Search PubMed⌕ Search

Biomedical subjects

R Nath

Publications and source records attributed to R Nath.

At least 91 records · Page 5Linked to original sources
PubMed1998

On the use of unshielded cables in ionization chamber dosimetry for total-skin electron therapy.

The dosimetry of total-skin electron therapy (TSET) usually requires ionization chamber measurements in a large electron beam (up to 120 cm x 200 cm). Exposing the chamber's electric cable, its connector and part of the extension cable to the large electron beam will introduce unwanted electronic signals that may lead to inaccurate dosimetry results. While the best strategy to minimize the cable-induced electronic signal is to shield the cables and its connector from the primary electrons, as has been recommended by the AAPM Task Group Report 23 on TSET, cables without additional shielding are often used in TSET dosimetry measurements for logistic reasons, for example when an automatic scanning dosimetry is used. This paper systematically investigates the consequences and the acceptability of using an unshielded cable in ionization chamber dosimetry in a large TSET electron beam. In this paper, we separate cable-induced signals into two types. The type-I signal includes all charges induced which do not change sign upon switching the chamber polarity, and type II includes all those that do. The type-I signal is easily cancelled by the polarity averaging method. The type-II cable-induced signal is independent of the depth of the chamber in a phantom and its magnitude relative to the true signal determines the acceptability of a cable for use under unshielded conditions. Three different cables were evaluated in two different TSET beams in this investigation. For dosimetry near the depth of maximum buildup, the cable-induced dosimetry error was found to be less than 0.2% when the two-polarity averaging technique was applied. At greater depths, the relative dosimetry error was found to increase at a rate approximately equal to the inverse of the electron depth dose. Since the application of the two-polarity averaging technique requires a constant-irradiation condition, it was demonstrated than an additional error of up to 4% could be introduced if the unshielded cable's spatial configuration were altered during the two-polarity measurements. This suggests that automatic scanning systems with unshielded cables should not be used in TSET ionization chamber dosimetry. However, the data did show that an unshielded cable may be used in TSET ionization chamber dosimetry if the size of cable-induced error in a given TSET beam is pre-evaluated and the measurement is carefully conducted. When such an evaluation has not been performed, additional shielding should be applied to the cable being used, making measurements at multiple points difficult.

Biophysical Phenomena↗
PubMed1998

A position-sensitive superheated emulsion chamber for three-dimensional photon dosimetry.

A position-sensitive detector chamber is introduced for the three-dimensional (3D) dosimetry of photon-emitting brachytherapy sources. The detector is based on an extremely fine suspension of monochloropentafluoroethane droplets emulsified in a gel. The droplets are highly superheated at room temperature and their evaporation can be triggered by photon interactions, leading to the formation of microscopic bubbles. Thus, when photon-emitting brachytherapy sources are inserted into the detector, bubble distributions form around them, enabling visualization of the radiation field. The tissue-equivalent emulsifier gel is highly viscous and keeps the bubbles immobilized at the location of their formation. Bubbles can then be imaged by nuclear magnetic resonance or optical scanning techniques. After the imaging, the detector can be pressurized in order to recondense the bubbles to the liquid phase. In a few minutes, the device is annealed and ready to be used again for repeated measurements improving the counting statistics. The photon sensitivity of the monochloropentafluoroethane droplets was determined with highly filtered, quasi-monochromatic x-ray beams and radionuclide gamma sources. The air-kerma response presents a broad maximum at low energies, due to the relatively high effective atomic number of the halocarbon molecule. A prototype chamber was built and successfully tested: bubble distributions deriving from the insertion of a 125I source were imaged by means of a slice-selective 3D gradient-echo technique. These experiments confirm the potential and viability of this new approach to 3D photon dosimetry.

Brachytherapy↗
PubMed1998

In-phantom dosimetry and spectrometry of photoneutrons from an 18 MV linear accelerator.

A combination of three superheated drop detectors with different neutron energy responses was developed to evaluate dose-equivalent and energy distributions of photoneutrons in a phantom irradiated by radiotherapy high-energy x-ray beams. One of the three detectors measures the total neutron dose equivalent and the other two measure the contributions from fast neutrons above 1 and 5.5 MeV, respectively. In order to test the new method, the neutron field produced by the 10 cm X 10 cm x-ray beam of an 18 MV radiotherapy accelerator was studied. Measurements were performed inside a tissue-equivalent liquid phantom, at depths of 1, 5, 10 and 15 cm and at lateral distances of 0, 10, and 20 cm from the central axis. These data were used to calculate the average integral dose to the radiotherapy patient from direct neutrons as well as from neutrons transmitted through the accelerator head. The characteristics of the dosimeters were confirmed by results in excellent agreement with those of prior studies. Track etch detectors were also used and provided an independent verification of the validity of this new technique. Within the primary beam, we measured a neutron entrance dose equivalent of 4.5 mSv per Gy of photons. It was observed that fast neutrons above 1 MeV deliver most of the total neutron dose along the beam axis. Their relative contribution increases with depth, from about 60% at the entrance to over 90% at a depth of 10 cm. Thus, the average energy increases with depth in the phantom as neutron spectra harden.

Biophysical Phenomena↗
PubMed1998

Correlation of medical dosimetry quality indicators to the local tumor control in patients with prostate cancer treated with iodine-125 interstitial implants.

The treatment of prostate cancer by 125I interstitial implants has been extensively studied with mixed results by one institution or another. A recent study from Hahnemann [Int. J. Radiat. Oncol., Biol., Phys. 21,955-960 (1991)] reported results that were extremely poor compared to those reported in an earlier study at Yale [Int. J. Radiat. Oncol., Biol., Phys. 14, 1153-1157 (1988)] or those in an Eastern Virginia Study [Cancer 63, 2415-2420 (1989)]; differences in 5-yr survival rates being more than a factor of 2. Such large discrepancies from institution to institution led us to a reexamination of the dosimetry. This study analyzed quantitatively three-dimensional dosimetric parameters of 110 prostate cancer patients treated with 125I interstitial implants. The study searched for "cutoff" values in each parameter that divided the patients into two groups with statistically significant differences in the local recurrence-free survival rates. A comparison of the three-dimensional isodose surfaces of patients with favorable values in all of the parameters to those patients with all unfavorable parameters show how these characteristics translated into poor dose coverage and much inhomogeneity within the implant even for cases that met the traditional criteria for adequacy (160 Gy to the tumor volume). Patients in the favorable group had 10-yr survival rates higher by a factor of up to 2 compared to those in the unfavorable group. The strong correlation of three-dimensional volume-dose parameters to the local control rate observed in this study further emphasizes how important it is to assess the three-dimensional dosimetric adequacy of interstitial implants before deciding on their clinical efficacy. If implants are performed with appropriate attention to dosimetry parameters, excellent clinical results are obtained. On the other hand, if dosimetry parameters are not correct, the implant results can be poor.

Adenocarcinoma↗
PubMed1998

Magnetic resonance imaging of microbubbles in a superheated emulsion chamber for brachytherapy dosimetry.

This paper describes development of magnetic resonance imaging (MRI) techniques for three-dimensional (3D) imaging of a position-sensitive detector for brachytherapy dosimetry. The detector is a 0.5 l chamber containing an emulsion of halocarbon-115 droplets in a tissue-equivalent glycerin-based gel. The halocarbon droplets are highly superheated and expand into vapor microbubbles upon irradiation. Brachytherapy sources can be inserted into the superheated emulsion chamber to create distributions of bubbles. Three-dimensional MRI of the chamber is then performed. A 3D gradient-echo technique was optimized for spatial resolution and contrast between bubbles and gel. Susceptibility gradients at the interfaces between bubbles and gel are exploited to enhance contrast so microscopic bubbles can be imaged using relatively large voxel sizes. Three-dimensional gradient-echo images are obtained with an isotropic resolution of 300 microns over a 77 mm x 77 mm x 9.6 mm field-of-view in an imaging time of 14 min. A post-processing technique was developed to semi-automatically segment the bubbles from the images and to assess dose distributions based on the measured bubble densities. Relative dose distributions are computed from MR images for a 125I brachytherapy source and the results compare favorably to relative radial dose distributions calculated as recommended by Task Group 43 of the American Association of Physicists in Medicine.

Algorithms↗
PubMed1998

Brachial plexus birth injuries and current management.

OBPP is a condition that, for the majority of patients, resolves spontaneously with appropriate nonoperative treatment. However, those patients who do not improve spontaneously now have a better chance for recovery owing to recent advances in microsurgery and nerve-transfer techniques. The most important aspect of therapy is timely recognition and referral.

Birth Injuries↗
PubMed1997

Treatment of recurrent pelvic and selected primary gynecologic malignancies with 241Am.

The purpose of this study was to update the experience and demonstrate the effectiveness and limitations of 241Am applicators for previously irradiated patients and for selected patients with primary gynecologic malignancies. Between October 1986 and May 1994, 30 patients were treated with 241Am. The median patient age was 68 years, ranging from 41 to 91 years. Patients were retrospectively categorized by treatment intent, i.e., palliative vs. curative. Patients undergoing curative therapy were further classified as to whether 241Am brachytherapy was directed at microscopic residua after surgery or to gross primary tumor. Of the 30 patients, 18 had recurrent pelvic malignancies from various primary sites and were reirradiated with 241Am for palliation. Six patients had microscopic disease after surgical resection and were managed with postoperative radiotherapy (RT) that included 241Am. Six patients had gynecologic cancers managed with primary RT that included treatment with 241Am. Overall, 50% (9/18) of the patients with recurrent pelvic malignancies were locally controlled after reirradiation with 241Am. Including surgical salvage, the ultimate local control rate was 61% (11/18). Postoperative 241Am with or without external beam radiation therapy (XRT) was effective in 83% (5/6) of the patients with microscopic disease. Including surgical salvage, 100% (6/6) of the patients were ultimately free of disease. Fifty percent (3/6) of the patients treated with primary RT that included 241Am brachytherapy experienced local control. Including surgical salvage, 67% (4/6) of the patients were ultimately controlled with 241Am. In conclusion, reirradiation utilizing 241Am was effective in palliating patients with recurrent pelvic malignancies. 241Am was effective in 83% (5/6) of the patients with microscopic disease managed with postoperative RT. 241Am was of marginal benefit in patients with gynecologic tumors managed with primary RT.

Aged↗
PubMed1997

A purine nucleoside phosphorylase (PNP) inhibitor induces apoptosis via caspase-3-like protease activity in MOLT-4 T cells.

Children with congenital homozygous deficiency of purine nucleoside phosphorylase (PNP) have abnormalities in purine metabolism that result in T-cell selective immune deficiency. The mechanism of action for cell death has been attributed to intracellular accumulation of dGTP, a potent inhibitor of ribonucleotide reductase and subsequently DNA synthesis, in thymocytes and T-cells but not B-cells. However, the mode of cell death has not been determined to be either necrosis or apoptosis. To examine the involvement of apoptosis in T-cells following PNP inhibition, MOLT-4 cells, a human T cell leukemia cell line, were co-treated with the PNP inhibitor, CI-1000 (2-amino 3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]-pyrimidin-4-one HCl), and 2'-deoxyguanosine (dGuo) which resulted in a concentration-dependent loss of cell viability (trypan blue) and inhibition of tritiated thymidine ([3H]-TdR) uptake. Staining of cells with the DNA dye Hoechst 33,258 showed nuclear morphology characteristic of apoptosis. Western blots (24 h lysates) were probed with antibodies against several proteins implicated in apoptosis. Anti-PARP revealed the presence of an 85 kD PARP breakdown product while, anti-alpha-spectrin revealed the accumulation a 120 kD breakdown product, both suggestive of CPP32 cleavage (caspase-3; an ICE-like cysteine protease). Western blots also detected the loss of the intact 32 kD caspase-3 isoform, a biochemical event associated with caspase-3 activation. Corresponding fluorometric activity assays detected a marked increase in caspase-3-like activity using the substrate Ac-DEVD-MCA. Lastly, a pan caspase inhibitor (Z-D-DCB) and 2'-deoxycytidine (dCyd), which is known to prevent dGTP accumulation following PNP inhibition, were able to prevent cell death and all indicators of caspase-3-like activity in MOLT-4 cells co-treated with dGuo and CI-1000. In summary, we provided several lines of evidence for the role of apoptosis and the contribution of caspase-3-like proteases in T-cell death following PNP inhibition.

Apoptosis↗
PubMed1997

Copper deficiency and heart disease: molecular basis, recent advances and current concepts.

Copper is an essential trace element and has profound influence on cardiac myopathy and heart metabolism. Dietary Cu restriction in rats results in cardiomyopathy, and affects the integrity of the basal lamina of cardiac myocytes and capillaries. Decreased levels of delta subunits of ATP synthetase and nuclear encoded subunits of cytochrome oxidase system have been observed. Alteration in expression of glutathione peroxidase and catalase in heart and liver in Cu deficiency (Cu-) has been noted involving both transcriptional and post transcriptional mechanisms. A short description of two genetically inherited disorders of Cu metabolism, i.e. Wilson's disease and Menkes' disease, and Indian childhood cirrhosis (environmental and/or genetic) have been included to illustrate that advances in the knowledge of Cu cellular transport gives a better understanding of the molecular basis of the pathophysiology of these diseases. Menkes' disease, a human model of defective Cu transport and Cu- has shown many pathological changes, similar to those of heart disease in Cu-. The recent cloning of four genes of putative Cu pumping ATPases (Cu-ATPases) from widely different sources, i.e. two from Enterococcus hirae and one each from Wilson's and Menkes disease patients (which are defective in Cu transport and metabolism), has opened a new chapter in the study of Cu cellular transport and metabolism. The encoded gene products, i.e. Cu-ATPases, show extensive homology and are members of a new class of ATP-driven Cu pumps involved in regulation of cellular Cu. Further, Cu transport by Cop B-ATPase (E. hirae) in membrane vesicles and in isolated rat liver plasma membrane has provided biochemical evidence of its role in ATP-driven Cu transport. In this short review I have critically examined the current evidence of the molecular basis of the pathophysiology of cardiomyopathy in Cu- and, have indicated the possible role of P-type Cu ATPase which may be one of the obligatory factors contributing to cardiomyopathy in experimental animals and probably humans. Experimental verification of this hypothesis will be the aim of future studies.

Adenosine Triphosphatases↗
PubMed1997

Alterations in isoforms of glutathione S-transferase in liver and kidney of cadmium exposed rhesus monkeys: purification and kinetic characterization.

Exposure of animals to cadmium (Cd) (25 mg kg(-1) body wt day(-1)) for 10 weeks resulted in preferential accumulation of the metal in liver and kidney. Cd accumulation concomitantly increased zinc (Zn) concentration in both the organs. However, significant decrease in copper level was observed in liver, whereas kidney showed increase in copper (Cu) level. Cd exposure resulted in decreased total GST activity in liver (63%) and kidney (41%) as compared to control group monkeys on normal diet (group I). On isoelectric focusing (IEF) control liver GST segregated into thirteen isoenzymes, while in Cd-treated experimental animals (group II) liver GST resolved into nine isoenzymes. Similarly kidney GST from control animals separated into seven isoenzymes as compared to four isoenzymes from Cd-treated animals. Kinetic analysis showed that Cd exposure did not alter the affinity constant (Km) of GST for GSH and CDNB whereas maximal velocity (Vmax) for these substrates decreased as compared to controls in both the organs, indicating inhibition in GST synthesis by Cd. Cd resulted in a noncompetitive type of inhibition with respect to GSH in vitro. On isoelectric focussing GST of liver and kidney in group II resolved into nine and four isoenzymes as compared to thirteen and seven in group I, showing loss of four basic isoenzymes in case of liver and three isoenzymes in case of kidney. Monkey liver and kidney expressed all the three classes of GST isoenzymes i.e. alpha, mu and pi, which were serologically identical to human alpha, mu and pi GSTs.

Animals↗
PubMed1997

Neuronal nitric oxide synthase and calmodulin-dependent protein kinase IIalpha undergo neurotoxin-induced proteolysis.

Calpain (calcium-activated neutral protease) has been implicated as playing a role of neuronal injury in cerebral ischemia and excitotoxicity. Here we report that, in addition to extreme excitotoxic conditions [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate challenges], other neurotoxins such as maitotoxin, A23187, and okadaic acid also induce calpain activation, as detected by m-calpain autolytic fragmentation and nonerythroid alpha-spectrin breakdown. Under the same conditions, calmodulin-dependent protein kinase II-alpha (CaMPK-IIalpha) and neuronal nitric oxide synthase (nNOS) are both proteolytically cleaved by calpain. Such fragmentation can be reduced by calpain inhibitors (acetyl-Leu-Leu-Nle-CHO and PD151746). In vitro digestion of protein extract from cortical cultures with purified mu- and m-calpain produced fragmentation patterns for CaMPK-IIalpha and nNOS similar to those produced in situ. Also, several other calpain-sensitive calmodulin-binding proteins (plasma membrane calcium pump, microtubule-associated protein 2, and calcineurin A) and protein kinase C-alpha are also degraded in neurotoxin-treated cultures. Lastly, in a rat pup model of acute excitotoxicity, intrastriatal injection of NMDA resulted in breakdown of CaMPK-IIalpha and nNOS. The degradation of CaMPK-IIalpha, nNOS, and other endogenous calpain substrates may contribute to the neuronal injury associated with various neurotoxins.

Animals↗
PubMed1997

Thapsigargin induces apoptosis in SH-SY5Y neuroblastoma cells and cerebrocortical cultures.

Thapsigargin, a specific inhibitor of the endoplasmic reticular Ca(2+)-ATPase, has been used previously to mobilize calcium release from intracellular calcium stores. We now show that thapsigargin (1-10 microM) induces apoptosis in a neuroblastoma cell line (SH-SY5Y) and in fetal rat cerebrocortical cultures. Cell death measured by lactate dehydrogenase release was observed 24-48 hours after treatment with thapsigargin. In both cases, DNA extracts from thapsigargin treated cells showed laddering, typical of endonuclease-mediated internucleosomal cleavages. The presence of DNA fragments was also confirmed by an ELISA designed for detecting nucleosomes in apoptotic cells. Cycloheximide reduced the extent of DNA fragmentation and injury in thapsigargin-treated cells. Dantrolene, an inhibitor of calcium release from intracellular stores partially abolished the effect of thapsigargin, suggesting that the initial Ca2+ rise may be the signalling event in this apoptotic cell death pathway. We propose that thapsigargin-induced cell death in cultured neuronal cells may be a useful system to study the molecular and genetic events involved in apoptosis.

Animals↗