Simultaneous multifocal polymorphous low-grade adenocarcinoma. Report of two cases.

The polymorphous low-grade adenocarcinoma is a recently described variant of salivary gland adenocarcinoma with a comparatively good prognosis. Polymorphous low-grade adenocarcinoma occurs most frequently in the palate with a peak incidence between 30 and 70 years of age. The female/male ratio is approximately 2:1, and the tumors exhibit slow growth with a low recurrence rate. The simultaneous occurrence of polymorphous low-grade adenocarcinoma has not been previously reported. This article reviews the existing literature and describes the first two reports of simultaneous intraoral polymorphous low-grade adenocarcinoma.

The use of socio-demographic profiling of patients to monitor changes in the provision of care by the Community Dental Service.

OBJECTIVE: To investigate the socio-demographic profile of patients using the Leeds Community Dental Service (CDS) in 1996/97 and to determine any changes in profile since 1991/92. DESIGN: Retrospective. SETTING: The area served by Leeds Health Authority. SUBJECTS: A total of 8,051 patients who had used the Leeds CDS in 1996/97 together with 9,372 patients from 1991/92. OUTCOME MEASURES: Socio-demographic profile, including age group; ethnicity; deprivation (Townsend index) and disability. RESULTS: Of children under 16 years old using the CDS in 1996/97, 24% were of South Asian ethnic origin, much higher than the 6% reported for Leeds in the 1991 census. Over the period of the study there was a reduction in the proportion of patients aged 5-15 years (75% to 65%, P < 0.001) and an increase in those aged 16-64 years (13% to 19%, P < 0.001). Increases were also seen in the proportion of patients from districts in the two most deprived quintiles (60% to 67%, P < 0.001) and for patients with special needs (19% to 28%, P < 0.001). CONCLUSIONS: This study indicated an increased emphasis by the CDS on targeting groups likely to be unable or unwilling to seek treatment from the GDS. Socio-demographic profiling can be useful in monitoring the progress of changes in primary dental care.

Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F.

Owing to the prevalence of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs), its constitutive activity, and ability to recapitulate the MPN phenotype in mouse models, JAK2V617F kinase is an attractive therapeutic target. We report the discovery and initial characterization of the orally bioavailable imidazopyridazine, LY2784544, a potent, selective and ATP-competitive inhibitor of janus kinase 2 (JAK2) tyrosine kinase. LY2784544 was discovered and characterized using a JAK2-inhibition screening assay in tandem with biochemical and cell-based assays. LY2784544 in vitro selectivity for JAK2 was found to be equal or superior to known JAK2 inhibitors. Further studies showed that LY2784544 effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively). In comparison, LY2784544 was much less potent at inhibiting interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC50=1183 and 1309 nM, respectively). In vivo, LY2784544 effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP (green fluorescent protein) ascitic tumor cells (TED50=12.7 mg/kg) and significantly reduced (P<0.05) Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model (TED50=13.7 mg/kg, twice daily). In contrast, LY2784544 showed no effect on erythroid progenitors, reticulocytes or platelets. These data suggest that LY2784544 has potential for development as a targeted agent against JAK2V617F and may have properties that allow suppression of JAK2V617F-induced MPN pathogenesis while minimizing effects on hematopoietic progenitor cells.

A plankton net designed to exclude air-sea interface phenomena.

For use in trace pollutant studies a description is presented of a protected closed plankton net whose purpose is to minimize the exposure of collected samples to surface films and debris. Tests described in this paper appeared to show that the protected closed net was not necessary for the environmental conditions encountered during our field studies. However, additional calculations based on the data of other investigators strongly imply that employment of such a net is heavily polluted surface waters may be highly advantageous.

Reduction of MR imaging time by the hybrid fast-scan technique.

The time taken to collect high-resolution and high signal-to-noise (S/N) data in magnetic resonance (MR) imaging may be the limiting factor in patient throughput and in reducing patient motion. A hybrid fast-scan technique combining static and oscillatory phase-encoding gradients from two-dimensional Fourier transform (2DFT) and echo-planar imaging can reduce the time needed to collect data at the expense of loss in S/N. The flexibility of this technique is that any amplitude or frequency of oscillation of the phase-encoding gradient can be used. The technique was used for different frequencies and amplitudes, and images are presented that were acquired in one-half and one-quarter the time required with standard 2DFT techniques. The images illustrate that the hybrid and 2DFT techniques produce comparable resolution and contrast under identical conditions.

Germline transformation of the malaria vector, Anopheles gambiae, with the piggyBac transposable element.

Germline transformation of the major African malaria vector, Anopheles gambiae, was achieved using the piggyBac transposable element marked with the enhanced green fluorescent protein (EGFP) injected into mosquito embryos. Two G1 generation male mosquitoes expressing EGFP were identified among 34 143 larvae screened. Genomic Southern data and sequencing of the piggyBac insertion boundaries showed that these two males arose from one piggyBac insertion event in the injected G0 embryos. Genetic cross data suggest that the insertion site of the element either resulted in, or is tightly linked to, a recessive lethal. This was demonstrated by a deficiency in the number of EGFP-expressing offspring from inbred crosses but expected ratios in outcrosses to non-transformed individuals and failure to establish a pure-breeding line. The insertion was weakly linked to the collarless locus on chromosome 2 and was shown by in situ hybridization to be located in division 28D of that chromosome. Particularly high levels of expression were observed uniformly in salivary glands and, in most individuals, in the anterior stomach. An improvement in the injection technique at the end of the studies resulted in increased G0 hatching, transient expression and EGFP-expression rates among G1 progeny.