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Biomedical subjects

Sanjay Singh

Publications and source records attributed to Sanjay Singh.

34 records · Page 2Linked to original sources

Control of molecular topology and metal nuclearity in multimetallic assemblies: designer metallosiloxanes derived from silanetriols.

Lipophilic N-bonded silanetriol RSi(OH)(3) (R=(2,6-iPr(2)C(6)H(3))N(SiMe(3))) can be utilized as an effective synthon for building a variety of multimetallic assemblies containing the Si-O-M motif. The type of metallosiloxane synthesized-its nuclearity and its molecular topology-can be readily modulated by the choice of the metal substrate, reaction stoichiometry, and reaction conditions. It is anticipated that the synthetic principles elaborated here will allow the design of many other multifunctional synthons.

Journal Article↗

Metalated hybrid polymers as catalytic reagents for phosphate ester hydrolysis and plasmid modification.

Pendant pyrazolylcyclophosphazene containing hybrid cross-linked polymer (CPPL) has been utilized for binding Zn(II). The metalated polymer (CPPL-Zn) has been found to be very effective catalyst for the hydrolysis of a RNA model phosphodiester substrate [2-(hydroxypropyl)-p-nitrophenyl phosphate, hNPP]. In addition, CPPL-Zn also cleaved supercoiled plasmid DNA pBR322 thus providing a novel structural motif of inorganic-organic hybrid polymers as synthetic nucleases.

Catalysis↗

Enzyme inhibition by the molluscicidal agent Punica granatum Linn. bark and Canna indica Linn. root.

Sublethal in vivo 24 h exposure to (40% and 80% of 24 h LC(50)) active fractions of Punica granatum bark or Canna indica root or in combination with other plant-derived molluscicides significantly inhibited the activity of acetylcholinesterase, acid/alkaline phosphatase, Na(+)K(+)ATPase and lactic dehydrogenase in the nervous tissue of Lymnaea acuminata. The inhibition kinetics of these enzymes indicates that active fractions of both the plants caused a competitive inhibition of AChE, LDH, ALP, ACP and Na(+)K(+)ATPase.

Acetylcholinesterase↗

Implications of dose rounding of chemotherapy to the nearest vial size.

GOALS OF WORK: There are practical implications of preparing cytotoxic doses calculated to the exact milligram. The objective here was to explore the magnitude of the effect of dose rounding to the nearest whole vial strength for some newly marketed expensive cytotoxic chemotherapy agents. PATIENTS AND METHODS: Body surface areas (BSA) of 2838 adult patients presenting for chemotherapy at the Peter MacCallum Cancer Centre between May 1996 and December 2000 were calculated by using the DuBois and DuBois linear equation to two decimal places. Each individual dose of docetaxel, liposomal doxorubicin, gemcitabine, oxaliplatin and vinorelbine was calculated from the actual BSA based on the dose recommended in the approved drug product information. This calculated dose was then rounded upwards to the full next vial if the calculated dose exceeded above 50% of the next appropriate vial strength and was rounded downwards to the full previous vial if the calculated dose did not exceed above 50% of the next appropriate vial strength. Potential impacts on cost were calculated in Australian dollars for each drug for both the calculated and rounded dose on those instances where the difference was no greater than +/-5%. MAIN RESULTS: The proportion of patients in whom the dose rounded to the nearest vial strength varied by not more than +/-5% was 89.5% for docetaxel, 60.4% for liposomal doxorubicin, 99.4% for gemcitabine, 34% for oxaliplatin and 56.3% for vinorelbine. The implications of dose rounding in financial terms are significant and project savings of 4-14.2%. CONCLUSIONS: The judicious application of dose rounding of chemotherapy agents is possible without any negative clinical effect. It is feasible to dose round to the nearest vial for those cytotoxic agents that are available in multiple vial sizes.

Antineoplastic Agents↗

A paradigm change in assembling OH functionalities on metal centers.

The synthesis of terminal hydroxide containing Group 13 and 14 metals [LAl(OH)(2)], LAlMeOH, [{LAl(OH)}(2)(mu-O)], LAl(OH)-O-AlLL', LGeOH, and [TsiSn(O)OH](3) [Tsi = (Me(3)Si)(3)C] has been accomplished using innovative synthetic methodologies. All of these compounds have been structurally characterized, both in solution as well as in the solid state. The utility of such metal hydroxides [{LAl(OH)}(2)(mu-O)] and LAlMeOH [L = HC{(CMe)(2,6-i-Pr(2)C(6)H(3)N)}(2)] in the preparation of homo- and heterometallic compounds has been demonstrated. It has also been possible to prepare unusual terminal SH- and SeH-containing compounds LAl(SH)(2), LAl(SeH)(2), and LAl(SeH)-Se-Al(SeH)L using dihydride LAlH(2) as a starting material. The synthesis, structure, and potential utility of these compounds is discussed.

Journal Article↗

Inorganic salts influence IAA ionization and adventitious rhizogenesis in Pongamia pinnata.

The basal cut end of coppice shoot cuttings of Pongamia pinnata was treated for 24 h with 0 (water treated control) or 5.0 mmol/L of KMnO4, KCI, and KH2PO4 or 2.5 mmol/L of K2HPO4 and K2SO4. Inorganic salts of P, S, Cl and Mn significantly influenced IAA ionization and adventitious rhizogenesis. P and S salts had lower IAA ionization potential, but more pronounced effect on adventitious rhizogenesis than Cl and Mn salts. The linear regression analysis also established negative correlations between salt induced IAA ionization with various characteristics of adventitious rhizogenesis such as sprouting (r = -0.83, p < 0.05), rooting (r = -0.82, p < 0.05), root number (r = -0.95, p < 0.01), and root length (r = -0.80, p < 0.1). The implication of IAA ionization in adventitious rhizogenesis has been discussed and the possible role of inorganic salts therein suggested.

Ions↗

Metastatic prostate carcinoma to the intradural extramedullary spinal compartment. Case report.

Despite the relatively high incidence of prostate carcinoma involving the spinal column, those that are associated with spinal intradural extramedullary metastases are rare. The role of surgery for metastases to this spinal compartment is limited and palliative because presentation tends to be late in the course of the disease, particularly for prostate carcinoma. It is also considered to be part of the spectrum of leptomeningeal carcinomatosis and is associated with a high incidence of brain metastases. The authors review a rare case of prostate carcinoma metastatic to the spinal intradural extramedullary space and discuss its clinical presentation, imaging features, and surgical management.

Carcinoma↗

Near simultaneous computed tomography image-guided stereotactic spinal radiotherapy: an emerging paradigm for achieving true stereotaxy.

PURPOSE: To report treatment setup data from an emerging technique using near-simultaneous computed tomography (CT) image-guided stereotactic radiotherapy for the treatment of spinal and paraspinal tumors. METHODS AND MATERIALS: A targeting system that integrates a CT-on-rails scanner with a linear accelerator (LINAC) was evaluated in the lead-in portion of a Phase I/II protocol for treating patients with paraspinal metastases. Patients were immobilized in supine position by a moldable body cushion vacuum wrapped with a plastic fixation sheet. Planning CT and immediately repeated CT were performed on the LINAC/CT-on-rails unit to assess respiratory-related vertebral body motion. Coplanar intensity-modulated radiotherapy (IMRT) using 7-9 beams was used to deliver 30 Gy in five fractions to the target volume, while limiting the spinal cord dose to <10 Gy. Pretreatment CT scans were fused with the planning CT scans to determine the correct target isocenter by accounting for any translational and roll (axial) rotational discrepancies from the planning CT. (Corrections caused by yaw and pitch rotations have not yet been implemented.) The reproducibility of the treatment isocenter as compared with the planned isocenter was measured with digitally reconstructed radiographs (DRRs), portal film imaging, and immediate post-treatment verification CT scans. Phantom measurements were taken for dose verification for each IMRT plan. RESULTS: Based on a total of 36 CT scans (3 for planning, 3 for respiration study, 15 pretreatment, and 15 post-treatment) from 3 patients, no respiration-associated vertebral body motion was seen. A comparison of the corrected daily anterior-posterior (AP) and lateral (LAT) digital portal images with the planning AP and LAT DRRs confirmed that the isocenter setup accuracy for the 15 treatments was within 1 mm of the planning isocenter. The results from the immediate post-treatment CT scans reconfirmed the findings from the portal images and verified the absence of spinal movement during the treatment. The ion-chamber measurement for the high-dose region was within 2% of the planning dose for three patient treatment plans. Film dose measurement in an IMRT quality assurance phantom demonstrated good agreement from 90% to 30% isodose lines between the planned and measured results. CONCLUSION: Preliminary experience suggests that the near-simultaneous CT image-guided verification technique can be used as a new platform technology for extracranial applications of stereotactic radiotherapy and radiosurgery to spinal and paraspinal tumors.

Equipment Design↗

Hypothalamic hamartomas: seven cases and review of the literature.

Hypothalamic hamartomas constitute rare developmental lesions associated with gelastic epilepsy and/or precocious puberty (PP). We elected to review cases encountered at our center (7 patients) and the existing literature (277 patients) to obtain a better understanding of the clinical aspects, pathogenesis, and treatment of this entity. Evidence suggests that gelastic seizures are due to intrinsic epileptogenicity. The cause of the subsequent development of other seizure types, cognitive decline, and diffuse spike-and-wave pattern remains unresolved and is addressed. Anticonvulsants often fail to control seizures and different surgical options are available. Available evidence suggests that a resection through a subtemporal approach is best for lesions that are pedunculated or with a significant prepontine component, while a transcallosal approach is more appropriate for sessile lesions with an intraventricular component. Gamma knife surgery may be especially useful for small sessile lesions, failed partial resections, or patients not appropriate or refusing open surgery.

Adolescent↗

Biochemical and immunological characterization of bacterially expressed and refolded Plasmodium falciparum 42-kilodalton C-terminal merozoite surface protein 1.

Protection against Plasmodium falciparum can be induced by vaccination in animal models with merozoite surface protein 1 (MSP1), which makes this protein an attractive vaccine candidate for malaria. In an attempt to produce a product that is easily scaleable and inexpensive, we expressed the C-terminal 42 kDa of MSP1 (MSP1(42)) in Escherichia coli, refolded the protein to its native form from insoluble inclusion bodies, and tested its ability to elicit antibodies with in vitro and in vivo activities. Biochemical, biophysical, and immunological characterization confirmed that refolded E. coli MSP1(42) was homogeneous and highly immunogenic. In a formulation suitable for human use, rabbit antibodies were raised against refolded E. coli MSP1(42) and tested in vitro in a P. falciparum growth invasion assay. The antibodies inhibited the growth of parasites expressing either homologous or heterologous forms of P. falciparum MSP1(42). However, the inhibitory activity was primarily a consequence of antibodies directed against the C- terminal 19 kDa of MSP1 (MSP1(19)). Vaccination of nonhuman primates with E. coli MSP1(42) in Freund's adjuvant protected six of seven Aotus monkeys from virulent infection with P. falciparum. The protection correlated with antibody-dependent mechanisms. Thus, this new construct, E. coli MSP1(42), is a viable candidate for human vaccine trials.

Amino Acid Sequence↗

Bacterially expressed and refolded receptor binding domain of Plasmodium falciparum EBA-175 elicits invasion inhibitory antibodies.

Malaria parasites make specific receptor-ligand interactions to invade erythrocytes. A 175 kDa Plasmodium falciparum erythrocyte binding antigen (EBA-175) binds sialic acid residues on glycophorin A during invasion of human erythrocytes. The receptor-binding domain of EBA-175 lies in a conserved, amino-terminal, cysteine-rich region, region F2 of EBA-175 (PfF2), that is homologous to the binding domains of other erythrocyte binding proteins such as Plasmodium vivax Duffy binding protein. We have developed methods to produce recombinant PfF2 in its functional form. Recombinant PfF2 was expressed in Escherichia coli, purified from inclusion bodies, renatured by oxidative refolding and purified to homogeneity by ion-exchange and gel filtration chromatography. Refolded PfF2 has been characterized using biochemical and biophysical methods and shown to be pure, homogenous and functional in that it binds human erythrocytes with specificity. Immunization with refolded PfF2 yields high titre antibodies that efficiently inhibit P. falciparum invasion of erythrocytes in vitro. Importantly, antibodies raised against PfF2 block invasion by a P. falciparum field isolate that invades erythrocytes using multiple pathways. These observations support the development of recombinant PfF2 as a vaccine candidate for P. falciparum malaria.

Animals↗

Association of HLA phenotype with primary non-response to recombinant hepatitis B vaccine: a study from north India.

The hepatitis B vaccine is considered to be highly immunogenic and has a good safety profile. In adults, it has a primary non-response rate of 5%-10%. Causes of nonresponse to hepatitis B vaccine include age, sex, obesity smoking. Certain human leucocyte antigen (HLA) phenotypes have been known to be associated with responsiveness to the vaccine, and found to be different in different ethnic groups, such as Caucasians and Orientals. The study was designed to identify the HLA phenotypes that are associated with non-responsiveness to hepatitis B virus (HBV) vaccination amongst a cohort of Indian subjects who agreed to participate in the vaccination programme. The study was offered to 107 volunteers, of whom 102 were found to be negative for HBV markers (hepatitis B surface antigen [HBsAg], anti-HBc, anti-HBe, anti-HBs, hepatitis Be antigen [HBeAg]) . All 102 volunteers were offered recombinant hepatitis B vaccine (20 microg) at 0, 1, and 6 months. Anti-HBs antibody titres were tested on days 90 and 210 of the first vaccine dose. HLA typing was done using standard microlymphotoxicity tests. The seroconversion rate of the hepatitis B vaccine was 86.3% (88/102). Fifteen nonresponders (15/102) and 15 of the 88 responders were randomly selected after age and sex matching for the purpose of studying the HLA phenotypes. HLA subtypes A1, B15, B40, A10 and DQ2 were found to be increased among nonresponders while HLA- A11, C3, DR10, DR51 (p>0.05) were the most common phenotypes amongst the responders. Further studies are needed to characterize the HLA phenotypes amongst the responders in different ethnic groups in India with respect to HBV vaccination.

Adult↗

Management of polypoidal lesions of gallbladder in laparoscopic era.

UNLABELLED: The detection of polypoidal lesion of gallbladder (PLG) has increased particularly with widespread use of ultrasonography (US) as a diagnostic modality. Most of the PLG are diagnosed incidentally during scanning. Differentiation of benign from malignant PLG is a major concern and further management is based on this differentiation. DATA SOURCE: A Pubmed database search was performed. Abstract and articles were reviewed in detail. Other references were extracted by cross-reference. CONCLUSION: The risk factors for malignancy in PLG are identified. The newer investigative procedures may differentiate benign from malignant PLG. Follow up of the asymptomatic patient and indication for surgery is established in PLG.

Algorithms↗