Search PubMed⌕ Search

Biomedical subjects

D A Davis

Publications and source records attributed to D A Davis.

At least 91 records · Page 5Linked to original sources

Inhibition of calcium-dependent pathways of B-cell activation by DMBA.

The purpose of the experiments described in these studies was to determine the effects of 7,12-dimethylbenz[a]anthracene (DMBA) on B-cell activation produced by anti-IgD antibodies and interleukin-4 (IL-4). B and T cells are known to share many of the same biochemical pathways for cell activation by mitogen and antigen receptors. Previous studies in this laboratory have shown that DMBA inhibits mitogen-induced Ca2+ mobilization in murine and human T cells and produces an increase in intracellular Ca2+ in resting cells. The results of the present studies demonstrate that DMBA increases Ca2+ in resting B cells and inhibits B cell activation produced by anti-IgD antibodies, as measured by mobilization of free intracellular Ca2+ and [3H]thymidine incorporation. The proliferative response of B cells to insolubilized anti-IgD was suppressed only when cells were preexposed to DMBA. In contrast, IL-4 pathways of B-cell activation were insensitive to inhibition by DMBA, even when cells were preexposed. The induction of Class II MHC antigen (Ia) antigens on B cells by IL-4 was also found to be insensitive to DMBA treatment. These results suggest that DMBA suppresses only Ca(2+)-dependent pathways of B cell activation and indicate that altered Ca2+ homeostasis may be responsible for immunosuppression induced by this agent.

9,10-Dimethyl-1,2-benzanthracene↗

Alterations in mitogen-induced calcium mobilization and intracellular free calcium produced by 7,12-dimethylbenz(a)anthracene in the Jurkat human T cell line.

The purpose of these studies was to assess the effects of 7,12-dimethylbenz(a)anthracene (DMBA), an immunosuppressive polycyclic aromatic hydrocarbon (PAH), on Ca+2 mobilization induced by phytohemagglutinin (PHA) in the Jurkat human T cell line. Intracellular levels of free cytosolic Ca+2 were examined by flow cytometry using Indo-1 loaded cells. At doses of 3-30 microM, DMBA was found to produce a dose and time-dependent inhibition of Ca+2 mobilization in Jurkat following in vitro exposure. The decrease in Ca+2 mobilization was correlated with an increase in baseline levels of cytoplasmic free Ca+2. Two non-immunosuppressive PAH, benzo(e)pyrene and anthracene, failed to inhibit PHA-induced Ca+2 mobilization or alter baseline levels of free Ca+2. These results suggest that DMBA may produce immunosuppression by inhibiting Ca+2 mobilization or by altering Ca+2 homeostasis in activated T cells.

9,10-Dimethyl-1,2-benzanthracene↗

Inhibition of lymphocyte activation in splenic and gut-associated lymphoid tissues following oral exposure of mice to 7,12-dimethylbenz[a]anthracene.

The hypothesis that 7,12-dimethyl-benz[a]anthracene (DMBA) suppresses immune function in mice via an inhibition of lymphocyte activation was examined in these studies. Daily exposure of B6C3F1 mice to DMBA (cumulative doses of 1.4 to 140 mg/kg) via the oral route for 14 days was found to inhibit phytohemagglutinin (PHA) and lipopolysaccharide mitogen responses in lymphoid cells obtained from the spleen. Peyer's Patches, and mesenteric lymph nodes. The 14 mg/kg cumulative dose of DMBA produced no significant decrease in the number of recovered viable cells, yet mitogen responses were suppressed by approximately 50% in the spleen and mesenteric lymph nodes, and by greater than 70% in the Peyer's Patches. DMBA inhibited PHA-induced Ca+2 mobilization measured by flow cytometry in each of these three lymphoid tissues. There was no change in the percentage of T cells recovered from the spleen, mesenteric lymph nodes, or Peyer's Patches. Peyer's Patch lymphocytes obtained from the GI tract appeared to be slightly more sensitive to inhibition of mitogen responsiveness and perhaps Ca+2 mobilization, potentially due to the oral route of exposure to DMBA. These studies provide evidence that DMBA inhibits early events associated with lymphocyte activation in mice.

9,10-Dimethyl-1,2-benzanthracene↗

Chloro-substituted, sterically hindered 5,11-dicarbo analogues of clozapine as potential chiral antipsychotic agents.

Variable-temperature proton nuclear magnetic resonance studies have shown that 5-(2-propylidene)-10-(4-methylpiperazino)-5H-dibenzo[a,d] cycloheptene, a 5,11-dicarbo analogue of the atypical neuroleptic agent clozapine [8-chloro-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]diazepine], exists as thermally stable configurational isomers. The presence of the 2-propylidene group at C-5 on the 5H-dibenzo[a,d]cycloheptene moiety did not interfere greatly, as compared to clozapine, with the in vitro affinity of this 5,11-dicarbo analogue of clozapine for muscarinic and dopamine D-1 and D-2 binding sites in rat brain. Since the presence and position of a chloro substituent on the 5H-dibenzo[b,e][1,4]diazepine moiety have a marked influence on the respective binding affinities of 1,4-diazepines related to clozapine, chloro-substituted 5,11-dicarbo analogues of clozapine were prepared in order to further examine structure-activity relationships. Evaluation of these analogues for binding to muscarinic and dopamine binding sites in comparison with clozapine and other 5H-dibenzo[b,e][1,4]diazepine analogues of clozapine shows that the dopamine D-1 and D-2 receptor affinities of both the 5-(2-propylidene)-5,11-dicarbo analogue and its corresponding distal-chloro derivative, 2-chloro-5-(2-propylidene)-10-(4-methylpiperazino)-5H- dibenzo[a,d]cycloheptene, are retained. Because of the susceptibility to acid-catalyzed hydrolysis of these tertiary enamines, however, these compounds serve only as model compounds for their structure-activity evaluation. Since the proximal nitrogen atom of the piperazine ring is redundant for biological activity, 5-(2-propylidene)-10-(1-methyl-4-pyridyl)-5H-dibenzo[a,d]cycloh eptene and its 2-chloro derivative are excellent candidates for resolution into enantiomers as a means to separate antimuscarinic and antidopaminergic activity, respectively, associated with only a single stereoisomer.

Animals↗

Continuing education through Telemedicine for Ontario.

Telemedicine for Ontario (TFO) is a continuing education program for health professionals. It is an interactive audio system, organized and operated by the five provincial medical schools, that is designed to offer otherwise unavailable educational programs to health professionals in northern or other isolated areas of Ontario. TFO has provided programs in three categories--medicine, nursing and allied health--and has covered a wide range of topics; the programs have been tailored to the stated needs and interests of the participants. By 1986 there were 199 sites throughout Ontario that participated regularly, and there were approximately 25,000 individual registrations in the 1985-86 seasons. Our results from this 3-year pilot study have indicated the feasibility of the medium and its acceptance by health professionals. The next stage of the program's evaluation will include analyses of its impact on clinical practice and on the health status of patients.

Allied Health Personnel↗

The resistance spectrum shown by a fenvalerate-resistant strain of blue tick (Boophilus decoloratus) to a range of ixodicides.

A strain of Boophilus decoloratus, resistant to fenvalerate, was subjected to larval immersion, adult immersion and stall tests using the following classes of ixodicides: organochlorines, organophosphates, a diamidide and pyrethroids. A susceptible reference strain of B. decoloratus was used for comparative purposes. The results indicated a high level of resistance to DDT and camphechlor, slight tolerance to dioxathion, chlorfenvinphos and pirimiphos ethyl, full susceptibility to bromophos ethyl and amitraz, but marked resistance to cyhalothrin, cypemethrin, deltamethrin and flumethrin. This marked resistance in the strain therefore appears to be widespread within the pyrethroid group of chemicals and may have developed as a result of organochlorine cross-resistance.

Animals↗

The computer-based anesthetic monitors: the Duke Automatic Monitoring Equipment (DAME) system and the microDAME.

From 1972 to 1983 the Duke University Department of Anesthesiology designed, built, and maintained most of its own operating room patient monitoring equipment. Construction of a new hospital facility in 1980 provided the opportunity to design and test a new computer-based system, the Duke Automatic Monitoring Equipment (DAME) System. The system consist of microcomputer-based instrumentation on monitoring carts, which communicate with a central minicomputer that allows selection of different software monitoring packages based on the needs of the patient. Multiple problems, including frequent total monitoring failures during surgery, plagued the DAME System in its first year of operation. Despite resolution of many of these problems, user acceptance was poor because of the large size and weight of the monitoring carts, the inadequate quality of displayed physiological waveforms, and inability to overcome the difficulties of the man-machine interface. Because the remaining problems could not be rectified with the existing monitoring carts, a new generation of monitors was designed. The smaller, multiprocessor microDAME was designed to be as automatic and user tolerant as possible. It would omit much of the flexibility that had proved undesirable in the DAME system. When the microDAME was nearly completed, however, departmental research in that area ceased. It remains for others to apply our experiences to further improve operating room patient monitors.

Anesthesiology↗

Inhibition of dopaminergic agonist-induced gnawing behavior by neuroleptic drugs in mice.

Several neuroleptic drugs cause the Parkinsonian syndrome (PS) in humans; however, this effect is not detectable in rodents. PS-inducing drugs inhibit gnawing or biting behavior induced by apomorphine, amphetamine, DOPA, and thozalinone. The effects of five narcoleptic drugs (chlorpromazine, haloperidol, perphenazine, thioridazine, and trifluoperazine) on this behavior were tested in ICR male mice (10 per dose level). The drugs were given ip 30 min before each of the following inducing agents: DL-DOPA (500 mg/kg, iv), apomorphine (100 mg/kg, ip), amphetamine (12.5 mg/kg, ip), and thozalinone (100 mg/kg, ip). The criterion for blocking effectiveness was the prevention of the biting or gnawing behavior. Prevention indexes (PI) were calculated from the LD50/ED50. Data are consistent with the PS-inducing potencies of these five drugs. Another selective index (SI) of each drug was established by the ED50/ND50 ratio. There is some correlation between PI values and clinical symptoms, but it is not as well defined as that between SI values and clinical symptoms. Data from the thozalinone test (SI) appear to provide the best prediction for the PS-inducing potencies of the drugs tested. Thus, this technique appears to be suitable for use as an animal model in preclinical toxicity studies.

Animals↗

The treatment of canine demodecosis with amitraz.

The treatment of a series of 27 clinical cases of canine demodecosis is reported. Three of 4 applications of a wash containing 0,025% amitraz, together with antimicrobial and antipruritic therapy where necessary, were sufficient to effect clinical cure in 25 out of 26 cases mildly to severely affected. In one case, very severely affected, 9 weekly applications, together with antimicrobial and antipruritic therapy, effected clinical and parasitological cure.

Animals↗

A critical appraisal of the efficacy of continuing medical education.

To determine the efficacy of continuing medical education (CME), we collected 248 original articles describing studies of CME interventions. These articles were reviewed for applicability and scientific credibility by applying preset methodological criteria. Thirteen percent of articles described randomized trials, but only 7% of all articles and 20% of randomized trials assessed the impact of CME on patient outcomes. Seven articles met all our criteria and were reviewed in detail. These studies provide convincing evidence that CME can improve physician behaviors. However, only three of these methodologically sound studies assessed patient outcomes and only one demonstrated any improvement in outcomes.

Certification↗

EEGs during high-dose fentanyl-, sufentanil-, or morphine-oxygen anesthesia.

In 49 patients undergoing open-heart surgery we compared the electroencephalographic (EEG) effects of high-dose morphine, fentanyl, or sufentanil with O2, using two computerized analysis and display techniques: a period analysis (the Klein method) and an aperiodic analysis (the Neurometrics monitor). During fentanyl or sufentanil anesthesia, both techniques revealed a general decrease in frequency, shown by the aperiodic analysis primarily as a marked increase in the very low frequency range: an increase in the 1-Hz bin (TP1, in muv2) from 2.80 X 10(4) +/- 3.20 X 10(4) (SD) to 45.1 X 10(4) +/- 27.2 X 10(4) for fentanyl and from 3.11 X 10(4) +/- 2.83 X 10(4) to 52.8 X 10(4) for sufentanil. The cumulative percent power at 3 Hz (CP3) increased from 27.2 +/- 6.8 to 83.0 +/- 11.0 for fentanyl and from 22.7 +/- 5.2 to 85.1 +/- 10.4 for sufentanil, while the frequency at 90% cumulative percent power (F90, in Hz) decreased from 17.8 +/- 2.9 to 7.9 +/- 2.8 for fentanyl and 16.4 +/- 5.2 to 5.6 +/- 4.3 for sufentanil. The changes with morphine were less obvious, with some attenuation of high-frequency power shown by the Klein method, and an increase from 24.1 +/- 8.6 to 59.3 +/- 20.7 with CP3, but no change in TP1. Low-frequency power with the period analysis and TP1 with the aperiodic analysis decreased between laryngoscopy and the incisions with fentanyl and sufentanil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗