Chromosomal abnormalities in giant cell tumors of bone.

Cytogenetic analysis of short-term cultures from ten giant cell tumors of bone revealed clonal and nonclonal chromosome abnormalities in three tumors and nonclonal changes only in seven. None of the clonal aberrations, inv(21)(p11q21) in one tumor, +5 in another, and t(15q22q), dic(4;22)(p16;p1?), double minutes, dicentrics, and ring chromosomes present in three separate clones in the third tumor, were identical to previously reported clonal changes in giant cell tumors. Telomeric associations were found in five tumors. The telomeres of chromosome arms 19q and 15p were particularly frequently involved.     

Novel 6-Month Treatment for Drug-Resistant Tuberculosis,United States

The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose.     

Effects of mechanical signaling on plant cell cytosolic calcium

Mechanical signals are important influences on the development and morphology of higher plants. Using tobacco transformed with the Ca(2+)-sensitive luminescent protein aequorin, we recently reported the effects of mechanical signals of touch and wind on the luminescence and thus intracellular calcium of young seedlings. When mesophyll protoplasts are isolated from these transgenic tobacco plants and mechanically stimulated by swirling them in solution, cytoplasmic Ca2+ increases immediately and transiently up to 10 microM, and these transients are unaffected by an excess of EGTA in the medium. The size of the transient effect is related to the strength of swirling. Epidermal strips isolated from transgenic tobacco leaves and containing only viable guard cells and trichomes also respond to the strength of swirling in solution and can increase their cytoplasmic Ca2+ transiently up to 10 microM. Finally, the moss Physcomitrella patens containing recombinant aequorin exhibits transient increases in cytoplasmic Ca2+ up to 5 microM when swirled in solution. This effect is strongly inhibited by ruthenium red. Our data indicate that the effect of mechanical stimulation can be found in a number of different cell types and in a lower plant as well as tobacco and suggest that mechanoperception and the resulting increase in cytoplasmic Ca2+ may be widespread.     

Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats.

BACKGROUND: Genetic background has a major influence on the manifestation of multifactorial diseases such as hypertension in which severe complications may be caused through an interaction with additional factors, which may be genetically determined. We have previously described a genetic model of malignant hypertension (MH) in rats carrying the mouse Ren2 gene (TGRmRen2-27), in which the phenotype is dependent on the genetic background. METHODS: Using a single homozygous TGRmRen2-27 male as transgene donor, we produced two F1 populations with (a) 100% penetrance of MH in progeny heterozygous for the Fischer F344 genetic background and (b) 58.5% penetrance in progeny heterozygous for the Lewis genetic background. To identify the modifier loci affecting the phenotype, a cohort of 252 males was produced by breeding the same single male with Fischer-Lewis F1 females. The progeny were phenotyped for clinical and pathological features of MH. RESULTS: Genome-wide screening and quantitative trait loci (QTL) analysis identified two loci, on chromosome 10 (LOD 4.4) and on chromosome 17 (LOD 3.9) close to the Ace and At1 genes, respectively, which contribute to the lethal MH phenotype. Their influence on mortality was consistent with a multiplicative effect of the two loci. In addition, we found higher plasma angiotensin-converting enzyme activity in progeny receiving the Fischer allele than in progeny receiving the Lewis allele (123.5 +/- 9.5 vs. 91.8 +/- 4.9 U/liter, P < 0.01), suggesting the association of angiotensin-converting enzyme and MH. CONCLUSIONS: Our study demonstrates the application of a transgene as a "major gene" to facilitate the identification of modifier loci, which can affect the phenotype of MH, and reveals Ace and At1 as candidate genes involved in the manifestation of the MH phenotype.     

Case-control study of bladder cancer and chlorination by-products in treated water (Ontario, Canada)

Chlorine is by far the most commonly used chemical for the disinfection of water supplies in North America. However, chlorine reacts with organic material in the raw water producing a number of halogenated hydrocarbon by-products. This population-based case-control study in Ontario, Canada examined the relationship between bladder cancer and exposure to chlorination by-products in public water supplies. Residence and water source histories and data from municipal water supplies were used to estimate individual exposure according to water source, chlorination status, and by-product levels (represented by trihalomethane [THM] concentration). Exposures were estimated for the 40-year period prior to the interview, using 696 cases diagnosed with bladder cancer between 1 September 1992 and 1 May 1994 and 1,545 controls with at least 30 years of exposure information. Odds ratios (OR) adjusted for potential confounders were used to estimate relative risk. Those exposed to chlorinated surface water for 35 or more years had an increased risk of bladder cancer compared with those exposed for less than 10 years (OR=1.41, 95 percent confidence interval [CI]=1.10–1.81). Those exposed to an estimated THM level50 g/liter for 35 or more years had 1.63 times the risk of those exposed for less than 10 years (CI=1.08–2.46). These results indicate that the risk of bladder cancer increases with both duration and concentration of exposure to chlorination by-products, with population attributable risks of about 14 to 16 percent. Chlorination by-products represent a potentially important risk factor for bladder cancer.Dr King is with the Department of Community Health and Epidemiology, Queen's University, Kingston, Ontario, Canada. Dr Marrett is with the Ontario Cancer Treatment and Research Foundation and the Department of Preventive Medicine and Biostatistics, University of Toronto Canada. Address correspondence to Dr King, Department of Community Health and Epidemiology, Queen's University, Kingston, Ont., Canada, K7L 3N6. This research was funded by Health Canada and also was supported by the National Health Research and Development Program through a fellowship to W.D.K.     

Biological monitoring and risk assessment in occupational settings

Summary and conclusion In summary, we have found biomonitoring to be a valuable adjunct to medical surveillance in a number of situations. Although the potential benefits are relatively easy to demonstrate, clear guidance must be provided to assure that no harm will result from a biomonitoring program. A critical step in this regard is attention to the communication of objectives and results. This is especially true where biomonitoring of carcinogenic substances or surrogate measures for these substances are being considered. In such situations, action levels are helpful for interpretative purposes and immediate decision-making, but not for determining individual health risks. However, the quantitative results may be suitable for use in future health studies and risk assessments.Work presented at the 23rd Congress on Occupational and Environmental Health in the Chemical Industry (Medichem 1995) The Chemical Industry as a Global Citizen — Balancing Risks and Benefits, 19–22 September 1995, Massachusetts Institute of Technology, Cambridge, Massachusetts