In vivo and in vitro models of demyelinating diseases--VIII: Genetic, immunologic and cellular influences on JHM virus infection of rats.
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Animals↗
Biomedical subjects
R Anderson
Publications and source records attributed to R Anderson.
Benoxaprofen: a pro-oxidant anti-inflammatory drug?
Benoxaprofen inhibited the random motility and migration to the leucoattractants endotoxin-activated serum (EAS) and f-met-leu-phe of human polymorphonuclear leucocytes (PMNL) in vitro. Inhibition of random and leucoattractant-induced migration was observed at drug concentrations of greater than 1 X 10(-6) M and 1 X 10(-5) M respectively. Benoxaprofen per se was not leucotactic but was pro-oxidative in that it stimulated PMNL hexose-monophosphate shunt activity, chemiluminescence, myeloperoxidase-mediated iodination reactions and degranulation. The drug also mediated auto-oxidation of PMNL as measured by cellular auto-iodination. The relationship between benoxaprofen-mediated inhibition of PMNL migration and activation of oxidative metabolism was investigated using the anti-oxidants ascorbate and levamisole at concentrations of 10(-2) M and 10(-3) M respectively. These agents prevented the decreased motility and auto-oxidation of PMNL induced by 10(-4) M benoxaprofen. Benoxaprofen (10(-4) M) did not inhibit the migration of PMNL from 3 children with chronic granulomatous disease thus showing that intact PMNL oxidative metabolism is required for the induction of drug-mediated inhibition of cell motility. Ingestion of therapeutic doses of benoxaprofen for 7 days by normal adults gave serum drug concentrations greater than those required for detectable effects on PMNL functions in vitro (mean serum value 126 micrograms/ml). Co-incubation of normal PMNL with serum from individuals who had ingested the drug caused decreased cell migration and increased chemiluminescence. These results show that benoxaprofen inhibits PMNL migration as a consequence of pro-oxidant properties and despite its withdrawal may be the prototype of the pro-oxidative anti-inflammatory drug.
Anti-Inflammatory Agents↗
Benoxaprofen activation of suppressor activity in mononuclear leucocytes by a pro-oxidative mechanism in vitro.
The effects of benoxaprofen on spontaneous and concanavalin A-induced suppressor activity in human mononuclear leucocytes (MNL) were assessed in vitro. The drug was used at a fixed concentration of 10(-4) M (30 micrograms/ml) in these studies. Benoxaprofen-treated MNL suppressed the responsiveness of untreated autologous MNL to the mitogen phytohaemagglutinin and potentiated the induction of suppressor activity in MNL by concanavalin A. Benoxaprofen at the same concentration increased MNL oxidative metabolism measured by chemiluminescence. Inclusion of the anti-oxidants ascorbate or cysteine (1 X 10(-3) M) in the assay system or depletion of adherent cells from MNL populations was associated with the elimination of both benoxaprofen-mediated suppression and increased MNL oxidative metabolism. Benoxaprofen per se was not an oxidizing agent nor did the drug possess peroxidase-like properties. These findings show that benoxaprofen induces suppressor activity in MNL by a pro-oxidative mechanism dependent upon intact cellular oxidative metabolism. Induction of suppressor activity in MNL by pro-oxidative drugs may be an important anti-inflammatory mechanism.
Adult↗
A reproducible microanalytical method for the detection of specific RNA sequences by dot-blot hybridization.
A rapid, microanalytical procedure for the reproducible isolation of RNA from small cultured cell samples and application to dot-blot hybridization is described. The procedure employs guanidine hydrochloride solubilization of whole cells, disruption by syringing, and selective precipitation of RNA with ethanol. The method can be performed in a single tissue culture tube and obviates the need for removal of nuclei or for organic solvent extractions. Recovery of RNA from small cell samples (10(6) cells) is 51%, while 97% of the DNA and 99% of the protein are eliminated by the procedure. Detection of specific RNA by dot-blot hybridization using a labeled probe demonstrates high reproducibility of recovered RNA and lack of "masking" with up to a 10-fold excess of starting cell material. Applicability of the procedure to detection of virus-specific RNA in cells persistently infected with mouse hepatitis virus is described.
Animals↗
Inhibition of polymorphonuclear leucocyte motility by benoxaprofen related to activation of cellular oxidative metabolism.
Incubation of human blood polymorphonuclear leucocytes (PMNL) with benoxaprofen at concentrations of greater than 1 X 10(-5)M caused inhibition of random and leucoattractant-induced migration of these cells in vitro. The drug at the same concentrations and in the absence of an added stimulant caused increased PMNL oxidative metabolism measured by chemiluminescence, hexose-monophosphate shunt activity and myeloperoxidase release. Furthermore benoxaprofen also induced PMNL auto-oxidation detected by cellular auto-iodination. Co-incubation of PMNL with the anti-oxidants ascorbate or levamisole prevented benoxaprofen-mediated inhibition of PMNL migration and cellular auto-oxidation. The drug per se was not an oxidising agent and its inhibitory effects on PMNL motility were dependent upon intact cellular oxidative metabolism. The inhibitory effects of benoxaprofen on PMNL migration in vitro are caused by the proxidant activity of the drug.
Adult↗
Children's health and play in rural Nepal.
A study of morbidity and mortality in a peasant village in Nepal describes chronic malnutrition and endemic infectious disease. More than one-third of village children between the ages of 1 and 5 die. Those who survive apparently pursue a spontaneous strategy of maximizing their physical growth potential by minimizing the expenditure of energy in play. This raises the possibility that psychological, social and motor development is impaired. It is found, however, that while less time and energy is devoted to play, the pattern of play that does occur is similar to that of healthier peasant children in other times and places. It is therefore probable that maturational levels of attainment are not impaired, but it is urgent that this assumption be further investigated.
Adolescent↗
Abortion, limited medical resources, and the meaning of health care.
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Abortion, Induced↗
Studies on the effects of ingestion of a single 500 mg oral dose of erythromycin stearate on leucocyte motility and transformation and on release in vitro of prostaglandin E2 by stimulated leucocytes.
Polymorphonuclear leucocyte (PMNL) and mononuclear leucocyte (MNL) migration to the leucoattractant endotoxin-activated serum as well as MNL mitogen-induced transformation were measured in normal adult volunteers before and 1 1/2 h and 96 h after the ingestion of a single oral dose of 500 mg of erythromycin stearate. Ingestion of the antibiotic was associated with a significant increase in PMNL migration at 1 1/2 h with a return to normal levels at 96 h. Slight but insignificant enhancement of MNL migration and of transformation to mitogens was detected after erythromycin. The mechanism of the slight stimulation of MNL transformation, which was consistently observed, was investigated further in vitro by measuring the effects of erythromycin base on the release of prostaglandin (PG) E2 by mitogen-stimulated MNL. Similar studies were performed using leuco-attractant-exposed PMNL. Inhibition of PGE2 release was observed for both MNL and PMNL with therapeutic concentrations of erythromycin. To assess the possible in-vivo significance of the immunopotentiating properties of the antibiotic the effect of a single intraperitoneal injection of 250, 500 or 1000 micrograms on the survival time of mice lethally infected with the erythromycin-resistant microorganism Candida albicans were investigated. Pre-treatment of the mice with erythromycin at each concentration used significantly increased the mean survival times. It is possible that these non-specific immunostimulatory properties of erythromycin potentiate in-vivo antimicrobial activity.
Adjuvants, Immunologic↗
Cell wall and phospholipid composition and their contribution to the salt tolerance of Halomonas elongata.
The salt-tolerant bacterium Halomonas elongata makes a variety of physiological adaptations in response to increases in the salt concentration of its growth medium. The cell walls become more compact and internally coherent. The overall lipid pattern shows an increased amount of negatively charged lipids. In addition, the peptidoglycan composition of H. elongata, although not changing in response to increased NaCl, contains the hydrophobic amino acid leucine which is unique among bacterial species. The results suggest that H. elongata is able to live in a wide variety of salt concentrations because it alters its cell physiology in ways which increase both structural integrity and the amount of less-mobile, "structured" cell water, making the cells less susceptible to NaCl-induced dehydration.
Acclimatization↗
A comparison of primary breast cancer management in small, intermediate and large community hospitals and a comprehensive cancer center.
The results presented above indicate clearly that the size of a hospital is associated not only with the type of patient population treated there in terms of demographic and disease related characteristics but also with the type of treatment given. Smaller hospitals were more likely to have older and later stage disease patients for whom they used fewer diagnostic tests and less conservative surgical procedures than larger hospitals. The patients in smaller hospitals also tended to stay for longer periods of time. Interestingly, in terms of the comparison between the community hospital groups and the comprehensive cancer center, no consistent pattern was found. Large hospitals were more like MSKCC in their patient population and length of stay, but the small hospitals were more like MSKCC in the number of tests and type of surgical procedures performed.
Aged↗
The enzyme-linked immunosorbent assay (ELISA) in the laboratory diagnosis of gonorrhoea. A comparative evaluation.
An enzyme-linked immunosorbent assay (ELISA) was used to detect levels of antibodies to Neisseria gonorrhoeae in 100 male patients with suspected gonorrhoea attending a clinic for sexually transmitted diseases. Although significantly higher antibody levels were detectable in patients with clinically diagnosed gonorrhoea confirmed by laboratory tests, positive results were also obtained in 26% of the control subjects, who were presumed to be healthy. Serum anticomplement activity was present in 8% of the subjects with false-positive results, while tests for rheumatoid factor were positive in 14%. However, these problems could be eliminated to a certain extent by including a negative control or background well for each serum sample. Because the ELISA was found to be of high sensitivity and moderate specificity it is concluded that it is a useful serodiagnostic test for gonorrhoea.
Agglutination Tests↗
Effects of cefotaxime on neutrophil and lymphocyte functions.
The effects of cefotaxime on neutrophil functions in vitro were investigated. The in vivo effects of intramuscular injection of 1 g cefotaxime on mitogen-induced lymphocyte transformation as well as neutrophil functions were also studied. Cefotaxime in vitro significantly inhibited migration of neutrophils towards endotoxin-activated serum at a concentration of 10(-3)M and towards the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine at a concentration of greater than 10(-5)M. Post-phagocytic hexose-monophosphate shunt activity was unaffected in vitro by cefotaxime. Post-phagocytic myeloperoxidase-mediated iodination, however, was inhibited only a concentration of 10(-3)M. In vivo studies before and after injection of therapeutic doses of cefotaxime caused no changes in neutrophil functions, but injection of cefotaxime showed that the drug binds to neutrophils. This was confirmed by assaying cefotaxime levels before and after addition of the drug to neutrophils. The neutrophils also released the bound antibiotic, which retained bactericidal activity.
Adult↗
Erythromycin--three decades later.
This article reviews some of the more recent developments relating to the clinical usage of erythromycin. The bactericidal and tissue-penetrating properties of this antibiotic are described and the suggestion that erythromycin has a very useful spectrum of activity in respiratory tract infections is supported by a variety of studies. We examine the increasing application of erythromycin in an extending number of problems such as sexually acquired disorders, a variety of diseases produced by infection with Legionella species and the enteritides associted with Campylobacter and Shigella species. The influence of erythromycin in particular, and of antimicrobial agents in general, on the immune system of the host is discussed. The immunomodulatory capacity of the antibiotics used deserves more attention. The interactions of erythromycin with theophylines and with carbamazepine are noted and amplified, and the consequences of the binding of erythromycin to plasma alpha 1-glycoprotein are examined. After some 3 decades of use, this remarkably safe antibiotic continues to display activities which deserve the attention of the clinician.
Adult↗
Fusion resistance and decreased infectability as major host cell determinants of coronavirus persistence.
Mouse hepatitis virus persists in cultures of a subline (designated LM-K) of mouse LM cells but produces a lytic infection in L-2 cells. Persistence in the LM-K cells was not accompanied by production of ts mutants or of soluble anti-MHV factors. Infectious center assay demonstrated an approximately 500-fold lower level of infectibility by MHV of the LM-K cells as compared to L-2 cells. On an infected cell basis, production levels of infectious progeny and viral RNA were comparable between the two cell lines. The extent of virus-induced cell-cell fusion, however, was markedly reduced in the LM-K cells. Cell-mixing experiments showed that both infected L-2 and LM-K cells have the capacity of fusing with neighboring uninfected L-2 cells but not with uninfected LM-K cells. This suggests that the decreased level of fusion observed in the LM-K infection is due not to absence of viral fusion protein at the cell surface, but rather to an inherent resistance of the LM-K cell membrane to MHV-induced fusion. It is believed that such fusion resistance in LM-K cells moderates virus dissemination throughout the culture, thereby contributing to a state of virus persistence.
Animals↗
Acquired immunodeficiency syndrome. A report of 2 South African cases.
This report documents the first 2 cases of the acquired immunodeficiency syndrome in male homosexuals identified in South Africa. Both patients died of Pneumocystis carinii pneumonia and both had cytomegalovirus infection. Neither had peripheral lymphadenopathy and in both cases the lymph nodes showed cortical and paracortical atrophy with marked plasma cell and histiocytic infiltration. It is suggested that this lymph node pattern represents the morphological expression of the immunological defect in this syndrome.
Acquired Immunodeficiency Syndrome↗
Immunological abnormalities in South African homosexual men.
Immunological tests of cell-mediated immunity (CMI), serological tests for antibodies to sexually transmitted and possibly immunosuppressive viruses, determination of serum immunoglobulin levels, full blood counts and serotyping for the HLA-DRw5 antigen were performed in 10 homosexual men with a mean age of 35 years (range 21-59 years). Five of these were associates of a patient who had died of confirmed acquired immunodeficiency syndrome (AIDS). At the time of investigation 9 of the men were apparently healthy and 1 had active pulmonary tuberculosis. Only in 2 subjects were no abnormalities of CMI found; they were 23 and 28 years of age and, interestingly, were also the only 2 whose sera were negative for antibodies to cytomegalovirus (CMV) and for the other viruses investigated. Of the remainder, 1 was lymphopenic, 6 had increased numbers of circulating suppressor T lymphocytes, 4 had reduced delayed-type hypersensitivity skin responses to recall antigens, and in 6 mitogen-induced lymphocyte transformation was decreased. Of these 8 subjects, 4 and 2 had antibodies to hepatitis B surface and core antigens respectively and 1 was positive for hepatitis B surface antigen and HBe antigen. The most severe abnormalities were observed in individuals who were seropositive for both CMV and hepatitis B virus. These findings indicate the existence of acquired immunosuppression in some members of the South African homosexual community. On the basis of these findings an immunological classification of potential sufferers of AIDS in the male homosexual community is proposed.
Acquired Immunodeficiency Syndrome↗
Comparison of the opsonic capacity of human immunoglobulin preparations.
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Antiviral Agents↗
The effects of benoxaprofen on mononuclear and polymorphonuclear leucocyte motility. An in vitro and in vivo study.
Benoxaprofen at concentrations well within the normal therapeutic range was found to cause significant inhibition of both mononuclear leucocyte (MNL) and polymorphonuclear leucocyte (PMNL) motility in vitro. The ingestion of benoxaprofen 600 mg also resulted in a significant reduction of MNL migration, while co-incubation of control PMNLs with 25% heat-inactivated serum from healthy subjects resulted in a very significant inhibition of PMNL motility. Serum IgG levels also dropped significantly after benoxaprofen ingestion. These results show that human PMNL and MNL migration is significantly suppressed by benoxaprofen both in vitro and in vivo and that the anti-inflammatory activity of the drug is mediated at least partly by inhibition of the migration of both the cell types and suppression of immunoglobulin production, possibly by induction of suppressor MNL activity.
Adult↗