A MOUSE TEST FOR MEASURING THE IMMUNIZING POTENCY OF ANTIRABIES VACCINES.

1. A quantitative practical mouse test is described for measuring the immunizing potency of antirabies vaccines. 2.

CELLULAR REACTIONS TO A DYE-PROTEIN WITH A CONCEPT OF THE MECHANISM OF ANTIBODY FORMATION.

1. The use of an antigen which can be seen within cells demonstrates that one may stimulate the phagocytic cells either of the liver and spleen or of the tissues and lymph nodes to produce antibodies. 2.

A SOLUBLE ANTIGEN OF LYMPHOCYTIC CHORIOMENINGITIS : I. SEPARATION OF SOLUBLE ANTIGEN FROM VIRUS.

The virus of lymphocytic choriomeningitis can be sedimented in the ultracentrifuge and washed repeatedly; the virus retains its activity provided that a small amount of normal serum is present in the diluent. A soluble substance capable of fixing complement in the presence of immune serum can be separated from the virus. Washed virus fixes complement poorly.

THE BEHAVIOR OF ABNORMAL HUMAN THYROID TISSUE CULTIVATED IN THE LINDBERGH APPARATUS.

1. Human thyroid tissue may be kept alive and in good condition in the Lindbergh apparatus for at least 3 weeks, in usable condition from 1 to 2 months, provided that the vascular tree remain patent and functioning. 2.

ARTIFICIAL MAINTENANCE MEDIA FOR CELL AND ORGAN CULTIVATION : II. THE CULTIVATION OF ORGANS IN ARTIFICIAL MEDIA.

Experiments have been described in which organs cultivated in the Lindbergh apparatus have been kept alive in artificial media for periods ranging from 3 days to 3 weeks, with life continuing in portions of some glands for from 35 to 62 days. The media used varied in composition from very simple and inexpensive ones in which some serum was used to a rather complex medium containing only that negligible amount of serum that is necessary as a solvent for vitamin A. The experiments performed demonstrate that artificial media can be used for organ cultivation, thus making it possible to study the behavior of human organs; to control the composition of the media at will; and to reduce the cost of experimentation.

STUDIES ON A BACTERICIDAL AGENT EXTRACTED FROM A SOIL BACILLUS : II. PROTECTIVE EFFECT OF THE BACTERICIDAL AGENT AGAINST EXPERIMENTAL PNEUMOCOCCUS INFECTIONS IN MICE.

In the first paper of this series, a description was given of a cell-free extract, obtained from autolysates of a particular strain of a soil bacillus, which selectively inhibits the growth of all the Gram-positive microorganisms so far tested, and exerts on them a bactericidal effect in vitro. In the present study it is shown that the same agent protects white mice against infection with large numbers of virulent pneumococci. It also exerts a curative effect when administered to mice several hours after injection of the infecting organisms.

THE BEHAVIOR OF POX VIRUSES IN THE RESPIRATORY TRACT : II. THE RESPONSE OF MICE TO THE NASAL INSTILLATION OF VARIOLA VIRUS.

Variola virus was cultivated in embryonated eggs from smallpox crusts and maintained through 85 passages. Therein it produced foci of cellular proliferation and necrosis on the chorioallantoic membrane but did not affect the embryo. The virus from egg cultures was inactive in the skin of the rabbit on primary injection and in the testis both initially and on passage.

STUDIES ON A BACTERICIDAL AGENT EXTRACTED FROM A SOIL BACILLUS : I. PREPARATION OF THE AGENT. ITS ACTIVITY IN VITRO.

A Gram-positive, spore-bearing, aerobic bacillus, capable of lyzing the living cells of many Gram-positive microbial species, has been isolated from soil. Cultures of this soil bacillus in peptone media release during autolysis a soluble agent which exerts a bactericidal effect on all the Gram-positive microorganisms so far tested, and inactivates their glucose dehydrogenases. It also inhibits the growth of the susceptible species in culture media.

AMOUNT AND DURATION OF IMMUNITY INDUCED BY INTRADERMAL INOCULATION OF CULTURED VACCINE VIRUS.

Continued cultivation of vaccine virus in a medium consisting of minced chick embryo tissue and Tyrode's solution has resulted in a virus qualitatively changed to such an extent that considerable amounts of it can be injected intradermally into human beings without danger or inconvenience. Individuals who are vaccinated intradermally with the cultured virus should be revaccinated dermally six months to a year later with a potent calf lymph virus in order to obtain a satisfactory immunity to smallpox without being subjected to the dangers and inconvenience associated with primary vaccinations with calf lymph virus.

SEROLOGICAL STUDIES OF SWINE INFLUENZA VIRUSES.

1. Cross-neutralization tests with sera from swine recovered from infection with swine influenza indicated the serological identity of 7 strains of swine influenza virus obtained from different sources. 2.

OSMOTIC PRESSURE STUDY OF PROTEIN FRACTIONS IN NORMAL AND IN NEPHROTIC SUBJECTS.

In serum of patients with nephrosis both albumin and globulin showed by osmotic pressure nearly double the molecular weights of normal albumin and globulin. In the urines of such patients, on the other hand, both proteins showed molecular weights lower even than in normal serum. The colloidal osmotic pressures were measured by the author's method at such dilutions that the van't Hoff law relating pressures to molecular concentrations could be directly applied.

EPIDEMIOLOGY OF LYMPHOCYTIC CHORIOMENINGITIS IN A MOUSE STOCK OBSERVED FOR FOUR YEARS.

A small mouse stock in which lymphocytic choriomeningitis is endemic has been observed over a period of 4 years. The disease has persisted during that time, but it has become so mild that it can no longer be recognized by clinical observation. In spite of this fact, all of the stock mice tested, both young and old, carried considerable amounts of virus in their organs and blood.

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS : VI. EXPERIMENTS ON THE SENSITIZATION OF GUINEA PIGS TO POISON IVY.

Experiments are described on the latency period in sensitization to poison ivy and on the time necessary for the agent to remain in contact with the skin. The chief matter of investigation concerned the manner in which the whole skin becomes sensitive following treatment at a particular site, and especially whether this is effected by way of the epidermis. Two methods were used to interrupt the continuity of the skin, one by cutting through both skin and the underlying thin muscular layer, the other by removing a strip of skin so as to spare the skin muscle.

ON THE SEROLOGICAL SPECIFICITY OF PEPTIDES. III.

Experiments are described dealing with immune sera to pentapeptides and peptide amides. Absorption and inhibition tests gave no indication of the presence in the immune sera of special antibodies for portions of a peptide molecule but the antibodies appeared to be specific for an entire pentapeptide even though the sera contained qualitatively different fractions. Marked disparity was found between the reactions of peptides and corresponding amides indicating differences between acid and other polar groups in their influence on serological specificity.

STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS : III. INTRAOCULAR INFECTION WITH FIXED VIRUS IN THE GUINEA PIG.

The behavior of a fixed strain of Eastern equine encephalomyelitis virus was studied in guinea pigs after intraocular inoculation. Such inoculation concerns the central and not the peripheral nervous system. The susceptibility to intraocular injection lies midway between the highly virulent intracerebral and the quite avirulent peripheral routes.

STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS : II. PATHOGENESIS OF THE DISEASE IN THE GUINEA PIG.

After inoculation with equine encephalomyelitis virus by various routes, guinea pigs were sacrificed at early stages, before symptoms were apparent. The brains were studied histologically, with serial sections; all lesions were noted, and subjected to topographical analysis. Nine cases are presented in detail.

THE ENHANCING EFFECT OF AZOPROTEINS ON THE LESIONS PRODUCED BY VACCINE VIRUS, THE SHOPE FIBROMA VIRUS, AND THE AGENT TRANSMITTING CHICKEN TUMOR I.

It is known that azoprotein solutions, like testicular extracts, possess the property of causing particles to spread through the dermis. The present work shows that azoproteins exhibit, like testicular extract, the power to increase the size of virus lesions in the skin of rabbits, and the size of tumors in chickens. The results indicate that the extent of the lesion is roughly proportional to the spreading power of the solution.

CAUSES OF THE CESSATION OF GROWTH OF FIBROBLASTS CULTIVATED IN EMBRYO JUICE.

Experiments designed to ascertain the reason for the cessation of growth of heart fibroblasts when they are cultivated in a plasma coagulum with embryo juice as nutrient fluid have shown that it is due, first, to the gradual removal of serum from the coagulum, and second, to an insufficient supply of embryo juice. In a medium containing embryo extract at 66 per cent concentration and serum at 8 per cent concentration, growth continued until the entire coagulum in a 3(1/2) cm. flask was covered with tissue.

EFFECT OF PREGNANCY UPON THE IMMUNITY OF MICE VACCINATED AGAINST ST. LOUIS ENCEPHALITIS VIRUS.

1. Virgin and pregnant Swiss mice are equally susceptible to intracerebral inoculation of St. Louis encephalitis virus.

VITAMIN C IN RELATION TO EXPERIMENTAL POLIOMYELITIS : WITH INCIDENTAL OBSERVATIONS ON CERTAIN MANIFESTATIONS IN MACACUS RHESUS MONKEYS ON A SCORBUTIC DIET.

In the experiments reported in the present communication it was found that vitamin C, both natural and synthetic preparations, had no effect on the course of experimental poliomyelitis induced by nasal instillation of the virus. The objection cannot be raised that too large an amount of virus was used, since recent studies (3) on the fate of the nasally instilled virus indicated that all but an undetectable amount of it is swallowed and disappears from the nasal mucosa within 3 hours or less, and that none is demonstrable in the central nervous system before the 3rd day. Vitamin C administration was begun immediately after the instillation of virus and if it were capable of exerting any effect on the virus or the tissues it could have done so even before multiplication of virus had begun.

THE ANTIBODY RESPONSE TO SWINE INFLUENZA.

Antibodies that neutralize swine influenza virus became detectible in the serum of swine on the 6th or 7th day after infection with swine influenza. Their appearance corresponded rather closely with clinical recovery. In swine with the milder filtrate disease, neutralizing antibodies did not appear until sometime between the 7th and 10th days.

THE KINETICS OF PENETRATION : XVII. THE EXIT OF AMMONIA IN LIGHT AND DARKNESS.

The exit of accumulated ammonia from the sap of Valonia macrophysa, Kütz., into normal (nearly ammonia-free) sea water, has been studied in light (alternation of daylight and darkness) and in darkness. Exit is always preceded by an induction period lasting 1 or more days.

THE KINETICS OF PENETRATION : XVI. THE ACCUMULATION OF AMMONIA IN LIGHT AND DARKNESS.

The accumulation of ammonia takes place more rapidly in light than in darkness. The accumulation appears to go on until a steady state is attained. The steady state concentration of ammonia in the sap is about twice as great in light as in darkness.

PURIFICATION AND CONCENTRATION OF ENTEROKINASE.

A concentrated solution of purified enterokinase is conveniently prepared from the fluid contents of pigs' duodena by means of fractional precipitation with ammonium sulfate under the proper pH conditions.