In vitro and in vivo gene delivery mediated by a synthetic polycationic amino polymer

The r?le of chemotherapy in the treatment of operable soft tissue sarcomas is still debatable. In high-grade tumors, randomized trials using adjuvant chemotherapy have resulted in controversial results. A recent meta-analysis showed a higher median disease-free survival in groups with chemotherapy compared to controls. Doxorubicin, ifosfamide and dacarbazine are the majors drugs. Their combination in adjuvant treatment is currently being investigated. Neoadjuvant chemotherapy has allowed conservative surgery in initially unoperable tumors, but its role in primarily operable tumors remains to be defined.     

Gastrointestinal autonomic nerve tumors. A clinicopathological, immunohistochemical, and ultrastructural study of 12 cases

The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor of the intestinal tract and retroperitoneum first described by Herrera and associates in 1984. Distinction of GAN tumors from other gastrointestinal stromal tumors is based on electron microscopic findings. Thus far there have been 12 reported cases. We present an additional 12 GAN tumors, identified by us during 4 years. There were seven male and five female patients and they ranged in age from 10 to 85 years (mean: 58 years). Sites of the tumors were stomach (three), jejunum (two), ileum (four), mesentery (one), and retroperitoneum (two). Eight of the tumors measured > 10 cm in greatest dimension. Usually well circumscribed, the neoplasms were tan to light pink, sometimes hemorrhagic, and soft. There was a variety of histologic patterns including fascicles, palisades, and whorls. Mitotic activity varied from 0 to 23 mitosis per 10 high-power fields (HPF). Using a panel of 10 immunohistochemical stains, only vimentin was consistently positive. There was neuron-specific enolase reactivity in six and S-100 protein reactivity in two cases. All muscle markers were negative. Ultrastructural studies showed neuron-like cells with long axonic cytoplasmic processes ending in bulbous synapse-like structures containing dense-core neurosecretory granules and clear vesicles. Basement membrane was absent. These features are reminiscent of ganglia of the intestinal autonomic nervous system. The patients were followed for 5-125 months (mean of 26 months). Tumor recurred or metastasized to the liver in seven patients (58%) and four patients died with tumor. There were correlations between tumor size (> 10 cm), mitotic count (at least five per 10 HPF), and aggressive behavior.     

Factors affecting serum selenium and vitamin E concentrations in dairy cows

Supplementation of selenium and vitamin E to enhance disease resistance in dairy cattle has become common, particularly to prevent periparturient reproductive disorders and mastitis. To establish reference values for serum vitamin E and selenium concentrations in postparturient dairy cattle and to determine whether serum concentrations of these micronutrients varied with season and stage of lactation, cows from a stratified random sample of 50 herds were studied for 1 year. Blood samples were collected from each of the 50 study herds twice, from the 10 most recently parturient cows or from 10% of the herd, whichever was greatest. Mean concentration of vitamin E and selenium was 2.55 micrograms/ml and 78.12 ng/ml, respectively. Vitamin E concentrations were significantly (P < 0.05) higher during the summer and fall than during the winter and spring. Selenium concentrations were significantly (P < 0.05) lower during the summer and fall than during the winter and spring. Herd, season of blood sample collection, and time since parturition were significant (P < 0.02) in explaining variation in vitamin E and selenium concentrations.     

Methionine Enrichment of Milk Protein by Enzymatic Peptide Modification

Methionine-enriched protein was produced from an enzymatically pre-hydrolyzed milk protein using an enzymatic peptide modification (EPM) method with α-chymotrypsin as catalyst. Methionine of the product was twice as high as that of the substrate protein. The incorporated methionine formed a covalent bond with the peptide chain in the product protein. The change in the number of peptide bonds was monitored by the degree of hydrolysis (DH). The slight change of the DH values revealed that a portion of the free amino acids was bound to the peptide chains during the reaction and that transpeptidation was the main process during the EPM treatment. The location of the newly incorporated amino acids was determined by identification of the terminal amino acids. The covalently bound methionine was located in C- and N-terminal positions in a ratio of 3:1.     

In vitro mutagenesis of the mitochondrial leucyl tRNA synthetase of Saccharomyces cerevisiae shows that the suppressor activity of the mutant proteins is related to the splicing function of the wild-type protein

The NAM2 gene of Saccharomyces cerevisiae encodes the mitochondrial leucyl tRNA synthetase (mLRS), which is necessary for the excision of the fourth intron of the mitochondrial cytb gene (bI4) and the fourth intron of the mitochondrial coxI gene (aI4), as well as for mitochondrial protein synthesis. Some dominant mutant alleles of the gene are able to suppress mutations that inactivate the bI4 maturase, which is essential for the excision of the introns aI4 and bI4. Here we report mutagenesis studies which focus on the splicing and suppressor functions of the protein. Small deletions in the C-terminal region of the protein preferentially reduce the splicing, but not the synthetase activity; and all the C-terminal deletions tested abolish the suppressor activity. Mutations which increase the volume of the residue at position 240 in the wild-type mLRS without introducing a charge, lead to a suppressor activity. The mutant 238C, which is located in the suppressor region, has a reduced synthetase activity and no detectable splicing activity. These data show that the splicing and suppressor functions are linked and that the suppressor activity of the mutant alleles results from a modification of the wild-type splicing activity.     

Ketamine and nifedipine protect cultured cortical neurons against injurious effect of glutamate]

The effects of glutamate on cultured cortical neurons and the protective effect of ketamine and nifedipine were studied. On day 10 after plating of the cortical cells from 16-18 day-old fetal rats, the cultures were exposed to 50 mumol.L-1 glutamate and low glucose (1 g.L-1) for 10 min-24 h. The results showed that a release of lactate dehydrogenase (LDH) into the culture supernatant was observed as a function of time. The values of LDH efflux in culture medium was significantly lower than those of controls when the cells were pretreated with ketamine or nifedipine 10 min prior to addition of glutamate. More significant decrease of LDH activity in culture medium was observed when the two drugs were used in combination. These results demonstrate that the dissociated cultured cortical neurons from fetal rat are seriously damaged by glutamate. Such damage could be attenuated by ketamine and nifedipine, suggesting that ketamine and nifedipine may protect neurons from the glutamate toxicity, and the effect of combining ketamine and nifedipine was greater than either ketamine or nifedipine alone.     

Cross sections of proton induced nuclear reactions on enriched 111Cd and 112Cd for the production of 111In for use in nuclear medicine

Proton induced nuclear reactions on enriched 111Cd and 112Cd have been studied up to 30 MeV in the context of routine production of the medically used isotope 111In with low and medium energy cyclotrons. The excitation functions of 111Cd(p,n)111m,gIn and 112Cd(p,2n)111m,gIn as production reactions and 111Cd(p,2n)110mIn, 111Cd(p,2n)110In, 111Cd(p,3n)109ml,m2,In, 112Cd(p,3n)110mIn, 112Cd(p,3n)110gIn as competing processes have been measured using the activation method involving the stacked-foil technique. The deduced thick target yields are compared with those obtained experimentally.