Regional myocardial motion and thickening assessed at rest by ECG-gated 99mTc-MIBI emission tomography and by magnetic resonance imaging

We have validated ECG-gated emission tomography using technetium-99m methoxyisobutylisonitrile for the assessment of regional ventricular function by comparing it with cine magnetic resonance imaging (MRI). Gated tomography was performed at rest in 24 patients referred for myocardial perfusion imaging [17 males and seven females with a mean age of 58 years, nine of whom had had a previous myocardial infarction (MI)]. Scores were assigned to each of nine myocardial segments for wall motion and for thickening. Cine MRI was analysed in an identical fashion. Four out of 216 (2%) segments were uninterpretable by gated tomography because of inadequate tracer uptake. In eight patients without coronary artery disease (CAD), wall motion and thickening were normal by both methods. Gated tomography showed abnormal wall motion or thickening in all patients with previous MI and in five of seven patients with CAD but no prior MI. Association between wall motion and thickening was good (rs=0. 86). Overall, there was good agreement between gated tomography and MRI for both wall motion (178/212 segments, kappa=0.66) and wall thickening (184/212 segments, kappa=0.69). In segments with severely reduced perfusion, however, there was poorer agreement (kappa=0.31). Interobserver and intraobserver agreement was high (kappa from 0.61 to 0.78). Thus, in patients investigated for CAD, there is good overall agreement between gated tomography and MRI but the agreement is lower in segments with severe perfusion defects.     

Postnatal development of respiratory function in lambs studied serially between birth and 8 weeks

The molecular structure of the telomeric region at the left arm of the second chromosome of the mosquito Anopheles gambiae has been determined in the transformed strain G418 that contains a pUChsneo transgene attached at the 2L chromosome end, and in the Pink eye laboratory strain (PE). Both strains contain the same complex satellite positioned distal to a unique region. FIGE mapping of the telomeric region of the PE strain revealed distinct DNA fragment lengths that segregated with individual chromosomes. Genomic DNA fragments were cloned from the 2L telomeric region, which accounted for about half of 2L chromosomes in the PE population. In all three cases studied, long fragments of different middle repetitive sequences were found attached to the distal ends of the 2L satellite. We propose that random fragments of DNA may be occasionally added during recombination between complex satellite repeats at the chromosome ends.     

Modulation of antigen processing and presentation by covalently linked complement C3b fragment

Ligands such as complement fragments (C3, C4), IgG or alpha 2-macroglobulin, which bind antigen (Ag) before their uptake by antigen-presenting cells (APC), are likely to modulate the different steps of Ag processing and presentation. These ligands contribute to internalization and endosomal targeting of Ag; they also influence its processing and, consequently, the binding of resulting peptides to major histocompatibility complex (MHC) class II molecules before presentation to T cells. Complement protein C3 contains, like other members of the alpha 2-macroglobulin family, an intrachain thiolester bond. Conformational alteration or limited proteolysis of C3 into C3b leads to breaking of the thiolester with transient capacity of the revealed carbonyl group to esterify hydroxyl groups of Ag. Ester-linked complexes including tetanus toxin (TT) and C3b were prepared to analyse the influence of bound C3b on TT processing and presentation by APC. Covalent binding of C3b to TT resulted in increased and prolonged stimulation of specific T-cell proliferation. This effect was observed with non-specific B cells, as well as with a TT-specific B-cell clone, as APC. On the other hand, SDS-PAGE analysis of proteolysates of TT or C3b-TT, obtained with endosome/lysosome-enriched subcellular fractions prepared from human Epstein-Barr virus (EBV)-transformed B cells, indicated a delay of TT proteolysis when TT was associated to C3b. Treatment of APC with protease inhibitors, before and during exposure of the cells to Ag, resulted in differences in the inhibition of TT and C3b-TT proteolysis. Using purified cathepsins B and D, we demonstrated that covalent binding of C3b to TT totally abolished TT proteolysis by cathepsin D, while proteolysis by cathepsin B was preserved. This finding and the absence of cathepsin B in endosomes may explain a delay in TT processing when it is associated to C3b. Confirming these data, presentation by formaldehyde-fixed cells of C3b-TT proteolysates showed higher stimulation of specific T-cell clones than formaldehyde-fixed TT proteolysates.     

The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.     

Human papillomavirus in laryngeal and hypopharyngeal carcinomas. Relationship to survival

OBJECTIVE: To determine the relationship between human papillomavirus (HPV) DNA detection in upper aerodigestive tract malignancies and patient outcome. DESIGN: Archival paraffin-embedded specimens from 78 previously untreated patients with squamous carcinomas of the larynx and hypopharynx were pathologically verified and analyzed by polymerase chain reaction for detection of HPV DNA. Charts were independently reviewed and coded until final analysis. SETTING: The University of Texas M. D. Anderson Cancer Center, Houston, a tertiary cancer referral center. RESULTS: DNA was successfully extracted from 65 archival patient samples (83%). The mean (+/- SEM) duration of follow-up for these patients was 42 +/- 21 months. Thirty specimens (46%) exhibited detectable HPV DNA. Detection of HPV was significantly related to decreased survival, independent of disease stage. Log rank testing revealed that HPV detection, pathologic vascular invasion, and nodal status were the most significant predictors of death of disease. CONCLUSIONS: Laryngeal and hypopharyngeal carcinomas with detectable HPV may represent a biologically distinct subset of tumors that carry a poorer prognosis than do cancers with no detectable HPV.     

Lack of evidence for inhibition of ovulation by aspirin in women

Prostaglandin synthetase inhibitors such as aspirin and indomethacin inhibit ovulation in experimental animals. The effect of therapeutic doses of aspirin on ovulation has been studied in 5 women. Ovulation, as assessed by measurements of urinary LH and plasma progesterone levels, basal body temperature and cervical mucus changes occured in all the control and treatment cycles. Serial sections of the corpora lutea failed to show any entrapped ova. The significance of finding a prostaglandin synthetase inhibitor which acts specifically at the ovarian level is discussed.