bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXPERIMENTAL IMMUNOLOGIC ADRENAL INJURY
Authors: Steiner Jan W. , Langer B. , Schatz D. L. , Volpe R. 
Published: June 2004

Twenty-three unilaterally adrenalectomized guinea pigs were injected with autologous and homologous adrenal tissue homogenates respectively, in Freund's adjuvant. Widespread adrenal lesions were found in 10 of 12 animals receiving auto-antigen and to a lesser extent in 6 of 11 animals injected with homologous pooled antigen. Widespread systemic lesions were present in both these and in control animals receiving Freund's adjuvant alone. These latter animals showed no adrenal involvement.
The early changes within the adrenal consisted of perisinusoidal cellular proliferations in the deeper layers of the cortex. Focal granulomata developing at a later stage tended to become confluent and to displace cortical cells. Some loss of these cells was attributable to ischemic injury.
The localization in the deep fasciculata and reticularis was thought to depend (a) on the varying antigenicity of adrenal cortical components, (b) the possible inhibitory effect of antiphlogistic adrenal cortical hormones on the development of lesions in the outer cortex, and (c) the presence of littoral cells in the deep cortex. These cells are thought to be involved in the mediation of the stimulus initiating differentiation of primitive mesenchymal cells in response to a circulating auto-antigen. The medullary lesions may be related to the presence of ectopic reticularis cells in this location.
It was suggested that the cellular response in the target organ to injections of adrenal homogenates may denote a specific "organ-self" recognition mechanism involving an immune (i.e. defensive) reaction. It was postulated that this may be an accentuation of the physiological function of immunologically competent cells. Their proliferation, under normal circumstances, would prevent by means of production of "binding" globulins, the escape and dissemination of endogenous freed adrenal antigens into the circulation. Although the experimental stimulus arose from without the gland, by virtue of the presence of a circulating adjuvant-bound antigen, the adrenal reaction followed the same pattern as would obtain if the antigen was liberated within the suprarenal cortex.
INACTIVATION OF BACTERIAL EXOTOXINS AND ENDOTOXIN BY IRON
Authors: Janoff Aaron , Zweifach Benjamin W. 
Published: June 2004

After incubation with various agents in vitro, the lethal effects of aqueous solutions of Cl. perfringens alpha toxin, C. diphtheriae toxin, and E. coli endotoxin were tested in mice, guinea pigs, and rabbits, respectively.
Iron, copper, cysteine, ascorbic acid, and versene counteracted the lethal effects of alpha toxin in mice, while magnesium, manganese, zinc, and citrate did not.
Iron also counteracted the lethal effects of diphtheria toxin in guinea pigs. After incubation of endotoxin with iron, its lethal effects and tissue-necrotizing actions in rabbits were counteracted. However, the pyrogenic properties of the toxin were not affected.
The solubilities of perfringens alpha toxin and diphtheria toxin were markedly reduced after incubation with detoxifying metals, and resolubilization of these toxins with chelators resulted in partial restoration of toxicity. Addition of versene to detoxified endotoxin also resulted in partial recovery of lethal effectiveness.
The inactivation of bacterial toxins by iron under in vitro conditions is not specific to this metal, is a reversible process, and may be due to desolubilization, reduction, or to competition by the metal for sites on the toxin normally bound by other cations in vivo.
Although no evidence is presented in this paper to support the view that there is a relationship between the inactivation of endotoxin and the storage iron in the reticuloendothelial system of shocked animals, the observation of an in vitro inactivation of endotoxin by inorganic iron warrants consideration of such a mechanism.
DEPRESSION BY ANTIBODY OF THE IMMUNE RESPONSE TO HOMOGRAFTS AND ITS ROLE IN IMMUNOLOGICAL ENHANCEMENT
Authors: Snell George D. , Winn Henry J. , Stimpfling Jack H. , Parker Stephen J. 
Published: June 2004

This paper reports tests of two hypotheses that have been proposed to account for the enhanced growth of tumor homografts in the presence of antiserum reactive with the graft (immunological enhancement). According to the first hypothesis, enhancement is due to some "physiological" alteration in the tumor, induced by its contact with antiserum, which insures its survival despite the hostile response of the host. According to the second hypothesis, antiserum alters the response of the host. By blocking the development of the cellular type of immunity, which is the main agent in graft destruction, it permits the graft to survive.
To test hypothesis 1, strain A tumor SaI was passed from A's, and from enhanced B10.D2's, into untreated B10.D2's. The per cent of deaths was essentially the same in both groups (48 and 44 per cent, respectively); there was no evidence that passage through enhanced B10.D2's altered the capacity of the tumor to grow in the foreign strain. Several other groups of mice included in the experiment all confirmed this conclusion. The experiment failed to confirm hypothesis 1.
In the tests of hypothesis 2, the effect of isoantiserum on immune responses of both the humoral and cellular type was measured. When antiserum was given together with foreign strain lymphoid cells (antigen), almost no additional antibody was manufactured; in contrast with this, controls receiving foreign cells only produced red cell agglutinating antibody in high titer.
The effect of antiserum on the development of immunity of the cellular type was tested by the method of Winn. In this assay, presumptively immune node cells, in various dilutions, are mixed with tumor cells and injected into appropriate mice. Immunity is indicated by inhibited tumor growth. Antiserum given at the same time as a tumor homograft greatly depressed the immunity of the cells expressed from the draining nodes. At 6 days after the graft, the level of immunity of cells from treated mice was 1/24th to 1/32nd that of cells from controls receiving tumor alone. The same sort of depressing effect was noted when the immunizing tissue was foreign thymus or embryo. Antiserum given 1 or more days after the immunizing tissue also resulted in a lower level of cellular immunity (but the assay used in this case was a less critical one).
These results provide an adequate explanation of the phenomenon of immunological enhancement, at least as it occurs in the particular test system used in these experiments. Since it is cellular immunity rather than humoral antibody that inhibits the growth of most grafts (transplantable leukemias are an exception), the depression of this immunity by antibody is favorable to the growth of a homograft.
THE NATURE OF STORAGE IRON IN IDIOPATHIC HEMOCHROMATOSIS AND IN HEMOSIDEROSIS
Authors: Richter Goetz W. 
Published: June 2004

Using three different methods of cells fractionation, hemosiderin granules were isolated from tissues (liver and/or spleen) of three patients. The samples were obtained from a case of idiopathic hemochromatosis, a case of thalassemia major with secondary (transfusional?) hemosiderosis, and a case of transfusional hemosiderosis associated with an unclassified anemia.
Iron, nitrogen, and protein content of the hemosiderin granules varied over a wide range. Electron microscopy of sectioned granules revealed aggregates of dense particles of different shapes, with diameters ranging from 10 A to about 75 A. In some of the granules dense particles corresponding to the iron hydroxide micelles of ferritin molecules were abundant. But many of the granules contained very few of these molecules.
The presence of ferritin and apoferritin in the samples of hemosiderin granules was demonstrated by means of precipitin tests in agar-gel, using rabbit antiferritin sera with known antibody nitrogen concentrations. At least three antigenic components were detected in highly purified crystalline ferritin prepared from tissues of the three patients; the hemosiderin granules contained the same antigens, but probably in much smaller quantities. Both ferritin and apoferritin molecules were extracted from hemosiderin granules, and were demonstrated in the electron microscope after suitable preparation.
The solubility curve of human ferritin in solutions of (NH4)2SO4 was investigated. The results indicate that substantial quantities of ferritin or apoferritin can be lost in saline, aqueous media during isolation of hemosiderin granules from cells.
It was shown by means of electron microdiffraction on selected hemosiderin granules that the dense particles represent forms of partly hydrated α-Fe2O3. The conditions necessary for electron microdiffraction in an electron microscope precluded an exact determination of the state of hydration of the α-Fe2O3 or of its structural relation to (FeOOH) micelles of pure ferritin in its undenatured state.
The findings were considered in the light of evidence on the structure and disposition of hemosiderin in situ in cells, and on the structure of ferritin. Differences between endogenous hemosiderin and hemosiderin derived from injections of colloidal iron compounds were pointed out. The evidence indicates that in hemochromatosis and in secondary hemosiderosis much of the inorganic storage iron in liver and spleen is derived from degraded ferritin.
The findings suggest that an abnormal cellular metabolic pathway of ferritin is implicated in the pathogenesis of hemochromatosis and transfusional hemosiderosis.
FURTHER STUDIES ON PASSIVE TRANSFER OF TOLERANCE TO PYROGENICITY OF BACTERIAL ENDOTOXIN
Authors: Freedman Henry H. 
Published: June 2004

The effect of various schedules for inducing tolerance to bacterial endotoxin in donor rabbits upon suitability for demonstration of passive transfer of tolerance to pyrogenicity in normal recipients has been investigated. Long-term treatment of donors, through 5 weeks, is no more effective than a brief series of injections, adding further evidence that tolerance is not attributable to specific antibody to the endotoxin. Qualitative differentiation of the febrile pattern of passively tolerant recipients from that seen in control animals depends upon the magnitude of the test dose of pyrogen.
Passively tolerant rabbits respond to endotoxin with an acute leucopenia equivalent to that seen in controls suffering a full biphasic fever. Animals given daily injections of endotoxin continue to show the acute leucopenia, despite the early modification of the course of fever characteristic of endotoxin tolerance. The assumption that the leucopenia reflects damage to the leucocytes, with release of endogenous pyrogen, is not consistent with these findings. Rabbits rendered leucopenic by nitrogen mustard and then given endotoxin exhibit a rapidly developing fever of greater than normal intensity, the exaggeration of the febrile response being proportional to the severity of the induced leucopenia.
The implications of these findings for the pathogenesis of endotoxin-induced fever are discussed. The evidence supports the hypothesis that endotoxin produces fever by direct action rather than by release of endogenous leucocytic pyrogen. It is postulated that the lesser fever, in animals having normal numbers of circulating leucocytes, reflects a limitation of available endotoxin by the known rapid sequestration in the white blood cells at the time of the acute leucopenia. It is further suggested that the biphasic febrile response of the normal rabbit results from reinoculation of the blood stream by the temporarily sequestered endotoxin, the RES of the tolerant animal clearing the released endotoxin at a rate sufficient to prevent triggering the second phase of fever.
FACTORS AFFECTING THE CHAIN LENGTH OF GROUP A STREPTOCOCCI
Authors: Ekstedt Richard D. , Stollerman Gene H. 
Published: June 2004

Minute amounts of M protein were detected in culture supernates of virulent Group A streptococci by type-specific inhibition of the long chain and the bactericidal tests for anti-M antibody. The amount of M protein that was detected by the inhibition of these biological systems was less than could be demonstrated by precipitation tests.
All strains of streptococci rich in M protein which were studied formed long chains when grown in sufficient concentrations of anti-M antibody. Very low concentrations of anti-M antibody escaped detection by the long chain test when strains of excessive M protein content were employed. Under such conditions the bactericidal test detected anti-M antibody more sensitively than the long chain test owing to the smaller inoculum employed in the former method.
The scission of streptococcal chains may be inhibited by union of antibodies with surface antigens other than M protein. Long chains were formed when M-negative, R-positive strains were grown in sera containing anti-R antibody.
INCREASED FIXATION OF SULFUR35 BY CARTILAGE IN VITRO FOLLOWING DEPLETION OF THE MATRIX BY INTRAVENOUS PAPAIN
Authors: McElligott T. F. , Potter J. L. 
Published: June 2004

The uptake in vitro of sulfur-35 by costal cartilage obtained from nine rabbits 11 days after an intravenous injection of crude papain solution was compared with that in costal cartilage from eight normal untreated rabbits. An increased fixation of the isotope was found in treated animals compared with controls.
The depletion of cartilage matrix by papain provided an experimental situation to test the hypothesis that the depletion of matrix which occurs in osteoarthritic cartilage can stimulate increased synthesis of chondroitin sulfate.
The results give further support to the view that the primary lesion in osteoarthritis occurs in the matrix rather than in the chondrocyte of articular cartilage.
PATHOGENESIS OF FEVER: EFFECTS OF VARIOUS ENDOGENOUS PYROGENS UPON THE LEVEL OF CIRCULATING GRANULOCYTES IN NORMAL RABBITS
Authors: King M. K. 
Published: June 2004

The endogenous pyrogen in the serum or plasma of rabbits 2 hours after the intravenous injection of typhoid vaccine had a marked effect on the circulating leucocytes of normal rabbits. Immediately following intravenous injection there was a brief, but marked, granulocytopenia which was quickly followed by a granulocytosis. Under the same circumstances pooled heterologous serum or plasma from normal rabbits produced no fever or significant change in the level of circulating leucocytes.
The cell-free fluid of sterile peritoneal exudates produced a marked leucocytosis without a preceding leucopenia when injected intravenously into normal rabbits. When comparably pyrogenic doses of typhoid vaccine were injected in the same manner no significant change in the level of circulating leucocytes occurred.
The relevance of these findings to the pathogenesis of fever is discussed.
DISTURBED REPRODUCTIVE FUNCTION FOLLOWING SECTION OF THE PORTAL VEIN
Authors: Huggins Charles , Okamoto Ryohei 
Published: June 2004

Integrity of the portal vein is a condition for normal function of the reproductive tract in female rats. Section of the portal vein (PVS) always abolished periodic sexual function. In a series of 23 animals, 6 developed continuous estrus and other signs of the presence of excessive amounts of estrogenic hormones; yet the ovaries of these rats were small. In 6 other rats there was growth of the prostate and additional evidence of increased activity of androgenic hormones. Many rats failed to become pregnant and nearly all pregnant rats aborted. Except for a decrease in lipid content, the composition of the liver of PVS rats resembled that of intact mates in the criteria which were applied.
The rapid passage of blood through the liver is necessary to conjugate the excessive amounts of steroids which the rat ovary normally produces and an intact portal vein is an essential unit in the mechanism necessary for their partial inactivation.
CELLULAR LOCALIZATION OF ROUS SARCOMA VIRUS AS STUDIED WITH FLUORESCENT ANTIBODY
Authors: Mellors Robert C. , Munroe J. Spencer 
Published: June 2004

A study has been made of the immunospecific, apple-green staining patterns imparted by fluorescent antibody to Rous virus in frozen sections of wing tumors produced in young chickens by various initiating doses of virus. Variations in the cellular site (cytoplasm, cell membrane, and nucleus), the distribution (particulate or homogeneous), and the quantity (little or much) of Rous viral antigens were seen. The per cent of sarcoma cells containing viral antigens was related to the tumor initiating dose of virus and to the infectivity titer of virus extracted from the wing tumor. With certain assumptions it was estimated that a quantity of virus approaching one tumor-producing dose (1 TD50) per tissue section was detectable with fluorescent antibody.
Sarcoma cells containing viral antigens were identified as early as 4 days after inoculation of Rous virus. At this time viral antigens were also localized in the skeletal muscle of the inoculated wing in a characteristic focal pattern of deposition near or on the sarcolemma. This association between viral antigens and skeletal muscle fibers was observed also at 3 days after virus inoculation, when sarcoma cells were not yet demonstrable in the tissue sections.
Viral antigens were detected in sarcoma cells in lung tumors of young chickens and in tumors of the chorioallantoic membrane of chick embryos.
HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS
Authors: Cremer Natalie , Watson Dennis W. 
Published: June 2004

The data presented in this study suggest that Group A streptococci produce two distinct pyrogenic toxins: one primarily an intracellular toxin and the other mainly an extracellular toxin.
Both of these toxins are not extractable by the conventional methods, phenol and TCA, used for isolation of Gram-negative bacterial endotoxin. Their chemical composition, therefore, differs from that of Gram-negative bacterial endotoxin.
On the basis of tolerance studies it appears that similar non-specific host factors may be involved in the detoxification of both the streptococcal intracellular pyrogenic toxin and the Gram-negative bacterial endotoxin. Detoxification of streptococcal exotoxin requires a more immunologically specific mechanism.
Because all the Group A sonic extracts studied elicited reciprocal tolerance to one another, it is suggested that tolerance to the intracellular pyrogenic toxin is not correlated with type-specificity.
TISSUE MAST CELLS AND ACUTE INFLAMMATION IN EXPERIMENTAL CUTANEOUS MUCORMYCOSIS OF NORMAL, 48/80-TREATED, AND DIABETIC RATS
Authors: Sheldon Walter H. , Bauer Heinz 
Published: June 2004

The role of the tissue mast cells in relation to the acute inflammatory reaction to experimental cutaneous mucormycosis was studied histologically in normal rats, in animals whose tissue mast cells had been depleted of their cytoplasmic granules prior to infection by the administration of compound 48/80 and in others in whom acute alloxan diabetes with acidosis had been produced before injection of the fungus.
The discharge of the tissue mast cell granules in normal rats occurred within minutes at the site of infection and appeared to initiate the rapid onset of acute inflammation. The degranulation of the tissue mast cells subsided in a short time and the cells reassumed a normal histologic appearance while inflammation progressed with the formation of circumscribed lesions. In animals pretreated with compound 48/80 in which the tissue mast cells contained no granules, the onset of inflammation was briefly delayed, the intensity of the process was somewhat decreased, fibroblastic proliferation was retarded, and the fungus growth in the early lesions was increased. However, the infection did not spread and the lesions were well localized. The tissue mast cells in the diabetic and acidotic rats completely failed to discharge their cytoplasmic granules, the onset and intensity of the acute inflammatory response were markedly delayed and decreased and the infection progressed rapidly with massive fungus growth invading adjacent tissues. A relationship between the discharged tissue mast cell granules and eosinophilic granulocytes was noted since the latter were numerous among the inflammatory cell exudate in normal rats and scarce in the lesions of the diabetic animals.
It is concluded that a function of the tissue mast cells in the normal rat is the rapid initiation of acute inflammation at the site of injury and that degranulation of these cells prior to infection somewhat delays the inflammatory response and therefore slightly diminishes host resistance. Furthermore, a severe metabolic disorder such as acute alloxan diabetes with acidosis, inhibits the normal function of the tissue mast cells, delays and decreases inflammation, and in this manner contributes to the greatly increased susceptibility of the host to infection.
STUDIES ON IMMUNE CELLULAR INJURY
Authors: Lepow Irwin H. , Ross Ann 
Published: June 2004

An initial separation of reaction stages in immune cytoxicity is described. Primary isolates of normal human amnion cells were reacted first with specific rabbit γ2-globulin antibody, then with human C'1 esterase in the presence of Ca++, and finally with human C'2, C'3, and C'4 in the presence of Mg++. Cytotoxicity, as measured by uptake of trypan blue, occurred only when these reactions were performed in the order given and did not occur when any of the constituents was omitted. Inhibition of immune cytotoxicity was achieved with partially purified preparations of human serum inhibitor of C'1 esterase under certain experimental conditions.
The data are discussed in relation to the role of C'1 esterase in initiating complement action and the partial biochemical definition of an early event in immune cytotoxicity.
STUDIES ON THE MECHANISM OF THE FORMATION OF THE PENICILLIN ANTIGEN
Authors: Levine Bernard B. 
Published: June 2004

Seven highly purified degradation products of penicillin G (PG) were examined with regard to their ability to cross-react allergically with PG. Guinea pig allergic contact dermatitis was employed as the test system. Three of these degradation products, D-benzylpenicillenic acid (BPE), D-penicillamine, and D-α-benzylpenicilloic acid were found to cross-react with PG and also to be capable of inducing delayed contact allergy in the guinea pig. BPE and PG cross-reacted with particularly intense reactions, and other immunologic experiments indicated that PG and BPE introduce identical allergic determinant groups into epidermal proteins.
These experimental results were correlated with the results of previous studies concerning the degradation pathways of PG under physiological conditions in vitro, and the chemical reactivities of these degradation products.
Based on these immunologic and chemical data, a schema is proposed which suggests the chemical pathways by which PG may react with epidermal proteins in vivo to form the penicillin antigen. The identity of the specific antigenic determinant groups of the penicillin antigen is suggested.
The relationship between PG allergy of the contact dermatitis type in the guinea pig and PG allergy of the immediate type in man is discussed.