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Biomedical subjects

V Knight

Publications and source records attributed to V Knight.

At least 37 records · Page 2Linked to original sources
PubMed1984

The hypertensive response to soman and its relation to brain acetylcholinesterase inhibition.

Intravenous injection of soman in the rat produced a rapid and dose related increase in blood pressure. The dose response curve was very steep, threshold responses occurring after intravenous injection of 10 micrograms/kg, and maximum increases of about 50 mmHg occurring after 40 micrograms/kg. Heart rate also generally increased. An increase in blood pressure also followed injection of soman subcutaneously, intramuscularly, intraperitoneally and into the cerebral ventricles, although the onset was slower and higher doses were required. The magnitude of the pressor response was correlated with the degree of AChE activity in the cortex, hypothalamus and brain stem, but not in the striatum. The pressor response was aborted or prevented by atropine, but not by methylatropine. It also was prevented by phenoxybenzamine. Atropine increased survival following an LD50 dose of soman; phenoxybenzamine prevented the pressor response but did not alter the survival rate.

Acetylcholinesterase↗
PubMed1984

Pulmonary deposition and clearance of aerosolized interferon.

Small particle aerosols of a hybrid DNA recombinant human alpha interferon, A/D bgl, and a related DNA recombinant leukocyte interferon, A, were generated and delivered to mice for 23.5 h a day for 4 consecutive days. The antiviral activity of these interferons in delivery reservoirs, in the aerosols generated, and in the lungs of test mice was monitored during and after aerosol administration in cytopathic effect inhibition assays, using vesicular stomatitis virus as the indicator virus. In addition, the activity of these interferons in primary mouse embryo cells against influenza A/HK/68 (H3N2) virus was determined. The results obtained indicated that the interferon particles generated in the continuous aerosol therapy system used in these studies remained biologically active and could be readily detected in both aerosol mists and lungs of test mice; levels of exogenous interferon in the lungs equalled or exceeded levels of interferons produced endogenously during experimentally induced influenza virus infection. Titers of the exogenously administered interferons decreased gradually and disappeared from the lungs between 24 and 48 h after cessation of aerosolization. Recombinant human alpha interferon A/D, but not recombinant leukocyte alpha interferon A, significantly inhibited replication of A/HK/68 virus in primary mouse embryo cells in the in vitro studies.

Aerosols↗
PubMed1984

Treatment of influenza A (H1N1) virus infection with ribavirin aerosol.

In a randomized, controlled study of ribavirin aerosol treatment of influenza A(H1N1) virus infection among college students, treated patients had a significantly shorter duration of fever than control patients. There was a trend of more rapid recovery in treated patients. Virus shedding was similar in treated and control patients, declining gradually from a 50% tissue culture infective dose of 3.5 log10 per ml at admission to 1.8 log10 per ml at 53 h after admission. There was no local or systemic intolerance and no hematological or biochemical abnormalities associated with ribavirin treatment.

Aerosols↗
PubMed1984

Interferon aerosol suppression of vesicular stomatitis virus replication in the lungs of infected mice.

Mice were inoculated intranasally with vesicular stomatitis virus 16 to 22 h after being exposed to small-particle aerosols of saline, natural mouse alpha interferon, recombinant human alpha interferon A, or hybrid recombinant human alpha interferon A/D bgl for 2, 4, or 8 h. Compared with comparably inoculated, untreated mice, significantly reduced levels of vesicular stomatitis virus were observed in the lungs of animals treated with any interferon preparation for 8 h and in groups treated with mouse alpha interferon or hybrid recombinant human alpha interferon A/D bgl for 4 h. No significant reductions in lung virus titers were observed in any group treated with interferon for 2 h or in any of the groups treated with saline.

Aerosols↗
PubMed1983

Ribavirin aerosol treatment of influenza B virus infection.

In a randomized, controlled study, ribavirin small-particle aerosol was found to be effective in the treatment of influenza B virus infection in a group of college students. Eleven treated patients experienced significantly more rapid defervescence, disappearance of systemic illness, and reduction of virus shedding in nasal secretions than ten control patients treated with a saline aerosol. Antibody response to infection was similar in both groups. The treatment was well tolerated, and hematologic and clinical chemical tests demonstrated no toxicity. The estimated dose of ribavirin aerosol retained was about 2 g in 39 hours of treatment during the first 60 hours in the hospital.

Adult↗
PubMed1983

Cell-mediated cytotoxic responses in lungs of cotton rats infected with respiratory syncytial virus.

Pneumonia induced in cotton rats (Sigmodon hispidus) after inoculation of respiratory syncytial virus (RSV) was accompanied by the appearance of leukocytes in infected lungs. The number of these leukocytes increased until Day 5 after inoculation when sixfold more leukocytes were recovered from infected lungs using transpleural lavage than were recovered from lungs of uninfected control animals. Although macrophages and lymphocytes constituted approximately 65 and 25%, respectively, of the cells observed in lavage suspensions from both infected and uninfected lungs, only leukocytes in suspensions from infected animals appeared to be activated, as judged by cellular morphologic examination, cytochemical staining, and bactericidal activity. Leukocytes from lungs and adjacent lymph nodes of infected cotton rats, but not similar cells from uninfected animals, caused significant chromium release when they were added to primary cotton rat embryo and Hep-2 tissue culture cells infected with RSV in cytotoxicity assays. Cytotoxic activity peaked 5 days after inoculation, was neither virus-specific nor H-2 restricted, and was associated with both adherent and nonadherent fractions of lung cells. There was a close temporal relationship between the appearance of cytotoxic activity in the lung and termination of virus replication in this organ, suggesting a role for cytotoxic effector cells in recovery from respiratory syncytial virus infection of cotton rats.

Animals↗
PubMed1983

Correlation of cytotoxic activity in lungs to recovery of normal and gamma-irradiated cotton rats from respiratory syncytial virus infection.

Cotton rats (Sigmodon hispidus) that were exposed to 300, 600, or 900 rads of gamma irradiation and inoculated intranasally 2 days later with respiratory syncytial virus (RSV) exhibited prolonged virus shedding and delayed humoral and cytotoxic immune responses compared with comparably inoculated nonirradiated control rats. In nonirradiated animals and in animals exposed to 300 and 600 rads, levels of virus declined and then disappeared from the lungs during the period in which cytotoxic activity was maximal in the lungs of these animals. In contrast, in the group of cotton rats exposed to 900 rads of irradiation, local cytotoxic activity remained low throughout the 11-day observation period, and virus was not eliminated from the lungs. Although virus-neutralizing antibodies in serum and lavage fluids from these animals may have been involved, correlation of antibody concentrations with virus clearance from lungs was not as evident. These data suggest that cytotoxic effector cells have a positive role in eliminating RSV from the lungs of unprimed cotton rats.

Animals↗
PubMed1983

Ribavirin aerosol treatment of influenza B virus infection.

In a randomized, controlled study, ribavirin small particle aerosol was found to be effective in the treatment of influenza B virus infection in a group of college students. Eleven treated patients experienced significantly more rapid defervescence, disappearance of systemic illness, and reduction of virus shedding in nasal secretions than 10 control patients treated with a saline aerosol. Antibody response to infection was similar in both groups. The treatment was well tolerated and hematologic and clinical chemical tests revealed no toxicity. The estimated dose of ribavirin aerosol retained was about 2 g in 35.5 hr of treatment during the first 60 hr in the hospital.

Adult↗
PubMed1983

Ribavirin aerosol treatment of bronchiolitis associated with respiratory syncytial virus infection in infants.

In a double-blind study, bronchiolitis associated with respiratory syncytial virus infection in 12 randomly selected patients treated with ribavirin aerosol improved more rapidly than in 14 control patients given saline aerosol (P = .044, Wilcoxon rank sum test, two-tailed). An estimated 10 mg of ribavirin per kilogram of body weight was administered in daily 12-hour treatments over a five-day period. Respiratory syncytial virus disappeared from secretions at about the same rate in treated and control patients. There was no local or systemic intolerance, and there was no evidence of hematologic or other organ toxicity in the ribavirin-treated patients.

Aerosols↗
PubMed1983

Replication of respiratory syncytial virus in lungs of immunodeficient mice.

Respiratory syncytial virus was frequently isolated during a 10-day test period from the lungs of 4- to 6-week-old immunodeficient nude (nu/nu) mice and from gamma-irradiated C3H mice inoculated intranasally with this virus, but not from similar aged and comparably inoculated normal littermates of these mice. Virus isolation rates and levels of virus in lungs in both groups of immunodeficient mice were similar. No extrapulmonary dissemination of virus was observed in any test group of mice.

Animals↗
PubMed1982

Selective inhibition of functional lymphocyte subpopulations by ribavirin.

The present studies were designed to examine the effects of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a broad-spectrum antiviral agent, on the generation of murine antibody responses in vitro. Whereas primary and secondary sheep erythrocyte-specific, plaque-forming cell responses by normal murine spleen cells were enhanced by low concentrations of ribavirin (1 microgram per culture), they were strongly inhibited by higher concentrations of ribavirin (5 to 10 micrograms per culture). Both phenomena occurred with the greatest magnitude when spleen cells were exposed to ribavirin 48 to 72 h after culture initiation. Enhancement appeared to result from selective interference with suppressor T cells, since ribavirin failed to augment lipopolysaccharide-specific plaque-forming cell responses in T cell-depleted spleen cell cultures but inhibited concanavalin A-induced lymphocyte proliferation and suppressor T cell generation in cultures of normal spleen cells. The immunosuppressive properties of ribavirin were mediated by a direct antiproliferative effect and, at higher concentrations, a cytotoxic effect for B lymphocytes, since the drug inhibited plaque-forming cell responses in T cell-depleted spleen cell cultures, suppressed lipopolysaccharide-induced lymphocyte proliferation and reduced viable spleen cell recoveries.

Animals↗
PubMed1981

Ribavirin small-particle aerosol treatment of influenza.

In an outbreak of influenza virus A/England/333/80(H1N1) infections in college students, 14 randomly selected patients were treated by inhalation of ribavirin small-particle aerosol through a face mask. They retained an average estimated 1.15 g of drug in 23 h of treatment given over 3 days. 17 patients served as controls. Ribavirin aerosol treatment had a therapeutic effect judged by the highly significant reduction in height and duration of fever, reduction in systemic illness, and disappearance of influenza virus from respiratory secretions. 1 additional patient with influenzal pneumonia caused by a strain of influenza virus A/Bangkok/79(H3N2) recovered promptly with ribavirin aerosol treatment.

Administration, Oral↗
PubMed1981

Inhibition of murine plaque-forming cell responses in vivo by ribavirin.

The effects of ribavirin, a potent inhibitor of RNA and DNA virus replication, on the generation of primary plaque-forming cell (PFC) responses in vivo has been investigated. Intraperitoneal administration of ribavirin 1 day after immunization of C3H/HeJ mice with sheep erythrocytes (SRBC) suppressed splenic IgM and IgG PFC responses by 60 to 90%. Primary IgM PFC responses of C3HeB/FeJ mice to bacterial lipopolysaccharides (LPS), a T-independent antigen, were also inhibited to a similar extent. Inhibition of splenic PFC responses, without significant reduction in nucleated cell recoveries, was dose dependent between 0.5 and 4 mg ribavirin. Varying the time of treatment determined that optimal inhibitory activity occurred when ribavirin was administered simultaneously or 1 day after antigen. Kinetic analysis of PFC responses in ribavirin-treated mice revealed that suppression did not result from a delay in development since reduced numbers of PFC were found at all times after immunization. Ribavirin-treatment after primary sensitization in vivo also impaired the capacity of spleen cells to develop secondary PFC responses in vitro, indicating that ribavirin also inhibited memory cell generation.

Animals↗
PubMed1980

Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice.

Ribavirin, amantadine, and the two drugs in combination given in small-particle aerosol were highly effective in the treatment of influenza A infection in mice. Treatment was started 72, 96, and 120 h after inoculation and was given continuously for 4 days. With increasing delay in start of treatment, there was a pronounced reduction in effectiveness of ribavirin but not in that of amantadine. The combination treatment reflected the loss of ribavirin activity. Leukocyte infiltration and virus titers in the lungs were inversely related to the effectiveness of treatment. Influenza B infection treated 72 h after inoculation responded only to ribavirin, as indicated by the criteria described for influenza A. Intraperitoneal administration of drug begun 72 h after inoculation in regimens equivalent to aerosol afforded less protection than aerosol treatment.

Aerosols↗