Biomedical subjects

A Liu

Publications and source records attributed to A Liu.

At least 109 records · Page 6Linked to original sources

PubMed1999

NMR structure of the sea urchin (Strongylocentrotus purpuratus) metallothionein MTA.

The three-dimensional structure of [(113)Cd7]-metallothionein-A (MTA) of the sea urchin Strongylocentrotus purpuratus was determined by homonuclear(1)H NMR experiments and heteronuclear [(1)H, (113)Cd]-correlation spectroscopy. MTA is composed of two globular domains, an N-terminal four-metal domain of the amino acid residues 1 to 36 and a Cd4Cys11cluster, and a C-terminal three-metal domain including the amino acid residues 37 to 65 and a Cd3Cys9cluster. The structure resembles the known mammalian and crustacean metallothioneins, but has a significantly different connectivity pattern of the Cys-metal co-ordination bonds and concomitantly contains novel local folds of some polypeptide backbone segments. These differences can be related to variations of the Cys sequence positions and thus emphasize the special role of the cysteine residues in defining the structure of metallothioneins, both on the level of the domain architecture and the topology of the metal-thiolate clusters.

Amino Acid Sequence↗

PubMed1999

Modeling and prediction of human behavior.

We propose that many human behaviors can be accurately described as a set of dynamic modes (e.g., Kalman filters) sequenced together by a Markov chain. We then use these dynamic Markov models to recognize human behaviors from sensory data and to predict human behaviors over a few seconds time. To test the power of this modeling approach, we report an experiment in which we were able to achieve 95% accuracy at predicting automobile drivers' subsequent actions from their initial preparatory movements.

Automobile Driving↗

PubMed1999

Peptides and proteins in neurodegenerative disease: helix propensity of a polypeptide containing helix 1 of the mouse prion protein studied by NMR and CD spectroscopy.

Transmissible spongiform encephalopathies (TSE) or "prion diseases" have been related to the "protein-only hypothesis", which suggests that the "scrapie form (PrPSc)" of the prion protein (PrP) is the TSE infectious agent. The nmr structure of the ubiquitous benign cellular form of PrP (PrPC) consists of a globular domain of residues 126-231 with three alpha-helices and a short beta-sheet, and a flexible extended "tail" of residues 23-125. The peptide segment of helix 1 has been implicated in various stages of hypothetical pathways to prion pathology on the basis of the protein-only idea, including that it takes part in the conformation change that leads from PrPC to PrPSc. In this paper we describe solution nmr and circular dichroism studies of the synthetic hexadecapeptide mPrP(143-158), with the sequence H-NDWEDRYYRENMYRYP-NH2, where the bold letters represent the segment that forms helix 1 in murine PrPC. In both H2O and a 1:1 mixture of H2O and trifluoroethanol this polypeptide segment shows high helix propensity, which is a key issue in discussions on potential roles of this molecular region in conformational transitions of PrP.

Amino Acid Sequence↗

PubMed1999

Regulation of the expression of MHC class I and II by class II transactivator (CIITA) in hematopoietic cells.

In order to develop an effective immunotherapy for hematological malignancies, we investigated the applicability of class II transactivator (CIITA), which had been demonstrated to regulate the expression of MHC class II (MHC-II) by assembling the transcription factors of MHC-II molecules, for immunotherapy by potentiating the antigenicity of tumour cells by inducing MHC expression. First, 32 hematopoietic cell lines were analysed for the expression of HLA-DR, CIITA, RFX5 or HLA-ABC. Fourteen cell lines were positive and 18 were negative for HLA-DR. All the 14 HLA-DR positive cell lines were demonstrated to express CIITA mRNA by RT-PCR. On the other hand, in all the 18 HLA-DR negative cell lines, the expression of CIITA was not demonstrated. RFX5, which is one of the transcription factors of MHC-II, was expressed ubiquitously in all 32 cell lines. Three cell lines out of 23 hematopoietic cell lines examined were negative for HLA-ABC, and all three of these cell lines were negative for both HLA-DR and CIITA expression. Furthermore, CIITA cDNA was transfected into K562 cells, which were negative for HLA-ABC, -DR and -DQ, but positive for HLA-DP. The transfection rendered HLA-DR negative to positive and increased the expression level of HLA-DP, but HLA-DQ remained negative. In addition to HLA-DR, HLA-ABC was also induced to express by the transfection of CIITA gene. The present study demonstrated that the expression of HLA-DR in hematopoietic cells is regulated in subordination to CIITA and the expression of HLA-DR (and HLA-ABC in K562) is induced by transfection with the CIITA gene. These findings revealed the applicability of CIITA in potentiating anti-tumour immunity of HLA-DR negative tumour cells for immunotherapy of hematological malignancies.

Acute Disease↗

PubMed1999

Tetrodotoxin suppresses morphological enhancement of the metastatic MAT-LyLu rat prostate cancer cell line.

Voltage-gated Na+ channels are expressed by highly metastatic MAT-LyLu cells, but not by poorly metastatic AT-2 cells, derived from the rodent Dunning model of prostatic cancer. We have investigated the possible involvement of these channels in the morphological development of the cells. Incubation of both the MAT-LyLu and the AT-2 cell line for 24 h with the Na+ channel blocker tetrodotoxin (TTX) at 6 microM altered the morphology only of the MAT-LyLu cell line. TTX produced significant decreases in: (a) cell process length and (b) field diameter, and increases in (c) cell body diameter and (d) process thickness. Importantly, 6 microM TTX had no significant effects on proliferation rates or cellular toxicity. The results suggest that Na+ channel activity plays a significant role in determining the morphological development of MAT-LyLu cells in such a way as to enhance their metastatic potential.

Animals↗

PubMed1999

Task-specific deactivation patterns in functional magnetic resonance imaging.

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function.

Adult↗

PubMed1999

Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness.

OBJECTIVE: The absence of endothelial cells at the luminal surface of a prosthetic vascular graft potentiates thrombosis and neointimal hyperplasia, which are common causes of graft failure in humans. This study tested the hypothesis that pretreatment with chronic in vitro shear stress enhances subsequent endothelial cell retention on vascular grafts implanted in vivo. METHODS: Cultured endothelial cells derived from Fischer 344 rat aorta were seeded onto the luminal surface of 1.5-mm internal diameter polyurethane vascular grafts. The seeded grafts were treated for 3 days with 1 dyne/cm2 shear stress and then for an additional 3 days with 1 or 25 dyne/cm2 shear stress in vitro. The grafts then were implanted as aortic interposition grafts into syngeneic rats in vivo. Grafts that were similarly seeded with endothelial cells but not treated with shear stress and grafts that were not seeded with endothelial cells served as controls. The surgical hemostasis time was monitored. Endothelial cell identity, density, and graft patency rate were evaluated 24 hours after implantation. Endothelial cell identity in vivo was confirmed with cells transduced in vitro with beta-galactosidase complementary DNA in a replication-deficient adenoviral vector. Histologic, scanning electron microscopic, and immunohistochemical analyses were performed 1 week and 3 months after implantation to establish cell identity and to measure neointimal thickness. RESULTS: The pretreatment with 25 dyne/cm2 but not with 0 or 1 dyne/cm2 shear stress resulted in the retention of fully confluent endothelial cell monolayers on the grafts 24 hours after implantation in vivo. Retention of seeded endothelial cells was confirmed by the observation that beta-galactosidase transduced cells were retained as a monolayer 24 hours after implantation in vivo. In the grafts with adherent endothelial cells that were pretreated with shear stress, immediate graft thrombosis was inhibited and surgical hemostasis time was significantly prolonged. Confluent intimal endothelial cell monolayers also were present 1 week and 3 months after implantation. However, 1 week after implantation, macrophage infiltration was observed beneath the luminal cell monolayer. Three months after the implantation in vivo, subendothelial neointimal cells that contained alpha-smooth muscle actin were present. The thickness of this neointima averaged 41 +/- 12 micrometer and 60 +/- 23 micrometer in endothelial cell-seeded grafts that were pretreated with 25 dyne/cm2 shear stress and 1 dyne/cm2 shear stress, respectively, and 158 +/- 46 micrometer in grafts that were not seeded with endothelial cells. CONCLUSION: The effect of chronic shear stress on the enhancement of endothelial cell retention in vitro can be exploited to fully endothelialize synthetic vascular grafts, which reduces immediate in vivo graft thrombosis and subsequent neointimal thickness.

Adenoviridae↗

PubMed1999

Registration of 3D cerebral vessels with 2D digital angiograms: clinical evaluation.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy and speed of a new, semiautomatic method of three-dimensional (3D)-two-dimensional (2D) vascular registration. This method should help guide endovascular procedures by allowing interpretation of each digital subtraction angiographic (DSA) image in terms of precreated, 3D vessel trees that contain "parent-child" connectivity information. MATERIALS AND METHODS: Connected, 3D vessel trees were created from segmented magnetic resonance (MR) angiograms. Eleven total DSA images were registered with such trees by using both our method and the current standard (manual registration). The accuracy of each method was compared by using repeated-measures analysis of variance with correction for heterogeneity of variance to evaluate separation of curve pairs on the view plane. Subjective clinical comparisons of the two registration methods were evaluated with the sign test. Registration times were evaluated for both methods and also as a function of the error in the initial estimate of MR angiographic position. RESULTS: The new registration method produced results that were numerically superior to those of manual registration (P < .001) and was subjectively judged to be as good as or better by clinical reviewers. Registration time with the new method was faster (P < .001). If the rotational error in the initial estimate of MR angiographic position is less than 10 degrees around each axis, the registration itself took only 1-2 minutes. CONCLUSION: This method is quicker than and produces results as good as or better than those of manual registration. This method should be able to calculate an initial registration matrix during endovascular embolization and adjust that matrix intermittently with registration updates provided by automatic tracking systems.

Angiography, Digital Subtraction↗

PubMed1999

Generation of bcr-abl specific cytotoxic T-lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients.

Dendritic cells (DC), the most potent 'professional' antigen-presenting cells, hold promise for improving the immunotherapy of cancer. In this study, we investigated the ability of normal donor DC pulsed ex vivo with 12 mer bcr-abl (b3a2) peptide to generate b3a2-specific autologous or HLA-identical sibling donor's cytotoxic T-lymphocytes (CTL). DC that were grown from normal peripheral blood adherent cells or purified DC precursors in the presence of GM-CSF and IL-4, were pulsed with b3a2-peptide then were induced to become mature and functional cells by the addition of TNF-alpha. These peptide-pulsed mature DC elicited a potent b3a2-specific CTL response in vitro. The b3a2-peptide pulsed DC-primed peripheral blood lymphocytes (PBL) displayed significantly higher cytotoxic activity compared with peptide non-pulsed DC-primed PBL against target cells, which are b3a2 positive marrow cells derived from HLA-identical sibling chronic myelogenous leukemia (CML) patient, or peptide-pulsed autologous macrophages (P < 0.001). In addition, the b3a2 peptide-pulsed DC-primed and non-pulsed DC-primed PBL showed no cytotoxic response against peptide non-pulsed autologous macrophages. These findings revealed that normal donor PBL pre-immunized with b3a2-peptide pulsed autologous DC could increase the graft-versus-leukemia effect without exaggerating graft-versus-host-disease. Both CD8+ and CD4+ T lymphocytes were shown to be involved in the effector cell populations. The b3a2 peptide-pulsed DC-primed T cells were significantly superior in their production of GM-CSF and TNF-alpha compared with peptide non-pulsed DC-primed T cells. These intriguing preclinical results imply the feasibility of developing b3a2 peptide-DC based protocol for in vitro sensitization of normal donor leukocytes before donor leukocyte transfusions for patients with CML, who relapsed after HLA-matched sibling bone marrow transplantation.

Blood Donors↗

PubMed1999

Y-chromosome specific YCAII, DYS19 and YAP polymorphisms in human populations: a comparative study.

Two hypervariable Y-specific markers, the YCAII and DYS19 STRs, and the more stable Y Alu Polymorphism (YAP) have been analysed in about 1400 individuals of 21 different populations, mainly from Europe but also from the Middle East, Africa and Asia. On the basis of the frequency distributions of these three Y-markers we compare, using different statistical analyses, their power in detecting population genetic structure and in distinguishing closely related groups. The pattern of populations' genetic affinities inferred from the three markers considered altogether suggests a strong genetic structure that, with a few exceptions, broadly corresponds to the linguistic relatedness and/or geographic location of the sampled populations.

Alleles↗

PubMed1999

Neutralizing TGF-beta1 antibody infusion in neonatal rat delays in vivo glomerular capillary formation 1.

BACKGROUND: The interruption of transforming growth factor-beta (TGF-beta) signaling with dominant negative type II TGF-beta receptors in bovine glomerular endothelial cells abrogates capillary morphogenesis in vitro, and genetic defects in the TGF-beta1 signaling cascade in mice and humans result in abnormalities of blood vessel morphology. This study sought to determine whether TGF-beta1 participates in renal glomerular capillary development in vivo. METHODS: To inhibit TGF-beta1 action, neutralizing anti-TGF-beta1 IgG was infused intra-arterially into the suprarenal aorta of three-day-old rats, and the glomerular endothelial cell appearance was evaluated two days later by immunohistochemical detection of the endothelium-specific von Willebrand factor, in situ analysis of vascular endothelial growth factor receptor binding, and morphometric study of developing glomerular structures by transmission electron microscopy. RESULTS: The infusion of neutralizing the TGF-beta1 antibody markedly reduced the invasion of comma- and S-shaped bodies by endothelial cells, and inhibited organization of endothelial cells into capillaries in these structures. In addition, capillary lumen formation and endothelial cell fenestration in developing cortical, but not in deep, already mature glomeruli were inhibited by neutralizing TGF-beta1 antibody. Seven days after TGF-beta1 antibody infusion, glomeruli appeared normal, and no reduction in glomerular number was observed. CONCLUSIONS: These findings suggest that TGF-beta1 plays a critical role in the formation of glomerular capillaries during renal development in the rat, and that flattening and fenestration of glomerular capillaries require the action of TGF-beta1.

Animals↗

PubMed1999

Intrapatient consistency of imaging biodistributions and their application to predicting therapeutic doses in a phase I clinical study of 90Y-based radioimmunotherapy.

Intrapatient variation in the biodistribution of the chimeric monoclonal antibody cT84.66 was assessed in 19 patients having a variety of carcinoembryonic antigen (CEA) positive tumors. The two studies, including whole-body imaging and blood and urine specimen collections, were conducted within 14 days of each other using (111)In-cT84.66 at a fixed total protein dose of 5 mg per patient per study. An initial pretherapy infusion of (111)In-cT84.66 was administered followed by a therapy coinfusion of (111)In-ct84.66 and 90Y-cT84.66 A closed five-compartment model was used to integrate source organ activity curves as residence time inputs into the MIRDOSE3 program. Normal organ absorbed doses were estimated for 90Y-cT84.66, the corresponding radiotherapeutic agent. For the two (111)In-cT84.66 biodistributions, all data were modeled with a R2 value of between 0.72 and 1.00 with the exception of the urine data taken during therapy. This was due to the need of diethylenetriaminepentaacetic acid during the therapy phase because of the possibility that yttrium might escape from the chelator attached to the antibody. With the assurance that the biodistributions were reproducible, we were able to estimate the 90Y-cT84.66 absorbed doses on a per-patient basis. Concordance coefficients showing the agreement between the imaging and therapy phase dose estimates were between the 0.60 and 0.99 levels for liver, spleen, red marrow, total body, and other organ systems. Median results were: 27, 17, and 2.7 rad/mCi of 90Y-cT84.66 for liver, spleen, and red marrow, respectively. Because of decreases in platelets and white cells as the amount of 90Y was increased, dose-limiting toxicity was found at 22 mCi/m2. We conclude that patient biodistributions were consistent over time to 14 days so as to allow absorbed dose estimation in a radioimmunotherapy trial involving the cT84.66 anti-CEA antibody.

Adult↗

PubMed1999

Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor.

PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). Examination of CSF for malignant cells, detection of LMD on spinal magnetic resonance imaging (MRI), or both are the methods routinely used to diagnose LMD. A recent study suggested 100% correlation between CSF and MRI findings in children with medulloblastoma. To determine the validity of this hypothesis, we compared the rate of detection of LMD between concurrent lumbar CSF cytology and spinal MRI performed at diagnosis in patients with medulloblastoma or PNET. PATIENTS AND METHODS: As a part of diagnostic staging, 106 consecutive patients newly diagnosed with medulloblastoma or PNET were evaluated with concurrent lumbar CSF cytology and spinal MRI. CSF cytology was examined for the presence of malignant cells and spinal MRI was reviewed independently for the presence of LMD. RESULTS: Thirty-four patients (32%) were diagnosed with LMD based on CSF cytology, spinal MRI, or both. There were 21 discordant results. Nine patients (8.5%) with positive MRI had negative CSF cytology. Twelve patients (11.3%) with positive CSF cytology had negative MRIs. The exact 95% upper bounds on the proportion of patients with LMD whose disease would have gone undetected using either CSF cytology or MRI as the only diagnostic modality were calculated at 14.4% and 17.7%, respectively. CONCLUSION: With the use of either CSF cytology or spinal MRI alone, LMD would be missed in up to 14% to 18% of patients with medulloblastoma or PNET. Thus, both CSF cytology and spinal MRI should routinely be used to diagnose LMD in patients with medulloblastoma or PNET.

Adolescent↗

PubMed1999

Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors.

PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with primary CNS tumors. Cytologic examination of lumbar CSF is routinely used to detect LMD. To determine whether examination of CSF obtained from ventricular shunt taps is a more sensitive method of detecting LMD in these patients, we designed a prospective study to compare the findings of cytologic examinations of CSF obtained from concurrent lumbar and ventriculoperitoneal (VP) shunt taps. PATIENTS AND METHODS: As a part of diagnostic staging, follow-up testing, or both, 52 consecutive patients underwent concurrent lumbar and shunt taps on 90 separate occasions, ranging from the time of diagnosis to treatment follow-up. CSF from both sites was examined cytologically for malignant cells. RESULTS: The median age of the 28 males and 24 females was 7.5 years (range, 0.6 to 21.4 years). The primary CNS tumors included medulloblastoma (n = 29), astrocytoma (n = 10), ependymoma (n = 5), germinoma (n = 3), atypical teratoid rhabdoid tumor (n = 2), choroid plexus carcinoma (n = 2), and pineoblastoma (n = 1). Each site yielded a median CSF volume of 1.0 mL. Fourteen of 90 paired CSF test results were discordant: in 12, the cytologic findings from shunt CSF were negative for malignant cells, but those from lumbar CSF were positive; in two, the reverse was true. Malignant cells were detected at a higher rate in lumbar CSF than in shunt CSF (P =.0018). When repeat analyses were excluded, examination of lumbar CSF remained significantly more sensitive in detecting malignant cells (P =.011). Analysis of the subset of patients with embryonal tumors showed similar results (P =.0008). CONCLUSION: Cytologic examination of lumbar CSF is clearly superior to cytologic examination of VP shunt CSF for detecting leptomeningeal metastases in pediatric patients with primary CNS tumors.

Adolescent↗

PubMed1999

FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate.

The mid/hindbrain junction region, which expresses Fgf8, can act as an organizer to transform caudal forebrain or hindbrain tissue into midbrain or cerebellar structures, respectively. FGF8-soaked beads placed in the chick forebrain can similarly induce ectopic expression of mid/hindbrain genes and development of midbrain structures (Crossley, P. H., Martinez, S. and Martin, G. R. (1996) Nature 380, 66-68). In contrast, ectopic expression of Fgf8a in the mouse midbrain and caudal forebrain using a Wnt1 regulatory element produced no apparent patterning defects in the embryos examined (Lee, S. M., Danielian, P. S., Fritzsch, B. and McMahon, A. P. (1997) Development 124, 959-969). We show here that FGF8b-soaked beads can not only induce expression of the mid/hindbrain genes En1, En2 and Pax5 in mouse embryonic day 9.5 (E9.5) caudal forebrain explants, but also can induce the hindbrain gene Gbx2 and alter the expression of Wnt1 in both midbrain and caudal forebrain explants. We also show that FGF8b-soaked beads can repress Otx2 in midbrain explants. Furthermore, Wnt1-Fgf8b transgenic embryos in which the same Wnt1 regulatory element is used to express Fgf8b, have ectopic expression of En1, En2, Pax5 and Gbx2 in the dorsal hindbrain and spinal cord at E10.5, as well as exencephaly and abnormal spinal cord morphology. More strikingly, Fgf8b expression in more rostral brain regions appears to transform the midbrain and caudal forebrain into an anterior hindbrain fate through expansion of the Gbx2 domain and repression of Otx2 as early as the 7-somite stage. These findings suggest that normal Fgf8 expression in the anterior hindbrain not only functions to maintain development of the entire mid/hindbrain by regulating genes like En1, En2 and Pax5, but also might function to maintain a metencephalic identity by regulating Gbx2 and Otx2 expression.

Animals↗

PubMed1999

Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT.

Cultures from high grade prostatic intraepithelial neoplasia (HGPIN) have been established and immortalized by HPV-18 infection. The cultures were identified as PIN by Western blotting with anti-cytokeratin (34betaE12) and prostate specific antigen (PSA) antibodies. We examined the growth capabilities of the cultures in the presence of TGF-beta1, activin-A, follistatin (FS), androgens (DHEA, DHT) and several cytokines (IL-10, IL-2, IL-4). IL-10, FS, and DHT stimulated cell proliferation and colony forming ability, while the other cytokines and growth factors had no discernable effect. In addition, DHT and to a lesser extent IL-10 both stimulated PSA production. Activin-A blocked IL-10, FS, and DHT stimulated growth and PSA production. We interpret the data to mean that IL-10 induction of FS secretion (and FS binding of activin A) restores the normal growth capabilities of HGPIN cultures.

Activins↗

PubMed1999

The association of opportunistic infections with the occurrence of trimethoprim/sulfamethoxazole hypersensitivity in patients infected with human immunodeficiency virus.

Hypersensitivity from trimethoprim/sulfamethoxazole (TMP/SMX) has been linked to a reactive nitroso intermediate from sulfamethoxazole metabolism, which may be altered in patients with human immunodeficiency virus (HIV) infection. The authors determined the clinical factors that are associated with TMP/SMX hypersensitivity in patients with HIV. In a case control study, 54 controls currently tolerating TMP/SMX prophylaxis were randomly matched by date of hypersensitivity reaction in case patients to 28 patients with a history of a rash consistent with erythema multiforme from TMP/SMX. Demographic data, coadministered medications, laboratory data, and histories of opportunistic infections were extracted on all patients. A highly significant association was observed between the number of opportunistic infections and the occurrence of TMP/SMX hypersensitivity (p < 0.001), despite comparability of CD4 counts between case patients and controls (p > 0.1). A tendency for protection from TMP/SMX hypersensitivity in blacks was also observed (p = 0.066). These observations suggest that the mechanisms by which HIV produces cellular immune dysfunction and alters drug detoxification may be linked.

AIDS-Related Opportunistic Infections↗

PubMed1999

A radionuclide therapy treatment planning and dose estimation system.

UNLABELLED: An object-oriented software system is described for estimating internal emitter absorbed doses using a set of computer modules operating within a personal computer environment. The system is called the Radionuclide Treatment Planning and Absorbed Dose Estimation System (RTDS). It is intended for radioimmunotherapy applications, although other forms of internal emitter therapy may also be considered. METHODS: Four software modules interact through a database backend. Clinical, demographic and image data are directly entered into the database. Modules include those devoted to clinical imaging (nuclear, CT and MR), activity determination, organ compartmental modeling and absorbed dose estimation. RESULTS: Both standard phantom (Medical Internal Radiation Dose [MIRD]) and patient-specific absorbed doses are estimated. All modules interact with the database backend so that changes in one process do not influence other operations. Results of the modular operations are written to the database as computations are completed. Dose-volume histograms are an intrinsic part of the output for patient-specific absorbed dose estimates. A sample dose estimate for a potential 90Y monoclonal antibody is described. CONCLUSION: A four-module software system has been implemented to estimate MIRD phantom and patient-specific absorbed doses. Computations of the doses and their statistical distribution for a pure beta emitter such as 90Y take approximately 1 min on a 300 MHz personal computer.

Humans↗