CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : VII. IMMUNOLOGICAL SPECIFICITY OF ANTIGENS PREPARED BY COMBININGalpha- AND beta-GLUCOSIDES OF GLUCOSE WITH PROTEINS.

The chemical and immunological properties of the p-aminophenol alpha- and beta-glucosides of glucose are described and correlated. The results are discussed with reference to their possible bearing on the chemo-immunological nature of the specific polysaccharides of bacterial origin.

CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : VI. THE SYNTHESIS OFp-AMINOPHENOLalpha-GLUCOSIDE AND ITS COUPLING WITH PROTEIN.

1. The synthesis of p-aminophenol alpha-glucoside has been described. This glucoside can be coupled to any protein to yield a synthetic alpha-glucoside-protein complex.

CYTOLOGIC STUDIES ON RHEUMATIC FEVER : I. THE CHARACTERISTIC CELL OF THE RHEUMATIC GRANULOMA.

Scrapings of subcutaneous nodules from ten patients with rheumatic fever were examined microscopically after being stained with supravital dyes. From the uniform results obtained, the following conclusions have been drawn. 1.

REACTION OF RABBITS TO STREPTOCOCCI: COMPARATIVE SENSITIZING EFFECT OF INTRACUTANEOUS AND INTRAVENOUS INOCULA IN MINUTE DOSES.

1. Rabbits were rendered very hypersensitive by relatively small doses of green streptococci given intracutaneously, and somewhat less hypersensitive by similar doses of heat-killed vaccine prepared from hemolytic streptococci. 2.

THE ACTION OF A SPECIFIC ENZYME UPON THE DERMAL INFECTION OF RABBITS WITH TYPE III PNEUMOCOCCUS.

The action of the enzyme which specifically decomposes the capsular polysaccharide of Type III Pneumococcus has been tested in Type III pneumococcus dermal infections in rabbits. When injected in sufficient amounts, this enzyme is capable of bringing about a favorable and early termination of the experimental disease which ordinarily is fatal in nearly all instances. The results of the present study yield further evidence that the capsular substance is of great importance in pneumococcus infection, since, in so far as known, the only action of which the specific enzyme is capable is that of decomposing the capsular polysaccharide.

FACTORS AFFECTING THE YIELD OF SPECIFIC ENZYME IN CULTURES OF THE BACILLUS DECOMPOSING THE CAPSULAR POLYSACCHARIDE OF TYPE III PNEUMOCOCCUS.

All improved method is described for the preparation, concentration, and purification of a bacterial enzyme capable of decomposing the capsular polysaccharide of Type III Pneumococcus. The cultural conditions for the growth of the specific microorganism must be such that the capsular polysaccharide is completely decomposed before any appreciable amount of free enzyme is released into the medium. This reduces to a minimum the decomposition of the specific substrate by the free enzyme.

DETERMINATION OF LUNG VOLUME BY RESPIRATION OF OXYGEN WITHOUT FORCED BREATHING.

A method is described for estimating the volume of air in the lungs by the familiar principle of mixing this air with a measured volume of oxygen, and determining the extent to which the nitrogen of the pulmonary air is diluted. By employing a scrubber to remove carbon dioxide, and by measuring the volume of gas in the extrapulmonary part of the system at the end instead of the beginning of the respiratory period, it is possible to prolong the period to as many minutes as are necessary for complete mixture of the gases, and thereby to carry out the estimation without forced breathing. The determination can be carried out with the Roth-Benedict or Krogh spirometer, or, more economically, with the simple spirometer, shown in Fig.

THE EFFECT OF DENATURATION ON THE VISCOSITY OF PROTEIN SYSTEMS.

The viscosity of a protein solution is increased by the denaturation of the protein. This is true both when there is the formation of protein aggregates which occlude water and when there is no aggregation. Under certain conditions, as a result of the aggregation following denaturation, a solution containing only one per cent of protein may be converted into a clear gel.

THE TRANSFORMATION IN VITRO OF R PNEUMOCOCCI INTO S FORMS OF DIFFERENT SPECIFIC TYPES BY THE USE OF FILTERED PNEUMOCOCCUS EXTRACTS.

1. Avirulent R pneumococci derived from S forms of a specific type may be changed by growth in broth containing anti-R serum and a heated, filtered extract of S pneumococci of a different type, into virulent S organisms identical in type with the bacteria extracted. This has been accomplished in the case of R strains derived from Type II pneumococci, employing extracts prepared from Type III and Type I S forms.

THE IDENTITY OF THE MECHANISMS OF TYPE-SPECIFIC AGGLUTININ AND PRECIPITIN REACTIONS WITH PNEUMOCOCCUS.

THE EXPERIMENTAL RESULTS WHICH HAVE BEEN DESCRIBED DEMONSTRATE THE FOLLOWING FACTS: 1. In the type-specific agglutination reaction, when the organisms are not present in sufficient numbers to absorb completely all the antibodies from the serum, more antibody is bound by cellular S than is required for the process of agglutination. 2.

THE DEVELOPMENT AND LOCALIZATION OF THE DERMAL PNEUMOCOCCIC LESION IN THE RABBIT.

An attempt has been made to analyze the factors involved in the development and localization of the dermal pneumococcic lesion in the rabbit. The character and quantity of the edema fluid which forms during the early phases of the lesion are intimately concerned in its development and spread. It contains an antithrombic substance, probably derived from the pneumococci, and delayed coagulation probably facilitates its movement through the tissue.

LOCALIZATION OF PNEUMOCOCCI IN THE LUNGS OF PARTIALLY IMMUNIZED MICE FOLLOWING INHALATION OF PNEUMOCOCCI.

1. When mice are passively immunized by the intraperitoneal injection of antipneumococcus horse serum or actively by the injection of heat-killed pneumococcus cultures, and are then alcoholized and sprayed with a culture of pneumococci of the same type as that of the bacteria employed in immunization, a considerable number die with localized lesions in the lungs. 2.

DURATION OF DEMONSTRABLE ANTIBODIES IN THE SERUM OF RABBITS IMMUNIZED WITH HEAT-KILLED TYPE I PNEUMOCOCCI.

In rabbits immunized by the injection of suspensions of heat-killed pneumococci the results obtained as regards not only the development of agglutinating and mouse protective antibodies, but also the persistence of these bodies in the blood depend to a considerable extent upon the route of immunization and the size of the inocula. Agglutinins may appear in the sera of all the rabbits except those inoculated subcutaneously, but in most instances they disappear within a short time. Protective antibodies appear in the sera of all rabbits, no matter which route of injection be employed and they persist much longer than do the agglutinins.

CUTANEOUS REACTIONS IN RABBITS TO THE TYPE-SPECIFIC CAPSULAR POLYSACCHARIDES OF PNEUMOCOCCUS.

The injection of the type-specific capsular polysaccharides of Pneumococcus Types I, II and III into the skin of rabbits, actively or passively immunized to one of these types of Pneumococcus, elicits a type-specific cutaneous reaction. The form of reaction resembles that described by Arthus. The reaction is produced only when type-specific precipitins for the homologous polysaccharide are demonstrable in the blood of the rabbit.

CULTIVATION OF VACCINE VIRUS FOR JENNERIAN PROPHYLAXIS IN MAN.

1. A dermal strain of vaccine virus has been adapted to a simple culture medium consisting of minced chick embryo suspended in Tyrode's solution. 2.

CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : V. THE IMMUNOLOGICAL SPECIFITY OF AN ANTIGEN PREPARED BY COMBINING THE CAPSULAR POLYSACCHARIDE OF TYPE III PNEUMOCOCCUS WITH FOREIGN PROTEIN.

1. Type-specific antipneumococcus immunity has been induced in rabbits by immunization with antigen prepared by combining a specific derivative of the capsular polysaccharide of Type III Pneumococcus with globulin from horse serum. 2.

CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : IV. THE SYNTHESIS OF THEp-AMINOBENZYL ETHER OF THE SOLUBLE SPECIFIC SUBSTANCE OF TYPE III PNEUMOCOCCUS AND ITS COUPLING WITH PROTEIN.

1. The p-amino and p-nitromonobenzyl ethers of the specific polysaccharide of Type III Pneumococcus have been prepared. 2.

PROTEIN COAGULATION AND ITS REVERSAL : SERUM ALBUMIN.

1. It is possible to prepare crystalline, soluble, heat-coagulable serum albumin from coagulated serum albumin. 2.

PSITTACOSIS : I. EXPERIMENTALLY INDUCED INFECTIONS IN PARROTS.

1. The virus of psittacosis is present in the nasal secretions, feces, blood, spleen, and liver of an infected parrot. 2.

THE PROTECTIVE ACTION OF A SPECIFIC ENZYME AGAINST TYPE III PNEUMOCOCCUS INFECTION IN MICE.

The bacterial enzyme which decomposes the purified capsular polysaccharide of Type III Pneumococcus in vitro also destroys the capsules of the living organisms growing in media and in the animal body. Potent preparations of this same enzyme protect mice against infection with virulent Type III Pneumococcus. The protective action is type-specific.

DECOMPOSITION OF THE CAPSULAR POLYSACCHARIDE OF PNEUMOCOCCUS TYPE III BY A BACTERIAL ENZYME.

1. An organism has been isolated from peat soil which decomposes the specific capsular polysaccharide of Type III Pneumococcus. 2.

THE PATHOLOGY OF EXPERIMENTAL DERMAL PNEUMOCOCCUS INFECTION IN THE RABBIT.

1. The pathology of the experimental dermal pneumococcic infection in the rabbit is described in detail and the findings are compared with the histological alterations seen in the human pneumonic lung. There would appear to be a basic similarity of the lesions in both tissues.

PSITTACOSIS : IV. EXPERIMENTALLY INDUCED INFECTIONS IN MONKEYS.

The virus of psittacosis inoculated intratracheally or intranasally in monkeys produces a pneumonia similar to that caused by the same active agent in man. Intracerebral inoculation of the virus induces a meningo-encephalitis characterized principally by a mononuclear reaction in the meninges. Indirect evidence has been adduced to show that the portal of entry of the virus in man is the upper respiratory tract.

PSITTACOSIS : III. EXPERIMENTALLY INDUCED INFECTIONS IN RABBITS AND GUINEA PIGS.

1. Rabbits and guinea pigs are susceptible to psittacosis virus introduced intracerebrally. By means of brain to brain passages in these animals the active agent is capable of propagation indefinitely.

PSITTACOSIS : II. EXPERIMENTALLY INDUCED INFECTIONS IN MICE.

The work presented in this communication concerning psittacosis in mice confirms Krumwiede's observations that mice inoculated intraperitoneally with emulsified livers and spleens containing the virus develop the disease and that the malady can in this way be passed serially through a number of mice. Furthermore, it has been shown that mice are susceptible to the virus administered intracerebrally and that the active agent can be propagated indefinitely by means of brain to brain inoculations. Moreover, by the use of mice, the presence of the virus of psittacosis in the sputum of a patient with the disease has for the first time been demonstrated.