Measurement of 23Na(α,p)26Mg at Energies Relevant to 26Al Production in Massive Stars.

26Al is an important radioisotope in astrophysics that provides evidence of ongoing nucleosynthesis in the Galaxy. The 23Na(α, p)26Mg reaction has been identified by a sensitivity study as being one of the most important reactions for the production of 26Al in the convective C/Ne burning shell of massive stars. Owing to large uncertainties in previous experimental data, model calculations are used for the reaction rate of 23Na(α, p)26Mg in this sensitivity study. Current experimental data suggest a reaction rate a factor of ∼40 higher than model calculations. However, a new measurement of this reaction cross section has been made in inverse kinematics in the energy range E(c.m.)=1.28-3.15 MeV at TRIUMF, and found to be in reasonable agreement with the model calculation. A new reaction rate is calculated and tight constraints on the uncertainty in the production of 26Al, due to this reaction, are determined.

Is γ-ray emission from novae affected by interference effects in the 18F(p,α)15O reaction?

The (18)F(p,α)(15)O reaction rate is crucial for constraining model predictions of the γ-ray observable radioisotope (18)F produced in novae. The determination of this rate is challenging due to particular features of the level scheme of the compound nucleus, (19)Ne, which result in interference effects potentially playing a significant role. The dominant uncertainty in this rate arises from interference between J(π)=3/2(+) states near the proton threshold (S(p)=6.411 MeV) and a broad J(π)=3/2(+) state at 665 keV above threshold. This unknown interference term results in up to a factor of 40 uncertainty in the astrophysical S-factor at nova temperatures. Here we report a new measurement of states in this energy region using the (19)F((3)He,t)(19)Ne reaction. In stark contrast to previous assumptions we find at least 3 resonances between the proton threshold and E(cm)=50 keV, all with different angular distributions. None of these are consistent with J(π)=3/2(+) angular distributions. We find that the main uncertainty now arises from the unknown proton width of the 48 keV resonance, not from possible interference effects. Hydrodynamic nova model calculations performed indicate that this unknown width affects (18)F production by at least a factor of two in the model considered.

Development and implementation of a new rapid aneuploidy diagnostic service within the UK National Health Service and implications for the future of prenatal diagnosis.

BACKGROUND: Prenatal diagnosis for chromosome abnormality is routinely undertaken by full karyotype analysis of chromosomes from cultured cells; pregnant women must wait on average 13-14 days for their results. Autosomal trisomies, which account for around 80% of significant abnormalities, can be detected by quantitative fluorescence (QF) PCR. We report on the development and implementation of this technique as the first such routine service within a diagnostic department of the UK National Health Service (NHS). METHODS: We designed a "one-tube test" comprising four primer pairs for polymorphic tetranucleotide repeat sequences on chromosome 21, four primer pairs for sequences on chromosome 18, three primer pairs for sequences on chromosome 13, and one primer pair to identify the sex chromosomes. All prenatal samples received by our NHS diagnostic department between April, 2000, and April, 2001, were tested. After DNA extraction, PCR amplification was done and the products separated on a capillary-based genetic analyser; the results were interpreted with dedicated software. Follow-up karyotype analysis was done on all samples. FINDINGS: 1148 amniotic fluid samples, 188 chorionic villus samples, and 37 fetal tissue samples were tested; the amplification failure rate was zero with our current protocol. QF-PCR results were obtained and reported on 1314 (98%) of the prenatal samples; the remaining 22 (2%) were uninformative because of maternal-cell contamination. One case of mosaicism in a chorionic villus sample, and two cases indicating somatic expansion of a tetranucleotide repeat were found. No false positive or false negative results were obtained. The mean reporting time for the last 4 months of data collection was 1.25 working days. INTERPRETATION: QF-PCR aneuploidy testing is an efficient and accurate technique for the detection of autosomal trisomies in prenatal samples. Implementation of this service has led to the rapid diagnosis of abnormalities and early reassurance for women with normal results.

Molecular mechanism of the synergistic phosphorylation of phosphatase inhibitor-2. Cloning, expression, and site-directed mutagenesis of inhibitor-2.

Inhibitor-2 (I-2) is the regulatory subunit of the ATP-Mg-dependent phosphatase, a cytosolic form of type 1 protein phosphatase. Phosphorylation of I-2 at Thr-72 by the protein kinase glycogen synthase kinase-3 (GSK-3) leads to activation of the enzyme. Casein kinase II action was shown to synergistically enhance phosphorylation and activation by GSK-3 (DePaoli-Roach, A.A. (1984) J. Biol. Chem. 259, 12144-12152). Rabbit skeletal muscle and liver I-2 cDNA clones have been isolated. Rabbit skeletal muscle cDNAs could be placed in two subtypes, differing in the length of the 3'-untranslated region. The coding sequence of 612 nucleotides was identical in the two skeletal muscle and the liver cDNAs and predicted a protein of 204 amino acids, consistent with analysis of the purified protein. Northern hybridization analysis indicated that the two mRNAs of 1.7 and 2.7 kilobase pairs were present in all rabbit tissues examined, except in liver, where only the larger transcript was detected, and in testis, where additional transcripts were present. Expression in Escherichia coli of wild-type and phosphorylation site mutants resulted in the production of I-2 polypeptides with apparent M(r) values of approximately 31,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The inhibitory activity of the recombinant proteins was similar to that of native rabbit skeletal muscle I-2 and was unaffected by the substitution of alanine for the GSK-3 site (Thr-72) and for the casein kinase II sites (Ser-86 and Ser-120/121) or by substitution of glutamic acid and aspartic acid for Thr-72 and Ser-86. Recombinant wild-type I-2 and the Ala-120/121 mutant were phosphorylated synergistically by GSK-3 and casein kinase II. The Thr-72 and Ser-86 mutants, however, did not undergo this synergistic phosphorylation. Our studies indicate that Thr-72 is the only GSK-3 site and that Ser-86 is the casein kinase II site required for the potentiation of GSK-3 action. Furthermore, acidic residues cannot substitute for the phosphate group either in enhancing GSK-3 phosphorylation or in activating the phosphatase.

Pulmonary uptake of sestamibi on early post-stress images: angiographic relationships, incidence and kinetics.

Early post-stress imaging with 99Tcm-sestamibi has the potential to reveal ancillary markers of severe coronary artery disease. Lung/myocardial ratios of sestamibi were assessed after pharmacologic, exercise or combined stress, and these were compared with historical controls who were stressed similarly, but imaged with 201Tl. Forty initial patients had planar imaging and correlating angiograms; pulmonary uptake for sestamibi related to severe coronary artery stenoses when measured on immediate images, started at 4 min post-stress (P = 0.04), but had a poor relationship to angiographic findings when measured on delayed clinical images. Of 180 subsequent studies, increased pulmonary uptake of sestamibi was seen more frequently (incidence = 34%) in those with abnormal tomograms compared to those with normal tomograms (incidence = 13%, P < 0.01), but appeared less frequently than on abnormal 201Tl studies (incidence = 60%). With sequential imaging for 5 min after injection, pulmonary uptake showed a greater fall with time on sestamibi studies than on matched 201Tl studies. No consistent differences were seen among the stress modalities. As an ancillary sign of haemodynamically severe disease, increased pulmonary uptake can be seen after various stress modalities, but may be more difficult to apply with sestamibi than with thallium imaging.

Chromosomal abnormalities in Dupuytren's contracture and carpal tunnel syndrome.

The cytogenetics of cell cultures derived from Dupuytren's tissue, adjacent palmar fascia and palmar skin from patients undergoing fasciectomy have been examined and the results compared to cell cultures established from palmar fascia, flexor retinaculum and palmar skin of patients undergoing carpal tunnel decompression. Chromosomal abnormalities were detected in cell cultures from Dupuytren's tissue in eight of the nine patients studied. Clones of cells trisomic for chromosome 8 were found in five of the nine patients. Trisomy 8 was also present in two of five flexor retinaculum cultures from carpal tunnel syndrome cases. These findings in both Dupuytren's contracture and carpal tunnel syndrome suggest the presence of chromosomal instability in the palmar fascia. The significance of the chromosomal abnormalities is however unclear, but they indicate a possible common pathway in the onset of pathological fibrosis.