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Biomedical subjects

N Sahoo

Publications and source records attributed to N Sahoo.

At least 19 recordsLinked to original sources

Measurement of transit time of a remote after-loading high dose rate brachytherapy source.

Quantification of transit time of a remote after-loading high dose rate (HDR) brachytherapy source is important both for accurate treatment planning and for quality assurance checks. In this investigation, an HDR-1000 well ionization chamber and a precision electrometer are used to measure the transit time of the Ir-192 source of a Nucletron Micro-Selectron HDR brachytherapy unit. The charge generated both during source dwelling at a selected position in an endobronchial catheter inserted into the chamber and during source travel to this position from another location at a distance of 0.5 to 10 cm from it was measured. A linear regression analysis of the measured charge as a function of dwell time was made. The interdwell position transit time was calculated from the ratio of the charge intercept and the slope of the straight line obtained from the regression analysis. The values of the effective transit time, which is a combination of interdwell position transit time and dwell time error of the after-loading unit, were found to be 0.03 and 0.45 s for 0.5 and 10 cm separation between two dwell positions, respectively. The average time for 1 cm travel of the source between two dwell positions was found to be 0.022 s, resulting in an average speed of 45.5 cm/s. This simple procedure has the potential to be utilized for routine quality assurance check of the interdwell position transit time of any remote after-loading HDR brachytherapy source.

Brachytherapy↗

A novel 70-kDa Triton X-114-soluble antigen of Plasmodium falciparum that contains interspecies-conserved epitopes.

In order to identify novel conserved integral membrane and other membrane-associated proteins of Plasmodium falciparum, lambda gt11-P. falciparum DNA library phages were immunoscreened with convalescent-phase mouse sera and rabbit antiserum against Triton X-114-soluble proteins of P. falciparum. One recombinant phage clone, L857, reacted with both of the antibody probes. Insert DNA (857 bp long) in L857 was 69% dA+dT rich and hybridized to a fragment of 1800 bp from mung bean nuclease-digested P. falciparum genomic DNA. The cloned parasite DNA did not show notable sequence homology with any known protein gene. The L857-encoded polypeptide, p34 (M(r) 34 kDa) was expressed in bacteria, fused to glutathione S-transferase (GST). The fusion peptide, GST-p34 (M(r) 62 kDa), was recognized by immune serum against Triton X-114-soluble antigens of P. falciparum and was reactive with anti-P. falciparum, anti-Plasmodium yoelii, and anti-GST sera. Rabbit antiserum raised against the fusion peptide recognized a 70-kDa protein from lysates of P. falciparum cells and a putative homologous 100-kDa protein from lysates of P. yoelii. The rabbit serum anti-fusion peptide antibodies bound to acetone-fixed P. falciparum-infected erythrocytes and, in immunofluorescent antibody tests, produced a punctate pattern of fluorescence suggesting that the 70-kDa native protein is associated with an apical organelle of the parasite.

Amino Acid Sequence↗

Analysis of factors affecting the therapeutic gain in high dose rate gynecological implants relative to low dose rate implants.

The radiobiological efficacy of high dose rate (HDR) intracavitary implant relative to that of low dose rate (LDR) implants has been represented quantitatively by the therapeutic factor lamba defined as [EDRtum/ERDorgan]HDR/[ERDtum/ERDorgan]LDR where ERD is the extrapolated response dose. The ERDs for the tumor and a critical organ are calculated using the linear-quadratic model and depend on the values of alpha/beta ratio, the tumor and normal tissue repair time constants (mu 1 and mu 1), number (N) of HDR fractions, the dose per fraction (d), and the fractional tumor and organ dose (ft and fl) relative to the dose at the reference point. We have studied the variation of gamma with d, mu t, mu l, ft, and ft and have derived specific conditions for which lamba can have a value equal to or greater than unity leading to a therapeutic gain in HDR. It is found that lamba is less than unity for commonly used parameter values, specifically when mu t is assumed to be equal to mu l. However, if mu t is greater than mu l, lamba can have a value greater than unity for many possible values of ft and fl.

Biophysical Phenomena↗

Quantifying the effect of dose inhomogeneity in brachytherapy: application to permanent prostatic implant with 125I seeds.

PURPOSE: To quantitate the influence of dose inhomogeneity on brachytherapy efficacy. METHODS AND MATERIALS: A computed tomography-based system of planning, implementation and evaluation was used to generate tumor-specific dose-volume histograms of eight permanent 125I implants of prostate cancers. The radiobiological effect was then assessed, voxel by voxel, in terms of the biologically effective dose and the associated cell inactivation. The overall cell survival of the entire target volume was then computed. To evaluate the influence of inhomogeneity, the dose-volume histogram was modified in an iterative fashion, with the corresponding surviving fraction calculated after each step. Specifically, the volume in the highest dose bin was combined with that in the next bin to give a new frequency distribution from which cell survival was generated. Tumor control probability (TCP) was also used as an endpoint, using the same iterative procedure. RESULTS: Doses 20-30% higher than D99 (the dose that covered 99% of the target volume) contributed to additional cell inactivation, but still higher doses did not further increase cell kill. With homogeneous irradiation at D99 as a reference, we defined the inhomogeneity enhancement factor as the ratio of the biologic effective dose of the actual implant to that of the reference dose distribution. The calculated enhancement factors were inversely dependent on tumor potential doubling time (Tp), about 1.2-1.3 for a Tp of 30 days, and between 1.3 and 1.7 if Tp = 10 days, with higher values for implants with low D99. Dose inhomogeneity enhanced TCP. For implants with high control probabilities does significantly higher (> 20%) than the D99 value did not further enhance the tumor control probabilities. In contrast, for implants with relatively low tumor control and D99 values, the control probability continued to increase with doses significantly higher than D99, up to a dose of 2 x D99. The underlying reasons were the incorporation of patient "population averaging" in the calculation and the saturation of tumor control dose response at about 120 Gy. CONCLUSION: Dose heterogeneity in implants increased tumor cell kill and local control probability, although doses > 20% higher than the prescription dose is wasted. The increase the beneficial effect of dose inhomogeneity may be greatest when most needed.

Brachytherapy↗

Serum antibody immunoglobulin G of mice convalescent from Plasmodium yoelii infection inhibits growth of Plasmodium falciparum in vitro: blood stage antigens of P. falciparum involved in interspecies cross-reactive inhibition of parasite growth.

We demonstrated that antibodies in the serum of BALB/c mice convalescent from Plasmodium yoelii infection inhibit the in vitro growth of Plasmodium falciparum. Blood stage P. falciparum antigens that cross-react with the convalescent-phase mouse serum antibodies were identified and partially characterized. Convalescent-phase mouse serum immunoglobulin G (IgG) reacted with P. falciparum lysates at up to a 1:15,000 dilution of the immune sera and bound to P. falciparum-parasitized erythrocytes at up to a 1:5,000 dilution of the sera. The cross-reactive moieties of antigens in parasite lysates were resistant to oxidation by periodate but sensitive to trypsinization. About 15 polypeptides (M(r)s of 15,000 to 110,000) of P. falciparum blood stages were recognized by the convalescent-phase mouse anti-P. yoelii sera; many of these antigens were metabolically 35S labeled and specifically immunoprecipitated. Also, virtually all of the cross-reactive antigens were recognized by human malaria-immune sera. The anti-P. yoelii serum antibodies bound, with high affinity, to at least five of the cross-reactive antigens (M(r)s of 107,000, 84,000, 53,000, 36,000, and 30,000). By phase separation in Triton X-114, eight interspecies cross-reactive antigens (M(r)s of 84,000, 76,000, 51,000, 31,000, 29,000, 28,000, 23,000, and 22,000) were found to be integral membrane proteins. Convalescent-phase mouse serum IgG strongly inhibited the differentiation of P. falciparum from schizonts to rings; 75 micrograms of IgG per ml caused 80% inhibition of release of merozoites and their invasion into erythrocytes. On the other hand, the anti-P. yoelii serum antibodies also inhibited intracellular development of P. falciparum from rings to schizonts; 25 micrograms of IgG per ml caused 50% inhibition. Inhibition of P. falciparum growth by anti-P. yoelii serum IgG suggests that some of the interspecies cross-reactive antigens contain important conserved epitopes and induce protective antibodies against P. falciparum.

Animals↗

High dose rate gynecological applications--radiobiological considerations based on the alpha-beta model.

We compare the relative efficacy of high dose rate (HDR) and low dose rate (LDR) irradiation in gynecological implants, using formulations based on the linear-quadratic (alpha-beta) model. We consider both acute reaction and late effect as endpoints in evaluating equivalence for HDR and LDR treatments, at Point A (as defined in the text) and at other locations. We define a therapeutic factor gamma as an index for relative efficacy, with gamma > 1 indicating a gain in substituting HDR for LDR. It is found that gamma < 1 for most clinical situations, although a modest decrease (of about 15%) in dose to critical organs for HDR would raise gamma above unity.

Brachytherapy↗

Towards the design of heterovalent anti-malaria vaccines: a hybrid immunogen capable of eliciting immune responses to epitopes of circumsporozoite antigens from two different species of the malaria parasite, Plasmodium.

The peptide CS.T3, corresponding to residues 378-398 of the Plasmodium falciparum (Pf) circumsporozoite (CS) protein sequence (except with cysteines 384 and 389 replaced by alanines), has been found to be almost universally recognized by human and mouse T lymphocytes. When colinearly linked to the repetitive B-lymphocyte-specific epitope (Asn-Ala-Asn-Pro)n of Pf CS protein, CS.T3 induces T-helper activity for an anti-(Asn-Ala-Asn-Pro)n antibody response in mice of different haplotypes. We constructed a double-epitope peptide, CS.T3-R3, by co-linearly joining a truncated 18-mer form (IEKKIAKMEKASSVFNVV) of CS.T3 to three tandem repeats (R3) of a B-cell-specific epitope, QGPGAP, of Plasmodium yoelii (Py) CS protein, via a two-glycine spacer. Whereas CS.T3 and R3 did not induce specific antibodies, CS.T3-R3 elicited anti-CS.T3 and anti-R3 antibodies in different mouse strains. Some human anti-Pf sera from malaria-endemic areas contained high-titred anti-CS.T3 antibody IgG, indicating that parasite-derived CS.T3 contains a B-cell determinant which is maintained in the alanine-substituted synthetic CS.T3. Antibody absorption experiments showed that CS.T3-R3 contains no new B-cell-specific determinants other than R3 and CS.T3. That the Pf CS protein epitope, CS.T3, supports T-cell help for antibody responses against the Py CS protein repeat epitope, QGPGAP, implies the possible use of CS.T3 in anti-sporozoite multiple-epitope vaccines against different species of Plasmodium. Colinearly linking CS.T3 to R3, via a two-glycine spacer, appears to be a useful model by which different T- and B-cell-specific determinants can be jointed into a heterovalent immunogen while retaining their distinct immunological properties.

Animals↗