early radiographic appearance of the adductor sesamoid bone.

Adolescent↗

Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients.

Ascites from ovarian cancer patients contain potent growth-promoting activity toward human ovarian cancer cells both in vitro and in vivo. This activity is associated with rapid increases in cytosolic free calcium ([Ca2+]i) as a consequence of phosphoinositide hydrolysis. In this study, we describe the purification, characterization, and identification of an ovarian cancer activating factor (OCAF) from ascites of ovarian cancer patients. We have isolated OCAF by a combination of solvent extraction, silica gel chromatography, and TLC. Mass spectral analysis, phospholipase sensitivity, and gas chromatographic behavior of purified OCAF indicate that OCAF is composed of various species of lysophosphatidic acid (LPA), including LPAs with polyunsaturated fatty acyl chains (linoleic, arachidonic, and docosahexaenoic acids). However, OCAF is more potent than sn-1 palmitoyl, oleoyl, or stearoyl LPA in increasing [Ca2+]i in ovarian cancer cells. The ability of OCAF to alter [Ca2+]i is sensitive to the effects of lipoxidase, whereas the activity of sn-1 oleoyl, stearoyl, or palmitoyl LPA is not, suggesting that polyunsaturated bonds in the fatty acyl chain of OCAF may account for its increased ability to activate ovarian cancer cells. Furthermore, a sn-2 linoleoyl LPA generated by phospholipase A1 treatment of synthetic phosphatidic acid is much more active than are sn-1 palmitoyl, stearoyl, or oleoyl LPA in increasing [Ca2+]i in ovarian cancer cells. Taken together, these data suggest that the ability of OCAF to increase cellular calcium may reside in the structure and/or location of the fatty acyl chain of LPA. Purified OCAF, at concentrations similar to those present in ascites from ovarian cancer patients, was sufficient to induce proliferation of ovarian cancer cells, as indicated by thymidine incorporation, reduction of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, or colony formation. However, even at optimal concentrations of OCAF, proliferation was lower than that induced by FCS or ascites from ovarian cancer patients, indicating that, although OCAF may be a major regulator of ovarian cancer cells in vivo, it is not the sole mediator present in ascites, and it likely functions in concert with other growth factor activities.

Ascites↗

High-efficiency synthesis of human alpha-endorphin and magainin in the erythrocytes of transgenic mice: a production system for therapeutic peptides.

Chemical synthesis of peptides, though feasible, is hindered by considerations of cost, purity, and efficiency of synthesizing longer chains. Here we describe a transgenic system for producing peptides of therapeutic interest as fusion proteins at low cost and high purity. Transgenic hemoglobin expression technology using the locus control region was employed to produce fusion hemoglobins in the erythrocytes of mice. The fusion hemoglobin contains the desired peptides as an extension at the C end of human alpha-globin. A protein cleavage site is inserted between the C end of the alpha-globin chain and the N-terminal residue of the desired peptide. The peptide is recovered after cleavage of the fusion protein with enzymes that recognize this cleavage signal as their substrate. Due to the selective compartmentalization of hemoglobin in the erythrocytes, purification of the fusion hemoglobin is easy and efficient. Because of its compact and highly ordered structure, the internal sites of hemoglobin are resistant to protease digestion and the desired peptide is efficiently released and recovered. The applicability of this approach was established by producing a 16-mer alpha-endorphin peptide and a 26-mer magainin peptide in transgenic mice. Transgenic animals and their progeny expressing these fusion proteins remain health, even when the fusion protein is expressed at > 25% of the total hemoglobin in the erythrocytes. Additional applications and potential improvements of this methodology are discussed.

Amino Acid Sequence↗

Crystal structure of the amino-terminal fragment of vaccinia virus DNA topoisomerase I at 1.6 A resolution.

BACKGROUND: Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. RESULTS: The crystal structure of a 9 kDa amino-terminal fragment of vaccinia virus DNA topoisomerase I has been determined at 1.6 A resolution. The fragment forms a five-stranded, antiparallel beta-sheet with two short alpha-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure. CONCLUSIONS: This is the first atomic structure of any region of a eukaryotic-like DNA topoisomerase I. It has provided insights into the structural bases of the phenotypes of some single-site mutants of the intact topoisomerase. The structure has enabled us to study the interactions within a well-folded protein fragment and the camptothecin resistance of the viral topoisomerase.

Amino Acid Sequence↗

Reversed-phase high-performance liquid chromatographic determination of taxol in mouse plasma.

A simple and selective high-performance liquid chromatographic technique was developed for the determination of taxol in mouse plasma. This technique employs a single extraction step followed by isocratic chromatography on a C18 analytical column and ultraviolet detection at 227 nm, and is suitable for the analysis of microsamples (50 microliters plasma). A series of aromatic and aliphatic benzamides were synthesized as internal standards; N-octylbenzamide was evaluated most extensively. The calibration curve is linear within the range 0.15-10 nmol/ml. The intra-day and inter-day coefficients of variation were below 7%. The specificity of the assay was confirmed by comparing the chromatographic properties of samples with authentic taxol, using a diode-array detector. The assay was used to conduct pharmacokinetic studies of taxol in mice after administration in different formulations.

Animals↗

Characterization of pPT23B, the plasmid involved in syringolide production by Pseudomonas syringae pv. tomato PT23.

Avirulence gene D (avrD) in strain PT23 of Pseudomonas syringae pv. tomato (Pst) specifies the production of syringolides, which are elicitors of plant defense reactions. An 83-kb indigenous plasmid (pPT23B) that carries avrD has been mapped and characterized and a putative par region was identified. pPT23B contains a large amount of DNA that is repeated in other native plasmids in PT23. A putative mobile insertion element that occurs on plasmid pPT23A as well as on the chromosome was also identified in strain PT23. New broad-host-range expression vectors that functioned in Pst were constructed for overexpression of the cloned avrD gene and high-level production of the syringolides. Introduction of an avrD overexpression plasmid into PT23 or plasmid-cured strains led to identical syringolide peaks on HPLC with no new peaks observed. These results suggested that neither pPT23B nor other indigenous plasmids in Pst carry additional genes required for syringolide production or metabolism. Pst strains lacking pPT23B were not impaired in virulence on tomato plants.

Bacterial Toxins↗

Encircling endocardial cryoablation for ventricular tachycardia after myocardial infarction: experience with 33 patients.

Encircling endocardial cryoablation, consisting of circumferential cryoablation of the infarct scar, can be curative in selected patients with ventricular tachycardia (VT). We describe our experience with and long-term outcome in 33 patients undergoing this procedure. The interval between myocardial infarction and the onset of tachycardia varied from 2 weeks to 22 years (mean 38 +/- 63 months and median 3 months). All patients had a left ventricular aneurysm (anterior in 20, posterior in 12, and lateral in 1) and significant coronary artery disease. Fourteen patients had clinical evidence of heart failure preoperatively. Twenty-eight patients had sustained monomorphic VT (incessant in 3); 3 had polymorphic or nonsustained tachycardia; 2 had primary ventricular fibrillation; and 1 had associated Wolff-Parkinson-White syndrome. Surgery was undertaken after failed drug therapy and consideration of left ventricular anatomy and function. At surgery, 32 patients had encircling endocardial cryoablation, and 1 patient had partial right ventricular free-wall disconnection (right ventricular infarct). Thirteen patients underwent concomitant coronary artery bypass grafting. An implantable cardioverter defibrillator (ICD) was implanted in 2 patients and prophylactic ICD patches in 1. One patient died postoperatively; 3 had recurrent VT perioperatively; 1 was treated with amiodarone; and 2 had ICD implantation. During long-term follow-up (mean 5 years), all patients who were free of tachycardia at discharge remained alive and free of arrhythmias or syncope. The patient receiving amiodarone sustained a cardiac arrest subsequently and received an ICD implant. One patient with an ICD continued to receive appropriate shocks frequently and died 2 years after surgery. Nine patients had congestive heart failure postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗