A case-referent study of lung cancer, occupational exposures and smoking. II. Role of asbestos exposure

In a hospital-based case-referent study of 176 incident lung cancer cases, ascertained during a five-year period from two county hospitals, the role of asbestos exposure and smoking has been studied. Information on asbestos exposure was obtained from personal interviews, and allocated to four exposure categories, according to the intensity and duration of the exposure. Twenty-five percent of the cases and 10% of the referents had been moderately to heavily exposed to asbestos during their working career. A statistically significant trend in risk ratio related to the degree of exposure was observed, with a more than fourfold risk among the heavily exposed. The strongest association was found between asbestos exposure and small cell carcinoma, and the weakest association between asbestos exposure and adenocarcinoma. Very high risk ratios were observed among asbestos-exposed subjects who were heavy smokers, and the interaction observed between asbestos and smoking conformed more closely to a multiplicative model than to an additive one. The results suggest that the observed association between lung cancer and occupational exposures in this study was, to a large extent, due to asbestos exposure. Information on such exposure was missing in 90% of the medical records of these patients.     

Oral hypoglycemic agents. Pyrimido[1,2-a]indoles and related compounds.

A series of pyrimido[1,2-a]indoles were synthesized and studied for their hypoglycemic activity following oral administration at a standard dose of 100 mg/kg to fed rats. The effect of 10-alkoxyalkyl, 10-alkyl, 10-aryl, and 3,3-dialkyl substitution on the activity of 10-hydroxypyrimido[1,2-a]indoles was investigated. Relative potencies of a number of the most active compounds were defined by three-point dose-response studies. The most potent compounds were those with either 3,3-dimethyl substituents, compounds 21, 22, and 38, or 3,3-spirocyclohexane substituents, compounds 39 and 49. 10-Aminopyrimido[1,2-a]indoles were in general less active than the 10-hydroxy analogues, and potency was further decreased by derivatizing the 10-amino group. The most potent 10-amino derivatives were 57 and 58.     

Locomotor strategies before independent walking: prospective study of 50 mentally retarded children.

To investigate the association between pre-walking locomotor strategies and psychomotor developments in children with mental retardation (MR), 50 children with non-specific MR were included in this study. There were 29 boys and 21 girls, 96% of whom had moderate to severe MR. They were followed from 4-53 months to 25-99 months of age, and their follow-up periods ranged from 10 to 48 months (mean 30 months). According to the pre-walking locomotor strategies, these children were categorized into three groups: the crawling group (n = 34) who used crawling or creeping as their main locomotion pattern before independent walking; the shuffling group (n = 9) who used shuffling prior to independent walking; and the direct-walking group (n = 7) who did not have any other locomotor strategies except rolling. In almost all motor developmental milestones, children in the direct-walking group developed earlier than those in the crawling and shuffling groups. Children in the crawling group had more advanced developments than those in the shuffling group. The difference in the mean ratio developmental quotients of the Bayley Mental Scale among the three groups was not significant. The present study showed that crawling may not be a necessary prerequisite for early ambulation or better cognitive function in MR children.     

High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines.

Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines.     

Real-time PCR for quantitation of porcine reproductive and respiratory syndrome virus and porcine circovirus type 2 in naturally-infected and challenged pigs

Real-time PCR assays were developed for quantitative detection of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2). The established real-time PCR for the quantitation of PRRSV cDNA and PCV2 DNA were found to be in the 9-log(10) linear dynamic range with excellent linearity and reliable reproducibility. Using these techniques, the distribution and quantitation of PRRSV and PCV2 in naturally infected and challenged pigs were investigated. The viral concentrations were expressed as the mean log(10) viral DNA or cDNA copy numbers per mg or ml of tested samples. For pigs infected naturally with both viruses, the lung, spleen, tonsil and lymphoid organs had the highest viral burdens with ranges from 5.73 to 8.38 and 5.65 to 6.91 for PRRSV and PCV2, respectively. The injection of formalin-inactivated Salmonella choleraesuis emulsified in complete Freund's adjuvant 1 week before and after the inoculation of both viruses resulted in PRRSV replication enhancement 2 weeks post-challenge. However, this facilitated the clearance of PRRSV 4 weeks post-challenge. Results from this study show that the established quantitative PCR could be a useful tool when applied to vaccine development and pathogenesis studies in the future.     

Genes for immunodominant protein antigens are highly homologous in Mycobacterium tuberculosis, Mycobacterium africanum, and the vaccine strain Mycobacterium bovis BCG.

The relatedness of immunodominant protein antigens in Mycobacterium tuberculosis, M. africanum, and M. bovis BCG was investigated by comparing the genes that encode major protein antigens in M. tuberculosis with their counterparts in the other two mycobacteria. Genes encoding homologs of M. tuberculosis major protein antigens were isolated from M. africanum and M. bovis BCG by constructing lambda gt11 recombinant DNA expression libraries and screening them with murine monoclonal antibodies and DNA probes. The antibodies were directed against four major protein antigens of M. tuberculosis with molecular masses of 71, 65, 19, and 14 kilodaltons. The isolated M. africanum and M. bovis BCG DNA clones were mapped with restriction endonucleases, and the maps of the mycobacterial genes were confirmed by Southern analysis of mycobacterial genomic DNA. The restriction maps of DNA containing the four genes in M. tuberculosis, M. africanum, and M. bovis BCG are identical, indicating that the immunodominant proteins that they encode are highly homologous in the three mycobacteria. Thus, the immunity against tuberculosis engendered by M. bovis BCG vaccination could be provided, at least in part, by the immune response to these homologous antigens.