We reviewed three of our ongoing interdisciplinary studies in environmental carcinogenesis. In the case of snuff dipping and cancer of the oral cavity our data strongly support the epidemiological findings. Bioassays have demonstrated that oral snuff induces cancer of the oral cavity of rats, that the major carcinogens in snuff are NNN and NNK and that swabbing of the mouth with a solution containing NNN and NNK induces tumors in rats at the site of application. Biochemical studies are currently underway to provide further documentation that oral snuff is a carcinogen in humans. The major leukemogenic agent in cigarette smoke is benzene. Biomarker studies with t,t-MA, a urinary metabolite of benzene, have shown significantly higher uptake of benzene by smokers than by nonsmokers and benzene uptake by smokers of the order found in the urine of workers with low occupational exposure to benzene. These studies are being continued. Laboratory studies have supported the concept that smokers of low-yield cigarettes are more likely to have higher risk for lung adenocarcinoma than smokers of high-yield cigarettes who were more likely to develop squamous cell carcinoma. Smokers of low-yield cigarettes smoke more intensely and inhale more deeply to satisfy a need for nicotine. These changes in smoking patterns lead to relatively greater exposure of the bronchioalveolar regions and smaller bronchi to lung carcinogens, some of which have organ specificity and may well be responsible for induction of adenoma or adenocarcinoma of the peripheral lung. Biomarker studies are in progress to verify this hypothesis.

Adenocarcinoma↗

PubMedDate not supplied

The changing cigarette.

BACKGROUND: Epidemiologic surveys have revealed accelerated increases in adenocarcinoma but less rapid increases in squamous cell carcinoma of the lung among cigarette smokers in recent decades. Changes in the makeup of cigarettes and corresponding changes in smoke composition along with nicotine-compensating smoking patterns, such as the frequency of puff drawing and depth of inhalation, are suggested to have contributed to the observed epidemiologic profiles of these major histologic types of lung cancers. METHODS: The various changes in cigarette makeup leading to declining smoke yields from sales-weighted averages of 38 mg "tar" and 2.7 mg nicotine to 12 mg "tar" and 0.9 mg nicotine per cigarette are described. RESULTS: Higher nitrate content of tobacco blends is shown to be one of the major influences on lower smoke yields of carcinogenic polynuclear aromatic hydrocarbons (PAH) while causing increased yields of carcinogenic, tobacco-specific N-nitrosamines (TSNA). In vivo and in vitro bioassays incriminate PAH as inducers of squamous cell carcinoma, while TSNA are known to elicit primarily adenocarcinoma of the lung. CONCLUSIONS: The product changes, the smokers' dependence on nicotine which governs their smoking patterns, and the modified smoke chemistry support the hypothesis that differences in PAH and TSNA exposure may be linked to the observed different incidences of squamous cell cancer and adenocarcinoma of the lung.

Adenocarcinoma↗

PubMedDate not supplied

Nicotine regulates smoking patterns.

BACKGROUND: Since 1953, the sales-weighted average "tar" and nicotine yields of commercial cigarettes in developed countries have significantly declined. However, the risk for chronic obstructive pulmonary disease (COPD) and for cancer of the lung has not decreased; adenocarcinoma incidence even continues to rise faster than the rate of squamous cell carcinoma of the lung. Undiminished risk of cigarette smokers for COPD and lung cancer is largely due to more intense smoking and deeper inhalation of the smoke of "low-yield" cigarettes and to significant changes in the smoke yields of certain lung carcinogens. METHODS: Puff frequency, puff duration, and puff volume of cigarette smokers were determined by a microcomputer-assisted flow transducer. These parameters were then programmed into a smoking machine to generate mainstream smoke for quantifying nicotine and lung carcinogens. RESULTS: Simulating the human smoking characteristics increases the yields of "tar" and nicotine per cigarette two- to threefold above Federal Trade Commission-reported levels. Smoke yields of lung carcinogens like benzo[alpha]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone parallel those of nicotine and "tar." CONCLUSIONS: The way people smoke and the total number of cigarettes consumed daily determine the uptake, i.e., the administered dose of nicotine, other toxic, and genotoxic smoke constituents. It is important to communicate this to consumers rather than letting the smokers believe that they are truly smoking a cigarette of lower smoke yields when they choose "light" or "ultralight" products.

Behavior, Addictive↗

PubMedDate not supplied

Impact of filter cigarette smoking on lung cancer histology.

BACKGROUND: The rates of lung adenocarcinoma cancer have risen more rapidly than the rates of lung squamous cell cancer over the past 2 decades. METHODS: A case-control study was carried out to assess the impact of long-term filter cigarette smoking on the risk of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the lung. RESULTS: Odds ratios for SCC among subjects who had smoked only filter cigarettes were reduced relative to lifetime nonfilter cigarette smokers by 30% for men and by 60% for women, but no risk reduction was observed for AC of the lung. CONCLUSION: The predominance of AC over SCC may be due in part to the fact that smokers of very low yield cigarettes tend to compensate for the lower nicotine levels by inhaling more deeply and frequently, leading to greater exposure of the peripheral lung to the carcinogens in tobacco smoke, and in part to the increased concentration of nitrosamines that preferentially produce AC in laboratory animals.

Adenocarcinoma↗

PubMedDate not supplied

Surface coverage effects on defibrillation impedance for transvenous electrodes.

Transvenous defibrillation electrodes are constructed by wrapping conductive elements around an insulating base. However, these conductive elements do not cover the entire area of the base. The effects of varying the surface area coverage on the defibrillation impedance (DZ) are unknown. To understand the effects, four transvenous right ventricular test leads were specially fabricated. A ring design was used with 3 mm diameter cylinders equally spaced along a 5 cm length, ending 11 mm from the pacing tip. Three leads consisted of 4, 8, and 15 rings each of length approximately 2.4 mm so that the coverages were 20%, 40%, and 70%, respectively. The fourth lead used 8 rings of length approximately 1.2 mm each and had a coverage of 20%. DZ for each lead was obtained using three methods: (i) computer simulation; (ii) in vitro measurement in a tank; and (iii) in vivo measurement in nine dogs during defibrillation testing. The DZs from either of the first two methods correlated very well (r = 0.98) with the mean DZs from the third method, indicating that in vivo DZs can be predicted from computer and in vitro models. The study shows that: (i) at the same ring length, DZ decreases as coverage (number of rings) increases; (ii) at the same coverage, DZ decreases as ring length decreases; and (iii) in vivo, a statistically significant difference was observed in DZ between the leads with 20% coverage and the leads with higher coverages. No statistically significant difference was observed between leads with coverages > 40%.

Animals↗

PubMedDate not supplied

Cellular and molecular aspects of insect immunity.

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Animals↗

PubMedDate not supplied

The inducible antibacterial peptides of dipteran insects.

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Amino Acid Sequence↗

PubMedDate not supplied

Antimicrobial peptides in insects; structure and function.

Antimicrobial peptides appear to be ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. During the past 15 years a multitude of these peptides have been isolated largely from insects. In spite of great differences in size, amino acid composition and structure, most of the antimicrobial peptides from insects can be grouped into one of three categories. The largest category in number contains peptides with intramolecular disulfide bonds forming hairpin-like beta-sheets or alpha-helical-beta-sheet mixed structures. The second most important group is composed of peptides forming amphipathic alpha-helices. The third group comprises peptides with an overrepresentation in proline and/or glycine residues. In general, the insect antimicrobial peptides have a broad range of activity and are not cytotoxic. Despite a wealth of information on structural requirements for their antimicrobial activity, the mode of action of these peptides is not yet fully understood. However, some data suggest the existence of two types of mode of action: 1. through peptide-lipid interaction or 2. through receptor-mediated recognition processes. This review presents the main results obtained during the last four years in the field of antimicrobial peptides from insects with a special focus on the proline-rich and cysteine-rich peptides.

Amino Acid Sequence↗