MOBILIZATION OF BASOPHILE SUBSTANCE (RIBONUCLEIC ACID) IN THE CYTOPLASM OF LIVER CELLS WITH THE PRODUCTION OF TUMORS BY BUTTER YELLOW.

Butter yellow (dimethylaminoazobenzene) causes degenerative changes in liver cells accompanied by chromatolysis of cytoplasmic structures that stain with basic dyes because they contain ribonucleic acid. These changes are profoundly modified by the protein content of the diet. Chromatolysis is succeeded by focal regeneration with reaccumulation of ribonucleic acid in the cytoplasm of liver cells; these foci of basophile hyperplasia have their origin in the parenchyma surrounding portal spaces and consist of cells arranged in columns or as tubules with lumina.

FRACTIONATION OF MAMMALIAN LIVER CELLS BY DIFFERENTIAL CENTRIFUGATION : II. EXPERIMENTAL PROCEDURES AND RESULTS.

1. A method is described whereby the major components of liver suspensions are segregated according to size into three main fractions: (a) a large granule fraction composed of elements approximately 0.5 to 2 micro in diameter; (b) a microsome fraction composed of submicroscopic elements approximately 80 to 150 mmicro in diameter; and, (c) a supernate fraction containing the soluble components of the extract.

FRACTIONATION OF MAMMALIAN LIVER CELLS BY DIFFERENTIAL CENTRIFUGATION : I. PROBLEMS, METHODS, AND PREPARATION OF EXTRACT.

1. Materials and technical procedures involved in the preparation of liver suspensions have been described and discussed. 2.

LOCALIZATION OF RIBONUCLEIC ACID IN THE CYTOPLASM OF LIVER CELLS.

The attempt has been made to determine the character of the basophile material that occurs normally in the cytoplasm of liver cells and accumulates in association with the hyperplasia of liver cells and of newly formed bile ducts when the azo dye butter yellow is administered to white rats. This substance in the normal liver cells, in the parenchymatous foci of basophile hyperplasia that are precursors of hepatomas, and in the hyperplastic basophile ducts that precede the cholangiomas produced by butter yellow has the characteristics of ribonucleic acid. It absorbs ultraviolet radiation of wave length 2537 A.

THE PREPARATION OF SECTIONS OF GUINEA PIG LIVER FOR ELECTRON MICROSCOPY.

1. A method is described whereby sections of guinea pig liver cells can be prepared for electron microscopy after fixation. 2.

FACTORS AFFECTING THE GROWTH OF TUBERCLE BACILLI IN LIQUID MEDIA.

1. Certain water-soluble esters of long chain fatty acids (in particular of oleic acid) favor submerged and diffuse growth of mycobacteria throughout the depth of synthetic liquid media. 2.

THE ACTIVATION OF SKIN GRAFTS.

Rabbit skin rendered hyperplastic by various agents showed less tendency than normal skin to contract when sliced off, and when used for grafts it united with the bed more rapidly and was vascularized sooner. The stimulated epidermis proliferated practically at once, and abundantly, to cover adjacent raw surfaces. Also the donor area healed much more swiftly than usual and became infected less often.

SUPPRESSION OF GROWTH OF BROWN-PEARCE TUMOR CELLS BY A SPECIFIC ANTIBODY : WITH A CONSIDERATION OF THE NATURE OF THE REACTING CELL CONSTITUENT.

Experiments are reported in detail which show that an antibody which appears in the blood of certain rabbits implanted with the Brown-Pearce tumor or injected with cell-free extracts of it is capable of suppressing the growth of the tumor cells under a variety of experimental conditions, the effects of the antibody being wholly distinct from those of unknown factors that frequently bring about regression of the growth. The implications of the findings are discussed with particular reference to facts indicating that the distinctive cell constituent with which the antibody reacts may play a significant part in the proliferative activities of the Brown-Pearce tumor cell.

SOME PROPERTIES OF PROTOPLASMIC GELS : I. TENSION IN THE CHLOROPLAST OF SPIROGYRA.

The chloroplast of Spirogyra is a long, spirally coiled ribbon which may contract to form a short, nearly straight rod. This happens under natural conditions and it can also be produced by a variety of inorganic salts and by some organic substances. It also occurs when the chloroplast is freed by centrifugal force from the clear peripheral protoplasm which is in contact with the cellulose wall.

ENDURING IMMUNITY FOLLOWING VACCINATION OF MICE WITH FORMALIN-INACTIVATED VIRUS OF RUSSIAN SPRING-SUMMER (FAR EASTERN, TICK-BORNE) ENCEPHALITIS : CORRELATION WITH SERUM-NEUTRALIZING AND COMPLEMENT-FIXING ANTIBODIES.

A single course of two intraperitoneal injections of formalin-inactivated virus of Russian spring-summer encephalitis induced in albino mice a solidly immune state which endured almost throughout life. Active virus is therefore not essential for the production of a high degree of lasting immunity. The immune response to vaccination consists of resistance to peripherally introduced active virus and development of circulating antibody.

WATER RELATIONS IN THE CELL : I. THE CHLOROPLASTS OF NITELLA AND OF SPIROGYRA.

Chloroplasts may contract under natural conditions and give up water to the rest of the cell, thus indicating changes in metabolism or constitution. Such contractions may be produced experimentally. In Nitella the chloroplasts are ellipsoid bodies which, under natural conditions, may contract to spheres with a loss of volume.

EFFECTS OF HYDROXYL ON NEGATIVE AND POSITIVE CELLS OF NITELLA.

Remarkable changes are brought about by KOH in transforming negative cells of Nitella (showing dilute solution negative with KOH) to positive cells (showing dilute solution positive with KOH). NaOH is less effective as a transforming agent. This might be explained on the ground that the protoplasm contains an acid (possibly a fatty acid) which makes the cell negative and which is dissolved out more rapidly by KOH than by NaOH, as happens with the fatty acids in ordinary soaps.

INCIDENCE AND SPECIFICITY OF THE ANTIBODY FOR A DISTINCTIVE CONSTITUENT OF THE BROWN-PEARCE TUMOR.

A detailed study has been made of an antibody which appears in the blood of certain rabbits implanted with the Brown-Pearce carcinoma or injected with extracts of it and which reacts specifically in vitro in mixture with a distinctive sedimentable constituent of the Brown-Pearce tumor cell. The observations as a whole seem to indicate that this constituent of the Brown-Pearce tumor differs notably from certain other sedimentable substances which can be extracted from various rabbit tissues and identified by serological means. The implications of the findings are discussed.

INDUCED ANTIBODIES THAT REACT IN VITRO WITH SEDIMENTABLE CONSTITUENTS OF NORMAL AND NEOPLASTIC TISSUE CELLS : PRESENCE OF THE ANTIBODIES IN THE BLOOD OF RABBITS CARRYING VARIOUS TRANSPLANTED CANCERS.

Antibodies were found in the blood of certain rabbits carrying one or another of four transplanted cancers (Brown-Pearce and V2 carcinomas; RSI and Kato sarcomas) which will fix complement in vitro in mixture with saline extracts of various normal and neoplastic rabbit tissues-including liver, kidney, spleen, and the four tumors mentioned-and chick embryo tissue as well. These antibodies, which have been called induced tissue antibodies, are similar to the natural antibodies previously described (2) in that they react with those constituents of the various tissue cells that prove readily sedimentable in the high speed centrifuge; they differ from the natural antibodies in being absent from the blood of normal rabbits and in withstanding 65 degrees C. for 30 minutes.

THE NEOPLASTIC POTENTIALITIES OF MOUSE EMBRYO TISSUES : II. CONTRIBUTORY EXPERIMENTS; RESULTS WITH THE SKIN OF C3H AND WEBSTER-SWISS EMBRYOS; GENERAL CONSIDERATIONS.

Experiments were carried out to learn whether the widely differing liabilities to induced epidermal tumors of individual mice and rabbits are due to a previous localization out of the blood of an agent capable of undergoing change when the skin is exposed to carcinogenic influences, and of producing tumors in consequence. On the assumption that such an agent would localize in increased quantity where cutaneous inflammation exists, like various inert substances of large molecule and the epidermotrophic viruses when circulating, skin areas on adult and new-born animals were for some weeks kept inflamed, and months later, when the areas appeared normal, methylcholanthrene was applied to them and to control areas on the same or other individuals. No differences were observable in tumor incidence.

THE NEOPLASTIC POTENTIALITIES OF MOUSE EMBRYO TISSUES : I. THE FINDINGS WITH SKIN OF C STRAIN EMBRYOS TRANSPLANTED TO ADULT ANIMALS.

A method has been devised whereby the transplanted epidermis of mouse embryos can be selectively exposed to the action of a chemical carcinogen. Scharlach R was dissolved in olive oil with the aim of stimulating and attracting the epidermal cells, methylcholanthrene was added to the solution, and numerous fine globules of it were injected into the thigh muscles of adult mice together with fragments of embryo skin. Much of the oil underwent primary inclusion in the resulting cysts, and the proliferating epidermis, while forming them, extended to not a few of the outlying droplets with result that they too were added to the cyst contents.

NUTRITION OF THE HOST AND NATURAL RESISTANCE TO INFECTION : I. THE EFFECT OF DIET ON THE RESPONSE OF SEVERAL GENOTYPES OF MUS MUSCULUS TO SALMONELLA ENTERITIDIS INFECTION.

1. A diet of whole wheat and whole dried milk has been shown to promote a higher survival rate, among W-Swiss mice subjected to S. enteritidis infection, than that promoted by a "synthetic" diet.

STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI : III. ANTIBODY RESPONSE IN MAN FOLLOWING THE ADMINISTRATION OF THE SPECIFIC ANTIGEN OF TYPE V SHIGELLA PARADYSENTERIAE (FLEXNER).

1. Volunteers have been immunized with the purified specific antigen of Type V Shigella paradysenteriae (Flexner). The subjects developed a high titer of bacterial agglutinins and mouse-protective antibodies.

STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI : II. THE CHEMICAL DEGRADATION OF THE SPECIFIC ANTIGEN OF TYPE Z SHIGELLA PARADYSENTERIAE (FLEXNER).

The chemical and enzymatic dissociation of the specific antigen of Type Z Shigella paradysenteriae has been studied. The chemical, toxic, and serological properties of the products of degradation have been investigated. The nature of the toxic component has been discussed.

STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI : I. THE SPECIFIC ANTIGENS OF SHIGELLA PARADYSENTERIAE (FLEXNER).

1. Methods for the isolation of the specific antigens of Types V, W, Z, and Newcastle Shigella paradysenteriae are given. 2.

DIFFERING RATES OF DEATH AT INNER AND OUTER SURFACES OF THE PROTOPLASM : III. EFFECTS OF MERCURIC CHLORIDE ON NITELLA.

The inner and outer protoplasmic surfaces in Nitella may differ greatly in behavior. When 0.01 M HgCl(2) is applied externally death arrives first at the inner surface.

A STUDY OF TISSUE CULTURE CELLS BY ELECTRON MICROSCOPY : METHODS AND PRELIMINARY OBSERVATIONS.

By means of a tissue culture technique, cells from chick embryos were procured in a state which proved to be suitable for electron microscopy. The electron micrographs disclosed details of cell structure not revealed by other methods of examination.