Polymorphic secreted kinases are key virulence factors in toxoplasmosis.

The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the responsible genes, we mapped virulence in F(1) progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.

Multiple metal contamination from house paints: consequences of power sanding and paint scraping in New Orleans.

Power sanding exterior paint is a common practice during repainting of old houses in New Orleans, Louisiana, that triggers lead poisoning and releases more than Pb. In this study we quantified the Pb, zinc, cadmium, manganese, nickel, copper, cobalt, chromium, and vanadium in exterior paint samples collected from New Orleans homes (n = 31). We used interior dust wipes to compare two exterior house-painting projects. House 1 was measured in response to the plight of a family after a paint contractor power sanded all exterior paint from the weatherboards. The Pb content (approximately 130,000 microg Pb/g) was first realized when the family pet died; the children were hospitalized, the family was displaced, and cleanup costs were high. To determine the quantity of dust generated by power sanding and the benefits of reducing Pb-contaminated dust, we tested a case study house (house 2) for Pb (approximately 90,000 microg/g) before the project was started; the house was then dry scraped and the paint chips were collected. Although the hazards of Pb-based paints are well known, there are other problems as well, because other toxic metals exist in old paints. If house 2 had been power sanded to bare wood like house 1, the repainting project would have released as dust about 7.4 kg Pb, 3.5 kg Zn, 9.7 g Cd, 14.8 g Cu, 8.8 g Mn, 1.5 g Ni, 5.4 g Co, 2.4 g Cr, and 0.3 g V. The total tolerable daily intake (TTDI) for a child under 6 years of age is 6 microg Pb from all sources. Converting 7.4 kg Pb to this scale is vexing--more than 1 billion (10(9)) times the TTDI. Also for perspective, the one-time release of 7.4 x 10(9) microg of Pb dust from sanding compares to 50 x 10(9) microg of Pb dust emitted annually per 0.1 mile (0.16 km) from street traffic during the peak use of leaded gasoline. In this paper, we broaden the discussion to include an array of metals in paint and underscore the need and possibilities for curtailing the release of metal dust.

Orally active benzamide antipsychotic agents with affinity for dopamine D2, serotonin 5-HT1A, and adrenergic alpha1 receptors.

New antipsychotic drugs are needed because current therapy is ineffective for many schizophrenics and because treatment is often accompanied by extrapyramidal symptoms and dyskinesias. This paper describes the design, synthesis, and evaluation of a series of related (aminomethyl)benzamides in assays predictive of antipsychotic activity in humans. These compounds had notable affinity for dopamine D2, serotonin 5-HT1A, and alpha1-adrenergic receptors. The arylpiperazine 1-[3-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]benzoyl]p ipe ridine (mazapertine, 6) was chosen because of its overall profile for evaluation in human clinical trials. The corresponding 4-arylpiperidine derivative 67 was also highly active indicating that the aniline nitrogen of 6 is not required for activity. Other particularly active structures include homopiperidine amide 14 and N-methylcyclohexylamide 31.

Core decompression for early osteonecrosis of the hip in high risk patients.

Thirty-four hips (22 patients) with history and physical findings consistent with osteonecrosis of the femoral head were evaluated preoperatively by radiographs, bone scans and magnetic resonance images. All patients with Stage 0, I, or II disease by the Ficat and Arlet classification underwent core decompression using the same technique. Osteonecrosis was confirmed histologically in all 34 hips. Eighteen of 22 patients had prognostic factors traditionally associated with poor outcome including collagen vascular diseases and continued use of steroids. Followup averaged 4 years for 18 patients with 29 hips. Four patients died secondary to systemic illness. Twelve patients had good or excellent results using the Modified Harris Hip Score with 6 patients needing hip arthroplasty. In this group of patients previously associated with poor prognosis, no hip fractures were seen and 66% good to excellent results were obtained.

Comparison of same-day sequential anterior and posterior spinal fusion with delayed two-stage anterior and posterior spinal fusion.

STUDY DESIGN: This was a retrospective review. Short-term outcomes were compared based on two different surgical techniques. OBJECTIVES: To determine the safety, efficacy, and cost effectiveness of two different surgical techniques of anterior and posterior spinal fusion for pediatric patients with spinal deformity. SUMMARY OF BACKGROUND DATA: Brown et al, Floman et al, and Bradford et al have reported on combined anterior and posterior spine fusions with a 1-2-week recovery period between stages. However, advances in surgical and anesthetic techniques combined with the prohibitive cost of prolonged hospitalization and theoretical advantages in pulmonary function and nutrition have led to increasing use of combined anterior and posterior spinal fusion under one anesthetic. METHODS: The authors reviewed records and radiographs of patients with pediatric spinal deformities who underwent anterior spine fusion/posterior spine fusion and instrumentation performed by the senior author (HAK) at one institution. RESULTS: Same-day sequential anterior spine fusion/posterior spine fusion resulted in less blood loss (575 +/- 275 ml; P < or = 0.0045), shorter hospital stay (8.00 +/- 2.68 days; P < or = 0.0001), and reduced hospital costs ($18,762 +/- $4,925; P < or = 0.0001). Operative time and complication rate were not affected. CONCLUSIONS: In selected patients with pediatric spinal deformity, experienced spinal surgeons can reduce blood loss, hospital stay, and costs by performing anterior and posterior spinal fusions sequentially under one anesthetic.

Benzothiazole hydroxy ureas as inhibitors of 5-lipoxygenase: use of the hydroxyurea moiety as a replacement for hydroxamic acid.

A novel series of N-[(2-benzothiazolylthio)alkyl]-N'-hydroxyurea derivatives (9-25) was synthesized and evaluated for biological activity as inhibitors of 5-lipoxygenase both in vivo (mouse zymosan peritonitis assay) and in vitro (Ca2+ ionophore-stimulated human peripheral blood leukocyte model). The compounds of this series were based on the corresponding hydroxamic acid derivatives (1, 3, 4, and 5) which were moderately active in vitro but inactive in vivo. A number of compounds in the hydroxyurea series exhibited oral activity for 5-lipoxygenase inhibition. Results of studies relating structure to in vivo and in vitro 5-lipoxygenase activity are reported.

Image reconstruction methods for the PBX-M pinhole camera.

We describe two methods that have been used to reconstruct the soft x-ray emission profile of the PBX-M tokamak from the projected images recorded by the PBX-M pinhole camera [Proc. Soc. Photo-Opt. Instrum. Eng. 691, 111 (1986)]. Both methods must accurately represent the shape of the reconstructed profile while also providing a degree of immunity to noise in the data. The first method is a simple least-squares fit to the data. This has the advantage of being fast and small and thus easily implemented on the PDP-11 computer used to control the video digitizer for the pinhole camera. The second method involves the application of a maximum entropy algorithm to an overdetermined system. This has the advantage of allowing the use of a default profile. This profile contains additional knowledge about the plasma shape that can be obtained from equilibrium fits to the external magnetic measurements. Additionally the reconstruction is guaranteed positive, and the fit to the data can be relaxed by specifying both the amount and distribution of noise in the image. The algorithm described has the advantage of being considerably faster for an overdetermined system than the usual Lagrange multiplier approach to finding the maximum entropy solution [J. Opt. Soc. Am. 62, 511 (1972); Rev. Sci. Instrum. 57, 1557 (1986)].