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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 14 (1985), S. 135-138 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary At a high dose, cyclophosphamide (Cy, 200 mg/kg) causes depression of the enzyme activity of the hepatic mixed function oxygenase (MFO) system in Sprague-Dawley rats. The present report provides evidence for the early regeneration of the depleted enzyme activity in Cy-treated rats by purified protein A (P) of Staphylococcus aureus. Enzymes of the MFO system, such as aminopyrine demethylase and aryl hydrocarbon hydroxylase, were assayed and the content of cytochrome P-450 was determined. Inoculation of P (60 μg/kg) prior to Cy inoculation provides a better effect than P administration after Cy. The exact mechanism of P action is unknown. P-treated animals appear to have an ability to repair the damage caused by the toxic metabolites of Cy earlier than those in the Cy group. This property of protein A may become useful in accelerated regeneration of the enzyme activity in the hepatic MFO system following the toxic insult of Cy metabolites.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 18 (1984), S. 29-34 
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This report confirms our previous observation that IV inoculation of purified protein A causes regression of rat mammary adenocarcinomas. In treated tumors, we have obtained histological evidence of changes indicating tumor cell destruction. Protein A treatment does not cause reduction in the body weight or organ weights of rats; nor does it cause any decrease in activity of the enzymes of the microsomal mixed function oxidase system in the liver. Protein A stimulates peripheral white cell counts in normal rats, but not in tumor-bearing rats. We found that protein A infusion reduced (P〈0.0005) the level of circulating plasma immune complex concentration. A homing study with 125I-labeled protein A indicated that liver, spleen, and kidney tissues are the major sites of protein A accumulation. Therefore, protein A seemed to exert its antitumor effects without causing any generalized toxicity to the system. It is postulated that the action of protein A may be related to its ability to cause a drastic reduction in circulating plasma immune complex concentration, thus potentiating the immune reactivity of the host observed earlier.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cyclophosphamide (Cy) is widely used as an effective cytotoxic drug, but its use is limited because of its toxicity. In this report, we describe for the first time the ability of purified protein A (P) of Staphylococcus aureus to reduce Cy-induced toxicity in rats. Protein A-treated animals recover quickly from the toxic effects of Cy. The antitumor property of Cy is not reduced in the P+Cy group. In fact, the latter showed a persistent decrease in tumor volume compared with the Cy group. Protein A may prove to be an effective agent in increasing the therapeutic index of Cy.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 196 (1999), S. 117-123 
    ISSN: 1573-4919
    Keywords: stress ; resistance ; protection ; stress gene superfamily ; protein A ; lipopolysaccharide ; heat shock protein ; calorie restriction ; metabolic stress ; carcinogenic stress ; chemical stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Stress genes can be ascribed to have been generated by the organism for their intrinsic urge to survive against the changing environmental odds, during the evolutionary process. This concept has been supported by a large number of reports describing individual types of phenomena. These have been reconciled and globalised in terms of their relevance in this article. Supporting evidences have been drawn from the literature which indicated that by using different types of inducer one can express heat shock proteins. Similarly, several types of stress inducers, such as calorie restriction, LPS stimulation and Staphylococcal Protein-A stimulation, it was possible to induce a wide array of biological, biochemical and immunological reactions. Such biological reactions rendered protection against toxic, carcinogenic, metabolic, as well as biological stresses induced by microorganisms. Heat shock proteins have been implicated as having a role in providing resistance to the host against different types of stressors. In this article, some mechanistic schemes have been proposed as possible pathways globalising such phenomena. A minute amount of stress inducers has been observed to have helped expression of stress resistance genes, providing increased capability to the host to protect itself against myriads of both biotic and abiotic stressors. More understanding about such phenomena would help in keeping our physiological systems vigilant and our bodies healthy, fighting out the stress-related events effectively.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-675X
    Keywords: apoptosis ; protection ; protein A ; pro- and anti-apoptotic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The word “Apoptosis” or pragrammed cell death is described as the ultimate end of multiple cellular events converging from numerous initiating events to the ultimate death of a cell or organism. Several processes, such as initiation of death signals at the plasma membrane, expression of pro-apoptotic oncoproteins, activation of death proteases, endonucleases etc., that ultimately coalesce to a common irreversible execution phase, lead to cell demise. Counteracting the death signals are cell survival factors. A balance between the cell death and cell survival factors plays a major role in the decision making process as to whether a cell should die or must live. It is, therefore, hypothesized that if the balance can be shifted in favor of cell survival, one might be able to arrest the aging process, save the injured cells or else if the balance is shifted toward cell-kill it might help destroy tumors and other undesirable cells. Protein A (PA) of Staphylococcus aureus has been found to have multifarious biological response modifying properties. It has been shown to possess anti-tumor, anti-toxic, anti-parasitic and antifungal activities. It also acts as a potent immunostimulator. PA can protect bone marrow progenitor cells from zidovudin(AZT)-induced apoptosis and can stimulate immunocyte proliferation, thereby helping to replenish/restore the depleted hematopoietic cell pool. Such ability to replenish hematopoietic cells is a common property of PA observed against a number of toxic drugs/chemicals, such as cyclophosphamide, benzene, aflatoxin, salmonella endotoxin, etc. Interestingly, it was further demonstrated in our laboratory that PA can selectively kill tumor cells without affecting normal cells of the host. A search for the mechanisms of PA action revealed that this bacterial protein could shift the balance between pro- and anti-apoptotic proteins in favor of survival in normal cells, but in favor of cell death in tumor cells at a particular dose level. This unique property of PA suggests that controlled use of such type of Biological Response Modifier might help in controlling both cell growth and death phenomena.
    Type of Medium: Electronic Resource
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