Measurement of regional aortic compliance by MR imaging: a study of reproducibility

The reproducibility of MR imaging for the measurement of aortic compliance was studied in 47 healthy volunteers. Long and short term reproducibility and intraobserver variability were tested. The method was modified to improve image quality and short term reproducibility and intraobserver variability retested. For comparison, spin echo imaging was compared with cine gradient echo imaging. Initial long term reproducibility showed a mean difference (+/-SE) of 3% (+/- 7%) with 95% confidence interval (CI) for limits of agreement of +/- 69%. Short term reproducibility (7% +/- 6%, 95% CI +/- 46%) and intraobserver variability (1% +/- 2%, 95% CI +/- 31%) were better. After modification of the technique and optimization of image quality, both short term reproducibility and intraobserver variability improved (0% +/- 3%, 95% CI +/- 17% and 5% +/- 2%, 95% CI +/- 16% respectively). Aortic compliance can be measured using spin echo MR imaging with good reproducibility provided care is taken to obtain good quality images with high spatial resolution.     

Prokaryotic ribosomes recode the HIV-1 gag-pol-1 frameshift sequence by an E/P site post-translocation simultaneous slippage mechanism

The mechanism favoured for -1 frameshifting at typical retroviral sites is a pre-translocation simultaneous slippage model. An alternative post-translocation mechanism would also generate the same protein sequence across the frameshift site and therefore in this study the strategic placement of a stop codon has been used to distinguish between the two mechanisms. A 26 base pair frameshift sequence from the HIV-1 gag-pol overlap has been modified to include a stop codon immediately 3' to the heptanucleotide frameshift signal, where it often occurs naturally in retroviral recoding sites. Stop codons at the 3'-end of the heptanucleotide sequence decreased the frame-shifting efficiency on prokaryote ribosomes and the recording event was further depressed when the levels of the release factors in vivo were increased. In the presence of elevated levels of a defective release factor 2, frameshifting efficiency in vivo was increased in the constructs containing the stop codons recognized specifically by that release factor. These results are consistent with the last six nucleotides of the heptanucleotide slippery sequence occupying the ribosomal E and P sites, rather than the P and A sites, with the next codon occupying the A site and therefore with a post-translocation rather than a pre-translocation -1 slippage model.     

Personality traits in the first degree relatives of outpatients with depressive disorders

Exposure to high levels of hydrogen sulphide (H2S) in humans has been associated with a number of respiratory and neurological symptoms. Acute toxicity following exposure to high concentrations is well-documented, however, there is little scientific information concerning the effects of exposure to low concentrations. The effects of low levels of H2S on electroencephalographic (EEG) activity in the hippocampus and neocortex were investigated on the freely moving rat (Sprague-Dawley). Hippocampal electrodes were implanted in the dentate gyrus (DG) and CA1 region. Activity was recorded for 10 min just prior to H2S exposure in the presence of air (pre-exposure). Rats were exposed to H2S (25, 50, 75, or 100 ppm) for 3 h/day; data was collected during the final 10 min of each exposure. The total power of hippocampal theta activity increased in a concentration-dependent manner in both DG and CA1; repeated exposures for 5 consecutive days resulted in a cumulative effect that required 2 weeks for complete recovery. The effects were found to be highly significant at all concentrations within subjects. Neocortical EEG and LIA (Large Amplitude Irregular Activity) were unaffected. The results demonstrate that repeated exposure to low levels of H2S can produce cumulative changes in hippocampal function and suggest selectivity of action of this toxicant.     

The cellular structure of the islands of Calleja Magna in the brain of carnivores

Complex study of the structure of islands of Calleja in carnivore brain (cat and dog) was conducted. Using Nissl and Golgi methods, HRP axonal transport and electron microscopy the islands were found to be composed of cells of 3 types varying in size, shape, dendrite spatial distribution and ultrastructure. The majority of cell population in the islands is formed by small granular cells with scarce medium-sized, mitral-like and larger cells among them. The administration of retrograde marker into posterolateral hypothalamus provided the evidence for the presence of cells in the islands of Calleja projecting to this area. These were found to be mitral-like cells. Other cells did not exhibit staining. The resemblance between mitral-like and granular cells of the large islands of Calleja with mitral-like and granular cells of olfactory bulb, respectively, supports our assumption that these islands compose the central sensory nucleus (presumably of the sensory terminal nerve).     

Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas

BACKGROUND/METHODS: Gliomas are common malignant neoplasms of the central nervous system. Among the major subtypes of gliomas, oligodendrogliomas are distinguished by their remarkable sensitivity to chemotherapy, with approximately two thirds of anaplastic (malignant) oligodendrogliomas responding dramatically to combination treatment with procarbazine, lomustine, and vincristine (termed PCV). Unfortunately, no clinical or pathologic feature of these tumors allows accurate prediction of their response to chemotherapy. Anaplastic oligodendrogliomas also are distinguished by a unique constellation of molecular genetic alterations, including coincident loss of chromosomal arms 1p and 19q in 50%-70% of tumors. We have hypothesized that these or other specific genetic changes might predict the response to chemotherapy and prognosis in patients with anaplastic oligodendrogliomas. Therefore, we have analyzed molecular genetic alterations involving chromosomes 1p, 10q, and 19q and the TP53 (on chromosome 17p) and CDKN2A (on chromosome 9p) genes, in addition to clinicopathologic features in 39 patients with anaplastic oligodendrogliomas for whom chemotherapeutic response and survival could be assessed. RESULTS/CONCLUSIONS: Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas.     

Molecular cloning and characterization of a highly conserved chicken cellular nucleic acid binding protein cDNA

Three variants of the Candida antarctica B lipase have been constructed and characterized. The variant containing the T103G mutation, which introduces the consensus sequence G-X-S-X-G found in most other known lipases, shows an increased thermostability but retains only half the specific activity of the native enzyme. Also in ester synthesis the activity is lowered but the specificity and enantioselectivity remains unchanged. The W104H mutant, in which more space is introduced into the active site, has more dramatically changed properties. Both the thermostability and the specific activity are slightly reduced but the activity and specificity in ester synthesis is highly different from the native enzyme. In general, the activity is very low and the enantioselectivity is, furthermore, highly reduced. Finally, the mutation M72L was introduced to increase the oxidation stability of the enzyme. This variant did exhibit an increased resistance towards oxidation but the thermostability was, unfortunately, also reduced.     

Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines

To improve its immunogenicity for children and adults and to make it suitable for routine immunization of infants against typhoid fever, the capsular polysaccharide of Salmonella typhi (Vi) was bound to the B subunit of the heat-labile toxin (LT-B) of Escherichia coli or the recombinant exoprotein A (rEPA) of Pseudomonas aeruginosa. The conjugates elicited higher levels of antibodies (micrograms per milliliter of serum) in mice and in guinea pigs than did Vi and, unlike Vi alone, elicited booster antibody responses in both species. In adult volunteers, Vi-LT-B and Vi-rEPA, respectively, elicited higher levels of antibodies than Vi alone after the first injection (4.74 versus 1.77 and 4.91 versus 1.77; P < 0.005) and 26 weeks later (2.32 and 2.69 versus 0.54; P < 0.04); a second injection of the conjugates did not elicit a booster response of Vi antibodies. None of the 51 vaccinees had fever or significant local reactions. Vi-rEPA elicited slightly higher levels of Vi antibodies than did Vi-LT-B at all intervals after injection, but these differences were not significant. Each conjugate elicited antibodies to its carrier protein. The antibody responses elicited in adults by Vi bound to LT-B and rEPA are similar to those of other polysaccharide-protein conjugates. These conjugates promise to be an improved Vi vaccine. Studies of Vi conjugates with adults and infants in areas where typhoid is endemic are planned.