THE IMMUNOLOGICAL RELATIONSHIP OF THE CAPSULAR POLYSACCHARIDE OF TYPE XIV PNEUMOCOCCUS TO THE BLOOD GROUP A SPECIFIC SUBSTANCE

1. The agglutination of human erythrocytes and the precipitation of the blood group A substance by Type XIV antipneumococcus horse serum are properties of the specific anticarbohydrate immune bodies in the serum. 2. Absorption of Type XIV antipneumococcus horse serum with the homologous bacterial polysaccharide removes the agglutinins for human erythrocytes as well as the precipitins for the group A substance. 3. Absorption of Type XIV antipneumococcus horse serum with the group A substance markedly diminishes the ability of the serum to agglutinate erythrocytes of all groups. 4. Absorption of Type XIV antipneumococcus horse serum with human erythrocytes causes a marked diminution in the precipitation with group A substance. 5. The chemical and immunological relationship between the specific substances of blood group A and the Type XIV Pneumococcus is discussed.     

CLASSIFICATION OF THE HEMOLYTTC STREPTOCOCCI BY THE PRECIPITIN REACTION

A method is described for the preparation from hemolytic streptococci of extracts containing a soluble precipitating substance. By the use of such extracts, it is shown that nearly all members of this family yield a common precipitable substance. So far, therefore, as concerns the precipitin reaction, the hemolytic streptococci form a practically homogeneous group.     

STUDIES ON THE ANTIGENIC SUBSTANCE OF THE BACTERIAL CELL

Putting together the results of such experiments as those outlined above, we can set down the following definite facts. 1. The substance of the bacterial cell can be roughly divided into two antigenic entities. One of these is the so called "nucleoprotein" substance, the other the residue substance or soluble material of Dochez and Avery and Avery and Heidelberger, both of which have been repeatedly characterized in preceding papers. 2. Immunization with the nucleoprotein, if such nucleoprotein is rendered free of bacterial bodies or fragments of bacterial bodies by Berkefeld filtration, incites the production only of antinucleoprotein antibodies which, with slight group overlapping, are species-specific but, as determined by the previous studies of Avery and, subsequently, those of Lancefield, are not type-specific to the same degree as the residue antibodies. 3. Immunization with dissolved residue alone leads to no antibody formation whatever. This residue, as indicated in several of our own previous studies, represents the haptophore group upon which specificity depends and which, in the simple process of solution, is disrupted from another substance together with which it represented a complete antigen in the antibody-forming sense. 4. The formation of specific antiresidue antibodies is apparently dependent upon the injection of morphologically formed elements, at least as far as experiment can determine at the present time; for, as in the pneumococcus experiments, the most available process of solution and the injection of all the materials so obtained from the whole bacteria fails to yield antiresidue antibodies, as though in the mere process of dissolving the residue haptophore group were dissociated from its association with the larger molecule to which, in the whole bacteria, it lends specificity. 5. While antiresidue antibodies are only formed when such undisrupted bacterial cell substances are present in the immunizing substance, immunization with whole bacteria, even when attempts are made to preserve them from solution by formalin, leads to the formation of both antiresidue and antinucleoprotein antibodies, probably because a certain amount of solution inevitably takes place after injection within the animal body.     

Some chemical and physical characteristics of pantomycin, and antiobiotic isolated from Streptomyces hygroscopicus.

The production, isolation, and some structural studies of an antifungal, antibacterial, and antiviral substance from cultures of Streptomyces hygroscopicus are described. This material, designated pantomycin, appears to be a polypeptide antibiotic with inclusion of fatty acids and carbohydrate residues. Amino acid analysis of pantomycin acid hydrolysates indicates that it contains threonine, serine, proline, glycine, alanine, valine, alloisoleucine, and an as-yet-unidentified amino acid which appears to be different from types encountered in proteinaceous materials. In addition to the aforementioned compounds, the antibiotic was shown to contain alpha-aminobutyric acid after hydrogenation. Analysis of ether extracts of the hydrolysate mixture indicated the presence of several fatty aicds; myristic, isotridecanoic, lauric, and undecylic acids. The amino and fatty acid composition of pantomycin is similar to the known antibiotic stendomycin. Pantomycin appears to also have at least one carbohydrate-like residue incorporated into its structure. The presence of carbohydrate was indicated by periodic acid-Schiff base staining of electrophoretic patterns as well as positive color formation in the phenol-sulfuric and Molisch tests, but the carbohydrate did not appear to be either a hexose or a pentose. The antibiotic, which appears to be dissociated in alcoholic solution, forms stable aggregates under aqueous conditons.     

PRECIPITATION AND COMPLEMENT FIXATION REACTIONS WITH RESIDUE ANTIGENS IN THE NON-HEMOLYTIC STREPTOCOCCUS GROUP

The applicability to the non-hemolytic streptococci of the technique used for the extraction of a soluble precipitating substance from the hemolytic streptococci is demonstrated. With this substance as antigen, it is demonstrated by means of precipitation and complement fixation that the non-hemolytic streptococci form an antigenically distinct, but entirely heterogeneous group. Such cross-reactions as do occur within this group are not useful in the systematic classification of these organisms.     

THE ISOLATION OF AN O SPECIFIC SUBSTANCE FROM GASTRIC JUICE OF SECRETORS AND CARBOHYDRATE-LIKE SUBSTANCES FROM GASTRIC JUICE OF NON-SECRETORS

1. The isolation of a group specific O substance from the gastric juice of human beings belonging to group O is described. Absorbed normal beef serum constitutes the anti-O reagent. 2. The O specific substance inhibits the agglutination of human red blood cells belonging to group O. The agglutination of A cells by the isoagglutinin anti-A, or B cells by the isoagglutinin anti-B, is not influenced by the O substance. 3. The A and B specific substances isolated from human gastric juices inhibit the agglutination of O cells by absorbed normal beef serum, frequently to about the same extent as does the O substance itself. 4. The carbohydrate fraction isolated from the gastric juice of non-secretors belonging to group B does not inhibit the agglutination of human red blood cells of group B by the isoagglutinin anti-B nor the agglutination of O cells by the anti-O reagent. The significance of these findings for the conception of the nature of the blood groups and their inheritance is discussed.     

THE ISOLATION OF THE BLOOD GROUP A SPECIFIC SUBSTANCE FROM COMMERCIAL PEPTONE

The isolation of the blood group A specific substance from commercial peptone has been described. The chemical and serological properties of the material from that source have been defined.     

IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS : IV. PREPARATION OF BLOOD GROUP A SUBSTANCES FROM HUMAN SOURCES AND A COMPARISON OF THEIR CHEMICAL AND IMMUNOCHEMICAL PROPERTIES WITH THOSE OF THE BLOOD GROUP A SUBSTANCE FROM HOG STOMACH

1. Blood group substances have been prepared from human saliva, stomach, and amniotic fluid from individuals of blood group A₁ and A₂. Several of the saliva samples were obtained from individuals shown to be heterozygous, A₁O. 2. The purified blood group A substances from human sources were similar in nitrogen, glucosamine, reducing sugar, and acetyl content. The A₁ and A₂ substances differed in optical rotation. All of the human A samples were levorotatory while those from hog stomach were dextrorotatory. 3. By two immunochemical criteria the various human preparations could be shown to fall into distinct groups, with respect to purity. The best products showed maximal activity and almost all of their glucosamine was specifically precipitable by anti-A. These samples of human A substance were only about one-half as effective in precipitating antibody to hog A substance formed in man as was homologous hog A substance although the same total amount of antibody was precipitable by excess of either antigen. 4. Human blood group A₁ substance was found to be antigenic in individuals of blood groups B and O but was not as good an antigen as hog A substance.     

血液透析串联血液灌流对病人血液中分子物质清除效果

目的探讨血液透析串联血液灌流对尿毒症病人血液中中分子物质清除的效果。方法将40例慢性尿毒症病人随机分为联合组及对照组，联合组采用血液透析串联血液灌流治疗，连续4周；对照组采用单纯血液透析治疗，连续4周。治疗前后抽取血液检测中分子物质的含量，并观察两组血压、皮肤瘙痒、睡眠不良等症状改善情况。结果两组治疗后，中分子物质均有下降，但联合组中分子物质下降的程度显著大于对照组（t=2．54，P〈0．05），皮肤瘙痒症状改善显著好于对照组（x^24．86，P〈0．05）。结论尿毒症病人血液透析串联血液灌流治疗可有效清除中分子物质及减轻皮肤瘙痒，改善血液净化效果，提高病人生存质量。     

ANTIGENIC PROPERTIES OF THE TYPE-SPECIFIC SUBSTANCE DERIVED FROM GROUP A HEMOLYTIC STREPTOCOCCI

1. A substance extracted from group A hemolytic streptococcus is described, which induces active immunity in mice, and in rabbits gives rise to precipitins and to protective antibodies passively transferable to mice. 2. The active immunity in mice is principally type-specific, but some degree of non-type-specific immunity is also developed. The passively transferable protective antibodies are type-specific with only a slight suggestion of non-type specificity. In the precipitin test, the rabbit immune sera give both type-specific and non-type-specific reactions which have not been fully analyzed serologically. 3. Substances contained in the extract absorb the protective antibodies from the serum of rabbits immunized with whole hemolytic streptococci. 4. The most satisfactory method of extraction so far developed is fully described. Chemical tests on the material are consistent with the presence of protein and nucleic acid. 5. The type-specific M substance, prepared as previously described, was compared in some of its antigenic properties with the above mentioned substance. It was found capable of inducing active immunity in mice and of absorbing protective antibody from anti-bacterial immune serum in a manner qualitatively similar to that obtained with the preparations made by the newer methods.     

AN EXAMINATION OF THE MECHANISM OF PNEUMOCOCCUS IMMUNITY BY MEANS OF BACTERICIDAL MEASUREMENTS : II. THE REACTION BETWEEN THE ANTICARBOHYDRATE ANTIBODY AND TYPE-SPECIFIC PRODUCTS OF THE ORGANISM

1. There is in the filtrate of a 5 day broth culture of Type III pneumococcus a type-specific substance which has a very powerful antibactericidal action. If the precipitinogen content of the broth filtrate and the specific carbohydrate is taken as the basis of comparison, it requires approximately one thousand times as much antiserum to neutralize the broth filtrate as is necessary to neutralize the specific carbohydrate. The active substance in the broth filtrate appears to be related to the specific carbohydrate. Its possible nature is discussed. 2. A similar substance, but in stronger concentration, was found in the filtrate of a lung from a Type III pneumonia autopsy. The influence of this substance on the disease is discussed. 3. One specimen of Type III convalescent blood, though comparatively weak in anticarbohydrate antibody (precipitin) was better able to neutralize the broth filtrate and the lung filtrate than a corresponding mixture of normal blood and antiserum. Two other specimens of Type II convalescent blood neutralized the Type III broth filtrate efficiently.     

THE ANTIGENIC COMPLEX OF STREPTOCOCCUS H?MOLYTICUS : II. CHEMICAL AND IMMUNOLOGICAL PROPERTIES OF THE PROTEIN FRACTIONS.

The chemical and immunological characteristics of the type-specific substance (M) of Streptococcus hæmolyticus are considered. 1. A summary of the evidence for the protein nature of this substance follows: (a) It is precipiated by the usual protein precipitants such as, dilute alcohol, dilute acetic acid, and picric acid. (b) It contains 14 per cent protein nitrogen after considerable purification. (c) It is progressively destroyed by removal of the NH₂ group by treatment with nitrous acid. (d) It is completely and readily digested by trypsin and by pepsin. 2. "Purified" extracts react in relatively high dilution with homologous antibacterial sera, but do not precipitate most heterologous antibacterial sera or sera potent in non-type-specific antibodies for the group reactive nucleoprotein P or for the species-specific probable carbohydrate C. Attempts to immunize rabbits with the type-specific protein have been unsuccessful, with simple salt solution extracts of streptococci as well as with purified solutions. This protein seems, therefore, to have the characteristics of a haptene. The type-specific substance (M) is contrasted with the so called nucleoprotein (P) which shows group relationships with nucleoproteins of related species and is the only fraction of hemolytic streptococcus extracts so far obtained which, after separation from the bacterial cell, is a true antigen leading to antibody production when injected into rabbits. The occurrence of another non-type-specific protein (Y) is suggested by occasional cross-reactions of purified M with certain antibacterial sera. Since it has not been separated from extracts containing the type-specific M, little is known of it either chemically or serologically. The cross-reaction disappears on tryptic or peptic digestion of the extract. The fact that such extracts do not show cross-reactions with anti-P sera is evidence that this non-type-specific protein is not P.     

THE FUNCTION OF THE SPLEEN IN THE EXPERIMENTAL INFECTION OF ALBINO MICE WITH BACILLUS TUBERCULOSIS : THIRD PAPER.

Experiments are reported which show that in all probability the increased resistance to tuberculous infection which is imparted to mice by the removal of the spleen is a consequence of the loss of a function of the organ. This function can be restored by the feeding of fresh spleen. For the present we attribute these changes to the removal and restoration, as the case may be, of a particular substance for which the designation tuberculosplenatin is suggested. This substance is assumed to be related to the spleen as adrenalin is related to the adrenal gland. It is peculiar to the organ but not to the species. It is not found in other organs of the body so far as our observations have extended. The absence of the substance from the lymphatic glands seems of especial importance in this connection.     

MANAGEMENT OF SUBSTANCE MISUSERS ON THE GENERAL HOSPITAL WARD

SUMMARY Since a high prevalence of physical morbidity is associated with substance misuse, drug misusers are frequently admitted to general hospitals. Medical staff often perceive drug misusers as a particularly difficult patient group, feeling that they lack the knowledge and skill to deal with them adequately without specialist support. We review the common physical complications of substance misuse likely to be encountered in a general hospital, and provide comprehensive guidelines for the assessment and management of drug dependence in this setting.     

IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS : I. ESTIMATION OF A AND B ISOANTIBODIES IN HUMAN SERUM BY THE QUANTITATIVE PRECIPITIN METHOD

1. With purified blood group A and B specific substances from the gastric mucin of pigs precipitin reactions can be obtained in sera containing homologous isoagglutinins. By microquantitative precipitin technics the anti-A and anti-B content of normal and immune isoagglutinin-containing sera can be estimated on a weight basis. 2. There was a general correlation between antibody N precipitable from the sera of groups O and B by A substance and the agglutinin titer for A erythrocytes before and after immunization with blood group substances. 3. The reaction between A substance and its homologous isoagglutinin present in the sera of immunized individuals was of the same type as in other antigen-antibody systems.     

THE RELATION BETWEEN THE TYPE SPECIFIC CARBOHYDRATES OF PNEUMOCOCCI AND THE BLOOD GROUP SPECIFIC SUBSTANCE A

1. A relationship between the soluble specific substances of pneumococci and the blood group substance A of man can be demonstrated by the inhibition of sheep cell hemolysis by a group specific A-antiserum. However, there are quantitative differences between the various types. 2. A striking difference exists between the acetyl and the de-acetylated polysaccharide of Pneumococcus Type I: The de-acetylated carbohydrate fails to react with the group specific A-antiserum, while the acetyl carbohydrate shows a strong reactivity. 3. The minimum amount of the acetyl polysaccharide, which inhibits sheep cell hemolysis by A-antiserum, is almost as small as that of the group specific carbohydrate isolated by Freudenberg and Eichel from urines of group A. 4. The reactivity of the acetyl polysaccharide can be demonstrated not only by the hemolysis inhibition test, but also by complement fixation and by inhibition of group specific iso-agglutination. 5. Feces filtrates, which possess the ability to destroy the blood group specific substances A and B of man, also affect the acetyl polysaccharide of Pneumococcus Type I. After incubation with an effective feces filtrate, the acetyl polysaccharide almost completely loses its potency toward the group specific A-antiserum and also its ability to inhibit the iso-agglutination of A blood cells. 6. Acetyl polysaccharide of Pneumococcus Type I, having lost its reactivity toward the group-specific A-antiserum after treatment with feces filtrate, still reacts with Type I pneumococcus antiserum which was previously absorbed with de-acetylated polysaccharide, Type I. Thus, the essential effect of the feces filtrate on acetyl polysaccharide, Type I, is not the cleavage of acetyl group, but some other chemical alteration.     

THE PATHOGENESIS OF THE HEMORRHAGIC DISEASES OF THE NEW-BORN

Those conditions of the new-born characterized by a hemorrhagic tendency, icterus, and fatty changes, are probably all syndromes which may occur as the result of a number of toxic agents. All of them, however, have been produced, in these experiments, by the action of a single experimental agent. Thus, a picture indistinguishable from that called Buhl''s disease has been obtained by the use of chloroform, as have also the pictures known as Winckel''s disease, melæna neonatorum, etc. Chloroform is not held to be the only substance that has this power. It stands rather as one member of a group of agents, the effects of which in general and in individual organs are similar to those caused by lack of oxygen. The essential features of these conditions have also been produced by direct asphyxiation of the fetus. The suggestion is therefore made that underlying all these symptoms and pathological complexes, there is a deficiency of oxidation, general, local, or selective, thus bringing this group of diseases into the general category of acute yellow atrophy of the liver, eclampsia, pernicious vomiting, cyclic vomiting, phosphorus poisoning, etc. In human beings, chloroform and asphyxia must, in many instances, be the determining causes. There remain, however, other cases in which different factors are to be sought.     

THE ABSENCE FROM THE URINE OF PERNICIOUS ANEMIA PATIENTS OF A MOSQUITO GROWTH FACTOR PRESENT IN NORMAL URINE

Extracts prepared from the urine of normal persons or patients with aplastic anemia or leukemia contain a substance, possibly flavine or a flavine compound, which under suitable conditions of test enhances the growth of larvae of the mosquito, Aëdes aegypti. This substance is lacking, or is present in much smaller amount, in extracts from the urine of pernicious anemia patients showing symptoms of the disease. Extracts from the urine of the same patients after adequate treatment contain as much of the substance as normal urine extracts.     

DISTRIBUTION OF BLOOD GROUP PROPERTIES AND BLOOD GROUP PROPERTY DESTROYING FACTORS IN THE INTESTINAL TRACT OF MAN

1. The blood group specific substance A is present in the contents of the jejunum and upper ileum of persons belonging to Group A. 2. A marked decrease in the amount of A substance occurs in the lower ileum and cecum, while colon and rectum contents of adults are more or less free of group substance A. 3. The blood group destroying agent first appears in the lower ileum or cecum and its effectiveness increases in the lower parts of the large intestine. 4. In two cases with intestinal obstruction the blood group destroying agent could be demonstrated in the contents of the jejunum and ileum.     

ON THE DIALYSABILITY OF THE GROWTH-ACTIVATING PRINCIPLE CONTAINED IN EXTRACTS OF EMBRYONIC TISSUES

These experiments appear to indicate that whatever substance in embryonic tissue extracts excites mitosis, and therefore would appear to be the growth-stimulating substance, is capable of passing through a collodion membrane which is impermeable to proteins, at all events in such concentration as would give rise to any biuret reaction. The substance is therefore diffusible.