a b s t r a c tInhaled aerosol dose models play critical roles in medicine, the regulation of air pollutants and basic research. The models fall into several categories: traditional, computational fluid dynamical (CFD), physiologically based pharmacokinetic (PBPK), empirical, semi-empirical, and "reference". Each type of model has its strengths and weaknesses, so multiple models are commonly used for practical applications. Aerosol dose models combine information on aerosol behavior and the anatomy and physiology of exposed human and laboratory animal subjects. Similar models are used for in-vitro studies. Several notable advances have been made in aerosol dose modeling in the past 80 years. The pioneers include Walter Findeisen, who in 1935 published the first traditional model and established the structure of modern models. His model combined aerosol behavior with simplified respiratory tract structures. Ewald Weibel established morphometric techniques for the lung in 1963 that are still used to develop data for modeling today. Advances in scanning techniques have similarly contributed to the knowledge of respiratory tract structure and its use in aerosol dose modeling. Several scientists and research groups have developed and advanced traditional, CFD, and PBPK models. Current issues under study include understanding individual and species differences; examining localized particle deposition; modeling non-ideal aerosols and nanoparticle behavior; linking the regions of the respiratory tract airways from nasal-oral to alveolar; and developing sophisticated supporting software. Although a complete history of inhaled aerosol dose modeling is far too extensive to cover here, selected highlights are described in this paper.

No abstract

Previous studies (1-9) have suggested that peripheral human T cells can be divided into two mutually exclusive functional subsets by the two monoclonal antibodies, OKT8 and OKT4. The OKT8+ subset does not provide helper activity but contains cells capable of suppressing B cell differentiation . Importantly, the suppression observed with OKT8+ cells requires the presence of radiosensitive OKT4 + cells . Potent helper activity is found in a radiosensitive OKT4' subset . Irradiated OKT4+ cells also induced B cell differentiation, but only at high ratios of T cells to B cells . In our previous studies (7), we also found that the addition of graded numbers of radiosensitive OKT4 + cells to B cells eventually decreased the net helper activity observed . These experiments raised the possibility that precursors of suppressor cells may be contained within the OKT4 + population .The current study was undertaken to further investigate the functional heterogeneity within the OKT4+ population. In particular, we asked whether OKT4 + cells could be induced to differentiate into immunoregulatory cells capable of suppressing B cell differentiation . In the experiments reported here, we observed that although in vitro pokeweed mitogen (PWM) -activated' OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression . This suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4 + population. These data emphasize the potential role of interactions of T cell subsets contained exclusively within the OKT4 + population in the immunoregulation of B cell differentiation . Volume 154 August 1981 459-467 Materials and MethodsLymphocyte Preparation and Isolation ofHuman T and B Cells . Fresh peripheral blood lymphocytes were isolated from consenting healthy human volunteers by Ficoll-Hypaque density gradient centrifugation . Highly enriched population of T and B cells were then isolated by methods previously described in detail (10) . In brief, human mononuclear cells were washed in minimum essential medium (Grand Island Biological Co ., Grand Island, N . Y .) containing 5% fetal calf serum (FCS ; Microbiological Associates, Bethesda, Md .) and then separated into surface Ig* Supported in part by grants AI-14969 and AI-11524 from the National Institutes of Health, and by The Robert Wood Johnson, Jr . Charitable Trust and The Arthritis Foundation .'Abbreviations used in this paper: C, complement ; E+ , E rosette positive ; FCS, fetal calf serum ; PFC, plaqueforming cells ; PWM, pokeweed mitogen. J . Exp . MED .

No abstract

No abstract