Architectural approaches for HL7-based health information systems implementation.

OBJECTIVE: Information systems integration is hard, especially when semantic and business process interoperability requirements need to be met. To succeed, a unified methodology, approaching different aspects of systems architecture such as business, information, computational, engineering and technology viewpoints, has to be considered. The paper contributes with an analysis and demonstration on how the HL7 standard set can support health information systems integration. METHODS: Based on the Health Information Systems Development Framework (HIS-DF), common architectural models for HIS integration are analyzed. The framework is a standard-based, consistent, comprehensive, customizable, scalable methodology that supports the design of semantically interoperable health information systems and components. RESULTS: Three main architectural models for system integration are analyzed: the point to point interface, the messages server and the mediator models. Point to point interface and messages server models are completely supported by traditional HL7 version 2 and version 3 messaging. The HL7 v3 standard specification, combined with service-oriented, model-driven approaches provided by HIS-DF, makes the mediator model possible. The different integration scenarios are illustrated by describing a proof-of-concept implementation of an integrated public health surveillance system based on Enterprise Java Beans technology. CONCLUSION: Selecting the appropriate integration architecture is a fundamental issue of any software development project. HIS-DF provides a unique methodological approach guiding the development of healthcare integration projects. The mediator model - offered by the HIS-DF and supported in HL7 v3 artifacts - is the more promising one promoting the development of open, reusable, flexible, semantically interoperable, platform-independent, service-oriented and standard-based health information systems.

Prognosis of breast cancers detected in women receiving hormone replacement therapy.

OBJECTIVE: To determine the influence of hormone replacement therapy (HRT) on various prognostic factors of breast cancer (BC). METHODS: A multi-centre case-control study was conducted, in which a comparison was made of the differences between various histological and biological clinical variables of BC detected in 121 women undergoing HRT at the time of diagnosis, and those cancers detected in 121 women of similar age not undergoing HRT. The variables were also analysed in function of the type of HRT and the length of time treated. RESULTS: The tumours detected in patients receiving HRT presented significantly lower tumoural stages, a lower degree of affected axillary lymph node dissemination, and a greater percentage of well-differentiated tumours and positive estrogen receptors than those detected in women not under HRT. Most of these results due principally to those patients who were undergoing CONCLUSIONS: Although the better prognosis of tumours detected in women receiving HRT may be due largely to their diagnosis at earlier stages, there is an increasing body of data leading one to think that these tumours present certain histological and biological characteristics that make such cancers less aggressive.

Relationship between arterial, mixed venous, and internal jugular carboxyhemoglobin concentrations at low, medium, and high concentrations in a piglet model of carbon monoxide toxicity.

OBJECTIVE: This study tested the hypothesis that mixed venous carboxyhemoglobin concentrations (V-COHb) and internal jugular carboxyhemoglobin concentrations (I-COHb) accurately predict arterial carboxyhemoglobin concentrations (A-COHb). In addition, this study tested the hypothesis that there is a high correlation at low (COHb, 0% to 10%), moderate (COHb, >10% to 40%), and high (COHb, >40%) concentrations between V-COHb, I-COHb, and A-COHb. DESIGN: The study was a prospective comparison of A-COHb, V-COHb, and I-COHb concentrations in piglets exposed to increasing concentrations of carbon monoxide over 6 hrs to achieve a concentration of > or =60% COHb. Carboxyhemoglobin measurements were evaluated by analysis of variance and correlation analysis. Agreement between V-COHb and A-COHb concentrations was examined by using a plot of arteriovenous differences against the mean of the two measurements. INTERVENTION: We simultaneously sampled arterial, mixed venous, and internal jugular blood every 30 mins over the 6-hr study period. RESULTS: Two hundred fifty arterial and mixed venous COHb concentrations were obtained, and 214 internal jugular COHb concentrations were obtained. One hundred additional arterial, mixed venous, internal jugular, and peripheral COHb concentrations were obtained. Correlation between samples at each concentration revealed r2 > = .94. CONCLUSION: Venous COHb concentrations predict arterial COHb concentrations with a high degree of accuracy and are correlated at low, moderate, and high concentrations of carbon monoxide exposure. Arterial or venous samples can be used to accurately measure COHb concentrations.

Early block in maturation is associated with thymic involution in mammary tumor-bearing mice.

We previously reported that mice implanted with mammary tumors show a progressive thymic involution that parallels the growth of the tumor. The involution is associated with a severe depletion of CD4+8+ thymocytes. We have investigated three possible mechanisms leading to this thymic atrophy: 1) increased apoptosis, 2) decreased proliferation, and 3) disruption of normal thymic maturation. The levels of thymic apoptosis were determined by propidium iodide and annexin V staining. A statistically significant, but minor, increase in thymic apoptosis in tumor-bearing mice was detected with propidium iodide and annexin V staining. The levels of proliferation were assessed by in vivo labeling with 5'-bromo-2'-deoxyuridine (BrdU). The percentages of total thymocytes labeled 1 day following BrdU injection were similar in control and tumor-bearing mice. Moreover, the percentages of CD4-8- thymocytes that incorporated BrdU during a short term pulse (5 h) of BrdU were similar. Lastly, thymic maturation was evaluated by examining CD44 and CD25 expression among CD4-8- thymocytes. The percentage of CD44+ cells increased, while the percentage of CD25+ cells decreased among CD4-8- thymocytes from tumor-bearing vs control animals. Together, these findings suggest that the thymic hypocellularity seen in mammary tumor bearers is not due to a decreased level of proliferation, but, rather, to an arrest at an early stage of thymic differentiation along with a moderate increase in apoptosis.

Elevated GM-CSF levels in tumor bearing mice upregulate IL-6 production by B cells via a mechanism independent of TNF-alpha.

During mammary tumorigenesis a profound dysregulation of cytokine production by various lymphoreticular cells has been documented. B lymphocytes from tumor bearers have an increased production of tumor necrosis factor alpha (TNF-alpha). We now report that these lymphocytes have elevated levels of interleukin 6 (IL-6) at the transcriptional and translational levels, that are reflected systemically. The mammary tumor used in our study constitutively produces several factors including granulocyte-macrophage colony stimulating factor (GM-CSF), prostaglandin E2 (PGE2) and phosphatidyl serine (PS), which directly or indirectly can affect the cells of the immune system. in vitro addition of GM-CSF resulted in a dramatic increase in IL-6 levels from B cells from normal mice. This effect does not appear to be due to elevated levels of TNF-alpha, known to upregulate IL-6. Rather, GM-CSF activates IL-6 production independently of TNF-alpha as demonstrated by neutralization studies using anti-TNF-alpha antibodies. Furthermore, the effect exerted by GM-CSF on IL-6 production by B lymphocytes appears to be direct since pretreatment of cultures with anti-GM-CSF completely abrogated the elevated production of IL-6. The elevated levels of IL-6 and TNF-alpha in tumor bearers may contribute to the cachectic state observed in tumor bearing mice.

Abnormal binding pattern and composition of the NF-kappaB complex components are involved in increased TNF-alpha production by tumor bearer B cells.

B lymphocytes from mammary tumor bearers are cytotoxic against tumor targets and produce TNF-alpha. A greater stability of RNA and a decreased rate of RNA degradation was observed in B cells of tumor bearers compared to those of normal mice. The TNF-alpha promoter contains regions that bind NF-kappaB, which regulate the rate of transcription. Supershift assays for the NF-kappaB region showed that there are p50-p65 heterodimers and p50 homodimers in the nuclear extracts of the two types of B cells, while those from tumor bearers lack the c-Rel component that is present in normal B cells. These results indicate that abnormalities in binding and composition of the NF-kappaB complexes may be involved in the increased TNF-alpha production by B cells of tumor bearers.

Altered binding of the NF-GMa transcription factor is involved in the upregulated production of TNF-alpha by macrophages of mammary tumor bearing mice.

Macrophages from D1-DMBA-3 mammary tumor bearing mice have profound alterations in various functions, i.e. diminished antigen presentation, decreased cytolytic activity and depressed synthesis of IL-12. In contrast, these cells display a significant enhancement in the levels of TNF-alpha, which may be involved in the cachexia observed in animals bearing large mammary tumors. The molecular mechanisms involved in the upregulation of TNF-alpha in macrophages from tumor bearers were investigated. The levels of TNF-alpha RNA were increased in macrophages from tumor bearers, but, this was not due to an increase in the RNA half-life. An analysis of the binding of transcription factors relevant to the TNF-alpha gene regulatory region by electrophoretic mobility shift assays (EMSA) revealed no differences in the binding of any NF-kB complex component between macrophages from normal and tumor bearing mice. Likewise, there were no changes in the binding patterns of SP-1 and NF-Y. In contrast, the binding of the transcription factor, NF-GMa, was altered in macrophages from tumor bearers. Our results and those reported in other models of disease suggest that the excessive production of cytokines in pathological conditions, could be the result of alterations of the production and/or binding of transcription factors.

CD4+, but not CD8+, T cells from mammary tumor-bearing mice have a down-regulated production of IFN-gamma: role of phosphatidyl serine.

IFN-gamma production is dramatically reduced in T cells from mice bearing large mammary tumors. This inhibition of IFN-gamma gene expression occurs mostly in CD4+ T cells, as determined by ELISA and reverse transcriptase-PCR. The effects of known mammary tumor factors in normal T cells and its subsets were evaluated. Pretreatment with granulocyte-macrophage CSF resulted in increased IFN-gamma levels by T cells, while PGE2 pretreatment equally decreased the levels of this cytokine in CD4+ and CD8+ T cells from normal mice. Interestingly, phosphatidyl serine (PS) down-regulated the IFN-gamma production of CD4+, but not that of CD8+, T cells. Methylation analysis indicated that the CpG dinucleotide in SnaBI site of the IFN-gamma 5' promoter flank region was hypermethylated in CD4+, but not in CD8+, T cells of large tumor bearers and of normal mice pretreated with PS. Electrophoresis mobility shift assay using an oligonucleotide probe corresponding to the IFN-gamma promoter core region sequence showed a greatly reduced binding of a 90-kDa nuclear protein in CD4+ T cells from tumor bearers and in those from PS-pretreated normal mice. Since IL-2 production is not affected in either CD4+ or CD8+ T cells from tumor bearers, these studies indicate that IFN-gamma production can be regulated independently from that of other type 1 cytokines in vivo. Our data further suggest that PS is involved in IFN-gamma gene down-regulation during mammary tumorigenesis and contributes to the generalized immunosuppression associated with tumor growth.

Phosphatidyl serine is involved in the reduced rate of transcription of the inducible nitric oxide synthase gene in macrophages from tumor-bearing mice.

Upon stimulation with LPS, peritoneal-elicited macrophages (PEM) from mammary tumor-bearing mice display a diminished ability to produce nitric oxide (NO) and lyse tumor targets. In contrast, when these cells are stimulated with LPS in combination with IFN-gamma, they perform these functions at normal levels. Kinetic studies revealed that these defects became more pronounced with tumor progression and were accompanied by similar changes in inducible nitric oxide synthase (iNOS) mRNA levels. Since this tumor is known to produce PGE2, granulocyte-macrophage CSF (GM-CSF), and phosphatidyl serine, we evaluated the effects of these products on NO production and cytolytic activity. Pretreatment of normal PEM with PGE2 or recombinant GM-CSF had negligible effects on NO production and cytolytic capacity. In contrast, phosphatidyl serine caused a concentration-dependent inhibition of these functions in response to LPS, which could be partially overcome by the addition of IFN-gamma. Moreover, iNOS mRNA levels paralleled these changes and were analogous to the alterations observed in the tumor-bearers' PEM. iNOS mRNA stability was not reduced in these cells; however, the rate of transcription was diminished relative to normal levels, suggesting that the defects causing these alterations are occurring at or before the level of iNOS transcription. These data implicate tumor-derived phosphatidyl serine in the alterations observed in tumor-bearers' macrophages and suggest that reduced iNOS transcription is responsible for the diminished capacity of these macrophages to produce NO and lyse tumor targets.

Down-regulation of IL-12, not a shift from a T helper-1 to a T helper-2 phenotype, is responsible for impaired IFN-gamma production in mammary tumor-bearing mice.

Altered cytokine production has been implicated in the down-regulation of cell-mediated immunity in mice bearing large mammary tumors. In several diseases, an imbalance between helper T lymphocytes Th1 and Th2 and their cytokines has been suggested as a contributing factor. In this study, although IFN-gamma from splenic T cells of D1-DMBA-3 mammary tumor-bearing mice was greatly diminished, other cytokine levels remained unchanged, indicating no clear shift between the Th1, Th2, or Th3 phenotypes. The IFN-gamma levels can be restored in vitro by addition of rIL-12 to cultured splenocytes from tumor bearers. Furthermore, IL-12 production is greatly down-regulated in macrophages from tumor-bearing mice as detected by ELISA, and this correlates with diminished expression of IL-12 p40 chain RNA. The mammary tumor used in our studies produces several factors, including granulocyte macrophage-CSF, PGE2, and phosphatidyl serine, that can affect the immune system. Addition of these tumor-derived factors in vitro to macrophages from normal mice resulted in decreased levels of IL-12 protein in cultures treated with PGE2 or phosphatidyl serine. These results indicate that the down-regulation of T cell-produced IFN-gamma in this tumor model is the result of decreased IL-12 production caused by tumor-derived factors and not a shift from the Th1 to the Th2 phenotype.

Cytokine production by lymphoreticular cells from mammary tumor bearing mice: the role of tumor-derived factors.

Mammary tumor development has multiple effects on the T cell, B cell and macrophage compartments of the hosts as evidenced by the alterations in their phenotype and functions. Cytokines are known to modulate the immune system, thus a study of the production of these factors has great relevance to tumor immunity. Here we present evidence that tumor progression causes a profound dysregulation of the cytokine production by various lymphoreticular cells. Furthermore, the tumors themselves are capable of secreting factors that can directly or indirectly affect the cells of the immune system, thereby resulting in the immunosuppressive and other deleterious effects that favor the progress of the neoplastic disease.

The altered tumoricidal capacity of macrophages isolated from tumor-bearing mice is related to reduce expression of the inducible nitric oxide synthase gene.

Nitric oxide (NO) is a major effector molecule in the destruction of tumor cells by activated macrophages. However, in many cases, developing neoplasms appear to be capable of impairing steps in the complex process leading to NO production as a means of avoiding immune destruction. After activation with lipopolysaccharide (LPS), peritoneal-elicited macrophages (PEM) from mice bearing mammary tumors display alterations in their ability to lyse tumor cells due to reduced production of NO. In contrast, when these same cells are stimulated with LPS in combination with interferon gamma (IFN-gamma), they are able to produce NO and lyse targets at normal levels. Since tumor-associated macrophages are intimately associated with the cells of the developing tumor, their ability to produce NO and lyse tumor targets is likely to be more relevant to controlling tumor growth. This population of macrophages exhibited a more profound inability to produce NO and lyse targets and, unlike the PEM, was not able to upregulate these functions even when treated with combinations of LPS and IFN-gamma. Northern and Western blots revealed that inducible nitric oxide synthase (iNOS) mRNA and protein levels correlated directly with the ability of each macrophage population to produce NO, and the levels of these macromolecules were altered sufficiently in tumor bearers' macrophages to account for the diminished NO production described. These results indicate that a spatial gradient of suppression of macrophage cytolytic activity and iNOS expression exists in mammary tumor-bearing mice, whereby macrophages from within the tumor exhibit a more pronounced suppression than the more distally located PEM. This suppression may be due to proximity of the macrophages to the developing tumor, macrophage maturational state, or both.

Epidermal Langerhans cells from mice bearing a granulocyte macrophage-colony stimulating factor-producing mammary tumor display impaired accessory functions.

A progressive depression of delayed type hypersensitivity reactions occurs during development of mammary tumors in BALB/c mice. This tumor constitutively produces prostaglandin E2 (PGE2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Epidermal Langerhans cells were found to have a decreased responsiveness to bacterial superantigen and to defined antigens in tumor-bearing mice, and also showed an impaired ability to induce proliferative responses in syngeneic or allogeneic responder T cells. Flow cytometric analysis revealed that the Langerhans cells of tumor bearers had decreased densities of the Ia molecule on their surfaces. No defects were observed in the potential of keratinocytes from tumor bearers to produce granulocyte-macrophage colony stimulating factor or to support the activation of syngeneic T cells. Incubation of normal Langerhans cells with tumor derived factors depressed their capacity to stimulate T cell syngeneic responses. Addition of indomethacin and anti-prostaglandin E2 did not reverse this depressed activity. These results indicate that epidermal Langerhans cells from tumor-bearing mice possess a functional deficit in acquiring accessory properties in vitro, which cannot be ascribed to a lack of GM-CSF in the local microenvironment or to production of inhibitory cytokines by their keratinocytes. The functional deficit of epidermal Langerhans cells of tumor-bearing mice may account for the depressed delayed hypersensitivity displayed by these mice, and factors elaborated by the tumor may be responsible for the deficiencies observed.

Aberrant antigen presentation by macrophages from tumor-bearing mice is involved in the down-regulation of their T cell responses.

Splenic T cells from BALB/c mice bearing mammary adenocarcinomas initially demonstrate a primed response to tumor-associated Ags (TAA), which declines to presensitization levels within 4 wk after tumor implantation. Associated with this decline in responses to TAA is the expansion of a subpopulation of Mac-1+ 2+ splenic macrophages (M phi). These Mac-1+ 2+ cells present TAA inefficiently to normal T cells primed to TAA by footpad injection, as compared with the Ag presenting ability of M phi from normal mice. The addition of anti-I-Ed, but not anti-I-Ad, Ab blocked the ability of Ag-pulsed Mac-1+ 2+ cells to present TAA to primed T cells. The converse was observed with macrophages from normal mice. However, presentation of human gamma-globulin or OVA was restricted by I-Ad molecules when APC from normal mice or tumor bearers were used, although less efficiently in the latter. Using cell depletion techniques, it was determined that the I-Ed-restricted presentation preferentially expanded CD8+ T cells, and not CD4+ cells, as was the case for I-Ad-restricted normal macrophages. These CD8+ cells were poor effectors of cytotoxicity against tumor cells; instead they down-regulated the proliferative activity of T cells. Limiting dilution assays indicated that Mac-1+ 2+ macrophages preferentially present TAA to a low frequency inhibitory T cell population that expanded and inhibited further responses to TAA. Thus, alterations of Ag presentation in tumor bearers may help the tumor to subvert potential beneficial host responses and allow the progression of the neoplastic process.

Detection of retroviral superantigen and products of the envelope gene from endogenous mouse mammary tumor virus in B cells from BALB/c mice.

Minor lymphocyte-stimulating antigens and other superantigens have been shown to be encoded by the 3' long terminal repeat (LTR) open reading frame (ORF) of the endogenous and exogenous mammary tumor viruses. We have previously reported the presence of an antigen(s) related to mouse mammary tumor virus (MMTV) env products in splenic B cells of BALB/c mice. By Western blots an MMTV-related molecule of 68 kDa was detected in splenic preparations of B lymphocytes, but not in T cells. Antibodies against the MMTV envelope proteins gp52 and gp36, obtained by elution after binding to nitrocellulose in the presence of purified MMTV, reacted in Western blots with a 68-kDa protein present in B cells, indicating that this molecule is related to both MMTV envelope proteins. Using antibody against the MMTV 3' LTR ORF coding sequence, 10-15% of splenic B cells reacted by immunoperoxidase staining with this reagent, while no such staining was observed in splenic T cell preparations. Furthermore, in preparations of splenic B cells, but not T cells, two bands of 68 and 33 kDa, respectively, were detected by Western blots using the anti-ORF. These results demonstrate that the superantigen protein is present in B cells of BALB/c mice in two distinct forms, i.e., as a 68-kDa molecule, possibly associated with products of the env gene, and as a 33-kDa form.

Decreased macrophage-mediated cytotoxicity in mammary-tumor-bearing mice is related to alteration of nitric-oxide production and/or release.

Peritoneal-exudate macrophages (PEM) from mammary-tumor-bearing mice have impaired cytotoxic activity against syngeneic and allogeneic tumor targets. The ability of PEM from normal and tumor-bearing mice to bind tumor targets was found to be similar in the presence or the absence of surrogate receptors, which enhanced the binding but not the killing of tumor targets by PEM from tumor-bearing mice, suggesting that other mechanisms are involved in their impaired cytolytic activity. Soluble and membrane-bound TNF-alpha, as well as H2O2, were found in higher amounts in PEM from tumor bearers upon stimulation with LPS, as compared with PEM from normal mice. However, tumor-bearers' macrophages displayed decreased capacity to produce and/or release nitric oxide, which could be reversed by the addition of increasing levels of IFN-gamma. These results indicate that the lack of macrophage cytotoxicity in mammary-tumor-bearing mice is related to impaired production and/or release of NO by these effector cells, possibly aggravated by the insufficient IFN-gamma production previously reported in these animals. Moreover, mammary-tumor progression results in dis-regulation of synthesis of macrophage-mediators, with over-production of molecules to which mammary-tumor cells are insensitive and deficient production of NO, the crucial molecule to which these cells appear to be highly sensitive.

Isolation of a nitric oxide inhibitor from mammary tumor cells and its characterization as phosphatidyl serine.

Macrophages from mice bearing large D1-DMBA-3 mammary tumors have a decreased capacity to kill tumor targets. This effect is due to an impaired ability to produce nitric oxide (NO) in response to lipopolysaccharide (LPS) stimulation. Here we report that the DA-3 tumor cell line, derived from the in vivo adenocarcinoma D1-DMBA-3, produces a factor that inhibits both NO production/release and cytotoxicity of LPS-activated peritoneal exudate macrophages (PEM). However, other complex macrophage functions such as phagocytosis, superoxide production, mitochondrial dehydrogenase activity, and synthesis of proteins were not reduced by this factor. The NO inhibitor has been found to be lipid in nature. Lipid extracts from DA-3 cell culture supernatants were purified by repeated silica gel column chromatography. The active molecule was unambiguously characterized as phosphatidyl serine (PS) by fast atom bombardment tandem mass spectrometry. Preliminary results indicate a lack of induced NO synthase (iNOS) activity in the lysates of LPS-activated PEM pretreated with PS. The ubiquity of PS in the inner leaflet of biological membranes and its NO inhibitory property, suggest that this phospholipid may be one of the long elusive molecules responsible for regulating physiological levels of NO in the host and hence preventing cellular dysfunction and/or tissue damage. Furthermore, the possible overexpression and shedding of PS by DA-3 tumor cells may represent a novel mechanism to impair macrophage cytotoxicity, a host function that contributes to the protection against developing neoplasms.

A study of Helicobacter-pylori in 100 pediatric patients from the Tri-State area.

Helicobacter pylori (HP) is a newly discovered pathogen implicated in the pathophysiology of peptic ulcer disease. The aim of this study was to review all pediatric patients who were evaluated by upper endoscopy through the Pediatric Gastroenterology Service at the Marshall University School of Medicine between July 1990 and March 1993. A total of 100 charts were retrospectively reviewed. HP was diagnosed by CLO-test and confirmed histologically. Results showed that the major presenting symptom was abdominal pain (53%). GI mucosal inflammation was found in 77 patients, and 41% of these cases were associated with HP. Two patients had duodenal ulcer; both were HP+. The incidence of gastritis was significantly higher in patients with HP+ compared to HP-. Follow-up on the HP-associated gastritis showed no significant difference in their clinical response irrespective to the treatment, we conclude that HP in children is highly associated with gastritis, but not duodenitis or esophagitis; and in our experience, that CLO has a high failure rate in identifying HP in the mucosa.

Noninvasive imaging of c-myc oncogene messenger RNA with indium-111-antisense probes in a mammary tumor-bearing mouse model.

UNLABELLED: The c-myc oncogene is amplified in leukemia and solid tumors, thus making the c-myc messenger RNA (mRNA) a suitable target for following the progression of malignancy by noninvasive imaging with radiolabeled antisense pharmaceuticals or radiolabeled antisense oligodeoxynucleotide (RASON) probes. Considering the higher stability of phosphorothioate over phosphodiester, the probe stability and tumor localization was compared with both derivatives. METHODS: The 15-mer oligonucleotide sequence was synthesized, aminolinked [sense and antisense phosphodiester (O) and monothioester (S)] and coupled with diethylenetriamine pentaacetate (DTPA)-isothiocyanate and aliquots were lyophilized to make a DTPAAHON kit. The radionuclide 111In was chelated to DTPAAHON derivatives, and free 111In was separated by gel filtration. The radiolabeled antisense and sense probes were injected intravenously in mammary tumor-bearing BALB/c mice (1 x 10(6) cells, 8 days postinoculation). RESULTS: The highest uptake was observed at 2 hr with both thio and oxo derivatives of RASON probes, and small tumors could be imaged noninvasively. Tumor uptake and tumor/blood and tumor/muscle ratios for the sense probe (control) were significantly lower (p < 0.001) than those of the antisense probe. CONCLUSION: The radiolabeled antisense probe may provide a new sensitive tool for noninvasive imaging of c-myc oncogene mRNA for a variety of malignant tumors at an earlier stage.