PubMed Health⌕ Search

Biomedical subjects

K N Masihi

Publications and source records attributed to K N Masihi.

At least 19 recordsLinked to original sources
PubMed2001

Fighting infection using immunomodulatory agents.

The last decade has seen the emergence of immunomodulators as promising therapeutic agents in infectious diseases. A diverse array of recombinant, synthetic and natural immunomodulatory preparations for prophylaxis and treatment of various infections are available today. Some of these substances, such as granulocyte colony-stimulating factor (G-CSF), interferons, imiquimod and bacterial-derived preparations are already licensed for use in patients. Others including IL-12, various chemokines, synthetic cytosine phosphate-guanosine (CpG) oligodeoxynucleotides and glucans are being investigated extensively in clinical and preclinical studies. Immunomodulatory regimens offer an attractive approach as an adjunct modality for control of microbial diseases in the era of antibiotic resistance. Practical application of the advances in molecular biology, bioinformatics, genomic mining and high-throughput peptide synthesis should foster future discovery and development of novel immunomodulators contingent upon scientific evidence rather than dictates of discursive empiricism.

Adjuvants, Immunologic↗
PubMed2000

Immunomodulators in infectious diseases: panoply of possibilites.

Infections which caused ravages in the past centuries are again resurgent and newly emerging pathogens capable of human diseases continue to surface. Multidrug antibiotic resistance has turned into a major medical problem. Judicious concepts for combating infections in the 21st century have acquired a new poignancy. Immunomodulators of natural, synthetic, and recombinant origin can stimulate host defense mechanisms for the prophylaxis and treatment of diverse viral, bacterial, parasitic and fungal diseases. Some immunomodulator preparations are already licensed for use in patients and numerous others are being extensively investigated in preclinical and clinical studies. Immunomodulators offer a novel adjunct to established antimicrobial therapies.

Adjuvants, Immunologic↗
PubMed2000

Immunomodulatory agents for prophylaxis and therapy of infections.

The advent of the antibiotic era ushered in a shift towards non-pathogen-specific therapy of infectious diseases. This led to an overt emphasis on targeting microbial pathogens while strategies directed towards enhancing host immunity were neglected. In an effort to decrease sole reliance on antimicrobials, the time has come for a critical reappraisal of nonantibiotic, albeit immune response-enhancing substances. The diverse array of natural, synthetic, and recombinant immunomodulators discussed in this review succinctly demonstrate the potential of these agents to stimulate host defense mechanisms for prophylaxis and treatment of various microbial infections.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

A highly sensitive cytotoxicity assay based on the release of reporter enzymes, from stably transfected cell lines.

The well-established methods of generating stably transfected cell lines, and the detection of nanomolar amounts of an enzyme in a fast and reproducible assay, were utilised to establish non-radiometric cytotoxicity assays. In these assay systems, the detection of released enzymes was used to quantitate the leakage of intracellular proteins after membrane disintegration. Target cell lines were transfected with a luciferase reporter gene under the control of a strong eucaryotic promoter. Release of the intracellular expressed enzyme into the culture supernatant occurred after membrane perforation and was measured as an indicator of cellular death. The quantitation of released enzyme was a reliable indicator of cell death initiated either by complement-mediated killing, or by cell-mediated cytotoxicity. This system was initially established with P815 mastocytoma cells as an example of a target cell line. Transfection with the firefly luciferase gene provided an intracellular enzyme absent in mammalian cells. In a parallel approach, P815 and BW5147 target cells were transfected with bacterial beta-galactosidase to provide a similar cytotoxicity system. This enzyme, however, has a considerably longer half life in tissue culture medium than luciferase. In a direct comparison between the standard 51Cr release and beta-galactosidase release, the enzyme release showed a much higher signal-to-noise ratio, i.e., low background and high induced release if spontaneous release and detergent induced maximal lysis were measured. Since a wide range of human and murine cell lines can be stably transfected and several reporter genes are available, the system should provide an alternative for conventional cytotoxicity assays. The detection of released enzymes by colorimetric or luminometric methods makes this cytotoxicity assay independent of radionuclides. The sensitivity of luminometric enzyme detection systems should also permit the measurement of apoptotic processes and might make in vivo studies of cellular death using transgenic animals feasible.

Animals↗
PubMed1995

Effects of trinitrotoluene (TNT) metabolites on chemiluminescence response of phagocytic cells.

The effects of TNT metabolites on the generation of activated oxygen species was investigated by a sensitive luminol-dependent chemiluminescence (CL) assay. Spleen cell suspensions containing 2,4-diaminotoluene, 2,4,6-triaminotoluene, 2-amino-6-nitrotoluene, 4-amino-3,5-dinitrotoluene and 2-amino-4,6-dinitrotoluene were stimulated with zymosan. Aminotoluenes and amino-nitrotoluenes induced a dose-dependent inhibition of CL response. The mixed substituted toluenes generally required higher doses than aminotoluenes for the suppression of CL response which was not due to the cytotoxic reduction of cell viability. CL appears to be a well-suited assay for determination of the immunotoxic potential of diverse molecules on phagocytic cells of the immune system.

Aniline Compounds↗
PubMed1992

Stimulation of microbicidal host defence mechanisms against aerosol influenza virus infection by lentinan.

The ability of polysaccharide immunomodulator lentinan to stimulate non-specific resistance against respiratory viral infections was investigated. Significant protection was conferred by lentinan administered intranasally before lethal influenza virus infection and could be corroborated by a reduction of the lung virus titres. Since the lung is the target organ of influenza virus infection, lentinan was also administered by the intravenous route. Lentinan conferred complete protection against a LD75 challenge dose of virulent influenza virus and significantly prolonged the survival time after a LD100 challenge. The effect on respiratory burst of broncho-alveolar macrophages was investigated by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. Enhanced CL activity was present at an early stage in groups receiving lentinan. Significant nitric oxide activity could also be stimulated by culturing broncho-alveolar macrophages in the presence of lentinan. TNF activity could not be detected in lung lavage but measurable IL-6 was produced already after 6 h in animals administered lentinan alone and in lentinan-pretreated influenza virus-infected mice. Influenza virus alone did not induce measurable IL-6 at 6 h but high activity was present at later time periods.

Aerosols↗
PubMed1990

Effect of immunomodulator adamantylamide dipeptide on antibody response to influenza subunit vaccines and protection against aerosol influenza infection.

Adamantylamide dipeptide (AdDP) is a novel synthetic compound combining the antiviral properties of amantadine and the essential adjuvant activity of immunomodulator muramyl dipeptide. Mice were immunized with influenza A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and influenza B/Beijing/1/87 subunit vaccines containing AdDP or aluminium hydroxide (Al(OH)3). Induction of homologous haemagglutination-inhibition (HI) antibodies and correlation to protection against lethal aerosol influenza A/PR/8/34 (H1N1) infection were investigated. Subunit vaccine containing A/Sichuan (H3N2) and Al(OH)3 stimulated high HI antibody titres but failed to provide protection against heterologous influenza A (H1N1) challenge infection following either the primary or the secondary immunizations. In contrast, similar treatment with A/Sichuan subunit vaccine containing AdDP conferred significant protection against heterologous challenge despite low levels of circulating antibody. Primary immunization with even influenza B/Beijing subunit vaccine containing AdDP, but not Al(OH)3, provided partial protection against influenza A challenge. These results suggest that appropriate immunomodulators like AdDP can convert restricted homotypic immunity induced by inactivated influenza subunit vaccines to advantageous cross-reacting type of heterologous response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Muramyl dipeptide inhibits replication of human immunodeficiency virus in vitro.

In the search for compounds capable of inducing endogenous production of colony-stimulating factor (CSF) and possessing activity against human immunodeficiency virus (HIV), an immunomodulator, muramyl dipeptide (MDP), was investigated. MDP can enhance monocyte-macrophage CSF in serum and promote nonspecific resistance against a variety of microbial pathogens. MDP exhibited an inhibitory activity against HIV infection of CD4+ H9 lymphocytes and U937 monocytoid cells. An inhibitor of viral reverse transcriptase, 2', 3'-dideoxyadenosine, produced potent inhibition in cultures which were similarly infected with HIV. MDP could partially reduce antigen production in persistently HIV-infected KE37/1 lymphocyte cultures.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Exacerbation of human immunodeficiency virus infection in promonocytic cells by bacterial immunomodulators.

Common bacterial infections are increasingly being diagnosed in HIV-infected individuals. Cells of the monocyte-macrophage lineage kill invading bacterial pathogens and subsequently release immunoadjuvant components from the degraded cell walls. Since monocytes can be infected with HIV, effects of bacterial immunomodulators on infected promonocytic U937 cells were investigated. Synthetic muramyl peptide, mycobacterial trehalose dimycolate, and detoxified endotoxin exhibited an initial reduction followed by a rapid increase in HIV p24 antigen production. The upregulation of virus expression was correlated with enhanced interleukin-1 beta levels and a decrease in TNF-alpha production.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Muramyl peptides confer hepatoprotection against murine viral hepatitis.

The hepatoprotection induced by synthetic muramyl peptides was investigated using a model of lethal murine mouse hepatitis MHV-3 virus infection. MDP and a nonpyrogenic analog, Murametide, inhibited the steep elevation of serum transaminases induced by MHV-3 irrespective of whether the immunomodulators were administered before or after the infection. A significant proportion of MDP or Murametide-treated animals, in contrast to controls, survived the MHV-3 infection. The histopathological examination of the liver revealed marked necrosis of the hepatic parenchymal cells and infiltration of the inflammatory cells in controls but not in MDP-treated animals.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Biomedical applications of chromatographic fraction containing trehalose dimycolate in squalane emulsion.

Trehalose dimycolate extracted from mycobacteria is a potent immunomodulator. Incorporation of trehalose dimycolate in a squalane-in-water emulsion leads predominantly to the formation of vesicular structures, which are observable by electron microscopy. The interaction between vesicles of trehalose dimycolate and the immunocompetent cells results in an enhancement of the host defence mechanisms and induction of non-specific resistance against viral, parasitic, and bacterial pathogens and certain tumors. A brief review of the pertinent observations is presented.

Adjuvants, Immunologic↗
PubMed1988

Effects of nontoxic lipid A and endotoxin on resistance of mice to Toxoplasma gondii.

Mice were administered nontoxic monophosphoryl lipid A (MPL) or refined standard bacterial endotoxin (RSE) prior to, simultaneously with, or after infection with Toxoplasma gondii. MPL and RSE given before or with the toxoplasma infection induced significant resistance. Administration of toxic RSE, but not nontoxic MPL, after the establishment of toxoplasma infection significantly shortened the survival time of mice.

Animals↗
PubMed1987

Modulation of natural killer cytotoxicity by muramyl dipeptide and trehalose dimycolate incorporated in squalane droplets.

The effect on natural killer (NK) cytotoxicity of splenic cells from BALB/c mice pretreated i.v. with squalane-in-water preparations of muramyl dipeptide (MDP), trehalose dimycolate (TDM), or the combination of MDP-plus-TDM was investigated. MDP or TDM augmented the NK cytotoxicity which peaked 48 h after the pretreatment whereas the combination of MDP and TDM induced an inhibition of the NK activity. Infection with influenza virus, a potent stimulator of NK cells, after the pretreatment with biological response modifiers resulted in a markedly enhanced NK activity on day 2 in MDP and control groups. Mice pretreated with TDM or the combination of MDP and TDM showed only moderate NK activity which peaked on day 3 after influenza infection. The NK activity was susceptible to asialo GM1 and complement treatment. The cytotoxicity of MDP-plus-TDM cells could be significantly enhanced after treatment with anti-macrophage monoclonal antibody and complement. NK activity induced by MDP or TDM was reduced by mixing MDP-plus-TDM cells. Addition of adherent cell-depleted MDP-plus-TDM suspension to MDP or TDM cells had a NK restorative effect. Splenic cells from mice pretreated 2 days earlier with MDP or TDM, but not MDP-plus-TDM, generated enhanced levels of luminol-dependent chemiluminescence.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Immunity to Acanthamoeba culbertsoni: experimental studies with Acanthamoeba and control antigen preparations.

Mice were intranasally immunized with living and killed Acanthamoeba as well as culture supernatant, living Toxoplasma and BCG, and challenged with pathogenic A. culbertsoni strain A-1. The best protection was achieved with killed amoebae of the same strain. A high rate of mortality was observed in immunized mice treated with immunosuppressives and challenged with A. culbertsoni A-1. The significance of the results in relation to environmental human infection is discussed.

Acanthamoeba↗
PubMed1987

Epidemiology and economic importance of hepatitis B in the Federal Republic of Germany.

Hepatitis is among the five most important notifiable infectious diseases in the Federal Republic of Germany where 15,000-20,000 new cases are reported annually. A total of 60,000 cases per year may actually occur when the presumed high incidence of unreported hepatitis is taken into consideration. Hepatitis B probably represents 35%-40% of these hepatitis cases. When considering the reported (7000/year) and unreported cases, 30,000 new infections may occur each year. Drug addicts with infection rates of over 80% and prison inmates with up to 72% of hepatitis B markers are the most important risk groups as well as patients from haemodialysis units (60%), haemophiliacs, and newborns of mothers who are HBV carriers. Medical personnel, with an infection rate of 15%-26%, are at significantly greater risk than the general public. Hepatitis B results in enormous annual health costs. Calculations based on 30,000 new cases per year indicate that the costs for therapy, rehabilitation, as well as loss of work-hours and income lie between 842 and 1113 million DM. The frequency of hepatitis B, its potential for temporary or prolonged health impairment, and the significant economic implications make it imperative to develop meaningful strategies for control.

Adolescent↗