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Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 307 records · Page 17Linked to original sources
PubMed1986

Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages.

Bacterial lipopolysaccharide (LPS) induced fresh murine splenocytes to produce interferon (IFN)-alpha/beta presumably by stimulation of the B lymphocytes and macrophages. However, when the splenocytes were "aged" for 24 to 72 hr in culture before addition of the LPS, the IFN response was significantly increased and was determined to be predominantly IFN-gamma. Because low levels of interleukin 2 (IL 2) were found to be spontaneously produced by the unstimulated splenocytes during the "aging" process, the effect of IL 2 on IFN induction by LPS in fresh splenocytes was examined. The addition of LPS to freshly prepared splenocyte cultures that were treated with human IL 2, either native or recombinant, before exposure to the LPS resulted in the LPS inducing large amounts of IFN-gamma. IL 2 alone induced little if any IFN in the splenocyte cultures. Depletion of T cells and large granular lymphocytes (LGL) from the cultures by anti-Thy-1.2 antibodies plus complement abrogated IFN-gamma production, and the addition of polymyxin B to "aged" splenocyte cultures resulted in loss of IFN production in response to LPS. Cultures that were enriched for T cells and LGL by passage through nylon wool produced significant amounts of IFN-gamma in response to LPS only if first treated with IL 2. Furthermore, the addition of splenic adherent cells to purified nylon wool-non-adherent (NWNA) cells augmented IFN-gamma production, whether or not the NWNA cells were pretreated with IL 2. This enhancement appeared to require direct contact between adherent cells and NWNA cells, because physical separation abrogated IFN production. The addition of recombinant IL 1 or LPS-conditioned supernatants of macrophage cultures did not replace adherent cell activity. These data demonstrate that LPS, which predominantly induces IFN-alpha/beta in fresh murine splenocytes, is able to stimulate T lymphocytes to produce IFN-gamma if the T cells are first exposed to endogenously produced or exogenously applied IL 2. Because IFN-gamma is a potent activator of the bactericidal and cytocidal potential of macrophages, the induction of IFN-gamma by bacterial LPS may play an important role in resistance/recovery mechanisms against bacterial infections.

Animals↗
PubMed1986

Enhanced bioavailability of triazolam following sublingual versus oral administration.

The rate and extent of the absorption of triazolam following sublingual and oral administration were evaluated in this study. Eight healthy volunteers received triazolam 0.5 mg in a commercially available tablet, by sublingual and oral routes on two occasions in random sequence. Plasma triazolam concentrations during 24 hours after each dose were measured by electron-capture gas-liquid chromatography. The mean total area under the curve for sublingual administration was significantly larger than that following oral dosage (28.9 vs 22.6 ng-hr/mL, P less than .025). The peak plasma concentration after sublingual dosage was also higher than after oral administration (4.7 vs 3.9 ng/mL, P less than .1). No significant differences between sublingual and oral administration were found for the elimination half-life of triazolam (4.1 vs 3.7 hr) and the time of peak concentration (1.22 vs 1.25 hr) after dose. Thus, the bioavailability of triazolam after sublingual administration is increased by an average of 28% compared with oral administration of the same dose, possibly because first-pass extraction is bypassed. Clinical effects of triazolam may likewise be enhanced by sublingual dosage.

Administration, Oral↗
PubMed1986

Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro.

The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.

Animals↗
PubMed1986

The pharmacokinetics of diazepam and desmethyldiazepam in rat brain and plasma.

The pharmacokinetics of diazepam (DZ) and its major metabolite desmethyldiazepam (DMDZ) in both plasma and brain after a single 5 mg/kg IP dose of diazepam were studied in rats. Four rats were sacrificed at 5 min, 15 min, 30 min, 1 h, 1.5, 2, 3, 4, 5 and 6 h after the dose. DZ rapidly disappeared from plasma and brain in parallel, with nearly identical overall half-lives of 0.88 and 0.89 h, respectively. Apparent volume of distribution was 19.3 1/kg and the apparent total clearance was 255 ml/kg/min. Free fractions were 19.6% and 15.8% for DZ and DMDZ, respectively. DMDZ rapidly appeared in both plasma and brain. Thereafter, DMDZ was likewise eliminated in parallel from both compartments, with nearly identical half-lives of disappearance from plasma (1.11 h) and brain (1.09 h). The rapid elimination of DZ was due to its very high clearance. Brain to plasma concentration ratios did not differ significantly over time either for DZ or for DMDZ. The overall ratios (mean +/- SE) were 4.5 +/- 0.1 for DZ and 3.5 +/- 0.2 for DMDZ. Equilibrium was attained at no more than 5 min after dose for both DZ and DMDZ. No evidence was found for persistence or sequestration of DZ or DMDZ in brain longer than could be predicted on the basis of first-order exponential disappearance.

Animals↗
PubMed1986

Imaging sacral nerve root cysts.

Sacral nerve root cysts usually are an incidental finding but may be found in patients with a history of pain. On computed tomography they are demonstrated as a soft tissue mass, possibly with associated bony erosion. Demonstrating the fluid-filled nature of these masses is important in establishing the diagnosis. The imaging of these cysts in two patients, including magnetic resonance, is described.

Aged↗
PubMed1986

Marijuana effects on immunity: suppression of human natural killer cell activity of delta-9-tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, was tested for its ability to modulate human natural killer (NK) cell function. THC was toxic for peripheral blood lymphocytes at 20 micrograms/ml but not at 10 micrograms/ml or less. This component of marijuana also was inhibitory for NK activity against K562, a human tumor cell line at concentrations down to 5 micrograms/ml when pre-incubated with the effector cells. Suppression of NK function was dependent upon the concentration of THC and the length of time of pre-incubation but was independent of the ratio of effector to target cells. Prostaglandins were not involved in suppression of NK activity.

Cannabis↗
PubMed1986

In vitro and in vivo suppressive effects of delta-9-tetrahydrocannabinol on interferon production by murine spleen cells.

Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, has been reported to be suppressive on some immune functions. Since interferons (IFNs) are important immunomodulatory proteins, the effect of in vivo or in vitro administration of THC on induction of IFN by various mitogens was examined. Splenocytes from normal mice in the presence of THC produced significantly less IFN when stimulated by phytohemagglutinin (PHA), concanavalin A (Con A), or Escherichia coli lipopolysaccharide (LPS). Induction of IFN by a bacterial antigen, Legionella pneumophila bacterial cells, was also suppressed by THC. Also, splenocytes which were incubated up to 24 h in the presence of THC partially recovered responses to mitogens when cells were washed before stimulation. This suggested that THC must be present in order to mitigate IFN induction. Splenocyte cultures from mice which were chronically injected with THC for 6-8 weeks were also less responsive to induction of IFN by the various mitogens. These results suggest that at least part of the immunosuppressive effects of THC may be related to depressed IFN production by stimulated lymphocytes. Since Con A and PHA are T cell mitogens and LPS is considered to be a macrophage and B cell stimulator, suppression of IFN production by these classes of cells indicate a wide range of effects of THC.

Animals↗
PubMed1986

Effects of anti-Bacteroides-antibodies on Escherichia coli and different Bacteroides species in vitro and vivo.

Bacteroides species are known to cause synergistic pathogenicity in mixed infections with Enterobacteriaceae. In vitro studies showed that anaerobes may compete with aerobes for opsonisation thus interfering with the phagocytosis and killing of the latter by leukocytes. The present study investigated the effect of anti-Bacteroides-antibodies on in vitro phagocytosis of E. coli and on experimental mixed infections. It was shown that in vitro, B. fragilis suppressed the phagocytosis of E. coli by leukocytes only moderately. The addition of specific antibodies to the phagocytosis mixture could enhance this effect. However, antibodies in the absence of B. fragilis were also active suggesting a nonspecific mechanism such as blockade of Fc receptors. Prophylactic treatment with the immunoglobulin preparations failed to protect mice from experimental infections with E. coli and Bacteroides species.

Animals↗
PubMed1986

Population study of triazolam pharmacokinetics.

The kinetics of a single 0.5 mg oral dose of the triazolobenzodiazepine hypnotic triazolam, were studied in 54 healthy young men aged 20-44 years, with a mean body weight of 77 kg. Triazolam kinetics were determined from multiple plasma concentrations measured during 14 h post-dose. The overall mean +/- s.e. mean (with range) kinetic variables were: peak plasma concentration, 4.4 +/- 0.3 (1.7-9.4) ng ml-1; time of peak, 1.3 +/- 0.1 (0.5-4.0) h after dose; elimination half-life, 2.6 +/- 0.1 (1.1-4.4) h; total AUC: 19.1 +/- 1.1 (4.4-47.7) ng ml-1 h; oral clearance, 526 +/- 38 (175-1892) ml min-1. All kinetic variables were consistent with Poisson distributions, based on the Kolmogorov-Smirnov Goodness of Fit test. None of the variables fit normal distributions. Four of five were consistent with a log normal distribution. Peak plasma level was highly correlated with clearance (r = -0.85, P less than 0.0001), and AUC (r = 0.85, P less than 0.0001) but not with body weight (r = 0.21, NS). Clearance and body weight were not correlated (r = -0.01). Triazolam clearance may vary widely even within a homogeneous group of healthy young men.

Adult↗
PubMed1986

Inhibition of macrophage phagocytosis by Bacteroides fragilis in vivo and in vitro.

A number of investigators have provided experimental evidence for synergistic effects in mixed infections with Escherichia coli and Bacteroides fragilis. In vitro studies have suggested that competition for serum opsonins and diminished subsequent phagocytosis by polymorphonuclear leukocytes might explain these effects. In the present study we evaluated the effect of B. fragilis on macrophage phagocytosis. It was shown that peritoneal macrophages from mice injected intravenously 6 to 12 h earlier with 10(8) CFU of encapsulated B. fragilis were markedly suppressed in their phagocytic ability. Injections of laboratory-passaged, less-encapsulated B. fragilis, other bacteria, or latex particles were either not suppressive of macrophage phagocytosis or less effective. When peritoneal macrophages were treated in vitro for 24 h with the same challenge organisms prior to assessing their phagocytic capacity, encapsulated B. fragilis also proved significantly more suppressive than challenges with other organisms or latex particles. We conclude that suppression of macrophage phagocytosis by B. fragilis seems to be an important mechanism contributing to synergistic effects described for mixed aerobic and anaerobic infections.

Animals↗
PubMed1986

Suppressive effect of delta 9-tetrahydrocannabinol in vitro on phagocytosis by murine macrophages.

Incubation of normal mouse peritoneal cells consisting of over 90% phagocytizing macrophages with delta 9-tetrahydrocannabinol (THC) resulted in a inhibition of phagocytic function. The THC in a dose-related manner suppressed the percentage of macrophages per culture which ingested yeast and the average number of yeast particles ingested by the phagocytizing macrophages. The vehicle used to suspend the THC in vitro, i.e., DMSO, had no detectable effect on macrophage function. Suppression of phagocytosis with no effects on viability or cell number occurred with doses of 10 micrograms or less THC per milliliter culture medium. Measurable suppression also occurred after 24- to 48-hr treatment of the macrophages with the THC. This compound had little if any detectable effect on phagocytosis when added directly to the cultures shortly before testing for phagocytosis. Further studies concerning the effects of THC on macrophage function appear warranted.

Animals↗
PubMed1985

The pharmacokinetics of doxylamine: use of automated gas chromatography with nitrogen-phosphorus detection.

Sixteen healthy male volunteers received a single oral dose of 25 mg doxylamine succinate. Doxylamine concentrations in plasma were measured by a newly developed gas chromatographic methodology, utilizing direct alkaline extraction into hexane:isoamyl alcohol followed by concentration and autoinjection. Doxylamine kinetics were determined from multiple plasma doxylamine concentrations measured during the 24 hours postdose. Mean kinetic variables were: peak plasma level, 99 ng/mL; time of peak, 2.4 hours postdose; elimination half-life, 10.1 hours; and apparent oral clearance, 217 mL/min. Analogous analytic methodology can be used to study the pharmacokinetics of other drugs of this class.

Adult↗