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Biomedical subjects

H Hof

Publications and source records attributed to H Hof.

At least 73 records · Page 4Linked to original sources
PubMed1995

Systemic immunization induces protective CD4+ and CD8+ T cell-mediated immune responses in murine Listeria monocytogenes meningoencephalitis.

The immune mechanisms underlying immunization-induced protection of mice from lethal central nervous system (CNS) listeriosis were evaluated by immunohistochemistry, flow cytometry of leukocytes isolated from the brain, reverse transcription-polymerase chain reaction analysis of intracerebral (i.c.) tumor-necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-1 beta, IL-10, granulocyte/macrophage colony-stimulating factor, and inducible nitric oxide synthase mRNA expression, and T cell depletion experiments. The data demonstrate that active immunization of mice prior to an i.c. infection with Listeria monocytogenes prevents the development of a fatal necrotizing encephalitis and accelerates the recruitment of an increased number of alpha beta T cell receptor (TcR)+ CD4+ and CD8+ T cells, gamma delta TcR+ T cells, B cells, granulocytes and macrophages to the brain compared to non-immunized animals. In addition, immunization induced a pronounced activation of i.c. macrophages and microglial cells as shown by an increased expression of MHC class II antigens. In parallel, transcript levels for all cytokine mRNA analyzed were higher in the brains of immunized mice. The protective effects of immunization were completely abolished by depletion of CD4+, CD8+, or both T cell subsets. All groups of T cell-depleted immunized mice developed a fatal necrotizing encephalitis with an increased i.c. bacterial load. In addition, cytokine mRNA synthesis was significantly impaired. The severity of disease was only slightly different between CD4+, CD8+ and CD4+/CD8+ T cell depleted mice, indicating that both subsets of T cells are required for an effective i.c. immune response to L. monocytogenes. This is in marked contrast to systemic listeriosis, and points to CNS-specific features of the immune response.

Animals↗
PubMed1995

Influence of staphylococcal enterotoxin B (SEB) on the course of murine listeriosis.

Confrontation of the immune system with bacterial superantigens leads to an initial activation of the immune system followed by a state of profound immunosuppression. To investigate the role of a superantigen in an acute infection with a facultatively intracellular bacterium, we have studied the effect of staphylococcal enterotoxin B on the course of murine listeriosis. Intraperitoneal injection of SEB led to a statistically significant growth restriction of Listeria monocytogenes in the organs of mice infected intravenously or intraperitoneally when treatment with SEB and infection with L. monocytogenes were given simultaneously or when the mice were treated two days before infection. No effect of SEB on murine listeriosis was found when SEB was given more than two days before infection or one or more days after infection. We conclude that initial immunostimulation by SEB which is indicated by a massive liberation of all interleukins measured (IL1 alpha, IL6, TNF alpha, IL2, IFN gamma, IL4) is responsible for the growth restriction of L. monocytogenes in the organs of treated mice. Apoptosis of V beta 8 positive T cells which was accompanied by a 30% reduction of these cells at day 7 after treatment seems to be totally compensated.

Animals↗
PubMed1995

Erythromycin is ineffective against Listeria monocytogenes in multidrug resistant cells.

Multidrug resistance of tumor cells is a well-known phenomenon in oncology. Among the substances excluded from the cells are not only antineoplastic drugs but also certain antibiotics, e.g. erythromycin. To prove the hypothesis that this might render infections with intracellular bacteria untreatable with these antibiotics we used erythromycin to treat intracellular infection of multidrug resistant (MDR) cells with Listeria monocytogenes. Erythromycin was unable to restrict the growth of L. monocytogenes in KBV-1 MDR cells in concentrations of up to 25 micrograms/ml. In contrast, 0.049 micrograms/ml of erythromycin were sufficient to restrict the growth of the bacteria in nonresistant KB 3-1 cells. When verapamil was added to the supernatant of KBV-1 cells, erythromycin regained its effectivity on L. monocytogenes multiplying in these cells. The fact that MDR cells may render intracellular bacteria inaccessible to certain antibiotics might have important implications for the persistence of these bacteria in the host and for the treatment of patients with genetically engineered MDR cells.

Dose-Response Relationship, Drug↗
PubMed1995

[Polio vaccination today: critical remarks].

Vaccination against poliomyelitis remains an absolutely mandatory measure to prevent resurgence of this dreadful viral infection. Today, however, when the chance to get infected is extremely low, one has to reconsider much more the inherent risk of such a living vaccine which is principally able to induce neurologic disease especially in immunocompromised host the number of which is increasing in our population. Since these attenuated vaccine strains multiply largely in the orointestinal tract of a vaccine, those viruses are shed and easily spread into surroundings so that other persons which are not aware of this event are exposed. But also in normal hosts the vaccine strains are able to produce disease because the genetic mutation leading to reduced virulence is not absolutely stable. Back mutations with increased virulence develop during multiplication in the vaccinee and may threaten the vaccinee as well as contact persons. For the sake of security these consequences should be respected much more. Since a dead vaccine of polioviruses is available, one should much more often profit from this choice.

History, Ancient↗
PubMed1995

Dynamics of the intracerebral and splenic cytokine mRNA production in Toxoplasma gondii-resistant and -susceptible congenic strains of mice.

Oral infection with a low-virulence strain of Toxoplasma gondii (Tg) induced a persisting encephalitis in resistant strains of mice. In the present study we have examined transcripts of various cytokines during acute and chronic stages of murine Tg encephalitis. In the brain of infected animals, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10 and IL-12 mRNA were induced to a significant extent, but only low levels of IL-4 mRNA were detectable. A similar cytokine profile was observed in the spleen. However, in contrast to the brain, the increase of IL-2 mRNA was particularly pronounced in the spleen, whereas the opposite was found for IFN-gamma and TNF-alpha mRNA. Thus, cytokines involved in T-cell proliferation were more prevalent in the spleen, but in the brain, where Tg actively multiplies, the effector molecules IFN-gamma and TNF-alpha were preferentially up-regulated. In addition, a detailed analysis of cytokine mRNA levels in major histocompatibility complex (MHC)-congenic strains of BALB and B10 mice revealed that the genetically regulated susceptibility to Tg was correlated with the amount of intracerebrally produced cytokine mRNA for IFN-gamma, TNF-alpha and IL-6. Mice with a strong increase of these cytokine mRNA were significantly better protected against Tg. This indicates that the outcome of toxoplasmosis may be critically dependent on an adequately regulated intracerebral immune response.

Animals↗
PubMed1995

[Antimicrobial oligopeptides--an important factor in non-specific defense against infection].

For survival of plants, animals as well as main in a nature full of aggressive microbes, endogenous antibiotics play an essential role, which is not yet fully appreciated in medicine and science. For example in the granules of polymorphonuclear granulocytes and macrophages or even of specialized epithelial cells such as Paneth cells in the crypts of the intestinal mucosa, oligopeptides are produced with a wide range of antimicrobial activity. According to their chemical structures and modes of action they can be grouped into various different families. The physiological role of these agents on the surface of skin and mucosa or within host tissue is only incompletely understood.

Bacteria↗
PubMed1995

[Rational use of antimycotics against yeast infections].

In clinical medicine mere colonization with yeasts is often hardly to be discriminated from true infection. Thus, a clear-cut separation of preventive from therapeutic use of antimycotics is not possible in practical medicine. The problem is that on the one hand one has no exact diagnosis of yeast infection, but on the other hand best therapeutic results are obtained when the drugs are given as early as possible. In comparison to the huge number of antibacterial compounds, the members of antimicrobials are limited. For prophylaxis, one can use the polyenes, such as amphotericin B and nystatin, or the azoles, such as fluconazole or itraconazole. Thereby the azoles act not only locally at the site of application but are absorbed and thus are distributed to remote sites, where the non-resorbable polyenes never arrive. Among the azoles, fluconazole has the advantage that resorption is independent from an acid pH in the stomach, whereas itraconazole resorption is variable in severely ill persons with neutralized gastric fluid. For therapeutic use systemically applied amphotericin B has certain disadvantages. Because of toxic reactions an optimal dose cannot be given; furthermore in some sites insufficient concentrations are achieved, particularly in the kidney and also in the CSF. In contrast, the azoles possess better pharmacologic and toxicologic properties. Resistance to antimycotics is principally possible but still rare, so that in practice a routine testing is not necessary. Candida glabrata as well as Candida krusei are primarily resistant to fluconazole.

Amphotericin B↗
PubMed1994

Activation of the innate immune system in murine congenital Toxoplasma encephalitis.

A murine model of congenital Toxoplasma encephalitis (CTE) was established in NMRI mice following prenatal infection with a low dose of Toxoplasma gondii (DX strain). Histopathologically, the disease exhibited the key features of human CTE including foci of necrosis, intracerebral calcifications, and ventriculitis. The inflammatory response in the brain of infected animals was predominantly mediated by macrophages and granulocytes with additional participation of astrocytes. These findings indicate that the prenatal Toxoplasma infection closely parallels human CTE, but differs significantly from adult toxoplasmosis.

Animals↗
PubMed1994

Fecal shedding of Listeria monocytogenes during murine listeriosis after intravenous infection.

Female NMRI SPF-Mice were intravenously infected with L. monocytogenes and the feces and urine samples were cultured to detect a possible presence of the bacterium. In 6 out of 10 mice, the bacteria occurred in the feces, but not in the urine samples. Listerial shedding was detected only during acute listeriosis from day 2 to day 9 post infectionem. Thus, listerial shedding after infection via routes other than the gastrointestinal tract is possible not only in newborns, but also in adult experimental animals.

Animals↗
PubMed1994

Differential expression of ICAM-1, VCAM-1 and their ligands LFA-1, Mac-1, CD43, VLA-4, and MHC class II antigens in murine Toxoplasma encephalitis: a light microscopic and ultrastructural immunohistochemical study.

Light microscopic and ultrastructural immunohistochemistry of cell adhesion molecules (CAMs) and major histocompatibility class II antigens (Ia) expression in experimental murine Toxoplasma encephalitis (TE) revealed a prominent upregulation of the intercellular cell adhesion molecule-1 (ICAM-1) and of Ia on cerebral endothelia, microglia, ependyma, and choroid plexus epithelium during acute and chronic TE. Microglia also expressed Mac-1 and leukocyte function-associated antigen-1 (LFA-1), which are both ligands of ICAM-1, as well as CD45. The prominent simultaneous expression of a multitude of these molecules on microglia is indicative of a central immunologic function of this cell type in TE. Additionally, occasional astrocytic processes slightly expressed Ia in full-blown TE. The vascular cell adhesion molecule-1 (VCAM-1) was restricted to endothelia of cerebral blood vessels, which frequently showed perivascular cuffing of inflammatory cells, ependyma, and choroid plexus epithelium. Upregulation of Ia, CAMs and their ligands correlated with disease activity. Immunohistochemical analysis of the functional state of infiltrating T cells showed a preferential recruitment of CD44+ memory and activated interleukin-2R+ T cells in TE.

Animals↗
PubMed1994

Bay Y 3118, a new quinolone derivative, rapidly eradicates Listeria monocytogenes from infected mice and L929 cells.

Bay Y 3118 is a new quinolone derivative with pronounced activity against gram-positive bacteria including the facultatively intracellular bacterium Listeria monocytogenes. Bay Y 3118 was tested in vitro and in animal models of listeriosis. All strains of L. monocytogenes and other Listeria spp. were highly susceptible in vitro; the MICs for these organisms ranged from 0.062 to 0.25 micrograms/ml. Bay Y 3118 was rapidly bactericidal in vitro, with a postantibiotic effect occurring for 3 h after removal of the antibiotic. L. monocytogenes was eliminated from infected L929 cells treated with Bay Y 3118, suggesting a bactericidal effect on the listeriae in these cells. Immunocompetent mice were rapidly cured by treatment with 4 mg every 12 h. Concomitantly, the levels of interleukin 6 and gamma interferon in mouse sera declined rapidly. In immunocompetent mice, treatment with 2 mg of Bay Y 3118 every 12 h resulted in a greater initial reduction in the listerial counts in the organs than treatment with 2 mg of ampicillin every 12 h. Bay Y 3118 completely eliminated L. monocytogenes from the livers and spleens of chronically infected nude mice. However, some of the bacteria reappeared after the cessation of therapy. In conclusion, Bay Y 3118 is an excellent candidate substance for the therapy of infections caused by facultatively intracellular gram-positive bacteria such as L. monocytogenes.

Ampicillin↗
PubMed1994

Toxoplasma encephalitis in congenic B10 and BALB mice: impact of genetic factors on the immune response.

Factors which determine the pathogenesis and course of Toxoplasma encephalitis are poorly understood. In the present study, the influence of genetic factors in congenic B10 and BALB mice of H-2q, H-2k, and H-2b haplotypes was examined following oral infection with a low-virulence strain of Toxoplasma gondii (DX). There were striking differences among these strains. Whereas B10 mice were highly susceptible, BALB mice had a less severe and more protracted disease. In all animals with a fatal outcome, Toxoplasma encephalitis was the cause of death. Within the two congenic groups, the major histocompatibility complex haplotype had a strong impact on the disease. The H-2k haplotype was associated with early death in B10 mice but with a favorable outcome in BALB mice, whereas the reverse was observed for the H-2q haplotype. These findings indicate that genetically determined factors are critically involved in determining the intracerebral immune response and the course of murine toxoplasmosis. Some of these factors appear to be associated with the major histocompatibility complex haplotype, but significant differences between B10 and BALB mice point to a modulating role of additional genetic loci. Immunohistochemical studies and cytokine analyses of cerebrospinal fluid and serum revealed significant differences in the intracerebral immune response between susceptible and resistant strains. A poor outcome was associated with a large number of intracerebral parasites, significant tissue necrosis, a reduced number of intracerebral CD4+ T cells, low intrathecal tumor necrosis factor levels, and, to a lesser extent, a reduced number of intracerebral CD8+ T cells.

Animals↗
PubMed1994

[Campylobacter fetus subsp. fetus in a patient with liver cirrhosis].

Campylobacter fetus subsp. fetus infections are very rare in adults but can occur in immunocompromised elderly people and in patients with chronic disease. We describe the clinical case of a 52-year-old woman with alcoholic liver cirrhosis, where we isolated C.fetus subsp. fetus from blood culture.

Campylobacter Infections↗
PubMed1994

[Macrolides, a group of antibiotics with a broad spectrum of activity].

The new macrolide derivatives, such as roxithromycin, clarithromycin or azithromycin, respectively, extend the spectrum of activity in antimicrobial chemotherapy. Their direct antibacterial activities are more or less similar to that of erythromycin, i.e., besides gram-positive cocci and rods the gram-negative cocci are likewise susceptible to these drugs. This holds true for aerobes as well as anaerobes. Especially the cell wall deficient bacteria, such as chlamydias, rickettsias, mycoplasmas, are generally rather susceptible. Among the gram-negative aerobic rods some genera are susceptible, for example Bordetella, Haemophilus or Legionella, whereas the Enterobacteriaceae are practically resistant, because their cell wall is rather impermeable. In a few examples, i.e. mycobacteria other than tuberculosis and certain protozoa, such as Toxoplasma, the new macrolides exert a definite greater activity than erythromycin. In particular, the property of the new derivatives to be highly accumulated within host cells, especially within phagocytes, renders these drugs extremely effective against intracellular pathogens, such as Mycobacteria, Legionella, Chlamydia, Listeria, Toxoplasma. Consequently, these new derivatives definitely improve and extend the indications for macrolide antibiotics.

Anti-Bacterial Agents↗
PubMed1994

[Rational therapy of salmonella enteritis].

One prerequisite for an effective treatment of a salmonella enteritis with antibiotics is a reliable direct antibacterial activity of the drug. In comparison to most of all other usual antibiotics quinolones, especially ciprofloxacin, fulfill these conditions, because its activity is high and resistance of Salmonella against quinolones is extremely rare. Since quinolone resistance is never plasmid coded, there will be even in the future no obvious risk of spreading of resistant strains. Another prerequisite is that the drug is able to have access to the site of residence of the microorganism. Salmonella spp. possess the virtue to penetrate into host cells and to reside and even to multiply there. Curing can be achieved only when these intracellular bacteria are eradicated. Elimination of Salmonella in the gut lumen alone is not satisfactory. Only few antibiotics are taken up into host cells, which could explain the rather frequent failure rate of antibiotic therapy of salmonella enteritis. Quinolones on the other hand are accumulated in host cells and in addition are able to act upon bacteria in this peculiar intracellular environment. Among the various quinolone derivatives ciprofloxacin is particularly qualified because it is excreted via the intestine to a considerable extent, so that high concentrations may be achieved at the proper site. The clinical experience demonstrates indeed that in most instances a rapid amelioration of the acute disease is achieved and in chronic carriers a high rate of curing occurs. Thus, for microbiological, pharmacological, and clinical reasons one can recommend ciprofloxacin for the treatment of enteric infections with Salmonella spp.

4-Quinolones↗
PubMed1993

Influence of S9 mix composition on the SOS response in Escherichia coli PQ37 by polycyclic aromatic hydrocarbons.

To investigate the variability in test results obtained with the SOS chromotest (Escherichia coli PQ37 genotoxicity assay) when varying the composition of the exogenous metabolizing system (S9 mix), we examined the influence of different S9 and NADP concentrations, of buffer pH value, of SDS concentrations, the effects of E. coli PQ37 density and centrifugation steps on the expression of beta-galactosidase (beta g) and alkaline phosphatase (ap) activity, the calculated induction factors (IFs) and SOS-inducing potencies (SOSIPs). Additionally we examined the metabolic potency (stability) of S9 mix when stored at 37 degrees C before use. Initially, we used 0-5000 ng (= 0-20 nmole) benzo[a]pyrene (B[a]P) as a reference compound for the test procedure in the presence of standard S9 mix. Subsequently, to evaluate the results of S9 mix variations we examined several polycyclic aromatic hydrocarbons (PAHs) using both the standard and a modified S9 mix composition and test protocol. We observed the highest beta g and ap activities and/or IFs using only 11-27 microliters 9000 x g liver supernatant (S9) from Aroclor 1254-induced rats per assay (20-50% of standard amount) and calibrating the S9 mix Tris buffer to pH 7.8-8.0. 60-300 micrograms NADP/assay (10-50% of standard) was sufficient for optimum activation of PAHs. In contrast to previous investigations about the variability of the SOS chromotest in the absence of a metabolizing system, higher induction factors were obtained when using higher bacterial densities (12-18 x 10(6) cfu/assay). Centrifugation steps as recommended by other investigators were not necessary when using optimum S9 amounts. The metabolic activity of S9 mix remained nearly constant approximately 20 min after preparation, but decreased to 80% of its activity in about 1 h.

Animals↗