Monocrotaline pyrrole induces apoptosis in pulmonary artery endothelial cells

Eosinophilic myocarditis followed by fibrosis of the cardiac muscle was observed in addition to peripheral blood eosinophilia in CBA/J mice infected with Toxocara canis. The infected mice were used as an experimental model of eosinophilic endomyocarditis associated with hypereosinophilic syndrome. Effects of in vivo treatment with MoAbs to adhesion molecules on eosinophilic myocarditis were examined using this experimental model. Expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of capillaries in myocardium were increased 1 and 2 weeks after infection. Infiltration of very late antigen (VLA)-4+ and/or CD11a+ cells into the cardiac muscles was also observed 1 and 2 weeks after infection. Infiltration of eosinophils into the heart was significantly suppressed by anti-CD18 MoAb and anti-VLA-4 MoAb, and focal fibrosis of the cardiac muscle was also significantly suppressed by combined administration of anti-CD18 and anti-ICAM-1 MoAbs. These results indicate that adhesion molecules may play important roles in eosinophilic myocarditis, and that blockade of interaction between adhesion molecules and their ligands may help to control it.     

The impact of genetic markers on selection

Genetic marker technologies, such as marker-assisted selection, parentage identification, and gene introgression can be applied to livestock selection programs. Highly saturated genetic maps are now available for cattle, swine, and sheep to provide the genetic framework for developing MAS programs. These programs rely on three phases for commercialization of the technology: the detection phase, in which quantitative trait loci are located and their effects on the phenotype measured; the evaluation phase, in which the markers are evaluated in commercial populations; and the implementation phase, in which markers are combined with phenotypic and pedigree information in genetic evaluation for predicting the genetic merit of individuals within the population. Predicting the economic impact of genetic technologies is a complex process that requires quantitative prediction and economic analysis. Evaluating the impact of these benefits across an industry can be achieved through a process in which gains from implementation of a genetic technology are assessed at the individual, enterprise, and industry levels. A pattern of annual benefits and costs can be predicted using gene flows that can be evaluated by conventional economic analysis.     

Cytogenetic abnormalities in pediatric myelodysplastic syndrome: a report of three cases

Three consecutive cases of pediatric myelodysplastic syndrome (MDS) diagnosed over a three-year period in Queen Mary Hospital, Hong Kong, were described. Depending on the classification system used, they comprised two cases of chronic myelomonocytic leukemia (CMMoL) of which one can be reclassified as juvenile chronic myeloid leukemia (JCML) and one cases of refractory anemia with excess of blasts (RAEB) or an alternative diagnosis of atypical CML. Cytogenetic abnormalities were detected in all of them on examination of bone marrow cells. Of the two CMMoL, one had monosomy 21, whereas the other had hypodiploidy. The patient with RAEB had a complex karyotype of 46,X,del(X)(q24),t(1;7) (p22;q32),add(15)(q26)(8). The balanced translocation (1;7) seen in this patient was exceedingly rare and, to the best of our knowledge, was reported only twice in the literature. The karyotypic abnormalities that we saw in our patients were not well recognized in pediatric MDS. This report emphasizes the importance of cytogenetic study in children suspected of suffering from MDS, which remains a rare disorder of childhood, and a need to rationalize current classification schemes.     

Immunohistochemical metallothionein expression in thymoma: correlation with histological types and cellular origin

In radioimmunotherapy, the long circulation times of antibody radioconjugates correlate with high relative radiation doses to nontumor tissues. Tumor/normal tissue ratios can be significantly improved by using targeting molecules with shorter circulation times. IFabs are multimers of VH-CH1-linker-VK-CK monomers. The lack of the Fc region in IFabs should lead to circulation times that are shorter than those of IgG molecules. The monomers assemble into disulfide-bond-stabilized multimers, 90% of which are 100 kDa dimers (IFab2). IFab2s should not be rapidly eliminated through kidney filtration because their molecular weight is above the threshold for renal passage. We report the first experimental in vivo tests for 125I-IFab radioconjugates derived from a humanized version of the anti-breast mucin monoclonal antibody BrE-3. Biodistributions are reported for athymic nude mice carrying human mammary tumor MX-1 xenografts. The T1/2 beta's for the different tissues ranged from 13.3 h for blood to 19.9 h for tumor. Therefore, IFab radioconjugates cleared the body with a rate comparable to that of F(ab')2 fragments. Except for stomach, tumor/nontumor dose ratios were significantly better for IFabs than for the parent antibody (BrE-3)4 days after injection.     

Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and pseudomonas exotoxin

Recently, we have demonstrated that a spectrum of human adenocarcinoma cell lines express binding sites for interleukin 13 (IL-13). These cells are killed by a chimeric protein composed of human (h) IL-13 and a derivative of Pseudomonas exotoxin, PE38QQR (Debinski et al., J. Biol. Chem., 270: 16775-16780, 1995). The cell killing was hIL-13- and hIL-4-specific, indicating that a common binding site for the two cytokines is present in several solid tumor cell lines. Herein, we report that an array of established glioma cell lines is killed by very low concentrations of hIL-13-PE38QQR, often reaching <1 ng/ml (<20 pM). Glioma cells express up to 30,000 molecules of IL-13 receptor/cell which has intermediate affinity toward hIL-13. hIL-13-PE38QQR is more active (up to 3 logs difference in cytotoxic activities) than are the corresponding chimeric toxins containing hIL-4 or hIL-6. The cytotoxic action of hIL-13-PE38QQR is blocked by an excess of hIL-13 on all cell lines studied, and it is not neutralized by hIL-4 on some of these cells. Our results show that human brain cancers richly express receptors for IL-13. Furthermore, the interaction detected previously between receptors for IL-13 and IL-4 on solid tumors cell lines is of a qualitatively different character in U-251 MG and U-373 MG glioma cells. The receptor for IL-13 may represent a new marker of brain cancers and an attractive target for anticancer therapies.     

Metanil yellow: a bifunctional inducer of hepatic phase I and phase II xenobiotic-metabolizing enzymes

Metanil yellow, a non-permitted food colour, has been found in various foodstuffs. The induction potential of metanil yellow on hepatic microsomal cytochrome P-450 (P-450)-dependent monooxygenases and cytosolic detoxification enzymes, namely, glutathione S-transferase (GST) and quinone reductase (QR), was investigated. Oral administration of metanil yellow (430 mg/kg body weight) to four animals for seven days caused significant induction of hepatic P-450 (48%) and its dependent aryl hydrocarbon hydroxylase (100%) activity and cytosolic GST (136%) and QR (92%) activities. Parenteral administration of metanil yellow (80 mg/kg body weight) to another set of four animals for 3 days resulted in higher induction of ethoxyresorufin-O-deethylase (228%) as compared to other monooxygenases (64-92%), while GST and QR were also found to be induced (59-95%). Spectra of metanil yellow-induced microsomes showed an increase in P-450 with a shift of 2.2 nm in the soret region. The results suggest that metanil yellow acts as a bifunctional inducer of specific isozymes of P-450 and cytosolic enzymes and thus may involve the cytosolic aryl hydrocarbon (Ah) receptor for this type of induction.     

Spread-spectrum techniques for the provision of packet access on the reverse link of next-generation broadband multimedia satellite systems

This paper will examine the potential performances of spread-spectrum-based access techniques via the interaction channel of an Internet protocol (IP)-based multimedia satellite system. In particular, a theoretical analysis of the spread-Aloha technique will be given for the case of forward error correction coded systems. Then, the performance of spread-Aloha access will be confirmed by simulation and compared with that of a conventional time-division multiple-access (TDMA)-based combined free/demand assignment multiple-access system. It appears that spread-Aloha-based techniques, although achieving a lower maximum throughput than the TDMA-based access scheme, may provide a better experience to the user due to the lower transmission latency. Finally, the prospect of a spread-spectrum-based access scheme combining Aloha and reservation mechanisms will be briefly overviewed.