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Biomedical subjects

M Bhat

Publications and source records attributed to M Bhat.

At least 19 recordsLinked to original sources
PubMed2005

A fast, high spatial resolution optical tomographic scanner for measurement of absorption in gel dosimetry.

A fast tomographic optical density measurement system has been constructed and evaluated for application in Fricke 3D gel dosimetry. Although the potential for full three-dimensional radiation dosimetry with Fricke gel dosimeters has been extensively reported, its application has been limited due to a lack of fast optical density measurement systems. In this work, the emphasis of the design has been to achieve a short scan time through the use of precision optics and minimal moving parts. The system has been demonstrated in the laboratory to be able to achieve better than 1mm resolution and a scanning time per tomographic slice of 2.4 seconds. Full volumetric sampling of a 10 cm diameter by 7cm long cylinder can be achieved in 3 minutes. When applied with a Fricke based gel dosimeter a linear response between reconstructed CT number and absolute dose was better than 3%.

Absorption↗
PubMed2005

Social outcome in treated individuals with inherited metabolic disorders: UK study.

Few data exist on the long-term social outcome of patients with inherited metabolic disorders, despite the fact that increasing numbers are surviving into adulthood. Here we report the findings of 329 patients aged from 11 to 70 years, of whom 172 had phenylketonuria, 38 had homocystinuria and 33 had galactosaemia. Twenty-eight per cent had no formal education qualifications, 59% were employed, but only 17% were in professional jobs (social classes I and II). The time of diagnosis and treatment had a significant impact on outcome in phenylketonuria, as did pyridoxine responsiveness or lack of it in homocystinuria. Effects on outcome in galactosaemia were not clear. Social integration is an important outcome of treatment of chronic disorders in childhood and warrants further study in this growing patient population.

Adolescent↗
PubMed2004

MRI and plain radiography in the assessment of displaced fractures of the waist of the carpal scaphoid.

We treated 50 patients with fractures of the waist of the scaphoid in a below-elbow plaster cast for up to 13 weeks. Displacement of the fragments was assessed independently by two observers using MRI and radiographs performed within two weeks of injury. The MRI assessments showed that only the measurement of sagittal translation of the fragments and an overall assessment of displacement had satisfactory inter- and intra-observer reproducibility and revealed that nine of the 50 fractures were displaced. Only three of the 49 fractures with adequate follow-up failed to unite, and all were displaced with more than 1 mm of translation in the sagittal plane. If the MRI assessment of displacement of the fracture was used as the measurement of choice, assessment of displacement on the initial scaphoid series of radiographs showed a sensitivity of between 33% and 47% and a positive predictive value of between 27% and 86%. Neither observer was able correctly to identify more than 33% to 47% of the displaced fractures from the plain radiographs. Although the overall assessment of displacement and gapping and translation in the coronal plane on the plain radiographs influenced the rate of union, none of these parameters identified all three fractures which failed to unite. We conclude that the assessment of displacement of scaphoid fractures on MRI can probably be used to assess the likelihood of union although the small number of nonunions limits the power of the study. In contrast, the assessment of displacement on routine radiography is inaccurate and of less value in predicting union.

Casts, Surgical↗
PubMed2004

Differential expression of CD40 and CD95 in ovarian carcinoma.

PURPOSE: The role of CD95 (Fas) as a mediator of apoptosis has been well documented. CD40 ligation has been recently shown to initiate apoptosis and modulate CD95 mediated apoptosis in normal and some neoplastic tissues. Here we report the expression of CD95 and CD40 in cryopreserved cell suspensions from ovarian cancer associated ascites, fresh primary and recurrent ovarian carcinoma (OVCA) specimens, and ten established ovarian cancer cell lines. The effect of CD95 and CD40 receptor binding on apoptosis is described in two cell lines. EXPERIMENTAL DESIGN: Ascites specimens, fresh primary and recurrent OVCA specimens were dissociated to single cell suspensions. Expression of CD95 and CD40 was analyzed using flow cytometry. Apoptosis was determined via annexin uptake by flow cytometry following incubation with anti-CD95 antibody, CH11 and trimeric CD40L. RESULTS: Ascites showed the highest expression of both CD95 and CD40. Recurrent OVCA, in contrast, expressed low levels of CD95 and CD40. Primary OVCA showed moderate expression of both receptors. CD40 expression in ascites was significantly greater when compared to solid specimens (p < 0.05). Both CD40 and CD95 were strongly expressed in eight of ten cell lines studied. Binding of CD40L did not influence CD95 mediated apoptosis. CONCLUSIONS: CD40 is ubiquitously expressed in ovarian carcinomas and expression differs between ascites and solid tumor. There may be differential expression of both CD40 and CD95 in recurrent vs primary ovarian carcinoma, which may contribute to increased clinical malignancy of recurrent disease. In contrast to other epithelial malignancies, CD40 ligation does not appear to modulate CD95 mediated apoptosis.

Apoptosis↗
PubMed2002

A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application.

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within +/- 3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at dmax). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice.

Breast↗
PubMed2001

Bcl-xL blocks transforming growth factor-beta 1-induced apoptosis by inhibiting cytochrome c release and not by directly antagonizing Apaf-1-dependent caspase activation in prostate epithelial cells.

The mechanism by which transforming growth factor-beta1 (TGF-beta1) induces apoptosis of prostate epithelial cells was studied in the NRP-154 rat prostate epithelial cell line. TGF-beta 1 down-regulates expression of Bcl-xL and poly(ADP-ribosyl)polymerase (PARP), promotes cytochrome c release, up-regulates expression of latent caspase-3, and activates caspases 3 and 9. We tested the role of Bcl-xL in this cascade by stably overexpressing Bcl-xL to prevent loss by TGF-beta 1. Clones overexpressing Bcl-xL are resistant to TGF-beta 1 with respect to induction of apoptosis, cytochrome c release, activation of caspases 9 and 3, and cleavage of PARP; yet they remain sensitive to TGF-beta 1 by cell cycle arrest, induction of both fibronectin and latent caspase-3 expression, and loss of PARP expression. We show that Bcl-xL associates with Apaf-1 in NRP-154 cells; but this association does not inhibit the activation of caspases 9 and 3 by cytochrome c. Together, our data suggest that TGF-beta1 induces apoptosis through loss of Bcl-xL, leading to cytochrome c release and the subsequent activation of caspases 9 and 3. Moreover, our data demonstrate that the antiapoptotic effect of Bcl-xL occurs by inhibition of mitochondrial cytochrome c release and not through antagonizing Apaf-1-dependent processing of caspases 9 and 3.

Apoptosis↗
PubMed2001

The influence of suspension nebulization or instillation on particle uptake by guinea pig alveolar macrophages.

Phagocytosis represents a crucial event in the host defense against pathogens. Experimental methods are required that allow a range of particle doses to be delivered. However, it is not clear that these methods result in the same sites of deposition or mechanisms of clearance. The effect of particle administration by nebulization or instillation on the uptake by guinea pig alveolar macrophages (AMs) has been studied. Suspensions of escalating quantities of 1-microm fluorescent polystyrene latex microspheres were delivered by 15 min of nebulization (1.4 x 10(7)-11.1 x 10(7) particles) or instillation (19 x 10(7)-152 x 10(7) particles) into the lungs of guinea pigs. These doses were selected to maximize delivery using each of these methods. Macrophages were collected by alveolar lavage 6 h postadministration. The total number of cells recovered was 3 x 10(6) and the cell viability was >97%, which was measured by trypan blue exclusion. Differential cell counts of lavaged cell suspensions were conducted and results showed no difference for the two methods of administration with various concentrations of latex particles and control samples. The uptake of particles was measured using epifluorescence, confocal microscopy, and flow cytometry. AMs showed a dose-dependent increase in associated particles measured by microscopy and flow cytometry. There was a direct correlation (R(2) =.99) in the phagocytic indices (PIs) measured by flow cytometry and fluorescence microscopy. The PI was 15 times higher after instillation than that obtained after particle nebulization. The percentage of AMs involved in phagocytosis observed after instillation was 55% and after nebulization 23%. The uptake of aerosolized particles by AMs and the number of cells involved in phagocytosis were dependent on the particle dose and the efficiency of aerosol delivery to the lungs.

Administration, Inhalation↗
PubMed2000

First clinical case of small de novo duplication of 19q (13.3-13.4) confirmed by FISH.

Partial trisomy of 19q has been reported in only 13 patients, of which all but one have been due to unbalanced translocations. Only one previous report of a de novo duplication of distal 19q has been described in a fetal chorionic villus sample. There was no description of clinical phenotype in this report. We describe the clinical manifestations and cytogenetic analysis in a child with an inverted duplication of 19q 13.3 to 13.4 confirmed by FISH using a chromosome 19 whole chromosome probe. This case represents the first report of a liveborn with "pure" distal trisomy 19q. Findings defining this uncommon aneusomy are a flat facies, down turned mouth, abnormal ears, and a short neck with redundant skin folds.

Abnormalities, Multiple↗
PubMed2000

Effect of chloroquine on phagolysosomal fusion in cultured guinea pig alveolar macrophages: implications in drug delivery.

The aim of this study was to evaluate the effects of chloroquine on phagolysosomal fusion (PLF) in cultured guinea pig alveolar macrophages (AMs). This technique may be of significance for antitubercular drugs, because.the survival of Mycobacterium tuberculosis is linked to evasion of PLF. Guinea pig AMs were obtained from anesthetized animals after exsanguination. The AMs were cultured at a density of 1 x 10(6) cell/mL in 24-well plates after attachment to 13-mm coverslips. Culture conditions were at 37 degrees C, with 95% air/5% CO2 in Roswell Park Memorial Institute (RPMI) 1640 medium with 10% heat-inactivated fetal bovine serum. Rhodamine-dextran (70 kd) was incubated with the cells at 0.25 mg/mL for 24 hours to label the lysosomes. Chloroquine treatment where indicated was performed at 10-20 microg/mL for 1 hour. Fluorescent BioParticles were then added, and PLF was monitored by formation of an orange-yellow fluorescence on fusion of green fluorescent BioParticles with rhodamine-labeled lysosomes. PLF endpoints were measured by scoring for the percentage of orange-yellow cells in the field of view. Image analysis to measure the intensity of the orange-yellow color was performed by obtaining a, b values for 5 x 5 pixel areas using the PhotoAdobe program 4.0.1. The results indicated that the rate of PLF was enhanced by chloroquine. Thus, chloroquine may be used to potentiate the effects of rifampicin. This may be confirmed by studies involving similar dual fluorophore labeling techniques of fluorescein-labeled formulation in macrophages infected with M.tuberculosis. Preliminary studies with the rhodamine-labeled formulation confirmed cellular uptake and persistence for up to 7 days in culture.

Animals↗
PubMed1999

A negatively charged region of the skeletal muscle ryanodine receptor is involved in Ca(2+)-dependent regulation of the Ca(2+) release channel.

The ryanodine receptor/Ca(2+) release channels from skeletal (RyR1) and cardiac (RyR2) muscle cells exhibit different inactivation profiles by cytosolic Ca(2+). D3 is one of the divergent regions between RyR1 (amino acids (aa) 1872-1923) and RyR2 (aa 1852-1890) and may contain putative binding site(s) for Ca(2+)-dependent inactivation of RyR. To test this possibility, we have deleted the D3 region from RyR1 (DeltaD3-RyR1), residues 1038-3355 from RyR2 (Delta(1038-3355)-RyR2) and inserted the skeletal D3 into Delta(1038-3355)-RyR2 to generate sD3-RyR2. The channels formed by DeltaD3-RyR1 and Delta(1038-3355)-RyR2 are resistant to inactivation by mM [Ca(2+)], whereas the chimeric sD3-RyR2 channel exhibits significant inactivation at mM [Ca(2+)]. The DeltaD3-RyR1 channel retains its sensitivity to activation by caffeine, but is resistant to inactivation by Mg(2+). The data suggest that the skeletal D3 region is involved in the Ca(2+)-dependent regulation of the RyR1 channel.

Amino Acid Sequence↗
PubMed1999

Off-axis x-ray spectra: a comparison of Monte Carlo simulated and computed x-ray spectra with measured spectra.

The off-axis x-ray spectra from a constant potential x-ray generator were measured with a high purity germanium spectrometer cooled to liquid nitrogen temperature. The measured spectra were compared with off-axis x-ray spectra calculated using a code based on the semiempirical model developed by Tucker et al. and Monte Carlo simulated x-ray spectra using the EGS4 code system. In this study, both the Tucker model, and the EGS4 code system, were found to produce off-axis bremsstrahlung x-ray spectra which agreed well with the spectra measured at three emerging angles. In the measured and the EGS4 generated spectra the total K-characteristic peaks were in increasing order, as observed in the anode to cathode direction, whereas the Tucker model produced maximum total K-characteristic peaks at the 6 degrees anode side, and lesser amounts at the central axis and the 6 degrees cathode side. Large differences in the total K-characteristic lines is seen among the three different methods. The EGS4 code system was able to produce x-ray spectra for a combination of target materials.

Computer Simulation↗
PubMed1998

High-performance liquid chromatographic determination of insulin in rat and human plasma.

A rapid and simple isocratic chromatographic procedure for the determination of insulin in human and rat plasma using reversed-phase (RP) high-performance liquid chromatography with an ultraviolet/visible detector is described. The method includes extraction of insulin from human and rat plasma into dichloromethane, followed by back-extraction into 0.05 N hydrochloric acid. The organic phase was evaporated under a stream of nitrogen. The aqueous phase was filtered and a 100 microliters aliquot was analyzed on a RP-C18 column eluted with a mobile phase consisting of a mixture of 74 vol of 0.2 M sodium sulfate anhydrous adjusted to pH 2.3 with phosphoric acid and 26 vol of acetonitrile. The flow rate was 1.2 ml/min and the wavelength was set at 214 nm. The calibration curve was linear over the range of 75-800 microIU/ml. The precision of the assay expressed as coefficients of variation was less than 6% over the entire concentration range. The recovery for insulin ranged from 79 to 81% from human and rat plasma, with coefficients of variation less than 6%. The intra- and interassay coefficients of variation were less than 5.7%. The limit of detection was 50 microIU/ml.

Adult↗
PubMed1998

Diagnostic x-ray spectra: a comparison of spectra generated by different computational methods with a measured spectrum.

A number of computer codes, developed using semi-empirical models, are available to compute x-ray spectra from a tungsten target for different tube parameters. In this study x-ray spectra measured with a high-purity germanium detector are compared with those computed using the empirical models and previously published measured data. The computer codes used to generate the spectra are based on models proposed by Birch et al. and Tucker et al. The measured x-ray spectra agreed well with the computed x-ray spectra using the model of Tucker et al. whereas the model of Birch et al. produced a "harder" x-ray spectrum compared to the measured spectra. Our measured x-ray spectra compared well with the previously published measured spectral data of Fewell et al.

Americium↗
PubMed1998

The effect on dose to computed tomography phantoms of varying the theoretical x-ray spectrum: a comparison of four diagnostic x-ray spectrum calculating codes.

Theoretical x-ray spectra calculated by four different codes for the same tube parameters are compared by calculating and measuring doses to computed tomography (CT) body and head phantoms. The effect on the 120 kV spectrum, and hence on the calculated dose, of varying the anode angle, tube voltage, and total filtration of the x-ray tube is investigated. Codes used were those of Nowotny and Höfer (XCOMP), Boone, Iles, and Tucker et al. The code based on the work of Tucker et al. produced calculated doses noticeably lower than the other codes and compared best to the measured value. The variation in calculated dose between the Tucker code and the others is of the same order as the variation introduced by uncertainties in total filtration of about 20%, in peak tube voltage of +/- 4 kV, and in change of anode angle from 7 degrees to 13 degrees.

Biophysical Phenomena↗
PubMed1998

Expression of beta-defensin genes in bovine alveolar macrophages.

Bovine alveolar macrophages (BAM) were examined for the expression of beta-defensins and to determine whether their expression could be upregulated by bacterial lipopolysaccharide (LPS), as observed with beta-defensins expressed in bovine tracheal epithelial cells. Four beta-defensins were expressed constitutively in BAM, with bovine neutrophil beta-defensin (BNBD)-4 and BNBD-5 being the most predominant. This is the first evidence of beta-defensin gene expression in a mature myeloid cell. LPS had no effect on beta-defensin expression in BAM, even though tumor necrosis factor alpha (TNF-alpha) production was induced. Nonbacterial inflammatory particles had little effect on beta-defensin gene expression or TNF-alpha production in BAM. We hypothesize that constitutively expressed beta-defensins of alveolar macrophages may have a role in lung host defense.

Amino Acid Sequence↗