Natural Host Defense Research Articles

Transgenic Plants with Enhanced Resistance to the Fungal Pathogen Rhizoctonia solani

The production of enzymes capable of degrading the cell walls of invading phytopathogenic fungi is an important component of the defense response of plants. The timing of this natural host defense mechanism was modified to produce fungal-resistant plants. Transgenic tobacco seedlings constitutively expressing a bean chitinase gene under control of the cauliflower mosaic virus 35S promoter showed an increased ability to survive in soil infested with the fungal pathogen Rhizoctonia solani and delayed development of disease symptoms.

The Influence of pH Elevation on the Incidence of Nosocomial Pneumonia

Nosocomial pneumonia, one of the most common hos pital-acquired infectious diseases, is associated with sub stantial morbidity and mortality, approaching 50% in selected patients. Patients with alterations in their tracheobronchial tree or natural host-defense mecha nisms are at increased risk of developing pneumonia. Organisms gain access to the normally sterile tracheo bronchial tree primarily by aspiration of colonized oro pharyngeal gastric secretions. Risk factors for bacterial colonization and the development of nosocomial pneu monia include increased age, elevated pH of gastric con tents, postoperative state, nutritional status, severe underlying disease (for example, chronic obstructive pulmonary disease), administration of corticosteroids or other immunosuppressive therapy, and intubation or mechanical ventilation. High gastric volume may also increase the chance of aspiration of secretions in some high-risk patients.

HIV-associated diseases: Acute and regressive encephalopathy in seropositive man

We observed the development of acute encephalopathy in a healthy human-immunodeficiency-virus(HIV)-seropositive man. HIV was isolated from cerebrospinal fluid but not from peripheral blood. Signs and symptoms resolved quickly without treatment. This viral isolate could be propagated only in umbilical cord lymphocytes, but not in peripheral blood T lymphocytes or in continuous lymphoblastoid cell lines such as CEM. The absence of the virus in the patient's T lymphocytes or infectivity of the virus for T lymphocytes may explain the unusual presentation of HIV-associated encephalopathy without immunodeficiency in an asymptomatic carrier. Moreover, it raises the possibility that acute expression of HIV can be controlled by natural host defence mechanisms and that clinical manifestations may be reversible despite the fact that the patient remains seropositive.

The effects of sub-toxic levels of phosphonate on the metabolism and potential virulence factors of Phytophthora palmivora

Potassium phosphonate (phosphite) altered the metabolism of P. palmivora in liquid cultures even under conditions where growth of the fungus was not restricted. However, under these conditions, the composition of the lipid and cell wall material was altered, as were the standing concentrations of intermediary metabolites (e.g. amino acids). The compound dehydroabietic acid, a diterpenoid, was detected as part of a neutral/cationic macromolecule in young Phytophthora mycelium. In the presence of phosphonate, this compound was absent. These changes in fungal metabolism and in the composition of the cell wall complex suggest a mechanism by which phosphonate may reduce the virulence of the pathogen in the host plant and consequently expose it to the natural host defences at an earlier stage of the invasion processes. Under the experimental conditions used, the fungus was able to reduce intracellular levels of phosphonate to levels below detection during the exponential growth stage. As phosphonate concentrations within the fungus fell, the number of metabolic changes observed in the fungus were also reduced.

Pasteurella multocida infections in mice with reference to haemorrhagic septicaemia in cattle and buffalo

Haemorrhagic septicaemia (HS) is an infectious disease of cattle and buffalo caused by particular serotypes of Pasteurella multocida and is one of the most economically important livestock diseases in South-East Asia. While HS has been recognized for many years, very little is understood about the disease, primarily because of the expense of cattle and a lack of suitable animal models. The suitability of using mice to study HS was assessed using parameters such as the critical pathogenic dose, kinetics of infection, pathology of disease and resistance to reinfection. Pasteurella multocida M1404, the type strain for Carter group B, the serotype responsible for Asian HS, was injected intraperitoneally into BALB/c mice. As few as 20 colony forming units produced an overwhelming septicaemia in mice in less than 30 h. The kinetics of infection demonstrated a very rapid in vivo multiplication rate. There was no evidence of inhibition of bacterial cell growth by natural host defence mechanisms, even with the very small inocula used. The gross pathology of the disease in mice was characterized by splenomegaly, lymphadenopathy and petechial haemorrhages similar to that observed in cattle and buffalo with HS. Mice were found to develop a short-lived resistance to reinfection following a primary infection which had been successfully treated with antibiotics. The mouse would seem to provide an ideal tool by which to study HS, but warrant further studies in order to be able to critically assess it as a model for this economically important disease.

びまん性汎細気管支炎に対するTE-031長期投与の検討

TE-031 (A-56268), a new macrolide antibiotics, was administered on a long-term basis (6 months) to 12 patients with diffuse panbronchiolitis (DPB). The causative microorganism was identified as H. influenzae in 5 cases, P. aeruginosa in 4 cases and B. catarrhalis in one case. The clinical picture of those patients was monitored, and some basic studies were also carried out. Clinically, all of the patients showed improvement in the symptoms and the various laboratory test values. Bacteriologically, as well, both H. influenzae and B. catarrhalis were eradicated. In addition, P. aeruginosa was eradicated from 2 of the 4 cases, reduced in one case and unchanged in one case. However, even in that one case in which P. aeruginosa was unchanged, the disease symptoms were alleviated. There were no instance of microbial replacement. In spite of the long-term administration of TE-031, There were no side effects. As the basic study, the DPB patients were examined for the presence of antibodies directed at viruses having affinity for the respiratory organs. It was found that a high percentage of the patients showed a high titer of antibodies for influenza virus type III and type II. It was thus surmised that it is likely that viral infection is involved in the progress of this disease. From the standpoint of the progress of DPB, the NK activity was investigated as part of the natural host defense mechanisms. It was found that, compared with healthy controls, the level of NK activity was higher in DPB patients and that it was even higher in patients on long-term TE-031 administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Protective Antibody to Endotoxin Core: The Emperor's New Clothes?

Once upon a time, in one of Hans Christian Andersen's best-loved tales, there lived an emperor as gullible as he was vain. Out of fear for his reputation he engaged in temporary self-deception and dragged most of his subjects along with him. On parade one day in some new clothes, he began to shiver, and he finally was forced to accept the possibility, suggested by a child, that his much-admired costume was not real. Similar worries have plagued investigators who report that passive transfer of antisera to oligosaccharide-deficient (rough) endotoxin mutants results in protection against challenge with smooth gramnegative bacteria and their endotoxins (lipopolysaccharides [LPS]). The rationale for research on antibodies to endotoxin core is straightforward and can be summarized simply in the following set of hypotheses. Endotoxin is capable of initiating many of the biochemical abnormalities associated with death from gram-negative bacteremia. Although antibiotics are required to clear bacteremia, they do not reverse evolving shock, because endotoxin free in the bloodstream or exposed on the surface of circulating bacteria continues to activate mediators of cell damage until natural clearance and detoxification mechanisms in the host are able to handle the load. Therefore, strategies for immunologic intervention in gram-negative shock have been focused on the LPS molecule and on its core determinants in particular. Unlike the type-specific oligosaccharide side chains (O antigens), endotoxin core structures (core sugars and lipid A) seem highly conserved over the wide range of gram-negative genera pathogenic for humans. It was thought that these common determinants might stimulate widely cross-reactive antibodies to LPS that could function to augment natural host defenses and/or decrease biologically

Current concepts in the treatment of staphylococcal meningitis.

As natural host defences are suboptimal in cerebrospinal fluid (CSF), and since antibiotics often penetrate poorly into this body site, meningitis remains one of the most difficult infections to cure. When the responsible pathogen is killed only by a relatively high concentration of an antibiotic, or is susceptible only to drugs with moderate penetration into the CSF, then treatment becomes even more complicated. Therapy of staphylococcal meningitis poses all these problems, and is even further complicated by its frequent development in the presence of a foreign body, such as a ventriculoperitoneal or ventriculoatrial shunt. In this review, we discuss the various options open to the clinician in the treatment of meningitis caused by methicillin-susceptible and methicillin-resistant staphylococci, both in the presence and in the absence of a foreign device.

Stimulation of natural host defence mechanisms in rodents by nesosteine

The effect of Nesosteine, a novel mucolytic agent, on natural host resistance mechanisms was investigated in different organs of mice and rats. Single or repeated administrations of nesosteine by the i.v. or oral route ( per os) were associated with significant increases in lung and spleen NK-mediated cytotoxicity, and in alveolar and peritoneal macrophages direct cytotoxocity. In both species the dose - response curve was bell-shaped, and optimal activity on both parameters seen at 1 mg/kg i.v. × 1, 100 mg/kg per os × 1 or 20 mg/kg per os × 5. Increases of at least 100% in lung NK and alveolar macrophages cytotoxicity were found in mice 48 h after single oral dosing at 100 mg/kg. The possible importance of Nesosteine immunostimulatory capacity in the activity of this compound in chronic hypersecretive bronchopulmonary disorders is discussed.

Bubble Oxygenation and Cardiotomy Suction Impair the Host Defense during Cardiopulmonary Bypass: A Study in Dogs

Decreased complement levels and impairment of polymorphonuclear leukocyte function increase the risk of infection during cardiopulmonary bypass (CPB). The effects of different types of oxygenator and of blood suction on this natural humoral and cellular host defense mechanism were investigated in dogs undergoing CPB during sham open-heart operations. Airborne contamination of the wound area and the CPB circuit was performed by aerosolizing Staphylococcus aureus. A membrane oxygenator in the CPB circuit maintained a normal host defense mechanism. The use of cardiotomy suction during CPB with this type of oxygenator affected the host defense to some extent. The use of a bubble oxygenator in the CPB circuit together with cardiotomy suction seriously impaired the host defense. Postoperatively bacteremia developed in no dogs in the membrane oxygenator group, whereas 8 of 15 dogs in the bubble oxygenator group had a positive blood culture for the indicator microorganism. We conclude that the use of a membrane oxygenator is helpful to maintain the host defense. Attention has to be paid to reduce the deleterious effects of cardiotomy suction.

Interaction of Urinary Tamm-Horsfall Protein with Transitional Cells and Transitional Epithelium

Uropathogenic E. coli that express mannose sensitive adhesins adhere to agglutinated urinary Tamm-Horsfall protein (THP) and to exfoliated transitional epithelial cells coated with THP. Whether THP interacts with the transitional epithelium in vivo and facilitates adhesin mediated attachment of E. coli is not known. Using immunohistochemical techniques we could not identify THP associated with formalin-fixed, paraffin-embedded transitional epithelium from a variety of sites within the urinary tract. However, varying levels of THP associated with the washed exfoliated transitional cells from 10 different subjects were detected by indirect radioimmunoassay methodologies. After in vitro incubation in human urine the mean interaction of THP with the exfoliated transitional cells increased significantly but closely paralleled the mean interaction of THP with exfoliated vaginal and buccal epithelial cells after identical incubation. We conclude that the interaction of THP with transitional cells in vivo is nonspecific and occurs after detachment from the mucosa. THP may act as a natural host defense against E. coli bacteriuria by inhibition of adhesin mediated bacterial adherence to the urothelium.

Hydroxylapatite Silver Phosphate Ceramics: Production, Analysis and Biological Testing of their Antibacterial Effectiveness

One important, and perhaps the crucial reason for lack of success in permanent implants is their colonization by bacteria (ref. 1,2 ). There are various reports of bacteria lodging the surface implants and their success in escaping from the host's defense mechanisms. Quantitative studies of ecosystems have established that more than 99,9% of the bacteria within the system live in microcolonies within biofilms that are adherent to inert surfaces ( ref. 3,4 ). Many of the bacteria that colonize the surfaces of clinical biomaterials also grow in thick, adherent biofilms ( 10, 11 ). - They may be introduced when a biomaterial is implanted or they may be carried to the surface of the biomaterial by a transient bacteriemia. Once there, their adherence is probably a virulence factor and it may enhance their protection against both antibiotics and natural host defences. The adherence of bacteria in industrial systems protect them from chemical and biocides and antiseptics. Adherence of autochtonous bacteria to ephitelium protects them from surfactants, opsonizing antibodies and phagocytic macrophages ( 12,13,14,15,16,17 ). - Apparently what is needed is antibacterial protection confined to the surface of the implant to prevent bacterial invasion of the implant. Antimicrobial penetration into the surrounding tissues is probably unnecessary.

A preliminary analysis of the effects of elliptinium on immune reactivities in mice.

The immune effects of Elliptinium (2-methyl-9-hydroxyellipticinium, 9-HME), a chemical recently shown to possess clinical antineoplastic activity, were investigated in mice. Primary antibody responses to T-dependent and T-independent antigens, DTH reactivity and responsiveness to mitogens were significantly depressed only by post treatment with single drug doses of at least 5 mg/kg i.v., i.e. doses clearly above those known to exert full antitumoral effectiveness and to induce lymphoid cell depletion in the same species. Only drug doses in the LD50 range (i.e. 10 mg/kg) reduced the capacity of NK cells and of activated macrophages to express non-specific cytotoxicity towards tumor target cells. When repeated dose regimens were used, significant immune depression was again seen at doses above those displaying chemotherapeutic activity. Data obtained suggest that at chemotherapeutically effective dosages 9-HME possesses in mice a comparatively low immunodepressive potential and that immune cells mediating natural host defence mechanisms appear especially resistant to this drug.

Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes.

We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.

Formula omitted] activity of biostim on natural host defense mechanisms in mice

formula omitted] activity of biostim on natural host defense mechanisms in mice

Investigations on staphylococcal infection of transvenous endocardial pacemaker electrodes

Infections of pacemaker electrodes and/or aggregate pockets are usually caused by staphylococci, primarily Staphylococcus epidermidis. From in vitro experiments it can be demonstrated that staphylococci are able to adhere to the plastic electrode sheath, to multiply there, and to form microcolonies. Furthermore, the staphylococci produce a slimy amorphous substance with which they are completely covered after a 24-hour incubation. No difference was noticed between the in vitro experiment situation and that occurring in pacemaker infection in humans. This slimy material may be responsible for the maintenance of the infection and the protection of the enclosed bacterial cells against natural host defense mechanisms and antibiotic treatment.

Pathogenesis of staphylococcal infections of implanted plastics and intravascular catheters

Coagulase-negative staphylococci are the predominant organisms causing infection of intravasal catheters and implanted plastic material. They are able to adhere to and grow on polymer surfaces. During the course of colonization they produce large amounts of an extracellular slime substance by which they are finally covered completely. It is supposed that this matrix of slime protects the embedded staphylococci against antibacterial substances and natural host defenses. The slime substance is not a true capsule but is loosely bound to the staphylococcal cells. It seems to have interesting biological properties such as an adhesin-like function and the ability to inhibit the lymphoproliferative response of mononuclear cells.

Interactions between the alternative complement pathway and proteases of the coagulation system.

The Complement system consists of more than twenty components and regulatory plasma proteins involved in both specific (immune) and natural host defense. Upon activation, the classical and the alternative pathways of Complement, both form specific proteolytic complexes named “C3 convertases” that cleave C3 and generate the major cleavage fragment C3b. The classical pathway is often activated after binding of C1 to an IgG or IgM-antigen complex; in contrast, activation of the alternative pathway by activating cell surfaces is dependent on their chemical composition and may occur in the absence of antibody. C3b binds to activating immune complexes or cell surfaces and may interact with the alternative pathway proteins B, D and P to form the amplification C3 convertase that augments C3 cleavage and generation/deposition of C3b. Accumulation of C3b molecules on the target surface changes C3 convertases to C5 convertases and activates the effector sequence C5–C9 generating leukocyte attracting, vasoactive and cytolytic activities of activated Complement. The molecular mechanisms of activation and regulation of the classical and alternative pathway have recently been reviewed in detail1,2.

Dichloromethylene diphosphonate (Cl 2MDP) reduces natural killer (NK) cell activity in mice

Daily administration of dichloromethylene diphosphonate (Cl 2MDP) to (C57BL/6 × DBA/2) F1 hybrid mice, from twc days of age (10 mg of P/kg body weight), resulted in a marked impairment of natural killer (NK) activity of spleer cells against YAC-1 lymphoma cells. The suppressive effecl increased with the duration of the treatment. Cessation of the treatment led to a rapid recovery (in 2 weeks) of NK activity while the osteopetrosic bone lesions persisted, Thus, the loss of natural killing cannot be explained by the simple reduction of bone marrow volume secondary to Cl 2MDP-induced osteopetrosis. However, as NK cells are considered to be dependent on the bone marrow because they cannot be sustained by extramedullary production, a direct effect of Cl 2MDP on the generation of NK cell precursors by the bone marrow was not excluded. Cl 2MDP was not directly toxic to the fully differentiated splenic NK cells, since the addition of Cl 2MDP to the in vitro assay (10 −5 − 10 μg/ml) did not reduce cytotoxicity. These studies suggest that impairment of NK activity during Cl 2MDP treatment may have clinical toxicologic implications since NK cells have been suggested to play an important role in natural host defenses against infection and neoplasia.

Host factors in bacteremia

Host factors in bacteremia can be divided into nonspecific and specific immune responses. The main components of the nonspecific immune response of the host are phagocytes and complement, and those of the specific response are immunoglobulin and cell-mediated immunity. All of these factors work in concert to protect against bacteria in the bloodstream. Immunoprophylaxis and immunotherapy have come about as a result of growing awareness of the importance of natural host defenses in combating serious bacterial infections. Although the prognosis for patients with bacteremia has improved substantially with recent advances in antibiotic therapy and supportive care, morbidity and mortality rates remain significant. Modulation of the immune system appears to be a promising means of improving the survival rate of patients with bacteremia.