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The Journal of Experimental Medicine Dec 1952Certain factors involved in the production of the generalized Shwartzman reaction with meningococcal toxin in rabbits were investigated. The optimal amounts of toxin for...
Certain factors involved in the production of the generalized Shwartzman reaction with meningococcal toxin in rabbits were investigated. The optimal amounts of toxin for the preparing and provoking injections, and the optimal time interval between injections were determined. Under suitable conditions of dosage and timing, bilateral cortical necrosis of the kidneys was produced in a high proportion of animals. When excessive amounts of toxin were used for preparation the incidence of the reaction was reduced. Animals undergoing the generalized Shwartzman reaction became severely prostrated within several hours after the provoking injection of toxin. The renal lesion became fully developed within 24 hours, and its occurrence was associated with a rise of the blood non-protein nitrogen. Edema and petechial hemorrhages in the ears were observed in rabbits with advanced renal lesions. The earliest change in the kidneys in the generalized Shwartzman reaction was the appearance of homogeneous, eosinophilic material, resembling fibrinoid, within the lumen of the glomerular capillaries. Occlusion of the capillaries by this material was regarded as the cause of subsequent tubular necrosis in the renal cortex. The material appeared to be derived from the blood, rather than from the capillary walls. Cortisone enhanced the lethal effect of a single, large dose of meningococcal toxin, as well as causing bilateral renal cortical necrosis. The generalized Shwartzman reaction produced by two injections of toxin was aggravated by cortisone and ACTH. Profound polymorphonuclear leukopenia was produced by both the preparing and provoking injections of toxin. When leukopenia was produced before the preparing injection of toxin, by treatment with nitrogen mustard, the generalized Shwartzman reaction was inhibited. During the intervals before and after leukopenia, and when leukopenia was prevented by shielding the femoral bone marrow from the action of nitrogen mustard, no inhibition of the generalized Shwartzman phenomenon was demonstrable. Various colloidal and particulate materials, which are capable of provoking the local skin Shwartzman reaction when injected intravenously, failed to provoke the generalized Shwartzman reaction. A working hypothesis was set up to account for certain events in the generalized Shwartzman reaction.
Topics: Animals; Hypersensitivity; Kidney; Leukopenia; Rabbits; Shwartzman Phenomenon
PubMed: 13022854
DOI: 10.1084/jem.96.6.605 -
The Journal of Experimental Medicine Jun 1953In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized...
In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied. Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours. The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation. Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast. Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin. Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin. Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin. Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin. In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur. These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.
Topics: Animals; Biomedical Research; Heparin; Humans; Hypersensitivity; Leukocytes; Rabbits; Shwartzman Phenomenon; Skin
PubMed: 13069642
DOI: 10.1084/jem.97.6.871 -
The Journal of Experimental Medicine Jul 1960The localized Shwartzman reaction has been demonstrated in a highly inbred mouse strain (BSVS). This reaction was produced with marked regularity in these mice by...
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.
Topics: Animals; Antigen-Antibody Complex; Endotoxins; Hypersensitivity; Immune System Diseases; Lung; Mice; Rabbits; Shwartzman Phenomenon; Skin
PubMed: 13684338
DOI: 10.1084/jem.112.1.167 -
European Journal of Biochemistry Apr 1985The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the... (Comparative Study)
Comparative Study
The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the following test systems: lethal toxicity, pyrogenicity, local Shwartzman reactivity, Limulus amoebocyte lysate gelation capacity, tumour necrotizing activity, B cell mitogenicity, induction of prostaglandin synthesis in macrophages, and antigenic specificity. It was found that synthetic and natural free lipid A exhibit identical activities and are indistinguishable in all tests.
Topics: Animals; Cell Survival; Drug Tolerance; Endotoxins; Epitopes; Escherichia coli; In Vitro Techniques; Lethal Dose 50; Limulus Test; Lipid A; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mitogens; Necrosis; Prostaglandins; Pyrogens; Rabbits; Sarcoma, Experimental; Shwartzman Phenomenon
PubMed: 2579812
DOI: 10.1111/j.1432-1033.1985.tb08798.x -
The Journal of Experimental Medicine Apr 19521. Cortisone, in a dose of 25 mg. daily and with a pretreatment period of 3 days, in rabbits weighing 1 to 1.5 kilos, did not inhibit the dermal Shwartzman reaction...
The effect of cortisone on the Shwartzman reaction; the production of lesions resembling the dermal and generalized Shwartzman reactions by a single injection of bacterial toxin in cortisone-treated rabbits.
1. Cortisone, in a dose of 25 mg. daily and with a pretreatment period of 3 days, in rabbits weighing 1 to 1.5 kilos, did not inhibit the dermal Shwartzman reaction produced by meningococcal or S. marcescens toxin. 2. In cortisone-treated rabbits, a single intradermal injection of toxin produced a primary reaction of hemorrhage and necrosis in the skin at the injected site. This lesion resembled the Shwartzman reaction in its gross and histological appearance. 3. Like the Shwartzman reaction, the primary hemorrhagic reaction in cortisone-treated rabbits was prevented by nitrogen mustard, and the preventive effect of nitrogen mustard was partly eliminated when the femoral marrow was protected against the latter agent. 4. A single intravenous injection of meningococcal or S. marcescens toxin, in cortisone-treated rabbits, was followed by bilateral cortical necrosis of the kidneys in the majority of instances. The renal lesions, as well as hemorrhages in the lungs, spleen, liver, and gastrointestinal tract, resembled the lesions of the generalized Shwartzman reaction. Histologically, the glomerular capillaries in both types appeared to be occluded by homogeneous, eosinophilic material which showed a strongly positive Schiff reaction. 5. The renal lesion following a single injection of toxin in cortisone-treated animals, and that following two intravenous injections in the generalized Shwartzman reaction, were both completely prevented by nitrogen mustard. This effect of nitrogen mustard was inhibited when the femoral marrow was protected against the latter agent. 6. The injection of S. marcescens toxin into the skin of normal rabbits did not cause systemic symptoms, nor was it possible to provoke the generalized Shwartzman reaction by this route. In cortisone-treated rabbits, a similar intradermal injection was regularly followed by the development of bilateral cortical necrosis of the kidneys, indicating that absorption of toxin from the skin occurred in these animals. 7. Possible mechanisms to account for the observations are discussed. The authors are obliged to Professor James R. Dawson for many helpful suggestions during the course of this investigation.
Topics: Animals; Bacteria; Bacterial Toxins; Capillaries; Cortisone; Hypersensitivity; Injections, Intradermal; Injections, Intravenous; Kidney; Liver; Necrosis; Rabbits; Shwartzman Phenomenon; Skin
PubMed: 14938509
DOI: 10.1084/jem.95.4.409 -
Drug Delivery Nov 2018This study sought to develop a simple nanoparticle-based approach to enhance the efficiency and tolerability of lipopolysaccharide (LPS), a potent ligand of Toll-like...
This study sought to develop a simple nanoparticle-based approach to enhance the efficiency and tolerability of lipopolysaccharide (LPS), a potent ligand of Toll-like Receptor 4 (TLR4), for immunotherapy in cancer. Despite holding promise within this context, the strong pro-inflammatory properties of LPS also account for its low tolerability given localized and systemic side effects, which restrict the administrable dosage. Herein, we investigated the effect of LPS decoration as a surface-active molecule on a polymeric matrix upon its efficiency and tolerability. The LPS-decorated nanoparticles (LPS-NP) were about 150 nm in size, with slightly negative zeta potential (about -15 mV) and acceptable LPS incorporation (about 70%). In vitro, the particles accounted for a higher induction of apoptosis in tumor cells cultured with murine splenocytes compared to LPS solution. When used for the treatment of a murine syngeneic colorectal tumor model, higher intratumoral deposition of the particle-bound LPS was observed. Furthermore, unlike LPS solution, which accounted for localized necrosis at high concentrations, treatment of tumor-bearing animals with equivalent doses of LPS-NP was well tolerated. We propose that the observed localized necrosis can be Shwartzman phenomenon, which, due to modulated 24-h post-injection systemic TNF-α and LPS concentrations, have been avoided in case of LPS-NP. This has in turn enhanced the therapeutic efficiency and enabled complete tumor regression at concentrations at which LPS solution was intolerable. The findings indicate that nanoparticles can serve as beyond carriers for the delivery of superficially decorated LPS molecules, but impact their overall efficiency and tolerability in cancer therapy.
Topics: Animals; Apoptosis; Cell Line; Cell Line, Tumor; Immunotherapy, Active; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms; Particle Size; RAW 264.7 Cells; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
PubMed: 29902933
DOI: 10.1080/10717544.2018.1469684 -
Canadian Medical Association Journal Jan 1969
Review
Topics: Abruptio Placentae; Adrenal Glands; Aminocaproates; Animals; Basement Membrane; Biopsy; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Brain; Female; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Hemorrhage; Hemorrhagic Disorders; Heparin; Humans; Hypertension, Malignant; Kidney Cortex Necrosis; Kidney Failure, Chronic; Kidney Glomerulus; Liver; Maternal Mortality; Microscopy, Electron; Myocardium; Placental Extracts; Pre-Eclampsia; Pregnancy; Rabbits; Shwartzman Phenomenon; Thromboplastin; Thrombosis
PubMed: 4883329
DOI: No ID Found -
The Journal of Experimental Medicine Jul 1974Enteric bacilli and meningococci (MGC) both contain potent endotoxins, but purpuric skin lesions indistinguishable from the experimental dermal Shwartzman reaction are...
Enteric bacilli and meningococci (MGC) both contain potent endotoxins, but purpuric skin lesions indistinguishable from the experimental dermal Shwartzman reaction are much more common during meningococcal bacteremia than during bacteremia with enteric organisms. Highly purified lipopolysaccharides (LPS), virtually free of contamination by protein, RNA, and capsule, were extracted by a modification of the phenol-water technique from MGC (serogroups A, B, and C) and enteric bacilli (Escherichia coli 04 and 0:111, and Salmonella typhimurium). Polysaccharides in these LPS were similar by gas chromatography except for one galactose-deficient strain of MGC (135B). LPS from MGC and enterics were equally potent for the general Shwartzman reaction and mouse lethality, but LPS from MGC was 5-10 times more potent in inducing the dermal Shwartzman reaction. The greater skin potency of LPS from MGC explains the prominence of purpura in meningococcemia. Comparison of the properties of LPS may explain other differences in clinical syndromes caused by gram-negative bacteria.
Topics: Animals; Endotoxins; Enterobacteriaceae; Lipopolysaccharides; Meningococcal Infections; Mice; Neisseria meningitidis; Polysaccharides, Bacterial; Purpura; Rabbits; Shwartzman Phenomenon; Skin
PubMed: 4209358
DOI: 10.1084/jem.140.1.159 -
Annals of the New York Academy of... Oct 2010I here describe a line of research that grew out of studies of spinal cord-damaging decompression sickness, focused on the blood-endothelial interface, that was... (Review)
Review
I here describe a line of research that grew out of studies of spinal cord-damaging decompression sickness, focused on the blood-endothelial interface, that was influenced by the local Shwartzman phenomenon, addressed innate immune and inflammatory mechanisms, and ultimately arrived at mucosal tolerance approaches to prevent stroke. Intranasal instillation of E-selectin is under development as a novel means of targeting immunomodulation to activating blood vessels within the vascular tree supplying the brain. The goal of this form of focused immunomodulation is to prevent recurrent strokes in patients that have previously suffered transient ischemic attacks or strokes.
Topics: Animals; Central Nervous System; E-Selectin; Humans; Inflammation; Rats; Shwartzman Phenomenon; Stroke; Tumor Necrosis Factor-alpha
PubMed: 20955418
DOI: 10.1111/j.1749-6632.2010.05785.x -
The American Journal of Pathology Apr 1972
Review
Topics: Arthritis; Blood Coagulation Factors; Blood Platelets; Chronic Disease; Complement System Proteins; Connective Tissue; Disseminated Intravascular Coagulation; Endotoxins; Factor XII; Fibrin; Fibrinogen; Fibrinolysin; Glomerulonephritis; Humans; Inflammation; Kinins; Leukocytes; Nephritis; Shwartzman Phenomenon
PubMed: 4261590
DOI: No ID Found