Co-operation between follicular ornithine decarboxylase and v-Ha-ras induces spontaneous papillomas and malignant conversion in transgenic skin

Ornithine decarboxylase (ODC) is aberrantly regulated in tumor cells and results in high basal levels of ODC and polyamines in many epithelial tumors. To determine if elevated ODC/polyamine levels can co-operate with a mutant Ha-ras gene in mouse skin tumorigenesis, double transgenic mice were generated by breeding K6/ODC transgenic mice with TG.AC v-Ha-ras transgenic mice. A K6 keratin promoter drives the ODC transgene in K6/ ODC transgenic mice, which results in elevated ODC/ polyamine levels directed to the outer root sheath cells of hair follicles. TG.AC transgenic mice carry a v-Ha-ras transgene while still retaining two normal c-Ha-ras alleles. Transgenic mice that possess only the K6/ODC or the v-Ha-ras transgene did not develop tumors unless treated with either a carcinogen or a tumor promoter, respectively. However, a high percentage of double transgenic mice possessing both the K6/ODC and v-Ha-ras transgenes developed spontaneous tumors. All tumors were well-differentiated keratoacanthomas, some of which progressed to carcinomas within 2 months. The development and the maintenance of these ODC/ras tumors was ODC-dependent since alpha-difluoromethylornithine (DFMO), a specific ODC inhibitor, prevented the formation and caused the regression of these tumors. These findings indicate that ODC overexpression and an activated Ha-ras are sufficient to produce a high rate of malignant transformation in an animal model. The ODC/ras double transgenic mouse provides a simple in vivo model without the use of chemical carcinogens or tumor promoters in which to test downstream effectors that play a key role in mediating the development of epithelial tumors resulting from the cooperation between ODC and v-Ha-ras.     

Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance

BACKGROUND: Drug-resistant tuberculosis threatens efforts to control the disease. This report describes the prevalence of resistance to four first-line drugs in 35 countries participating in the World Health Organization-International Union against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug Resistance Surveillance between 1994 and 1997. METHODS: The data are from cross-sectional surveys and surveillance reports. Participating countries followed guidelines to ensure the use of representative samples, accurate histories of treatment, standardized laboratory methods, and common definitions. A network of reference laboratories provided quality assurance. The median number of patients studied in each country or region was 555 (range, 59 to 14,344). RESULTS: Among patients with no prior treatment, a median of 9.9 percent of Mycobacterium tuberculosis strains were resistant to at least one drug (range, 2 to 41 percent); resistance to isoniazid (7.3 percent) or streptomycin (6.5 percent) was more common than resistance to rifampin (1.8 percent) or ethambutol (1.0 percent). The prevalence of primary multidrug resistance was 1.4 percent (range, 0 to 14.4 percent). Among patients with histories of treatment for one month or more [corrected], the prevalence of resistance to any of the four drugs was 36.0 percent (range, 5.3 to 100 percent), and the prevalence of multidrug resistance was 13 percent (range, 0 to 54 percent). The overall prevalences were 12.6 percent for resistance to any of the four drugs [corrected] (range, 2.3 to 42.4 percent) and 2.2 percent for multidrug resistance (range, 0 to 22.1 percent). Particularly high prevalences of multidrug resistance were found in the former Soviet Union, Asia, the Dominican Republic, and Argentina. CONCLUSIONS: Resistance to antituberculosis drugs was found in all 35 countries and regions surveyed, suggesting that it is a global problem.     

Regiochemistry of Azide Additions to [70]Fullerene

In this paper we report for the first time on the reaction of C₇₀ with alkyl azides and show that the [3+2]-cycloaddition occurs preferably at bond 7 followed by bond 5 to give two regioisomeric A/B-triazolines and one C/C-triazoline Thermal extrusion of N₂ from these triazolines leads to open [5,6]-bridged iminofullerenes as A/A- and B/C-isomers as well as to the ring closed [6,6]-bridged analogues as A/B- and C/C-isomers. These results are in line with the corresponding thermal reaction of C₇₀ with diazomethane.     

Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal cases and controls

Leptin reflects the amount of energy stores, regulates energy balance and is associated with circulating levels of reproductive hormones and insulin-like growth factor-I (IGF-I). Breast cancer has also been associated with obesity, reproductive hormones and circulating IGF-I levels. To determine whether leptin is involved in the etiology of breast cancer, we compared serum leptin levels in 83 cases of pre-menopausal carcinoma in situ of the breast and 69 healthy controls recruited in Massachusetts. Serum leptin levels were 13.69 + 1.3 ng/ml in cases and 16.03 + 1.7 ng/ml in controls. Data were also analyzed using multiple logistic regression with adjustment for known risk factors for the development of breast cancer as well as anthropometric, demographic and hormonal variables, including estradiol, prolactin, IGF-I and IGF-binding protein-3. Odds ratios were 1.75 (95% CI, 0.73-4.21) for the second control-defined tertile and 1.54 (0.46-5.16) for the third control-defined tertile relative to the first. Thus, leptin does not appear to increase the risk of pre-menopausal breast cancer in situ substantially.