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Biomedical subjects

H Northoff

Publications and source records attributed to H Northoff.

At least 19 recordsLinked to original sources
PubMed1998

Low endotoxic potential of Legionella pneumophila lipopolysaccharide due to failure of interaction with the monocyte lipopolysaccharide receptor CD14.

Legionella pneumophila, a gram-negative bacterium causing Legionnaires' disease and Pontiac fever, was shown to be highly reactive in in vitro gelation of Limulus lysate but not able to induce fever and the local Shwartzman reaction in rabbits and mice. We analyzed the capacity of purified L. pneumophila lipopolysaccharide (LPS-Lp) to induce activation of the human monocytic cell line Mono Mac 6, as revealed by secretion of proinflammatory cytokines and desensitization to subsequent LPS stimulation. We showed that despite normal reactivity of LPS-Lp in the Limulus amoebocyte lysate assay, induction of cytokine secretion in Mono Mac 6 cells and desensitization to an endotoxin challenge required LPS-Lp concentrations 1,000 times higher than for LPS of Salmonella enterica serovar Minnesota. Therefore, we examined the interaction of LPS-Lp with the LPS receptor CD14. We demonstrated that LPS-Lp did not bind to membrane-bound CD14 expressed on transfected CHO cells, nor did it react with soluble CD14. Our results suggest that the low endotoxic potential of LPS-Lp is due to a failure of interaction with the LPS receptor CD14.

Animals↗
PubMed1998

Induction of cytokines and expression of surface receptors in Mono Mac 6 cells after infection with different Legionella species.

The ability of Legionella species to multiply within human mononuclear phagocytes is usually regarded as being associated with their pathogenicity. Activation of host cells results in inhibition of intracellular Legionella multiplication. The most effective substance to induce macrophage activation, both in vivo and in vitro, is interferon-gamma. In addition, some evidence exists that macrophage-derived cytokines may contribute to the host defense against L. pneumophila, but the production of pro- and antiinflammatory cytokines by monocytes after infection with different Legionella species has not been reported with regard to their ability to multiply within the host cells. We therefore examined the production of TNF-alpha, IL-1, IL-6, IL-8, IL-10 and TGF-beta by Mono Mac 6 cells after infection with Legionella species of different human prevalence that differ in their ability to replicate within this macrophage-like cell line. After infection, Mono Mac 6 cells showed a cytokine response with time kinetics characteristic for the cytokine. Maximum cytokine levels produced differed with Legionella species, but were not related to intracellular multiplication rates. Moreover, LPS-tolerant Mono Mac 6 cells, which failed to produce cytokines, showed intracellular increase or decrease of bacterial numbers identical to that of untreated Mono Mac 6 cells. By FACS analysis, an up-regulation of CD14 (LPS receptor) and CD54 (ICAM-1) could be demonstrated. We conclude that, in the Mono Mac 6 cell line, induction of macrophage-derived cytokines after infection with members of the genus Legionella mimics an inflammatory reaction without association with intracellular multiplication rate.

Antigens, CD↗
PubMed1998

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Journal Article↗
PubMed1998

Zinc, iron, and magnesium status in athletes--influence on the regulation of exercise-induced stress and immune function.

Intense physical exercise has been shown to be associated with immunosuppression and increased rate of infection. The immunosuppressive effect of exhaustive exercise has been attributed to a reduced helper/suppressor T-cell ratio, low salivary levels of immunoglobulin-A, decreased lymphocyte proliferative response and natural killer cell activity, and elevation of stress hormones. Yet some athletes can withstand intense training periods without health problems while others are prone to infections. Thus it has been postulated that other factors may interfere with immunoregulation. The notion that macro- and micronutrients are involved in the regulation of immunological processes and the ability to cope with muscular and systemic exercise stress has been gaining attention. Particularly trace elements have been shown to be related to cell mediated and humoral immunity such as NK-cell activity, T- and B-cell functions, and cytokine release. Many investigations have reported decreased concentrations of trace elements in blood and tissues after training and competition. However, the magnitude of losses is highly dependent on the type and intensity of exercise, the individual regulatory state, and most important, nutrition. This paper reviews the data on zinc, iron, and magnesium status in athletes and summarizes the consequences of deficiencies in these trace elements regarding exercise tolerance and immune function. These elements were chosen since there is evidence they are related to exercise-induced stress and immune function.

Animals↗
PubMed1998

Importance of TNF-alpha and leptin in obesity and insulin resistance: a hypothesis on the impact of physical exercise.

Obesity is associated with an increased incidence of insulin resistance, dyslipoproteinemia, and hypercoagulability. In a more recently established hypothesis of body weight control and regulation of metabolism, the adipocyte secretes leptin and locally expresses TNF-alpha, the latter being responsible for the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression and TNF-alpha protein are greatly increased in adipose tissue from obese animals and humans. Elevated TNF-alpha expression induces insulin resistance by downregulating the tyrosine kinase activity of the insulin receptor and decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis, and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover, adipocytes secrete leptin, a molecule with a secondary cytokine structure whose concentrations correlate with the amount of fat tissue. Increased leptin levels downregulate appetite and increase sympathetic activity and thermogenesis in the hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and serum leptin levels and is associated with improved insulin sensitivity and lipid metabolism. Although exercise has also been shown to reduce leptin levels, an influence on TNF-a expression in adipocytes or muscle cells has not yet been demonstrated.

Animals↗
PubMed1997

[Effects of leukocyte depletion on the storage quality of whole blood].

BACKGROUND: According to the German Guidelines for Hemotherapy, preoperative autologous blood donations can be stored and transfused as whole blood. In contrast to the storage of blood components, however, storage of whole blood results in deterioration of the biological quality due to contamination with leukocytes and platelets. In this study we examined the influence of prestorage leukocyte depletion on the quality of filtered whole blood donations during storage. MATERIAL AND METHODS: Whole blood was donated by healthy volunteers (n = 14,500 ml, 70 ml CPDA-1) and was filtered using an integrated whole blood filter system (Leukotrap A1, Fa.Pall, Dreieich, Germany). The leukocyte-depleted whole blood units were then stored for up to 49 days. Several hematological and biochemical parameters indicative of the quality of blood donations were determined during storage. RESULTS: Our data indicate a quality of leukocyte-depleted whole blood donations comparable to buffy-coat-free red blood cell units. CONCLUSIONS: The Leukotrap A1 whole blood filter system is an interesting option for hospitals lacking the technical capacity to separate whole blood into components. The clinical suitability remains to be investigated by means of clinical studies.

Adult↗
PubMed1997

[Rationale for a specific diet from the viewpoint of sports medicine and sports orthopedics. Relation to stress reaction and regeneration].

The relation between nutrition and sport has been studied extensively during recent decades. Nevertheless, research interest was focused mainly on the role of dietary macro- and micronutrients as ergogenic aids. Today, there is increasing support for the hypothesis that the nutrient status also has relevance for the prevention and rehabilitation of systemic and muscular stress induced by intense physical exercise. The increase in muscular stress is indicated by the rise in creatine kinase and myoglobin; the systemic stress is associated with characteristic immunological and hormonal changes and an acute-phase response. During and following exercise, the course of cytokines (especially interleukin 6) and acute-phase proteins (C-reactive protein, fibrinogen) as well as cortisol levels are an indirect measure of the exercise intensity and the individual ability to cope with physical stress. It has been shown that the dietary intake and, consequently, the systemic or intracellular concentrations of minerals such as magnesium and zinc, vitamins with antioxidant capacity (vitamin E, C, E, and beta carotine), and the composition of fatty acids can be related to the exercise-induced stress response. Therefore, this review deals specifically with the impact of these nutritional components on the reduction of sports specific muscular damage and systemic stress, especially under the aspect of increased losses during and following intense physical exercise.

Antioxidants↗
PubMed1997

Impaired production of cytokines in a case of human leishmaniasis.

A patient presented with the unique clinical picture of diffuse cutaneous and mucosal leishmaniasis caused by Leishmania tropica. Elevated serum levels of several cytokines including interleukin (IL) 2, interferon gamma (IFN-gamma), and tumor necrosis factor alpha were found. All cytokine levels returned to normal during therapy. No IL-10 or IL-4 levels were detectable. In whole blood cultures, induction of IFN-gamma by lipopolysaccharide (LPS) was completely negative, even after therapy. Concanavalin A (Con A)-induced release of IFN-gamma, like Con A-induced release of the other cytokines, was only initially impaired but returned to normal during therapy. Induction of the other cytokines by LPS was never impaired. The low expression of human leukocyte antigen DR on monocytes increased during IFN-gamma therapy but dropped when IFN-gamma treatment was ceased. We conclude that in this patient one or more of the routes of IFN-gamma production was impaired, thus resulting in insufficient IFN-gamma production in the infected lesions (although IFN-gamma was systemically present).

Adolescent↗
PubMed1997

Effect of exhaustive exercise stress on the cytokine response.

Fifteen athletes were investigated 24 h before, 1 h after, and 20 h after an exhaustive exercise stress test (mean duration 68 min). Testing for cytokines was done in serum, urine, and the supernatants of whole blood cell cultures, which were stimulated with lipopolysaccharide (LPS), concanavalin A (Con A), or phythaemagglutinin (PHA). Elevated levels of interleukin 6 (IL-6) and soluble IL-2 receptor (sIL-2R) were found 1 h after the run in both serum and urine samples. TNF-alpha in serum was also increased, whereas IL-2 in urine was decreased after the exercise. All other testings in serum and urine (including IFN-gamma) gave borderline or negative results. In cell cultures, the LPS-induced release of the inflammatory cytokines TNF-alpha, IL-1, and IL-6 was suppressed 1 h after exercise. Also, the Con-A-induced and LPS-induced release of IFN-gamma, and the PHA-induced release of IL-2 were suppressed 1 h after exercise. In contrast, Con-A-induced release of IL-2 was mildly increased after the run. We conclude that exercise of the intensity and duration described here causes an activation of the immune system, which is immediately counter-regulated. Twenty hours after the exercise, most of the observed changes were back to pre-exercise levels, indicating only a short duration for this suppressive counter-regulation.

Adult↗
PubMed1997

Essential fatty acids, immune function, and exercise.

The immunologic response to exercise comprises numerous alterations within the immune system, but how these processes are regulated is still largely unknown. Exercise-related immunological changes include signs of inflammation, such as release of inflammatory mediators, activation of various white blood cell lines and complement, and induction of acute phase proteins. Nevertheless, signs of immunosuppression, such as decreased T and B cell function or impaired cytotoxic or phagocytic activity, can also be observed. Some data suggest that essential fatty acids help regulate inflammatory processes, modulating both cytokine release and the acute phase response. Positive effects of changing dietary essential fatty acids have been demonstrated in chronic inflammatory diseases. In contrast, little is known about the contribution of fatty acids to the exercise-induced immunologic reaction. Essential fatty acids may determine alterations within the immune system following exercise. Therefore, future studies are necessary to evaluate the influence of the fatty acid composition on the inflammatory or immunosuppressive component following heavy exertion.

Acute-Phase Reaction↗
PubMed1996

Frequency and specificity of platelet-specific alloantibodies in HLA-immunized haematologic-oncologic patients.

The frequency and specificity of platelet-alloantibodies to human platelet antigens (HPA) -1, -3 and -5 was investigated in 59 multitransfused, HLA-immunized patients. Using the MAIPA test (monoclonal antibody specific immobilization of platelet antigens) platelet alloantibodies could be demonstrated in 10 (17%) patients. In one patient the antibody was present prior to any transfusions and probably induced by multiple previous pregnancies. This antibody was directed to HPA-5b. The remaining nine antibodies were found in patients (n = 36) with HLA-antibodies reacting with over 95% of unselected lymphocytes. In these patients the target antigens were HPA-1b in six, HPA-3a in one and both antigens in two patients. Our findings demonstrate platelet alloimmunization induced by transfusions to be restricted to patients with high HLA-immunization. 25% of these patients (9/36) show platelet-specific antibodies, primarily HPA-1b.

Antibodies, Monoclonal↗
PubMed1996

Reactivation of recipient antibody to blood cell antigens soon after allogeneic bone marrow transplantation.

Reactivation of recipient antibody to HLA and red blood cell antigens is described in 8 patients after allogeneic bone marrow transplantation. These IgG antibodies can be detected between day 10 and day 40 after transplantation and, in 1 patient, can be shown to be antigen-independent. We hypothesize that, induced by graft recognition of recipient antigens, antigen-independent activation of sensitized recipient B cells takes place leading to transient antibody production.

Antibodies↗
PubMed1996

Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation.

The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.

Adenosine↗
PubMed1995

Antigen-independent reactivation of anti-E, years after allogeneic bone marrow transplantation: a case report.

Nine years after allogenic bone marrow transplantation a strong anti-E was observed in a patient transplanted with bone marrow from his HLA-identical brother. This IgG anti-E, with a titre of 4000, was detected together with autoantibodies to red blood cells and platelets and was not induced by transfusion with E+ cells. The hypothesis is proposed that the anti-E represents either antigen-independent desuppression of the donor immune system sensitized at the time of bone marrow transplantation by E antigens in the recipient, or antigen-independent memory B-cell activation by Epstein-Barr virus infection.

Autoantibodies↗
PubMed1994

Rat microglial interleukin-3.

Interleukin-3 (IL-3, multi-CSF) is a growth factor for a variety of hematopoietic progenitor cells. Recently, microglial cells, the resident macrophages of the central nervous system (CNS) have been shown to proliferate in the presence of IL-3 both in vivo and in culture. Data obtained from cultured astrocytes gave rise to the hypothesis that astrocytes synthesize the microglial growth factor. This is the first report identifying rat microglial cells themselves as a source of IL-3. Culture media conditioned by isolated microglia enhanced microglial proliferation above fresh media controls. IL-3 polypeptide was detected in both conditioned media (CM) and in microglial cells by Western blotting and immunoprecipitation. Furthermore, anti-IL-3 antibodies were able to inhibit microglial proliferation induced by conditioned media. mRNAIL-3 was present in single microglial cells as revealed by in situ hybridization. Total RNA prepared from purified microglia yielded a single PCR amplification product. Identity of the PCR product was confirmed by Southern blot hybridization using a cDNAIL-3 probe and by DNA sequencing. Expression of mRNAIL-3 was observed in both absence and presence of lipopolysaccharide, a bacterial endotoxin, that commonly induces expression of inflammatory cytokines and inhibits microglial proliferation. It is concluded that IL-3 expression in ensuring the recruitment of enhanced numbers of immunocompetent cells at sites of lesion. In the light of weak immune reactions in the brain, it is hypothesized that the expression of a characteristic T cell feature in monocyte-derived microglia may be a partial compensation of T cell functions in brain lesions.

Animals↗
PubMed1994

The cytokine response to strenuous exercise.

Several groups have now investigated the cytokine response to strenuous exercise. In this article we try to summarize known data on this topic. Significant, albeit mild increases in plasma levels of the monokines IL-1, TNF-alpha, IL-6, and of soluble IL-2 receptor have been reported following strenuous exercise. Increased excretion of cytokines after exercise can also be shown in the urine of athletes. Modulation of cytokine release by strenuous exercise can also be demonstrated using in vitro cell cultures. Several authors have shown an increase in endotoxin-stimulated monokine release following exercise. In contrast, using whole blood cultures we found strongly depressed production of interferon gamma (in response to mitogen or endotoxin) following strenuous exercise. The potential significance of cytokine modulation for exercise-related immunological problems is discussed.

Cells, Cultured↗
PubMed1994

Reactivation of antibodies of donor and recipient origin to platelet antigens early after allogeneic bone marrow transplantation: a case report.

Reactivation of platelet-reactive antibodies of donor and recipient origin is described in a patient following allogeneic BMT (donor: anti-HPA-5b; recipient: anti-HLA, anti-HPA-1b). The antibodies were detected around day 15 after BMT, peaked around day 25, and then decreased. These antibodies are interpreted as an antigen-independent reactivation of secondary B-cell responses, activated in the context of recognition of host antigens by the graft.

Adult↗