PATHOLOGY
C. EXPERIMENTAL STUDIES (19) Effect of Cortisone on Bone
Worker: E. Storey
The investigation of changes in the bone of both rabbit and rat has been continued. Although osteoporosis is normally produced in the rabbit, sclerosis occurs in the rat. This difference has been shown to be due to variations in absorption and utilization of calcium in the two animals. I t has been possible, using appropriate diets, to induce porosis in the rat which thus becomes a valuable means of studying the action of cortisone. These investigations are proceeding.
(20) Effect of Aminoacetonitrile on Bone Fractures in Rats Workers: E. Storey and G. Varasdi
The inhibiting action of aminoacetonitrile ( A A N ) on connective tissues is best demonstrated on actively growing tissues. In fractures of bones of rats, large masses of soft callus arc formed. Previous reports of the literature have been misleading since, to minimize technical difficulties, administration of A A N has been discontinued to allow bones to thicken before manipulations associated with histo- logical examination have been carried out. The observations made have been recorded and published.
(21) Effect of Aminoacetonitrile and Cortisone on Soft Tissues Workers: J. V. Hurley, E. Storey and Kathryn N. Ham
Both aminoacetonitrile (AAN) and cortisone produced demon-
190 F A C U L T Y OF M E D I C I N E
strable changes in the growing connective tissue (granulation tissue) in the wall of aseptic abscesses (induced by turpentine injection) i n the rat. A A N results in a persistence of amorphous intercellular substance and a delay in the formation of mature collagen in the abscess wall; fibroblast proliferation is not affected. Cortisone grossly delays the proliferation of fibroblasts. The effects of A A N and cor- tisone are thus independent of each other.
(22) Ear Chamber Technique in Rabbits Worker: I. K. Buckley
Observations on changes occurring in tissues following mild (electrical) injuries have demonstrated the development of globules in relation to various connective tissue cells. Serial photomicrographs have shown that these occur on the surface of the cells, may be separated and remain in a recognizable form in thc serum or tissue fluids for some time. Examination of tissue freshly removed from the body and of tissue cultures show that these globules arise from a variety of cells. The nature of the material is still uncertain and investigation into this is continuing.
(23) Liver Changes Following Acute Heliotrine Poisoning Worker: G. S. Christie
After the administration of the pure alkaloid to rats, thc animals were killed at various times, to investigate the progress of the toxic change in liver tissue. Papers have been published on the changes in respiratory enzyme activity, thc loss of which was found to be due to a depletion of available D P N ; and on the histological changes considered to be significant in elucidating the mode of action of the toxin. Further work is in progress on the changes in oxidative phos- phorylation and in nuclear D P N phyrophosphorylase activity. Follow- ing the demonstration of hcliotrinc's mutagenic properties, experi- ments are in progress to test its ability to induce congenital abnor- malities in the rat.
(24) Factors Influencing Healing of Wounds Worker: A. M. Cuthbcrtson
Serial observations were made on skin wounds in thc rat with precise measurements at various stages of healing. Changes in con- nective tissue (with contraction) and changes in vascularity and epithelial proliferation were observed. The proportion of tissue con- traction to epithelial growth was determined and thus the mechanism of healing studied. Changes occurring with cortisone administration and vitamin C deprivation were also observed and compared.
l ' A T H O L O C Y 191
(25) Production of Glass Knives for Electron Microscopy Worker: S. Weincr
The production of glass knives has presented a number of technical problems so that a yield of only a small proportion of thc number fabricated is generally accepted as a normal feature. A more precise technique which enables a high proportion of technically suitable knives to bc obtained is being developed.
(26) Preneoplastic Changes in Rat Liver Worker: P. E. Hughes
When rats are fed carcinogenic dyes, at a stage before tumours develop, islands of morphologically normal cells are found which have lost their affinity for fluorescein-globulin stains. A group of substances chemically related to 4: dimethylaminoazobenzene were tested and a correlation was found between thesc islands of 'loss of staining' and thc actual carcinogenicity of the dyes. Thc islands are regarded as precancerous in character.
(27) Production of Bone Tumours
Workers: E. S. J. King and G. Varasdi
Although bone tumours are readily produced in the rabbit by bone plantation of pellets containing beryllium oxide or 20-Mcthyl- cholanthrene, these seldom occur in rats. Tumours of bone and of tissues in the vicinity of bone have been developed in Sprague- Dawlcy strain rats following introduction of these materials into ihe upper part of the tibia.
(28) Production of Thyroid Tumours Worker: C. J. Louis
As an adjunct to the study of naturally-occurring thyroid tumours in man by thc fluorescein-globulin staining technique, neoplasms have been produced in rats by administration of thiouracil.
(29) Production of Bowel Tumours Workers: E. S. J. King and G. Varasdi
Intestinal tumours occur rarely, following administration of the difficult carcinogens which commonly give rise to tumours in various other organs. Parenteral injection of 33': dimethyl-4-aminodiphenyl and 32': dimethyl-4-aminodiphenyl is followed by a considerable yield of polyps and carcinomas of the alimentary canal, principally in the small and large intestines. Tumours of other organs occur either in association with, or independently of, thesc bowel growths.
Thc study is still in progress.
192 F A C U L T Y OF M E D I C I N E
(30) Study of Transplantable Tumours Workers: E. S. J. King and G. Varasdi
Some transplantable tumours have been developed following use of chemical carcinogens of the polycyclic hydrocarbon types. Those occurring in randomly bred strains did not persist through many transplantations, but those in line-bred strains were transplantable consistently and in practically all cases. Significant differences had been found in different substrains with recognized transplantable growths such as the Walker carcinoma 256. These growths have been used for other investigations.
(31) Production of Mammary Tumours in Dogs Worker: Anne G. Jabara
The study of effects of carcinogens of the acetamidofluorene type have been continued. There have been further examples of reticulo- endothelial proliferations but tumours of other tissues have not been observed.
(32) Effects of Diethylstilboestrol in Dogs Worker: Anne G. Jabara
During the experiments with various carcinogens, the possible co- carcinogenic effects of hormones were also noted. Diethylstilboestrol was specifically employed. Gross effects were noted in several organs:
skin changes with loss of hair, abdominal herniae and changes in some viscera were prominent. These are being investigated further.
(33) Testing of Carcinogens Worker:. (Mrs) Stella Ovenden
The testing of various potentially carcinogenic materials including those from heated foods have been continued. Mice have been em- ployed principally and a number of strains have been used.
(34) Fluorescein-Globulin Stains
Workers: E. S. J. King, P. E. Hughes and C. J. Louis
Following the demonstration that fluorescein-globulin obtained by using normal rabbit scrum (as opposed to antibody-containing serum) could be used in the differential staining of malignant and normal tissues, an extensive study of a series of globulins was carried out.
A l l reacted in the typical manner and it was found that this applied also to conjugates prepared from serum of the same species as the tissue stained and even to serum from the same animal. This was thus further evidence for the simple physico-chemical, as opposed to the serological, explanation of the phenomenon of fluorescein- globulin staining.
P A T H O L O G Y 193
(35) Carcinogenicity of Brown Coal Tar
Workers: G. S. Christie and N. E. W. McCallum
The study of the relative carcinogenicity of tars from brown and black coal has been completed. The carcinogenicity of the brown coal tar is demonstrably less than that of thc black coal tar in mice.
The results have been published with the recommendation that the former should be employed in pharmaceutical preparations intended for prolonged application to human skin.
(36) Developmental Anomalies Worker: C. R. Green
Thc production of developmental abnormalities in rats by means of irradiation at various periods during gestation has been continued.
Microdissection of the foetuses has demonstrated a series of anoma- lies; this work is being continued and histological studies are being made. The effects of hcliotrine and dimethylnitrosaminc are being investigated.
(37) Studies of Blood Alcohol
Workers: N. E. W. McCallum and J. G. Scroggie
Owing to the dearth of precise information regarding thc rates of absorption and the exclusion of ethyl alcohol (and thus of the re- lation of blood alcohol levels to the amount ingested), a series of experiments has been carried out and the influence of concentration and rates of ingestion of blood levels have been recorded. The in- vestigation is proceeding.
(38) Studies of Alcohol in the Breath
Workers: N. E. W. McCallum and R. C. Bayly
The observation that blood alcohol levels change considerably and, for a time, rise after ingestion of alcohol, has made necessary the rapid and easy obtaining of specimens for analysis. I t was also essential that this should be done in a simple manner. A comparison of the results obtained from analysis of the breath and urine with thc blood is being made. The value and accuracy of special apparatus
—the breathalyser—is being examined. Thc small discrepancies be- tween the results of breath and blood analyses are being studied.
D. CHEMICAL INVESTIGATIONS