bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF ANTIBODY ON INTRACELLULAR PARASITISM OF SALMONELLA TYPHIMURIUM IN MONONUCLEAR PHAGOCYTES IN VITRO
Authors: Gelzer Justus , Suter Emanuel
Published: June 2004

The effect of antibody on the fate of Salmonella typhimurium within mononuclear phagocytes (MN) of rabbits was studied in vitro. Monocytes and bacteria were incubated either in absence or presence of antibody. After 45 minutes during which phagocytosis occurred infected cells were washed to remove extracellular bacilli and free antibody. The cells were then reincubated in a medium without addition of antibody, and the interaction between the MN and bacteria was followed, correlating bacterial viability and the morphology of the mixture. The following results were obtained.

The anti-Salmonella antibody was not bactericidal even in presence of complement and did not enhance phagocytosis.

Regardless of whether antibody was present or absent during phagocytosis, the bacteria appeared to multiply within the cells. When no antibody was present during phagocytosis the infected cells were severely damaged within a few hours of incubation, and extensive extracellular multiplication was dominating. When antibody was present during phagocytosis MN packed with bacteria persisted for a long time. Little or no extracellular growth occurred.

It was possible to demonstrate the presence of the antibody within the infected MN, using the fluorescent antibody technique. The antibody appeared as a coat around the bacteria. Antibody entered the cells only during phagocytosis, presumably attached to the bacteria.

The active factor of the immune serum was found in the gamma globulin fraction and reacted specifically with the somatic antigen of Salmonella typhimurium. The antiflagellar portion of the antiserum was not involved in the phenomenon described.

It is concluded that this antibody protects monocytes against the effect of intracellularly located Salmonella.
SEVERE ACTIVE CUTANEOUS HYPERSENSITIVITY IN THE RAT PRODUCED BY HEMOPHILUS PERTUSSIS VACCINE
Authors: Rowley Donald A. , Chutkow Jerry , Attig Charles
Published: June 2004

Hemophilus pertussis vaccine injected into normal rat skin produced local edema lasting several days. Four to 6 days later the injected site became severely inflamed. When uninjected skin was challenged 5 to 28 days after the initial injection, severe inflammation developed at the site of challenge within 12 to 24 hours. This secondary hypersensitive response was elicited by a dose of vaccine which produced little or no initial or delayed inflammation in a normal rat. Specific cutaneous hypersensitivity to a particulate antigen (i.e. typhoid vaccine) or a soluble antigen (human or rabbit gamma globulin) developed when rats were injected with a mixture of the antigen and pertussis vaccine. Pertussis vaccine mixed with typhoid vaccine did not enhance circulating agglutinin formation to typhoid vaccine. Cutaneous hypersensitivity to pertussis vaccine was passively transferred to normal rats by lymph node cells but not with serum from hypersensitive rats. Sensitization with pertussis vaccine did not enhance the edema-producing activity of histamine, serotonin, or 48/80 given subcutaneously. Mast cells in areas of hypersensitive inflammation were not damaged appreciably. The hypersensitive inflammation was not inhibited by treatment with anti-serotonin and antihistaminic drugs. Hypersensitive rats "depleted of mast cells" responded to challenge with pertussis vaccine with severe inflammation though their response to 48/80 was depressed. Hypersensitive rats treated with x-irradiation showed decreased hypersensitive inflammation though they responded normally to 48/80 and histamine.

These studies failed to demonstrate a role for circulating antibody in the cutaneous hypersensitive inflammation produced in the rat by pertussis vaccine. Furthermore, the findings indicated that the cutaneous hypersensitive inflammation is not mediated by tissue serotonin and/or histamine.
THE DEPOSITION OF EXOGENOUS COPPER UNDER EXPERIMENTAL CONDITIONS WITH OBSERVATIONS ON ITS NEUROTOXIC AND NEPHROTOXIC PROPERTIES IN RELATION TO WILSON'S DISEASE
Authors: Vogel F. Stephen
Published: June 2004

Goldfish kept in water containing ionized copper and a detergent added with the aim of decreasing coagulation of the mucus on the gills, took in and retained this metal in their brains, livers, and kidneys, in concentrations comparable to those that occur naturally in Wilson's disease, as chemical assays disclosed. Histochemical studies made it clear that much copper had accumulated within the large neurons, principally in those of the telencephalon and anterior horn region of the spinal cord and in the tubular epithelial cells of the kidneys, the nuclei of the parenchymal cells of the liver, the sarcoplasm of the skeletal muscle, and in the epithelial covering of the gills.

The intraneuronal deposition of copper was regularly associated after a time with conspicuous cytologic changes, notably contraction and hyperchromaticity of the nerve cells with tortuosity and fragmentation of the axis cylinders and lysis and loss of neurons. The accumulation of metal in the renal epithelium was frequently accompanied by necrosis and was regularly associated with hyperplasia and calcification of the epithelial cells of the larger renal tubules in all goldfish kept for prolonged periods in copper-rich water. The deposition of copper in the liver was not accompanied by consistent cytologic changes.

The similarity of the cytologic alterations induced in the central nervous systems by copper and those that occur naturally in hepatolenticular degeneration in human beings provides evidence that copper itself plays an important role in the pathologic alterations of the brain in Wilson's disease.
MORPHOLOGIC EVIDENCE FOR COLLAGEN CHANGES IN CHICH EMBRYOS TREATED WITH ß-AMINOPROPIONITRILE
Authors: van den Hooff Arnold , Levene Charles I. , Gross Jerome
Published: June 2004

Electron microscope analysis of thin sections of intact skin from 17 day chick embryos injected with ß-aminopropionitrile 3 days earlier, revealed markedly increased dispersion in fibril diameter both above and below the narrow distribution of normal fibril size. Extraction with cold 1 M neutral saline caused a dissolution of the fibrils to fine filaments of varying diameters.

Histologic examination of the connective tissue of lathyritic skin prior to extraction revealed little difference from the normal. After extraction the collagen either disappeared almost entirely or was observed as a homogeneous smear.

These results of morphologic analysis are consistent with previous chemical studies, supporting the thesis that lathyrogenic agents induce disruption of intermolecular cross-linking within normally insoluble collagen fibrils, allowing them to dissolve in cold neutral salt solutions.
THE RELATIONSHIP OF TOXIN AND ANTITOXIN INJECTION SITE TO TETANUS DEVELOPMENT IN THE RAT
Authors: Fedinec Alexander A. , Matzke Howard A.
Published: June 2004

The pattern of development of symptoms was studied following injection of 3 MLD (minimum lethal dose) of tetanus toxin in each of the following sites in the rat: vein, muscle, endoneurium, epineurium, spinal cord, subarachnoid space, and subdural space. Similar observations were made when 3 MPD (minimum protective dose) of antitoxin were injected into each of the above sites a few minutes after the intramuscular injection of toxin.

Local tetanus followed intramuscular, endoneurial, and epineurial injection of the toxin; blood-borne tetanus also appeared in the latter instance. Tetanus dolorosus followed intraspinal injection of toxin. Both dorsal tetanus and blood-borne tetanus developed after subdural administration of toxin. Blood-borne tetanus, alone, appeared following intravenous and subarachnoid injection of toxin.

In no case did injection of antitoxin at the various sites listed above prevent local tetanus from developing after intramuscular injection of toxin. Of the various sites injected with antitoxin, the intramuscular, intraspinal, and intravenous were the most effective.

It is suggested that the endoneurial tissue spaces serve as a conduit for tetanus toxin from the muscle to the CNS. The perilemma of the peripheral nerve trunk may act as a selectively permeable membrane which permits tetanus toxin to pass from the epineurium to the endoneurium. Outward diffusion of toxin from the endoneurial spaces is apparently markedly reduced. The antitoxin probably is prevented from permeating this barrier in either direction. The importance of absorption of tetanus toxin by the lymphatic and blood circulation is discussed.
FACTORS DETERMINING PATHOGENICITY OF VARIANTS OF ECHO 9 VIRUS FOR NEWBORN MICE
Authors: Eggers Hans J. , Sabin Albert B.
Published: June 2004

While some strains of ECHO 9 virus were found to be completely incapable of multiplying in newborn mice or even of being adsorbed by their tissues (e.g., the prototype Hill strain), other naturally occurring strains readily multiplied even after inoculation of as little as 3 TCD50 of virus. With the multiplying strains, the infection remained clinically inapparent except after inoculation of very large doses, usually in the range of 105 to 107.5 TCD50. Investigation of the question why such large doses were required to produce paralysis indicated that for paralysis to occur virus multiplication had to reach a level of 108 TCD50 or more within 4 days after inoculation of mice less than 1 day old. The reason for this was found in the fact that at 5 to 6 days of age the mice lost their susceptibility to paralysis even when multiplication was capable of progressing to the indicated high level. Thus, speed of multiplication and extent of muscle involvement before the 5th day of life were the determining factors. Passage in tissue culture had no effect except to yield a larger dose for inoculation, while serial propagation in mice resulted in a gradual enrichment of virus particles capable of more rapid multiplication in mice and in a concurrent greater paralytogenic activity of smaller doses.
SUPPRESSION OF EXPERIMENTAL "ALLERGIC" ENCEPHALOMYELITIS IN GUINEA PIGS BY ENCEPHALITOGENIC PROTEINS EXTRACTED FROM HOMOLOGOUS BRAIN
Authors: Shaw Cheng-Mei , Fahlberg Willson J. , Kies Marian W. , Alvord Ellsworth C.
Published: June 2004

The intradermal injection of aqueous solutions of certain homologous neural proteins will suppress the encephalomyelitis which is induced in guinea pigs by the previous injection of whole homologous brain with Freund's adjuvants. These neural proteins extracted by dilute acid from defatted guinea pig brain are themselves highly encephalitogenic when injected with adjuvants, but the specificity of this suppression for encephalitogenic as compared to non-encephalitogenic extracts remains to be proven.

Suppression is probably not due to a non-specific stress reaction, as indicated by the absence of suppression by intradermal injections of alcohol and by statistically insignificant and inconstant effects of similar injections of tuberculin.
IMMUNOCYTOCHEMICAL STUDY OF GAMMA GLOBULIN IN LIVER IN HEPATITIS AND POSTNECROTIC CIRRHOSIS
Authors: Cohen Seymour , Ohta Goroku , Singer Edward J. , Popper Hans
Published: June 2004

Gamma globulin was demonstrated by immunocytochemical fluorescence technique in many reticuloendothelial cells of the hepatic sinusoids and of the fibrous tracts in various forms of hepatitis and in postnecrotic cirrhosis. In other liver diseases and in normal livers, even in the presence of hypergammaglobulinemia, few if any gamma globulin-containing cells were found. In contrast, spleen and lymph nodes showed no difference between postnecrotic cirrhosis or hepatitis and other types of cirrhosis or non-hepatic hypergammaglobulinemias. The gamma globulin-containing cells in the liver are on cytologic grounds considered reticuloendothelial cells showing transition to plasma cells and exhibiting little or no phagocytosis of tissue breakdown products. These cells are assumed to form rather than engulf gamma globulin. The possibility that the gamma globulin formed represents antibody to liver cell breakdown products is discussed.
THE SPECIFICITY OF ALLERGIC REACTIONS
Authors: Salvin S. B. , Smith R. F.
Published: June 2004

Guinea pigs sensitized with either hen, duck, or goose egg albumin showed delayed hypersensitivity followed by Arthus reactions to the homologous antigen, but tended to have much weaker delayed responses and slower antibody formation to heterologous antigens. Guinea pigs with delayed hypersensitivity to one of the avian antigens had a slower antibody response to a secondary injection of heterologous antigen than to one of the homologous antigen.

Sensitization with a protein conjugated with a hapten such as picryl chloride (Pi) or dinitrofluorobenzene (DFB) resulted in delayed hypersensitivity to the homologous conjugate, the homologous protein, and the homologous protein with a heterologous hapten. Circulating antibody and Arthus reactions occurred subsequently to the homologous conjugate, as well as to the homologous hapten attached to a heterologous protein. Delayed hypersensitivity thus seemed associated with the protein moiety, and Arthus responses with the hapten.

Anamnestic responses followed injection of an antigen causing delayed hypersensitivity, but not of a hapten not causing delayed reactions. Thus, animals sensitized initially with Pi·HEA, DFB·HEA, or HEA produced antibodies sooner after a secondary injection of Pi·HEA than did unsensitized animals. No anamnestic response resulted when animals sensitized to Pi·BGG were injected with Pi·HEA.

Thus, delayed hypersensitivity is indicated to be a preliminary and immature step in the immune process, with specificity directed against broad, more general features of the protein antigen. This intermediate step is followed by production of circulating antibody to any antigen having a similar basic structure, with the specificity of the antibody also directed against smaller immunologically active sites on the antigen molecule.
BIOLOGICAL PROPERTIES OF RIBONUCLEIC ACID FROM VIRULENT AND ATTENUATED POLIOVIRUS
Authors: Gerber Paul , Kirschstein Ruth
Published: June 2004

Concentrates of type I poliovirus were extracted with phenol by Gierer and Schramm's method. The infectivity of these extracts in tissue culture and mice appeared to be associated with viral RNA.

Studies on neurovirulence based on the "t" marker and intraspinal pathogenicity in mice demonstrated that the viral progeny of RNA isolated from virulent viruses had the "t+" character and were highly neurotropic for mice. Conversely, RNA extracted from attenuated virus gave rise to a progeny of "t" type which were avirulent for mice.

The results suggest that the infective RNA from type, I poliovirus carries the genetic information which determines the degree of neurovirulence.
A METHOD OF SELECTING FOR AUXOTROPHIC MUTANTS OF HELA CELLS
Authors: De Mars Robert , Hooper J. Leonard
Published: June 2004

1. Aminopterin prevents the multiplication of HeLa cells in Eagle's medium. The joint addition of adenine and thymidine removes the inhibition.

2. The aminopterin-induced thymine deficiency specifically results in a cessation of cell division and a doubling in the average protein content of the cells. Continued starvation for thymine results in the inability of cells to proliferate after aminopterin is removed. After 6 days only 10–6 to 10–5 of the original population proliferates.

3. The omission of a single essential amino acid, such as arginine or glutamine, from the medium during deprivation of thymine prevents a net increase in protein and results in about a 105-fold greater cell survival after 6 days, when aminopterin is removed and the missing amino acid is supplied.

4. Glutamine-requiring, auxotrophic mutants of HeLa exhibit a high survival after exposure to aminopterin in a glutamine-free medium. Glutamine-independent HeLa cells show a much lower survival in the same medium. Low frequencies of the auxotrophs can be specifically and efficiently selected for in artificial mixtures of the two cell types by treatment with the glutamine-free medium containing aminopterin.
STUDIES ON THE MECHANISM OF THE SHWARTZMAN PHENOMENON
Authors: Lee Leung , Stetson Chandler A.
Published: June 2004

Rabbits given single injections of endotoxin and then skin-tested with endotoxin from 1 day to 1 month later exhibit accelerated skin reactions resembling the Arthus phenomenon.

Injection of one endotoxin alters the subsequent reactivity of rabbits to other endotoxins as well.

The state of altered reactivity can be transferred with serum, and appears to be related to the presence of non-precipitating cross-reactive antibody, rather than to specific precipitating antibody.
THE EXTENSION OF THE SHWARTZMAN PHENOMENON TO THE MOUSE AND SOME ECOLOGICAL DETERMINANTS OF THE SINGLE-INJECTION REACTION
Authors: Arndt William F. , Schneider Howard A.
Published: June 2004

The localized Shwartzman reaction has been demonstrated in a highly inbred mouse strain (BSVS). This reaction was produced with marked regularity in these mice by administration of relatively small doses of bacterial endotoxin or other Shwartzman-active agents. It is considered the equivalent of the phenomenon described in the rabbit inasmuch as it has conformed to all the operational and histopathological aspects of the classical reaction that have been tested, including elicitation by various endotoxins, heterologous preparation and provocation, inhibition by anticoagulants, and provocation by antigen-antibody complexes.

A reaction similar to the above but differing in its manner of production was also investigated and has been termed the single-injection Shwartzman reaction. This phenomenon was identical with the normal Shwartzman reaction in all ways except for the fact that it was elicited with but a single intradermal injection of bacterial endotoxin. In investigating the lesion it has been demonstrated that inapparent in the gross, but elicitible infection of the lungs with a Gram-negative microflora was uniformly associated with single-injection reactivity. Because of this constant association it has been suggested that a causal relationship exists between the infected state and the skin reaction, not on the basis of known immunological events but on the basis of the Shwartzman mechanism in which the lung flora, demonstrably excited by the preparative injection, appears to mediate natural "endogenous" provocation of the lesion at the prepared skin sites.
PREPARATION AND ANTIGENICITY OF M PROTEIN RELEASED FROM GROUP A, TYPE 1 STREPTOCOCCAL CELL WALLS BY PHAGE-ASSOCIATED LYSIN
Authors: Kantor Fred S. , Cole Roger M.
Published: June 2004

The lysis of Group A type 1 streptococcal cell walls by phage-associated lysin has been described. In the preparation of lysin, a new semisynthetic non-protein media to support growth of the propagating strain of Group C streptococci was employed. Following lysis of the cell walls, the resulting digest was partially purified by ion-exchange chromatography and ammonium sulfate precipitation. In addition to M protein, the resulting preparation (called lysin M protein) contained the group-specific carbohydrate and the T protein—but did not contain antigens, detectable by precipitin tests, which cross-reacted with absorbed heterologous group or type antisera. Capillary precipitin reactions between the lysin M protein and type-specific antiserum did not occur in the presence of high ionic strength buffers; these buffers did not similarly affect precipitin reactions of acid M protein.

Type 1 lysin M protein is shown to be a good antigen. A total of 1.5 mg. injected intradermally in saline produced bactericidal antibody in eight of nine rabbits; when injected in adjuvant in one rabbit, protective serum antibodies developed. Streptococci grown in sera from seven of nine rabbits immunized with lysin M protein demonstrated significantly longer chains than when grown in normal rabbit serum. Antibody as demonstrated by each of these three tests was shown to be type-specific.

No local or systemic toxicity was noted following intradermal injection in rabbits of lysin M protein.
BIOCHEMICAL STUDY OF CELLULAR ANTIGEN-ANTIBODY REACTION IN TISSUE CULTURE
Authors: Hayashi Hideo , Tokuda Akira , Udaka Keiji
Published: June 2004

The correlation between morphological and biochemical changes produced by the antigen-antibody reaction was studied in cultures of tissue monocytes taken from sensitized animals. The cells were grown under conditions which allowed collection of samples from the culture fluid as well as microscopic observation.

Introduction of the antigen into the culture medium causes rapid release of a protease characterized by its susceptibility to sulfhydryl block and its optimum pH in the neutral range. Protease activation occurs simultaneously with morphological changes in the cytoplasm of the cultured cells. Delayed changes affecting the mitochondria and Golgi bodies appear after the peak of the proteolytic reaction and may be secondary to it. The gradual inactivation of the protease observed in the course of the antigen-antibody reaction will be discussed in a separate paper.
ON THE COLLAPSE OF BACTERIAL ENDOTOXIN RESISTANCE FOLLOWING HEMORRHAGE
Authors: Greisman Sheldon E.
Published: June 2004

Unanesthetized immature albino rabbits exposed to 2 hours of severe but reversible hemorrhagic shock induced with aseptic precautions by multiple cardiac bleedings exhibited no increase in susceptibility to single intravenous injections of 200 µg./kg. E. coli endotoxin administered 4 hours post retransfusion, a quantity of endotoxin that was found to be the largest dose uniformly non-lethal to normal rabbits. Paired and randomly selected rabbits treated identically except for the additional procedure of a femoral arterial cutdown and ligation (without aseptic precautions) exhibited increases in susceptibility to the same endotoxin of several hundredfold. This effect could not be attributed to the femoral cutdown and arterial ligation alone since such trauma when coupled with sham cardiac bleedings failed to increase susceptibility to 200 µg./kg. of endotoxin. These data appear valid since sham cardiac bleedings produced no detectable impairment of myocardial contractility, while 2 hours of hemorrhagic shock at 50 mm. Hg with the Lamson reservoir technique caused an increase in endotoxin susceptibility comparable to that seen when cardiac bleedings were combined with a non-sterile femoral arterial cutdown and ligation.

The mechanisms increasing the susceptibility to E. coli endotoxin were investigated. It was found that (a) rabbit femoral skeletal muscle is normally contaminated with clostridia, (b) the use of aseptic femoral wounding precautions exerted some suggestive protective influence, (c) the use of aseptic wounding precautions combined with immediate topical sulfanilamide and wound closure exerted a significant protective influence, and (d) prophylactic polyvalent gas gangrene antitoxin protected in a manner not demonstrable when diphtheria antitoxin was employed as a control. These observations suggest that clostridial wound infection is one mechanism whereby a femoral arterial cutdown lowers endotoxin resistance of the rabbit following hemorrhagic shock.

It is, however, not the only mechanism since the ligation of a femoral artery during hemorrhagic shock led to edema following retransfusion equivalent to a mean of approximately 30 per cent of the original circulating plasma volume. The intensification of shock caused by this transudation presumably intensified reticulo-endothelial injury, and thus further lowered the resistance of the rabbit to an intravenous injection of endotoxin 4 hours following retransfusion.
IN VITRO STUDIES ON THE INTERACTION BETWEEN MOUSE PERITONEAL MACROPHAGES AND STRAINS OF SALMONELLA AND ESCHERICHIA COLI
Authors: Jenkin Charles , Benacerraf Baruj
Published: June 2004

Virulent strains of Salmonella opsonized with normal mouse plasma are never phagocytosed as well as avirulent strains.

The virulent strains of Salmonella phagocytosed after opsonization with normal mouse plasma are able to multiply within normal mouse peritoneal macrophages, whereas under similar experimental conditions the avirulent strains are killed.

When virulent strains of Salmonella are opsonized with specific antiserum or plasma from BCG-infected mice, they are treated by normal mouse macrophages as if they were avirulent.

Virulent bacteria opsonized with BCG plasma are phagocytosed and killed better by peritoneal macrophages from BCG-infected mice, than peritoneal macrophages from normal mice.
THE MOVEMENT OF ELECTROLYTES AND OF WATER IN SURVIVING TISSUE OF THE LIVER
Authors: Broome John D. , Opie Eugene L.
Published: June 2004

When liver slices immediately after their removal from the body are immersed in graded solutions of sodium chloride, movement of water does not follow a course determined by movement of sodium ions. From hypotonic solutions sodium enters slowly and swelling proceeds rapidly but with increasing concentration entrance of sodium increases and swelling diminishes in accord with the osmotic relations between tissue and the medium.

The extracellular fluid of liver has the same osmotic pressure as blood plasma, and entrance of water into liver slices from media with greater molar concentration is determined by the intracellular pressure of the parenchymatous cells of the tissue.

The plasma membrane of the liver cell is semipermeable to electrolytes but its semipermeability is imperfect, may be impaired, and when in media isotonic with the cells some of the electrolyte enters them. With continued entrance permeability to both electrolyte and water increases and in case of sodium become evident after 15 or 20 minutes.

A medium more favorable to the tissue prolongs the period of isotonicity. In solutions with electrolytes otherwise similar to those of the blood plasma, e.g. Krebs-Ringer solution, but with molar concentration of electrolytes approximately doubled by addition of sodium chloride isotonicity may be prolonged during a period of 1 hour or more.

When potassium chloride is added to the Krebs-Ringer solution so that its potassium content has been increased 10-fold the water intake of liver cells has not varied in accord with the potassium content of the medium.

In a medium with the electrolyte contents of blood plasma (Krebs-Ringer solution) liver cells after 1 hour gain sodium and lose potassium, but later potassium maintains a nearly constant level though swelling increases.

Less sodium enters and less potassium is lost from liver cells at 0°C. than at 38° and 0°C. swelling is greater.

Movement of water between cells and extracellular fluid may occur independently of changes in the sodium or of potassium content of cells and doubtless is in part determined by substances associated with metabolism.
STUDIES ON THE EFFECT OF CERTAIN MACROMOLECULAR SUBSTANCES ON THE RESPIRATORY ACTIVITY OF THE LEUCOCYTES OF PERIPHERAL BLOOD
Authors: Strauss Bella S. , Stetson Chandler A.
Published: June 2004

The oxygen, uptake of lightly heparinized human blood was found to increase markedly upon the addition of bacterial endotoxins, soluble antigen-antibody complexes, or polystyrene latex particles. The effect apparently reflects a transitory stimulation of respiratory activity of the blood leucocytes.

The effect did not occur in the presence of anticoagulant amounts of citrate or ethylenediaminetetraacetate, was inhibited by iodoacetate and fluoride ions, and may be related to the energy-yielding processes involved in histamine release or phagocytosis.
ELECTRON MICROSCOPIC OBSERVATIONS ON ALLERGIC ENCEPHALOMYELITIS IN THE RABBIT
Authors: Luse Sarah A. , McDougal David B.
Published: June 2004

Allergic encephalomyelitis was produced in rabbits by injection of white matter from bovine brain plus adjuvants. Electron microscopy revealed focal demyelinization in both the spinal roots and cord. The peripheral lesions were characterized by vacuolization of Schwann cytoplasm, destruction of the myelin sheath, and by some appearances suggesting remyelinization. In the cord there was a marked perivascular inflammatory infiltration with focal destruction of the blood-brain barrier as demonstrated by formation of an abnormal interstitial space about capillaries. Mitochondria of oligodendroglia were strikingly swollen whereas those of other cells were morphologically normal. Axons were denuded of their myelin sheaths and the myelin detritus sequestered within gitter cells. Fibrous astrocytic gliosis occurred to some degree. Focal evidences of myelin reformation were noted centrally as well as peripherally. Allergic encephalomyelitis, as a primary demyelinating lesion, is contrasted with Wallerian degeneration in which myelin degeneration is secondary to destruction of the axon.
CORRELATION OF PRODUCTION OF INFECTIOUS VIRUS WITH SEQUENTIAL STAGES OF CYTOLOGIC ALTERATION IN HELA CELLS INFECTED WITH ADENOVIRUSES TYPES 5 AND 7
Authors: Boyer Georgianna S. , Denny Floyd W. , Miller Irving , Ginsberg Harold S.
Published: June 2004

Studies correlating the production of infectious adenovirus (types 5 and 7) and the progression of the stages of virus-induced cytologic change in HeLa cells are presented. The results reveal a close relationship between the development of the characteristic nuclear changes and adenovirus synthesis. They suggest that cells manifesting the first stages of nuclear change, characterized by the appearance of eosinophilic, Feulgen-negative inclusions, contain little or no mature infectious virus, whereas cells in the later stages, with Feulgen-positive and basophilic inclusions, contain relatively large amounts.
DEGRANULATION OF POLYMORPHONUCLEAR LEUCOCYTES FOLLOWING PHAGOCYTOSIS OF MICROORGANISMS
Authors: Hirsch James G. , Cohn Zanvil A.
Published: June 2004

A marked reduction in numbers of cytoplasmic granules in rabbit and human polymorphonuclear leucocytes takes place following ingestion of various microorganisms or of a yeast cell wall preparation. The degranulation occurs within 30 minutes of phagocytosis, and is directly related to the quantity of material engulfed. White cells completely degranulated following phagocytosis of large numbers of microorganisms remain viable for at least 1 hour.

The granules of polymorphonuclear leucocytes contain the antimicrobial agent, phagocytin, and various digestive enzymes. These substances thus are released into the cytoplasm or into vacuoles following ingestion of foreign material. The granule system and granule lysis mechanism may well play a central role in the primary function of these specialized cells; namely, that of destroying invading microorganisms.
THE INFLUENCE OF PHAGOCYTOSIS ON THE INTRACELLULAR DISTRIBUTION OF GRANULE-ASSOCIATED COMPONENTS OF POLYMORPHONUCLEAR LEUCOCYTES
Authors: Cohn Zanvil A. , Hirsch James G.
Published: June 2004

Control and phagocyting populations of rabbit polymorphonuclear leucocytes have been compared in terms of the content and distribution of phagocytin and selected hydrolytic enzymes. Following incubation at 37°C., the cells were disrupted by homogenization and separated into an 8,200 g pellet and supernatant fluid. The high speed pellet from control leucocytes contained all the larger particulate elements of the cell including intact cytoplasmic granules.

The ingestion of large numbers of heat-killed bacteria was accompanied by a fourfold reduction in the total phagocytin content of the leucocyte, whereas phagocytosis did not influence the recovery of histone-like bactericidin from nuclei. Engulfment of microorganisms led to a progressive decrease in the activity of phosphatases, beta glucuronidase, and cathepsin extractable from the 8,200 g pellet, with a concomitant increased activity of these enzymes in the supernatant fraction. No significant difference in the total enzyme content of control and phagocyting cells was noted.

These findings are consistent with the lysis of granules following phagocytosis and the liberation of granule constituents into the cytoplasm of the leucocyte.
STUDIES ON INFECTION AND IMMUNITY IN EXPERIMENTAL TYPHOID FEVER
Authors: Gaines Sidney , Tully Joseph G. , Tigertt William D.
Published: June 2004

Chimpanzees recovered from typhoid fever induced by ingestion of large numbers of phage-type T S. typhosa were rechallenged approximately a year and a half later with a like number of a phage-type E1 strain. Control animals exhibited febrile responses, bacteriemia, and other significant laboratory and clinical findings, including increases in C-reactive protein levels and sedimentation rates. All of the previously infected and recovered chimpanzees were negative with respect to the aforementioned observations, and appeared to have resisted significant re-infection. On the other hand, recovery from typhoid fever induced by smaller numbers of S. typhosa failed to protect completely against rechallenge with larger numbers of these organisms.

These findings indicate that chimpanzees recovered from typhoid fever may be protected against re-infection, even though the re-infecting organism is of a different phage type. Differences in the magnitude of the original and subsequent infecting inocula appear to influence the response to rechallenge.
COLICINE K
Authors: Matsushita Hiroshi , Fox Maurice S. , Goebel Walther F.
Published: June 2004

The synthesis of colicine K by the colicinogenic bacillus E. coli K235 has been studied in the chemostat.

It has been found that colicine production is influenced by the pH of the medium, by the nature of the primary carbon source, and by the generation time of the microorganism.
SPECIFIC INHIBITION OF WHEAL-AND-ERYTHEMA RESPONSES WITH UNIVALENT HAPTENS AND UNIVALENT ANTIBODY FRAGMENTS
Authors: Farah Fuad S. , Kern Milton , Eisen Herman N.
Published: June 2004

Wheal-and-erythema responses were studied in normal human volunteers and in a single human subject who is sensitive to the 2,4-dinitrophenyl group. In the normal subjects, reactive skin sites were established by intradermal injection of purified rabbit antibody specific for the 2,4-dinitrophenyl group. In both the active and passively sensitized subjects, wheal-and-erythema was elicited by intradermal injection of a 2,4-dinitrophenyl protein, but not by injection of the same conjugate mixed with certain low molecular weight 2,4-dinitrophenyl haptens or with univalent fragments split by papain from anti-2,4-dinitrophenyl antibody. The latter fragments, unlike intact, bivalent, antibody, do not sensitize normal human skin sites. From these and other observations it is concluded that the wheal-and-erythema response in human skin requires mutually multivalent antigen and antibody. This requirement suggests that multimolecular complexes, containing at least 2 antigen and 2 antibody molecules, are essential in the pathogenesis of this allergic response.
SOME IMMUNOCHEMICAL PROPERTIES OF PENICILLENIC ACID
Authors: de Weck Alain L. , Eisen Herman N.
Published: June 2004

Under mild conditions, benzylpenicillin in aqueous solution rearranges to benzylpenicillenic acid, which reacts, under suitable conditions, to form stable disulfides and mercaptides. Through reaction with native proteins or especially with proteins that are enriched in SH groups ("thiolated"), penicillenic acid forms, ma mixed disulfide linkages, stable highly substituted conjugates.

These conjugates are potent antigens, inducing the formation of substantial amounts of antibodies specific for the penicillenic acid structure. The implications of these findings for penicillin hypersensitivity in man are discussed.
BILIRUBIN AND UROBILINS IN GERMFREE, EX-GERMFREE, AND CONVENTIONAL RATS
Authors: Gustafsson Bengt E. , Lanke Lisa Swenander
Published: June 2004

No urobilinogens are present in the feces or urine of germfree rats. After contamination of germfree animals with feces from conventional animals the exgermfree rats produced urobilins to the same extent as conventional animals on the same diet. The negative urobilin test turned positive in germfree animals infected with a single Clostridium-like microorganism isolated from the intestinal contents of rats with urobilins in the feces. The output increased in these monoinfected animals after superinfection with a strain of E. coli but never reached the values of conventional animals.
STUDIES OF THE FATE OF TYPE 1 POLIOVIRUSES IN FLIES
Authors: Gudnadóttir Margrét G.
Published: June 2004

Studies on the fate of type 1 polioviruses in two common species of flies were carried out. The amount of virus in carcasses and excreta at different times was determined by the plaque assay method. Flies and their excreta remained infective for 11 days when kept at room temperature or when incubated at 36°C. for 2 hours a day. Flies remained infective for 3 months when kept in hibernation. A relative increase in titer was found to occur between 9 and 18 hours after feeding if the flies were incubated at 36°C. for 5 to 15 hours a day. The peak occurred later, at 40 to 52 hours after feeding if less incubation was used. Titers in excreta were parallel to titers in carcasses. A twofold increase in titer over the initial feeding was observed on 3 occasions with type 1 Mahoney but not with the LSc strain of virus.
ENUMERATION OF CELL-INFECTING PARTICLES OF NEWCASTLE DISEASE VIRUS BY THE FLUORESCENT ANTIBODY TECHNIQUE
Authors: Wheelock E. Frederick , Tamm Igor
Published: June 2004

A procedure has been developed for the determination of the concentration of infective Newcastle disease virus (NDV) based on the enumeration of singly infected and distributed HeLa cells which are visualized by staining with fluorescent antibody. Infective virus assayed by the fluorescent cell-counting procedure is expressed in terms of cell-infecting units (CIU).

Adsorption of NDV to HeLa cell monolayers reached a plateau 1 to 1.5 hours after inoculation of coverslip cultures, and 12 per cent of the infective particles inoculated failed to adsorb. The half-life of NDV in protein-free Eagle's medium at 37°C. was 2.1 hours. There was a linear relationship between virus concentration and the number of infected cells. The coefficient of variation of the mean of replicate determinations of infective NDV was 8.2 per cent. The distribution of single infected HeLa cells in the monolayer corresponded to the Poisson distribution. With NDV the cell-infecting unit (CIU) determined in HeLa cells is equivalent to the plaque-forming unit in chick embryo cells and the egg infective dose.

In experiments on the mechanism of dissemination of NDV in monolayer cultures of HeLa cells, NDV was found to spread from cell to cell through the extracellular milieu.
THE RELATION OF OXYGEN SUPPLY TO WATER MOVEMENT AND TO UREA FORMATION IN SURVIVING LIVER TISSUE
Authors: Opie Eugene L.
Published: June 2004

Liver slices have been immersed during periods up to 4 hours at 38°C. in Krebs-Ringer solution with bicarbonate buffer and exposed to varied oxygen supply in the presence of carbon dioxide equal to that of venous blood. Water movement, urea, and amino acid formation by the liver tissue have been measured.

Water contents of surviving liver tissue diminishes with increased oxygen supply, but during life the maximum limit of oxygen is determined by that brought by the arterial blood and has an approximate partial pressure of 100 mm. Hg.

Urea formation by liver slices is increased by increased oxygen supply but does not occur with anoxia.

Osmotic pressure within liver cells is maintained in part by amino acids and related substances, and in part by electrolytes. Diminished osmotic pressure and loss of water is explainable by oxidation of nitrogenous substances with formation of urea which leaves the cells. These changes within a limited range of variation are adjustable to functional needs.
SOME EFFECTS OF PROTEOLYTIC INHIBITORS ON TISSUE INJURY AND SYSTEMIC ANAPHYLAXIS
Authors: Zweifach B. W. , Nagler A. L. , Troll W.
Published: June 2004

A study was made of the development of various forms of local and systemic injury in animals treated with inhibitors of proteolytic activity. The agents used were tosylarginine methyl ester (TAME), epsilon aminocaproic acid (EACA), and soybean trypsin inhibitor (SBTI).

1. Hemorrhagic necrosis in the skin of the rabbit following intradermal epinephrine in combination with bacterial endotoxin (either intravenous or local) was clearly suppressed by EACA, TAME, and SBTI, given systemically. Tosylarginine (TA) was ineffective.

2. No effect was observed on the classical Shwartzman reaction, the local Arthus phenomenon, or inflammation induced by xylene.

3. The lethal effects of systemic anaphylaxis in the mouse, acute endotoxemia in the rat and mouse, and drum shock in the rat are suppressed by EACA and TAME.

4. There was no effect on the generalized Shwartzman phenomenon in the rabbit and on anaphylaxis in the guinea pig.

5. The effects of EACA or TAME on the injury reactions under investigation were not due to a pharmacological or chemical action on vascular behavior per se.

6. The data provide corroborative evidence for a proteolytic step in injury phenomena which may be mediated through some common activation system.

7. The working hypothesis is advanced that local or systemic stress through the release of epinephrine may result in an increase of a circulating activator of proteolysis and that this in turn may give rise to the release of vasoactive substances,—possibly histamine, serotonin, or a polypeptide.
AN IMMUNIZING SUBSTANCE FOR SEMLIKI FOREST VIRUS IN THE LIVERS OF IMMUNE MICE
Authors: Shope Richard E.
Published: June 2004

A material capable of rendering mice resistant to Semliki Forest virus is present in the livers but not in the muscles, brains, or spleens of mice that have survived a usually fatal dose of virus.
ANAPHYLAXIS IN CHOPPED GUINEA PIG LUNG
Authors: Austen K. F. , Brocklehurst W. E.
Published: June 2004

The quantitative release of histamine and slow reacting substance by specific antigen from perfused, chopped, sensitized guinea pig lung has been used to study the opposing effects of monobasic and certain dibasic fatty acids on the anaphylactic reaction.

The anaphylactic release of histamine and slow reacting substance is doubled by the addition of 0.5 mM of succinic or maleic acid to the reaction mixture, and enhancement is definite with as little as 0.05 mM of succinic acid. Prolonged preincubation of the tissue with the dibasic acids is not required, for 60 to 90 per cent of maximal enhancement is apparent when the antigen is added to the tissue only 10 seconds after succinic or maleic acid. The increased histamine release is not due to a qualitative change in the time course of histamine release, is not the result of increased histamine formation, and cannot be attributed to an effect on the tricarboxylic acid cycle. The enhancement seems to be due to potentiation of some step activated by the antigen-antibody interaction and common to both the release of histamine and slow reacting substance. The structural configuration required for a dibasic acid to enhance the anaphylactic reaction in guinea pig lung is quite specific; the carboxyl groups should be separated by a two carbon chain, and must be free or fixed in the cis position.

The monobasic fatty acids from valeric to dodecanoic inhibit the anaphylactic release of histamine, and the concentration needed to produce 50 per cent inhibition decreases with increasing chain length. The introduction of a polar group, amino or carboxyl, into the hydrocarbon residue diminishes or abolishes inhibitory capacity. The inhibition produced by the fatty acids is neither due to calcium binding nor due to prevention of effective antigen-antibody interaction; the fatty acids probably inhibit by acting on an antigen-antibody-activated step.

The inhibition of the anaphylactic release of histamine and slow reacting substance produced by caproic or decanoic acid can be reversed by the enhancing effect of succinic acid, and vice versa. Thus, compounds normally present in mammalian tissue can greatly influence the intensity of the in vitro anaphylactic reaction in the guinea pig.
STUDIES ON HYPERSENSITIVITY
Authors: Gell P. G. H. , Benacerraf B.
Published: June 2004

In earlier observations with the picryl system, it was concluded that contact sensitivity was a form of delayed (cellular) hypersensitivity to conjugates of sensitizer with autologous proteins indistinguishable in its immunological mechanism from other classical forms of delayed hypersensitivity to proteins. This conclusion has been confirmed and extended with the picryl and chlorbenzoyl chloride systems.

1. It is shown that to induce a state of contact sensitivity, the minimal necessary amounts of hapten are of the same order of magnitude, whether this hapten is conjugated with protein or the free reactive chemical itself. From this, it is evident that contamination of conjugates with small amounts of unreacted sensitizer plays no part in the induction of contact reactivity by the conjugate. With the dinitrophenyl system, no contact sensitivity could be induced by the conjugates used; possible reasons for this discrepancy are discussed.

2. Animals sensitized to contact by homologous conjugate can be completely desensitized by injections of such a conjugate in large amount; a similar injection schedule has no effect on the contact sensitivity of animals sensitized with the free reactive sensitizer.

3. The capacity of heterologous (ovalbumin) conjugates to evoke anti-hapten antibodies is shown to be greater than that of homologous (guinea pig seralbumin) conjugates: the reverse is true of their capacity to induce delayed reactivity.

4. Evidence is brought forward to suggest that in animals sensitized with homologous albumin conjugates, the specificity of the delayed reaction involves more than the hapten alone, even though the carrier protein is non-antigenic on its own. The contrast with the apparent lesser specificity of the antibodies later produced is discussed.
STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION
Authors: Conti Charles R. , Cluff Leighton E. , Scheder E. Patricia
Published: June 2004

Intracutaneous and intravenous injection of pyrogenic, non-lethal doses of bacterial endotoxin were found to increase the infectivity of pathogenic but not non-pathogenic staphylococci in rabbit skin. The increased infectivity of the microorganism was characterized by accelerated multiplication at the site of inoculation and by the production of necrosis and hemorrhage locally. Histologically, the infection of skin in endotoxin-prepared animals was characterized by necrosis, masses of bacteria, but absence of leukocytic infiltration into the area of bacterial growth.

The infectivity of staphylococci in skin of endotoxin-prepared rabbits could be controlled by antibody to the alpha hemolysin of the microorganism.

The effect of endotoxin upon staphylococcal infection was demonstrable only within 4 hours after injection of the endotoxin. It could not be prevented with chlorpromazine or dibenamine and was closely related to the effect of endotoxin upon leukocytes.

It was suggested that the effect of endotoxin upon leukocytes was probably responsible for its influence upon staphylococcal infection.

The implications of these findings in the pathogenesis of staphylococcal infection are discussed.