Biomedical subjects

J E Boyer

Publications and source records attributed to J E Boyer.

4 recordsLinked to original sources

PubMed1991

Cyclic AMP mediates the direct antiproliferative action of mismatched double-stranded RNA.

Previous experiments have demonstrated that double-stranded RNAs (dsRNAs) can exert an antiproliferative effect on human tumor cells, independent of interferon (IFN) induction. However, the mechanism by which dsRNAs inhibit tumor growth has not been elucidated. As a first step in determining the molecular events responsible for growth arrest, we have explored the role of signal transduction through the cAMP system in the antiproliferative effect of the mismatched dsRNA, r(I)n.r(C12,U)n (Ampligen). These studies utilized the human glioma cell line A1235, which does not produce detectable levels of IFN-alpha, -beta, or -gamma in response to mismatched dsRNA treatment. Treatment of A1235 cells with mismatched dsRNA in combination with either 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), which inhibits cAMP-dependent protein kinase and protein kinase C, or N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), which preferentially inhibits the cAMP-dependent protein kinase, yielded an antagonism of the mismatched dsRNA-induced antiproliferative effect. Measurement of adenylate cyclase activation showed a dose-dependent increase in activity at antiproliferative mismatched dsRNA concentrations, but not at lower, nonantiproliferative doses. This increase in activity was rapid, seen as early as 30 sec after initiation of treatment, and it was sustained at peak levels for 1-2 hr. Analysis of the intracellular cAMP concentration gave similar kinetics of induction. Exposure of cells to the stable cAMP analogue dibutyryl cAMP yielded dose-dependent inhibition of cell growth. The cAMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also inhibited proliferation. In contrast, neither H-7 nor HA1004 had an effect on growth inhibition induced by human natural IFN-alpha treatment. In addition, antiproliferative doses of IFN-alpha did not increase cAMP concentrations. These results indicate that the cAMP system is utilized by mismatched dsRNA as an early signal transduction mechanism for growth control. Furthermore, the antiproliferative effects induced by mismatched dsRNA and IFN can occur by different mechanisms of action.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1987

Ruminal microbial development in conventionally or early-weaned calves.

Eight bull calves (four Holsteins and four Ayrshire calves with mean birth weight of 38.8 kg) were ruminally cannulated at 3 d of age and allocated to one of two weaning programs. All calves were fed colostrum for 3 d after birth and milk until weaning. Calves in the conventional-weaning program were fed a starter diet from 3 d of age and weaned at 6 wk of age. In the early-weaning program, calves were fed a highly palatable pre-starter diet from 3 d of age until they consumed 227 g/d, and then fed a mixture of pre-starter (227 g) and starter diet ad libitum. Calves in this group were weaned at 4 wk of age. Ruminal samples were collected at 3 and 7 d, then weekly thereafter through 8 wk and at 10 and 12 wk of age to assess microbial activity. Calves in the early-weaned group had a higher concentration of total ruminal volatile fatty acids at an earlier age than the calves in the conventional-weaning program. This was accompanied by a trend toward higher lactate concentrations and lower ruminal pH in the early-weaned group during their first 4 wk of age. Lactate and ammonia concentrations decreased with calf age. The total anaerobic bacterial counts increased slightly with calf age, whereas Streptococcus bovis and facultative bacterial populations decreased with calf age. Amylolytic, proteolytic, lactobacilli, lactate-utilizers, cellulolytic and methanogenic bacterial populations increased progressively in both groups. Cellulolytic and methanogenic bacteria were present in both groups at 3 d of age. No protozoa were detected in calves of either group. In general, the most significant changes in bacterial populations and metabolic activity in both groups occurred between 4 and 6 wk of age. Although calves in both groups had similar patterns of bacterial development, calves in the early-weaning program tended to have high ruminal microbial activity at an earlier age than the conventionally weaned calves.

Animals↗

PubMed1987

In vitro lactic acid inhibition and alterations in volatile fatty acid production by antimicrobial feed additives.

Batch culture fermentations were used to determine the effects of avoparcin, lasalocid, monensin, narasin, salinomycin, thiopeptin, tylosin, virginiamycin, monensin + tylosin combination, and two new ionophore compounds (RO22-6924/004 and RO21-6447/009) on lactic acid and volatile fatty acid (VFA) production. Ruminal fluid from cattle fed a high alfalfa hay diet was incubated with glucose for 12 h in a buffered medium to determine the effect of antimicrobial compounds on lactic acid concentration. Fermentations treated with antimicrobial compounds had higher final pH and lower L(+) lactic acid concentration. Narasin and salinomycin were more inhibitory than other ionophore compounds. Monensin and tylosin in combination was more effective than monensin alone. Among the nonionophore compounds, avoparcin was the least effective and thiopeptin, tylosin and virginiamycin were extremely effective in reducing lactic acid concentration. Ruminal fluid from cattle fed a diet of alfalfa hay and grain (50:50) was incubated with a mixture of sugars, casein and urea for 12 h in a buffered medium to determine the effect of antimicrobial compounds on VFA production. Generally, total VFA concentration was not affected by antimicrobial compounds except RO22-6924/004, tylosin and virginiamycin, which caused a reduction at high concentrations. Tylosin, monensin and tylosin mixture, thiopeptin and virginiamycin at high concentrations (greater than 6.0 micrograms/ml) increased the acetate proportion. All compounds increased the molar proportion of propionate. Tylosin and virginiamycin at high concentrations (greater than 6.0 micrograms/ml) decreased the proportion of propionate. Monensin and tylosin in combination had no effect on propionate proportion. Among the compounds tested, narasin and salinomycin were the most effective in enhancing propionate proportion. Ionophore compounds were more inhibitory to butyrate production than the nonionophore compounds. Batch culture fermentations may be used to quantitate the relative efficacy of antimicrobial compounds to alter ruminal fermentation characteristics.

Animals↗

PubMed1976

Impregnated disk method for antifungal antibiotic testing.

Sixteen clinical fungal isolates were tested for antibiotic susceptibility by using disks impregnated with growth medium and antibiotic. The procedure was easier to perform, less time consuming, and as reliable as other currently available methods.

Antifungal Agents↗