Online annotation tool for digital mammography

RATIONALE AND OBJECTIVES: To develop a software tool for radiologists to annotate mammograms online. MATERIALS AND METHODS: The tool is web-based with a Java development environment and composed of a Digital Image and Communication in Medicine (DICOM) image viewer, a clinical information collector, and a database. The use of the tool with a sample case is demonstrated in this article. RESULTS: An online tool for the annotation of digital mammograms for teaching and research purposes has been developed. CONCLUSION: This annotation tool can be used to provide an annotated-case library on mammography education for residents and fellows.     

Hepatocellular carcinoma with nodule-in-nodule appearance: demonstration by contrast-enhanced coded phase inversion harmonic imaging

OBJECTIVE: A nodule-in-nodule hemodynamic pattern, namely a vascular spot in a hypovascular nodule, is specific for the diagnosis of early-stage hepatocellular carcinoma (HCC). The purpose of this study was to assess whether this unique hemodynamic pattern can be detected by contrast-enhanced coded phase inversion harmonic imaging (PIHI). METHODS: 159 consecutive patients with HCC who underwent contrast-enhanced coded PIHI were retrospectively reviewed. Cases with nodule-in-nodule patterns were selected, and findings were compared with those on computed tomography (CT) angiography (CTA) and intraarterial contrast-enhanced ultrasonography (US angiography). RESULTS: Contrast-enhanced coded PIHI successfully displayed the nodule-in-nodule hemodynamic pattern in two cases of histologically proven HCC and the hemodynamic transition in one of the two cases, which corresponded well with findings on CTA and US angiography. CONCLUSIONS: Contrast-enhanced coded PIHI can demonstrate the special nodule-in-nodule hemodynamic pattern. It is useful in the diagnosis and follow-up of early-stage HCC or suspected nodules because of its noninvasiveness and easy performance.     

Cyclin-dependent kinase 5 increases perikaryal neurofilament phosphorylation and inhibits neurofilament axonal transport in response to oxidative stress

Cyclin-dependent kinase 5 (cdk5) phosphorylates the high molecular weight neurofilament (NF) protein. Overexpression of cdk5 inhibits NF axonal transport and induces perikaryal accumulation of disordered phospho-NF cables. Experimental and clinical motor neuron disease is characterized by oxidative stress, increased cdk5 activity, and accumulation of phospho-NFs within perikarya or proximal axons. Because oxidative stress increases cdk5 activity in experimental motor neuron disease, we examined whether oxidative stress induced cdk5-mediated NF phosphorylation. Treatment of cultured neuronal cells with hydrogen peroxide inhibited axonal transport of green fluorescent protein-tagged NF subunits and induced perikaryal accumulation of NF phosphoepitopes normally confined to axons. These effects were prevented by treatment with the cdk5 inhibitor roscovitine or transfection with a construct expressing the endogenous cdk5 inhibitor peptide. These findings indicate that oxidative stress can compromise NF dynamics via hyperactivation of cdk5 and suggest that antioxidants may alleviate multiple aspects of neuropathology in motor neuron disease.     

Novel bifunctional drugs targeting monoamine oxidase inhibition and iron chelation as an approach to neuroprotection in Parkinson’s disease and other neurodegenerative diseases

Iron has been shown to accumulates at site where neurons degenerate in neurodegenerative diseases of Parkinson's disease, Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis and Friedreich ataxia. Iron is thought to participate or initiate oxidative stress via generation of reactive oxygen species (ROS), such as hydroxyl radical. Iron chelators are neuroprotective and prevent 6-hydroxydoapmine and MPTP dopaminergic neurotoxicity in rats and mice. However, their action on monoamine oxidase (MAO) A and B have not been determined previously since MAO-B inhibitors have been shown to be neuroprotective in cellular and animal models of Parkinson's disease. The chelators 8-hydroxyquinoline, O-phenanthroline, 2,2'-dipyridyl, U74500A and U74600F showed a preference for inhibition of rat brain mitochondrial MAO-A over MAO-B. Their IC(50) ranged from 10(-3) M to 10(-6) M, with 21-amino steroids (U74500A and U74006F) showing a greater selectivity and potency for MAO-A. Desferrioxamine (desferal), a prototype potent iron chelator, exhibited relatively poor MAO inhibitory. The inhibitions of MAO-A and B by 21-amino steroids (Lazaroids) were time dependent and irreversible. Those initiated by 8-hydroxyquinoline, 2,2'-dipyridyl and O-phenanthroline were fully reversible by enzyme dilution experiments. Both Fe(2+) and Fe(3+) reverse the MAO-A and B inhibition induced by the latter chelators, but not those initiated by 21-amino steroids. The data infer that either the inhibition of MAO by 21-amino steroids is either the resultant of their conversion to an irreversible covalently bound ligand or that the iron chelation moiety and MAO inhibitory activity in these compounds are not mutually shared. The results suggest that bifunctional brain penetrable drugs with iron chelating property and MAO inhibitory activity in could be the most feasible approach for neuroprotection in neurodegenerative diseases. Such drug would prevent participation of elevated iron in oxidative stress and formation of reactive hydroxyl radical, via its interaction with H(2)O2 (Fenton chemistry), generated as a consequence MAO and other oxidative enzyme reactions to generative cytotoxic reactive hydroxyl radical. We have now developed several of these compounds with neuroprotective, MAO inhibitory and iron chelating properties from our prototype iron chelators, VK-28 possessing propargylamine moiety of our anti-parkinson drug, rasagiline.     

Morphine preconditions Purkinje cells against cell death under in vitro simulated ischemia-reperfusion conditions

BACKGROUND: Morphine pretreatment via activation of delta1-opioid receptors induces cardioprotection. In this study, the authors determined whether morphine preconditioning induces ischemic tolerance in neurons. METHODS: Cerebellar brain slices from adult Sprague-Dawley rats were incubated with morphine at 0.1-10 microM in the presence or absence of various antagonists for 30 min. They were then kept in morphine- and antagonist-free buffer for 30 min before they were subjected to simulated ischemia (oxygen-glucose deprivation) for 20 min. After being recovered in oxygenated artificial cerebrospinal fluid for 5 h, they were fixed for morphologic examination to determine the percentage of undamaged Purkinje cells. RESULTS: The survival rate of Purkinje cells was significantly higher in slices preconditioned with morphine (> or = 0.3 microM) before the oxygen-glucose deprivation (57 +/- 4% at 0.3 microM morphine) than that of the oxygen-glucose deprivation alone (39 +/- 3%, P < 0.05). This morphine preconditioning-induced neuroprotection was abolished by naloxone, a non-type-selective opioid receptor antagonist, by naltrindole, a selective delta-opioid receptor antagonist, or by 7-benzylidenenaltrexone, a selective delta1-opioid receptor antagonist. However, the effects were not blocked by the mu-, kappa-, or delta2-opioid receptor antagonists, beta-funaltrexamine, nor-binaltorphimine, or naltriben, respectively. Morphine preconditioning-induced neuroprotection was partially blocked by the selective mitochondrial adenosine triphosphate-sensitive potassium channel antagonist, 5-hydroxydecanoate, or the mitochondrial electron transport inhibitor, myxothiazol. None of the inhibitors used in this study alone affected the simulated ischemia-induced neuronal death. CONCLUSIONS: These data suggest that morphine preconditioning is neuroprotective. This neuroprotection may be delta1-opioid receptor dependent and may involve mitochondrial adenosine triphosphate-sensitive potassium channel activation and free radical production. Because morphine is a commonly used analgesic, morphine preconditioning may be explored further for potential clinical use to reduce ischemic brain injury.     

Induction of caspase-dependent apoptosis by betanodaviruses GGNNV and demonstration of protein alpha as an apoptosis inducer

Betanodaviruses, members of the Nodaviridae family, are the causative agents of viral nervous necrosis in fish and infection by which cause high mortality in larvae and juveniles in a wide range of marine fish species in Asia, Europe, Australia, Martinique, and Tahit. Greasy grouper (Epinephelus tauvina) nervous necrosis viruses (GGNNV) were investigated for their apoptotic activity in culture cells. GGNNV infection of sea bass (SB) cells appeared to induce a typical cytopathic effect (CPE), i.e., cytoplasmic vacuolation, thinning, rounding up, detachment of infected cells from the cultured dish, and eventually cell lysis and death. The infected SB cells underwent DNA fragmentation and stained positive in terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay, suggesting that GGNNV infection induced apoptosis in SB cells. In addition, GGNNV-infected SB cells showed an increased activity of caspase-8-like proteases (IETDase) and caspase-3-like proteases (IETDase), whereas inhibitor of caspase-8 and caspase-3 reduced GGNNV-induced apoptosis. This suggests that GGNNV may promote apoptosis via the extrinsic pathway in SB cells. Protein alpha, the precursor of GGNNV capsid proteins, was transiently expressed in SB and Cos-7 cells. The DNA fragmentation and TUNEL positive signal were apparent in SB and Cos-7 cells expressing protein alpha, suggesting that protein alpha may serve as an apoptotic inducer in these cells. Moreover, expression of protein alpha resulted in the activation of caspase-3-like proteases in both cells, which could be inhibited by a caspase-3-like protease specific inhibitor DEVD-CHO peptide. These results suggest that fish caspases are important elements in GGNNV-meditated apoptosis.     

Phylogenetic analysis of rubella virus isolated during a period of epidemic transmission in Italy, 1991-1997

To study the molecular epidemiology of rubella virus during endemic transmission, phylogenetic analysis of the nucleotide sequence of the E1 gene was done with 31 isolates collected in northern Italy during 1991-1997, a period spanning 3 epidemics. The viruses segregated into distinct genotypic strains. Cocirculation of genotypic strains was detected; however, each epidemic was associated with specific strains, and strain displacement occurred concomitantly with each epidemic. Although most of the viruses from Italy belonged to rubella genotype I and many were related to viruses isolated concurrently in other European countries, 3 viruses belonged to rubella genotype II, which previously had been isolated only in Asia. Thus, intercontinental importation of viruses also occurred.     

Pedal Tc-99m phytate lymphoscintigraphy in primary chylopericardium

This paper describes a case of 65-year-old woman with primary chylopericardium. She received Tc-99m phytate lymphoscintigraphy after pericardial drainage and was managed with medium-chain triglycerides without surgical intervention. This was the first reported case of primary chylopericardium diagnosed with Tc-99m phytate lymphoscintigraphy.     

E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells

Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both E1B19K and E1B55K resulted in cellular DNA degradation. However, less than 20% of human lung cancer cells infected with a virus deleted for both E1B19K and E1B55 K had evidence of chromatin condensation and multiple-micronuclei formation (apoptotic hallmarks); these cells could not produce infectious viral particles. The majority of cancer cells infected with viruses deleted for the entire E1b gene did not undergo extended apoptosis and produced abundant viral progeny. Thus, only a fraction of cancer cells underwent apoptosis and did not allow E1b-deleted viruses to replicate, while the majority of cancer cells were resistant to E1A-induced apoptosis and could support virus-selective replication. The results of this study imply that, in addition to inhibiting E1A-induced apoptosis, E1B proteins may contribute other important roles in the viral life cycle. Our results also suggest that combining virus-induced apoptosis and selective viral replication into one vector will be a novel approach to destroy cancer cells.