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NO. 573R1. . .. . :. Activated: 10 66 'IiE COUNCIL FOR TCBACCO RESEARCH - U.S.A. NEW YORK. N.. Y. 10017 Application For Renewal of Research Grant :Hastings Professor of Medicine and Pathology, USC School of Medicine 1. NameofInvestigator(s):Gndudetitleanddegrees) Clayton G. Loosli, Ph.D., M.D. 2025 Zonal Avenue, Los Angeles, California 90033 ' The Attenc}ing Staff Association Los Angeles County General Hospital 1200 North State Street ° Los Angeles, California 90033 LUNG TISSUE REACTIONS TO AIRBORNE CHEMICAL AND BIOLOGICAL AGENTS 4. Proposed Renewal Starting Datet (Anniversary or other) Oc tober 1, 1967' after which the mice began to die. The rapidity of development of lung lesions is directly related to the concentration of N02 in the air. In order to observe what the lung c anges were iTce in the final stages*before death, the higher concentration was chosen. This coming year, with the availability of several separate exposure chambers, comparative studies will be made of the lungs of animals exposed to on animals exposed to 38 to 42 ppm over periods from 1 day to 8 weeks,, The objectives are the same. This past year the pathogenesis of lung changes in mice exposed'to atmospheres of N02 in concentrations of 10, 20, 40 ppm have been made. Most of our studies have been made S. Discuss any Importanti Changes or Additions to Objectives or Specific Aims: the three concentrations (10, 20, 40 ppm of NOZ) by histological, histo- chemical, biochemical and electronmicroscopic procedures. -.Studies of the lungs and other organs (liver, spleen, kidney, L adrenal, brain, heart) of mice exposed to different concentrations of So2 will be continued. Studies of the pathogenesis of PR8 influenza A virus infections in N02 and S02 exposed animals will be continued. An attempt will be made to elucidate the mechanism(s) of increased resistance of N02 exposed mice to influenza A infections. The patho- genesis of PR8 inflvenza A airborne virus infections in S02 mice will be studied to determine if they, as do N02 exposed mice, develop a resistance. The susceptibility of N02 and S02 exposed mice to airborne staphy- lococcus aureus will be continued and, in addition, the pneumococcus and hemophilus influenza organisms will be employed. 6. Givea 8rief Statement ofyourHMorking Hypothesis if altered or modified: There is no change in our working hypothesis. Our aim is to define the lesions due to NO2 and SO exposure, the 1'esions ue to bactc>ria and influenza A virus, an `t e e ec of super imposition of these lesions in the same animal. N 0 0 w CA ~ C deem `_ .

7. Changes or Additions to Experimental Design and Procedures: (Attach Separate Pages) ~,"F~>~'M14 zThere is no basic change in the experimental design and procedures. - A full complement of skilled and experienced technical personnel have been procured in histology, biochemistry, histochemistry, bacteriology, d 1 ' f t I b l h ronmicroscopy. viro ogy an e ec e ieve t e great importance o :our study rests in the simultaneous study of the histological, biochem- 'ical and histochemical changes in the lungs and other organs of mice `subjected to N02 and 802 exposure alone and in combination with .exposure to the above named viruses and bacteria. This past year oxygen consumption, alkaline and acid phosphatase and lactic dehydrogenase measurements have been made in N02 exposed animals. This coming year glycolysis, lipid metabolism and anti- trypsin activity will be measured in the lungs of N02 exposed animals, as well as urinary steroids and transaminase in the serum. Generally, all the facilities to carry on the above studies are chambers in which to expose mice to different concentrations of NO2 available. The output can be greatly increased by having several - and S02 for different periods of time. This will allow us to make short term observations while allowing other mice to be observed estimated that very satisfactory chambers can be constructed for $500 each, including fans, flexible exhaust piping, etc. :for longer periods of time at low levels of NO2 and S02. It is Also, a drying oven is needed in the biochemistry section to facilitate the analysis of tissues. 9. Changes in Penonnel'w•rth BiographicaliSketches o6new Personnel (append) There are no changes in personnel. Ramon D. Buckley, Ph.D., Assistant Professor of Biochemistry, directs the biochemical studies, and is co-director with salary support from the NIH grant. Between the two grants he devotes 80 percent of his time to the studies. The technical personnel are all experienced. 10. Publicotions or Papers in Press resulting from the Projqct or closely related'work No papers have been published or are in press as yet from studiess supported by this grant.

1, 6udgat(ior coming year) } 0. Sclarics (P rsonnol by names or category) <' Professionot -. . . , _ '-Clayton G. Loosli, M.D.,* Ph.D. _ 50• None _,*Ramon D. Buckley, Ph.D. 75. None Edna M. Stone, M.S., Histology-Histochem. John Hardy, B.S., Electronmilcroscopist 100 7,560 .Ernestine Pruiet, B.S., Bacteriologist 100 7,119 Mary Bresnahan, B.S., Virologist 100 $7,560 *Elizabeth Vinceguerra, B.S., Biochemist 100 None *Johnnie Bilbrew, Jr., Animal Caretaker 100 None *SyIviaMoss, M.S., Histol-Biochemist . 100 None Technical Technician 100 8,820 Fringe Benefits, 8% 2,485 S b T 1 - 33 544 4) u o.o $ , t 1- NI= *P id f page ro:n gran a S- Consumob'.a Supp!1as (iist b•/ cotegoriesj - Glassware......... .................. ... 500 Gen.&spec.chem.reagents,enzymes,cofactors 1,000 Supplies, histol., bacteriol. & virol.... 2,500 Mice and'rabbits........... - ........... 6..$ 2,000 Dry ice, wa er e-ionizers, e c.......... . 7,000' SWb-TOPOI' . 7 , 000 -. Travel for Principal Investigator C. OtGer EXC3:1Sa. C:e.'.:Iza}' and Dr. Buckley ........ ................$ 750 Service, Spinco, spectrophotometers, etc. 1,000 .chambers•Wlt1 motors, fans, etc. Construction of three exposure Sub-Totat 3,000 D. Permener.t:cuipmeat ite:nixe) I,5-00 E. Gver:acd(15%of:,=3=C) 15% of $43,544 6,532 Total 51,576 i undea:ccd that tnenpplkcct and insatu:ior.ei aficers fcr a g:or.t have recc end'found eccep:cble the Cc.,ncii: "S:o:ernent of ?oiity Cor.:oining Conci:ions end Tt:rms Under Wnicn 2re;ec: vrants Are N.eda:" Signatura Mj,; ~~ ~~~'• ZrLY~t~ f" ~ Di,.< e: ,.i.o _ - , x 17 5 225-1511, Exi<. 203 Off' f h 1 i'l i 6 ( 1 1 . 1 Id:ip}a :J 225-31i15 YU 1 . • I , Y 01 Vrr.. O S. Gbtlt Ext. 3826 Taic~4onc •Business Manager Repairs on equipment, office supplies, publication costs, misc, supplies ....... 1,250

list financial support for research from all sources, including own institution, for this and/or reiated research projects. Source I Duration Jan-Dec 1967 1968 1969