Article

Heterogenetic antibodies in acute hepatitis

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Abstract

A heterogenetic antibody showing fixation of complement with human liver and agglutination of sheep erythrocytes was found in certain cases of acute infective hepatitis. The antigen concerned in these reactions was apparently heat stable and alcohol soluble. Differences from other heterogenetic antigen-antibody systems have been noted. The possible relation of the heterogenetic antibody to liver damage was considered.

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... The hematological picture of the early phase of both naturally occurring (17 to 20) and experimentally induced (21) infectious hepatitis may closely simulate that of infectious mononucleosis and as many as 60 per cent of the lymphocytes have been described as atypical in infectious hepatitis (18). Increases of the characteristic heterophile antibody of infec-tious mononucleosis have not been described in infectious hepatitis (18), although Eaton and his associates (22) have found a heterogenetic antibody in a few such cases that could be differentiated only by absorption tests. Since increases of the heterophile antibody may not always be demonstrable in the serum of patients with infectious mononucleosis, occasional cases of these 2 diseases may be nearly indistinguishable. ...
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Am Beispiel rheumatischer Polyarthritiden mit positivem Nachweis komplementbindender Gewebs-Auto-Antikörper wird gezeigt, daß dem Vorkommen derartiger serologischer Vorgänge keine obligate pathogenetische Bedeutung zugemessen werden darf, was sich am Modellversuch der experimentellen Streptokokkeninfektion beim Kaninchen bestätigt. Andererseits muß davor gewarnt werden, unter dem Sammelbegriff der „Auto-Immunisierung“ serologisch verschiedenartige Vorgänge mit; ganz verschiedener Beziehung zur klinischen Grunderkrankung zu verschmelzen.
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Clinical, morphological and serological features in the course of chronic hepatitis propose a definite role of an immunopathological mechanism in this autonomously progressive disease. From the clinical standpoint it is especially the syndrome of the socalled lupoid hepatitis which because of the close symptomatological relationship to the collagen diseases has contributed to this conception. However there is a lack of a definite morphological criterium which could prove the supposition of an immunological mechanism in chronic liver disease. The circulating antibodies detectable in chronic inflammatory liver disease are defined as autoantibodies as they are demonstrated by serological and fluorescent microscopic techniques to be bound to autologous and homologous liver tissue. However, basing on present evidence the pathogenicity of these antibodies is unlikely. To be sure, different indications denote that immunological factors in the sense of an autosensitivity process are participating in the development of chronic hepatitis; presently however, on the basis of clinical and experimental pathologic data, no definite evidence of a autosensitivity process has been produced.
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1. Es wird zur Definition und Terminologie der Heteroagglutination Stellung genommen. 2. Experimentell und theoretisch wird der Antikrper der Heteroagglutination und seine Reaktionsweise betrachtet. 3. Einzelne Agglutinintypen der Heteroagglutination und ihre Antigene werden zur Diskussion gestellt. Hieraus ergeben sich fr die Serologie diagnostische Mglichkeiten (Differentialtest). 4. Um die Voraussetzung einer weiteren gemeinsamen Bearbeitung des Problems zu ermglichen, wurde eine Technik zur Durchfhrung der Heteroagglutination erarbeitet.
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In an attempt to evaluate the significance of mononuclear cells in the experimental allergic hepatitis which was previously studied, lymphocytes from inbred strain C57 BL mice with the hepatitis was passively transfered into x-ray irradiated isologous mice. Early histological changes in the liver of the recipient mice consisted of an extensive coagulation necrosis on the 2nd or 3rd day after the transfer, and delayed changes occurring on the 7th to 10th post-transfer day included a marked infiltration of mononuclear cells in the portal areas, various types of liver cell necrosis and degeneration, a mononuclear cell infiltration in the sinusoid as well as an activation of the Kupffer cells as compared with control groups. These histological changes, however, were transient and subsided in 2 to 3 weeks post to the transfer of the cells. There was no tendency to the development of a feature of chronic hepatitis. The present experiment indicated that the passive transfer of sensitized lymphocytes obtained from mice with the experimental allergic hepatitis made by the previous experiment produced an allergic hepatitis comprising a coagulation necrosis and others in isologous mice, but this hepatitic change was transient and by no means transformed to a chronic status similar to a human chronic hepatitis as in the previous experiment.
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Chapter
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Chapter
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Chapter
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Using photoluminescence (PL) and current deep-level transient spectroscopy (I-DLTS), we investigated the electronic defects of indium-doped detector-grade CdMnTe:In (CMT:In) crystals grown by the vertical Bridgman method. We similarly analyzed CdZnTe:In (CZT:In) and undoped CdMnTe (CMT) crystals grown under the amount of same level of excess Te and/or indium doping level to detail the fundamental properties of the electronic defect structure more readily. Extended defects, existing in all the samples, were revealed by synchrotron white beam x-ray diffraction topography and scanning electron microscopy. The electronic structure of CMT is very similar to that of CZT, with shallow traps, A-centers, Cd vacancies, deep levels, and Te antisites. The 1.1-eV deep level, revealed by PL in earlier studies of CZT and CdTe, were attributed to dislocation-induced defects. In our I-DLTS measurements, the 1.1-eV traps showed different activation energies with applied bias voltage and an exponential dependence on the trap-filling time, which are typical characteristics of dislocation-induced defects. We propose a new defect-trap model for indium-doped CMT crystals.
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Auto-Immunisierungsvorgänge lassen sich beim Menschen nicht nur bei der subchronischen und chronischen Glomerulonephritis, sondern auch im Verlauf der Hepatitis nachweisen, sind aber auf entzündlich bedingte Parenchymschädigungen beschränkt. Dabei weichen die im Vergleich zur klinischen Symptomatologie gewonnenen Verlaufskurven der Ak.-Titer beim Menschen deutlich von den unter ähnlichen Voraussetzungen gewonnenen Verlaufskurven beim Tier ab; auch im klinischen Bild besonders der Hepatitiden ergeben sich keine Symptome, die mit Sicherheit als Folge der während der Erkrankung auftretenden Auto-Immunisierung ermittelt werden können. Eine pathogenetische Bedeutung der Auto-Ak. für die Klinik der entzündlich bedingten Parenchymschädigungen der Leber und Niere ist damit beim Menschen nicht zu beweisen, obwohl die Entstehung der tierexperimentellen Parenchymschädigung durch die Reaktion eines serologisch gleichgearteten Auto-Ak. mit dem Gewebs-Antigen als gesichert gelten kann. Die Beschränkung der Auto-Immunisierung nur auf entzündlich bedingte Parenchymerkrankungen macht es möglich, den Auto-Ak.-Nachweis zur Differentialdiagnose von degenerativen Pyrenchymveränderungen des gleichen Organs oder von Tumoren mit auszuwerten.
Article
1.1. Twenty-two young men with clinical manifestations of infectious mononucleosis were studied by liver function tests and liver biopsy in an attempt to clarify aspects of hepatitis in this disease.2.2. Function tests and/or biopsy indicated hepatic involvement in all cases, biopsy specimens showing return to normal in all but one instance within five weeks.3.3. One case of persistent hepatitis, studied by function tests and serial biopsies, showed continuation of the disease for approximately eight months, and is still being followed up.4.4. In three of the twenty-two cases heterophil antibody determinations remained below diagnostic evels. All three had abnormal liver function tests and two biopsy specimens yielded positive findings despite lack of confirmation of the diagnosis by the Paul-Bunnell test.5.5. The significance of these results in the light of previous studies by other observers is discussed.
Article
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Article
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Article
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Article
In der vorliegenden Arbeit wurde ber die Fhigkeit verschiedener Seren, Erythrocyten des Macacus rhesus zu agglutinieren, berichtet. Wir fanden, da 52% der Seren von Patienten mit Virushepatitis einen erhhten Hmagglutinationstiter aufwiesen. Seren von Patienten mit Mononueleosis infectiosa verhielten sich hnlich, denn 43% besaen einen erhhten Titer. Bei klinisch gesunden Blutspendern war der Titer in 10% erhht. Als erhht wurde ein Titer von mindestens 1256 angesehen. Statistisch lie sich zeigen, da die erhhten Titerwerte bei Hepatitis und bei Mononueleosis infectiosa wahrscheinlich nicht rein zufllig sind. Im Verlauf einer Virushepatitis kann es zu einem signifikanten Titeranstieg kommen. Ein Zusammenhang zwischen Hmagglutinationstiter und Leberfunktionsproben scheint nicht zu bestchen. Paul-Bunnel-Test und Hoyt-Morrison-Test (Hmagglutinationstest mit Macacus rhesus-Erythrocyten) weisen keine eindeutige Korrelation auf. Die Natur des hmagglutinierenden Faktors ist bis heute unbekannt.
Article
A modified indirect Coons' immunofluorescent technic was used to determine whether or not there exist circulating anti-liver tissue antibodies in the sera of 20 patients with various chronic liver diseases and 25 patients other than liver diseases. The normal liver tissue obtained from victims of traffic accident within 3 hours of death was used as antigen. For the control gamma-globulin in the normal liver was stained by direct Goons' technic. Even in the normal liver, intracytoplasmic gamma-globulin was observed in a certain cytoplasm of the hepatic cells in three out of five cases, and also in the cytoplasm of Kupffer's cells in one of them. The incidence of circulating antibody to the cytoplasm of hepatic cell was 13 out of 20 cases (65%), anti-nucleus antibody was one in 20 (5%), and anti-cytoplasm of bile ductular cell antibody was two in 20 patients (10%) with chronic liver diseases, whereas the sera of normal persons as well as of patients other than liver diseases were all proved to be negative. The anti-nucleus antibody was non-specific in species and organs. No close correlation was found among the appearance of anti-liver tissue antibodies, gamma-globulin quantities in sera, and tissue reactions such as single cell necrosis, piecemeal necrosis, and cell infiltration in the Glisson's capsule. Nonetheless, the appearance of circulating antibody to the cytoplasm of hepatic cell was detected in seven of 8 patients (87.5%) with active chronic hepatitis. The results imply an etiological role of anti-liver tissue antibody on the progression and prolongation of liver diseases.
Article
The foregoing experiments have shown that complement fixation takes place when the blood serum of normal adult rabbits is mixed with fresh saline extracts of normal rabbit tissues under controlled conditions. A natural antibody, which reacts in vitro with a sedimentable constituent of normal tissue cells, is responsible for the phenomenon.
Article
1. Techniques for the preparation of skin antigen suitable for intramuscular injection in rabbits, and of skin antigens (autolysate) for serological experiments are described. 2. A method was evolved which produced a soluble skin antigen (autolysate) suitable for performing precipitin tests. 3. Injection of the rabbit skin antigen and of staphylococcus toxin in rabbits resulted in the formation of antibodies (precipitins) to homologous skin. 4. When homologous skin alone was injected into rabbits, the antibody formation was questionable, or at most, slight. 5. The injection of staphylococcus toxin alone resulted in antibody formation, this antibody being specific for the toxin and not reacting with broth. 6. By utilization of the synergistic action of staphylococcus toxin and of homologous skin antigen, it has been possible for the first time to produce specific antiskin antibodies in experimental animals.
Article
Continued serological investigations of the sedimentable constituents of normal and neoplastic tissues have shown that the blood serum of normal rabbits will fix complement in mixture with saline extracts of normal rabbit tissues. The phenomenon has proved referable, not to anticomplementary effects of serum or antigen nor to so called non-specific complement fixation, but to a naturally occurring serum principle, hitherto unrecognized, which reacts specifically in vitro with a sedimentable constituent of normal tissue cells. The principle exists in the blood of nearly all adult rabbits but is absent from that of rabbits less than 1 month old. It can be salted out from serum with ammonium sulfate and is destroyed when heated at 65 degrees C. for 20 to 30 minutes. Its titer was found to run parallel in general with that of two natural antibodies also present in normal rabbit's blood (natural Wassermann reagin, natural anti-sheep hemolysin); but absorption tests showed it to be distinct from these. Because of its properties, the serum principle has been termed the natural tissue antibody. The substance with which the natural tissue antibody reacts is regularly present in saline extracts of many normal tissues,-those of rabbits and of other species as well. Kidney and liver tissues always yield it in abundance, while spleen, brain, and testicle provide somewhat less; heart and voluntary muscle extracts contain relatively little, and non-nucleated erythrocytes and skin are practically devoid of it. The results of affinity and absorption tests indicate that it is nearly or quite the same from whatever tissue or species derived. It is readily sedimentable in the high-speed centrifuge, little or none remaining in the supernatant liquid of potent suspensions spun at 25,000 R.P.M. (45,400 g) for 1 hour. It either does not come away into alcohol or is inactivated thereby, is readily destroyed by heat (56-70 degrees C. for 30 minutes), and diminishes notably in antigenic potency upon standing overnight in saline suspension or when the tissues containing it are kept in glycerol. Its properties suggest that it may be a protein. The implications of the findings are discussed in relation to the formation of the natural antibody and its place amongst serological phenomena, to so called "non-specific" fixation of complement and other serological complexities, and with particular reference to the character of the sedimentable constituents of normal and neoplastic tissue cells.
Article
Rabbits injected with emulsions of homologous kidney to which staphylcoccus or streptococcus toxins had been added produced complement fixing antibodies which reacted with both rabbit kidney and brain. By absorption tests it was demonstrated that the sera contained at least two antibodies, one specific for kidney, the other non-specific. Similar kidney antibodies were found in the blood of a majority of patients with scarlet fever but in only a few normal persons. The possibility that a similar or related antibody may be concerned in the etiology of scarlatinal nephritis is discussed.
Article
Nephritis can be induced in rats by the injection of anti-kidney sera obtained from rabbits immunized with suspensions of perfused rat kidney. Anti-kidney sera, thus prepared, contain a number of antibodies capable, on injection into rats, of inducing a severe anaphylactoid reaction with general vascular manifestations that involve the kidney as well as other organs. These sera also contain a nephrotoxic agent that affects the kidney primarily. The nephrotoxic effect is characterized clinically by severe persistent albuminuria with casts, and transient anasarca during the acute disease, but no significant hematuria occurs. When a severe anaphylactoid reaction is superimposed on the nephrotoxic injury, hematuria is an outstanding feature. Nephrotoxin is demonstrable in vivo and is not related quantitatively to the precipitins in the anti-kidney serum against kidney extract. It is most readily obtained by immunization with kidney suspensions, but may occasionally appear after injections of other organ preparations; it does not result from immunization with erythrocytes or serum. Nephrotoxin is present in the globulin fraction of anti-kidney serum. The nephrotoxic action of anti-kidney serum is easily removed by absorption with kidney cells or fat-free kidney tissue. Similar preparations of liver likewise remove it, but less readily. Neither kidney, liver, or brain lipids affect it, nor does absorption with red blood cells or serum. Nephrotoxin appears to be an antibody that is relatively organ specific in its affinities. It differs from the more common antibodies involved in reverse anaphylaxis in one respect, at least: The animal rapidly becomes desensitized against the latter and fails to react, whereas desensitization to nephrotoxin is difficult to secure.
Article
The degree of immunization and sensitization of rabbits following injections of beef lens is markedly increased when the animals are under the influence of staphylotoxin. Since the effect of the latter is exerted when the two substances are introduced separately into the same tissues with several hours elapsing between injections, or into different veins, it appears that an intimate association of them is unnecessary. A stimulating action of the toxin on the antibody-forming cells is a more probable explanation of the phenomena observed. Animals actively immune to staphylotoxin fail to show any synergic effect of this toxin when introduced with beef lens. Neutralization of the toxin in vitro, on the other hand, fails to eliminate this stimulating effect.
Article
Two substances differing in immunological behavior as well as in certain chemical properties have been isolated from soluble extracts of B. proteus X-19. Both substances appear to be polysaccharides. The first substance is precipitated from X-19 crude extracts by a relatively low percentage of alcohol and electrolytes (from one to two and a half volumes of alcohol). When purified as far as possible, it gives a negative biuret reaction, a positive Molish and has a nitrogen content of 4 per cent. This material, which we call X factor, has the immunological properties of the common antigenic factor in Proteus X-19 and typhus Rickettsiae, described elsewhere. It has the property of precipitating with typhus serum as well as anti-Proteus serum, even after treatment with hot alkali. The second substance we call P factor, suggesting a material which is proper to Proteus X-19 and has nothing to do with the Weil-Felix reaction. It is obtained from the crude extracts of B. proteus X-19 by treating the fluids from which the X factor has been removed with an excess of alcohol (seven to ten volumes, according to electrolytes in solution). The purified material shows a nitrogen content of a little less than 1 per cent, gives a negative biuret and a positive Molish reaction. The P factor produces precipitates with anti-Proteus serum in considerable dilution, but has no effect on typhus serum. It is quickly destroyed on treating with alkali, a fact in accordance with the results already cited, which were obtained by White with whole extracts of B. proteus X-19. The duality of the X-19 extracts seems to be explained by the isolation of two immunologically different factors; one which is alkali-labile and which is proper to B. proteus X-19; and the other which is alkali-stable and is the common antigenic factor in Proteus X-19 and typhus Rickettsiae.
Article
The repeated intramuscular injections of aqueous emulsions and alcohol-ether extracts of sterile normal rabbit brains in some manner produced pathological changes accompanied by myelin destruction in the brains of 7 of 8 monkeys (Macacus rhesus). Eight, control monkeys remained well. Cultures from the involved brains remained sterile, and no transmissible agent was demonstrated by means of intracerebral inoculations of emulsions of bits of the brains into monkeys, rabbits, guinea pigs, and white mice.
Article
Rabbits injected with fresh emulsions of homologous brain developed few or no antibodies capable of fixing complement in the presence of aqueous emulsions or alcoholic extracts of rabbit brain. Complement-fixing antibodies, however, were produced in rabbits by means of injections (1) of sterile emulsions of homologous brain which had been allowed to stand at room temperature for 5 to 30 days and (2) of emulsions of homologous brain experimentally infected with vaccine virus. The antisera that were produced following injections of emulsions of autolyzed homologous brain were shown by absorption tests to contain both specific and non-specific antibodies. The specific brain antigen was found to be approximately six times as abundant in the white matter as in the grey. It was almost absent from the brain of fetal and newly born rabbits, but increased in amount with the age of the animal to reach a maximum concentration at maturity. The specific antigen seemed to parallel the myelin content of brain tissue.
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