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Biomedical subjects

A Nowotny

Publications and source records attributed to A Nowotny.

At least 37 records · Page 2Linked to original sources
PubMed1985

Effects of toxic and nontoxic endotoxin derivatives on glucose kinetics.

Although the polysaccharide portion of bacterial endotoxins (ET) and other components of the bacterial cell wall are known to possess biological activity, the toxic effects produced by ET have been attributed mostly to the lipid-A component. The present study examined the influence of selected gram-negative cell wall components on in vivo carbohydrate homeostasis. Chronically catheterized conscious rats were injected with either ET, lipid A, the White polysaccharide supernatant (WPS-S; polysaccharide-rich and lipid-A-free) or the WPS-precipitate (WPS-P; rich in cell wall components and lipid-A-free) at sublethal doses of 100, 10, and 1 microgram/100 g. The acute hypotensive response to ET and lipid A were similar, while the WPS-P induced a smaller reduction in pressure. Endotoxin, lipid A, or the WPS-P (100 and 10 micrograms) all produced hyperglycemia. Hyperlactacidemia was evident in rats receiving ET, lipid A, and WPS-P; ET-treated animals exhibited the highest lactate concentrations. At the highest doses used, these three fractions increased the rate of glucose appearance. The polysaccharide-rich WPS-supernatant elicited no significant alterations in any of the variables studied. These results indicate that cell wall components of gram-negative bacteria, other than the lipid A of endotoxin, induce changes in carbohydrate metabolism that are similar to those produced by the toxic, lipid-A component of endotoxin.

Animals↗
PubMed1984

Effects of bacterial endotoxins and their detoxified derivatives on serum and liver lipids in mice.

The influence of different endotoxins (lipopolysaccharides, LPS) obtained from Serratia marcescens 08, Escherichia coli 089, and their derivatives, detoxified either by partial hydrolysis or irradiation, on serum and hepatic lipids and on serum lipase activity in C57Black mice was studied. Endotoxic LPS elevated the serum total lipids and lipoproteins, particularly the very-low-density lipoproteins, and induced a reversible accumulation of triglycerides in the liver. Since nontoxic preparations did not cause such alterations, it is assumed that the toxicity of LPS is an essential factor in causing lipid metabolism disorder. A nearly identical increase in the lipase activity was detected in 5 to 10 hr in the sera of experimental animals treated by both toxic and nontoxic preparations. Results indicated the potential advantage of using detoxified derivatives of bacterial endotoxins in human therapy.

Animals↗
PubMed1984

Bacterial invasion of oral tissues of immunosuppressed rats.

The periodontia of immunosuppressed rats were examined by light and electron microscopy. Bacterial invasion was noted in the periodontal tissues of septicemic ligature-treated animals. Invading bacteria consisted of gram-negative rods which were morphologically similar to the Pseudomonas aeruginosa strain isolated from the mouth of one of the septicemic animals.

Alveolar Process↗
PubMed1983

Induction of nonspecific tolerance to endotoxins reduces the alveolar bone resorption in ligature-treated rats.

Previous experimental data from various laboratories indicate that endotoxin of gram-negative oral microorganisms might be one of the most important bacterial products involved in bone resorption during periodontitis. Immunologically nonspecific tolerance to endotoxins in rats was induced by repeated application of Serratia marcescens trichloroacetic acid-extracted endotoxin. Silk ligature was placed on the second maxillary molar of the endotoxin-tolerant rats as well as of control rats in which tolerance to endotoxin had not been induced. The animals were sacrificed 8 days later. The rats showed no specific immune response to the tolerance-inducing endotoxin as measured by passive hemagglutination and by the lymphoblast assays, but we found that bone resorption was significantly reduced in the endotoxin-tolerant rats as compared with ligature-treated animals in which tolerance to endotoxin had not been induced.

Alveolar Process↗
PubMed1983

Studies on the optimal conditions of CSF generation by endotoxic LPS and its PS derivative in mice.

Not only the endotoxic LPS preparations, but a non-toxic, lipid-free, non-mitogenic hydrolytic breakdown product of it (called PS) is also capable of inducing colony stimulating factor (CSF) release (1). Due to difficulties to reproduce above findings it became necessary to study the optimal conditions to obtain CSF active PS preparations. It was found that the CSF generating component of the highly heterogeneous PS mixture is sensitive to acidic hydrolyses, but it is less sensitive than the toxic site in the lipid moiety of the LPS. Carefully controlled optimal hydrolytic conditions give PS preparations which have less than one percent residual endotoxicity but maintained 40 to 80% of the original CSF generating capacity. Prolonged hydrolysis will destroy this activity too. Optimal dose of LPS and PS for CSF induction in mice differed widely. For LPS the optimal dose is 25 micrograms, injecting more gave a much reduced or non-detectable CSF level. Optimal dose for PS was 160 micrograms, and this generated a significantly higher CSF level than 25 micrograms LPS. At concentrations below 25 micrograms, LPS was clearly more active than PS. The CSF level reached its peak at 3-4 hours after other LPS or PS injection. Intravenous route was sometimes but not always more effective than intraperitoneal.

Animals↗
PubMed1982

Studies on host defenses enhanced by endotoxins: a brief review.

The findings reported here indicate that toxic reactions to endotoxin do not have to be part of the mechanisms leading to clinically improved status of patients or of experimental animals. It seems to be possible to mobilize the host defenses without the unwanted or dangerous side effects which were encountered during fever therapy. For the demonstration of activated host defenses, several experimental models are available. Non-specific resistance to bacterial infections, to lethal irradiation or to experimental challenge with viable tumors are clear manifestations of enhanced capacity of the endotoxin-treated host to compensate for the induced damage, or to cope with an otherwise overwhelming number of pathogenic cells. Immunopotentiation is obviously one of the contributing factors in some of the above parameters. How these results are applicable to human therapy remains to be seen. Such use of endotoxin derivatives, or better, the mediators of beneficial endotoxic effects, must wait until we learn more about the nature of the alternating positive and negative effects of endotoxin application. The importance of the proper timing of such a therapeutic modality cannot be overemphasized.

Adjuvants, Immunologic↗
PubMed1982

Release of toxic microvesicles by Actinobacillus actinomycetemcomitans.

Oral isolates of Actinobacillus actinomycetemcomitans (strain Y4) release spherical microvesicles in large numbers during normal growth. The biological activities of these products were studied, and it was estimated that approximately 1/10 of their dry weight was made up of heat- and proteolysis-resistant endotoxin. The chicken embryo lethality and bone-resorbing activity of the microvesicles were heat stable but proteolysis sensitive. Other laboratories have reported the presence of a heat- and proteolysis-sensitive leukotoxin in similar preparations. Accordingly, the microvesicles released by strain Y4 may contain, in addition to endotoxin, several potent substances which are highly toxic and active in bone resorption, and these may be significant factors in the pathogenesis of periodontal diseases.

Actinobacillus↗
PubMed1981

Immunization against bacteria- and endotoxin-induced hypotension.

The characteristics of hypotension induced in rabbits by intravenous injection of viable Salmonella typhosa 0901 organisms were studied and found to be a function of the number and age of the bacterial cells. Effective neutralization of the blood pressure lowering was achieved by immunization with homologous organisms as well as heterologous endotoxins and a detoxified derivative. In addition, native endotoxins derived from a number of different genera of gram-negative bacilli, as well as lipopolysaccharides deficient in either the polysaccharide or lipid components, were tested for their ability to induce hypotension in rabbits and tolerance to the lowering of blood pressure. Hypotension was elicited by intravenous injection of all native endotoxins as well as polysaccharide-deficient endotoxins, but was absent in preparations from which the lipid was removed. On the other hand, protection against the hypotension effect could be induced after injection of either the lipid- or polysaccharide-deficient derivatives.

Animals↗
PubMed1981

Humoral immunity and reduced periodontal bone loss in Eikenella corrodens-monoassociated rats.

Germfree Sprague-Dawley rats monoassociated with Eikenella corrodens exhibited alveolar bone loss. This progressive bone loss occurred over a period of weeks, during which time the hosts developed an immune response toward the infective microorganism. By means of repeated bacterial vaccination resulting in elevated serum antibody titers, reduced bone loss was observed.

Alveolar Process↗
PubMed1980

Effect of gram-negative bacterial lipopolysaccharide-derived polysaccharides, glycolipids, and lipopolysaccharides on rabbit and human platelets in vitro.

The in vitro effect of gram-negative bacterial LPS-derived polysaccharide (PS), glycolipid (GL), and lipopolysaccharide (LPS) was investigated both on rabbit and human platelets. Rabbit platelets aggregated when they were treated with either GL or LPS, but no aggregation occurred when PS was used. No aggregation occurred when human platelets were treated with LPS, PS, or GL. However, when either human or rabbit platelets were treated with LPS-antibody complexes (LPS-ab), aggregation took place. Guinea-pig serum inhibited the aggregation caused by LPS-ab, but had no effect on rabbit platelet aggregation caused by LPS or GL alone. The factor(s) in guinea-pig serum that inhibited aggregation was heat-stable. These results suggest that there may be two different mechanisms involved in rabbit platelet aggregation by endotoxin in vitro. Using human platelets, only one mechanism was observed.

Animals↗
PubMed1980

Biological and chemical characterization of endotoxin from Capnocytophaga sputigena.

An endotoxin was isolated from Capnocytophaga sputigena strain 4 by a modification of the hot phenol-water method. The extraction procedure yielded a lipopolysaccharide which accounted for approximately 1.5% of the dry weight of the cells. The material was composed of 18.6% lipid (as C(15) fatty acid), 46.5% neutral sugar including 9.6% hexose, 18.3% 6-deoxy sugar, 1.0% 2-keto-3-deoxy sugar, and 4.8% heptose. Hexosamine, protein, and phosphorus were found in quantities amounting to 9.0, 2.9, and 2.0% of the dry weight, respectively. No pentose or nucleic acid was detected. Acid hydrolysis resulted in the release of the constituent sugars and the formation of an insoluble precipitate. The lipopolysaccharide was tested for numerous biological activities characteristic of endotoxins. The pyrogenicity was relatively low; the fever index 40 was 17 mug, and 10 mug was required to give the characteristic biphasic fever response. The toxicity of the extract was very low, with a 50% chicken embryo lethal dose of 15.6 mug and a 50% mouse embryo lethal dose of greater than 8 mg. Similarly, the C. sputigena endotoxin had modest effects on leukocytes when compared with endotoxin standards from other organisms. The extract exhibited little or no mitogenicity when tested on mouse spleen lymphocytes. It was not toxic to human peripheral polymorphonuclear leukocytes and caused the release of only a small (13%) portion of lysosomal enzymes. Although the C. sputigena lipopolysaccharide caused significant activation of mouse peritoneal macrophages, the dose required was twice that of an Escherichia coli endotoxic standard. However, the Limulus amoebocyte lysate clotting activity of the lipopolysaccharide was comparable to that of an Serratia marcescens lipopolysaccharide standard, and passive hemagglutination tests revealed that 1 mug of the lipopolysaccharide was capable of sensitizing 1 ml of a 2% sheep erythrocyte suspension for agglutination with an antiserum prepared against C. sputigena whole cells.

Animals↗
PubMed1979

Restoration of depressed antibody responses of leukemic splenocytes treated with LPS-induced factors.

Lipopolysaccharide and a nontoxic derivative, PS, from Serratia marcescens were studied in terms of their effects on normal and Friend leukemia virus depressed splenocytes. These materials caused a marked increase in the number of antibody producing cells by both groups of splenocytes. MDP, a synthetic analogue of myobacterial cell walls, produced a similar adjuvant response by normal and leukemic splenocytes. Combinations of PS or LPS and BCG or MDP resulted in synergistic immunostimulatory responses. A soluble factor associated with these materials appeared to mediate the response, since cell-free supernatants from LPS stimulated splenocytes or serum from LPS treated mice resulted in similar immunostimulation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Effect of immune sera upon enhanced in vitro antibody responses.

Immunization of rabbits with S marcescens bacteria in Freund's incomplete adjuvant resulted in development of anti-Serratia sera with bacterial agglutinating properties as well as LPS modulating properties. The antisera reacted with the LPS in counterimmunoelectrophoretic assays. Such antisera also stimulated the LPS induced enhancement of specific anti-SRBC responses from normal spleen cell cultures but did not further enhance the stimulated responses of similar cultures incubated with the smaller molecular weight PS-rich derivative. The antisera had no effect on LPS or PS enhanced nonspecific background anti-SRBC response as compared to normal rabbit serum-treated controls. These results point to a possible role for immune complexes as an enhancer of the immunostimulating activities of LPS antibody-treated cultures and also indicate a difference between LPS and PS as immunomodulators.

Animals↗
PubMed1979

Studies on the endotoxin induced tumor resistance.

In summary, this report has discussed the immunologic mechanisms involved in the enhancement of nonspecific resistance to tumor by endotoxin. The optimal conditions for tumor protection involved pretreatment with approximately 25 mug LPS administered at the siteof subsequent tumor challenge. In an attempt to relate endotoxin structural components to the ability to enhance TUR, a variety of whole LPS's, endotoxic glycolipids and PS preparations were compared. While all of the intact LPS's and several of the glycolipids were effective in enhancing TUR, some endotoxic glycolipids were totally inactive although they were equally toxic. Some lipid-free PS preparations were also active although less than whole LPS. Evidence was presented to suggest that mechanism for enhancement of TUR involves B cells and macrophages but not T cells. The mechanism also involves the production of soluble factors which are released into the serum of mice in response to LPS or PS. These factors can transfer and mediate the antitumor effects of LPS. The preinfection of mice with BCG enhanced the activity of LPS and PS in the production of antitumor activity.

Animals↗