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D Davis

Publications and source records attributed to D Davis.

At least 37 records · Page 2Linked to original sources
PubMed1990

Immunosuppressive and monooxygenase induction activities of polychlorinated diphenyl ether congeners in C57BL/6N mice: quantitative structure-activity relationships.

The dose-response effects of several polychlorinated diphenyl ether (polyCDE) congeners on the inhibition of the splenic plaque-forming cell (PFC) response to sheep red blood cell antigen and the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities were determined in male C57BL/6 mice. The immunotoxic potencies for the polyCDE congeners (ED50 values for the suppression of PFCs/spleen and PFCs/10(6) cells) followed the order 2,3,3',4,4',5-hexaCDE (0.5 and 2.2 mumols/kg) greater than 3,3',4,4',5-pentaCDE (8.8 and 5.1 mumols/kg) greater than 2,3',4,4',5-pentaCDE (21.8 and 14.2 mumols/kg) greater than 3,3',4,4'-tetraCDE (50.6 and 28.7 mumols/kg) greater than 2,2',4,4',5,5'-hexaCDE (81.2 and 56.5 mumols/kg) greater than 2,2',4,5,5'-pentaCDE (258 and 228 mumols/kg) greater than 2,2',4,4',5,6'-hexaCDE (greater than 400 mumols/kg for both responses). The potencies of the polyCDE congeners as inducers of hepatic microsomal AHH and EROD activities were similar to their immunotoxicities and only one compound, namely, 2,3',4,4',5,5'-hexaCDE, did not cause dose-response immunosuppressive effects in the mice. The structure-activity relationships for the polyCDEs exhibited both differences and similarities. For example, the coplanar 3,3',4,4'-tetraCDE and 3,3',4,4',5-pentaCDE congeners were less immunotoxic than their monoortho 2,3',4,4',5-pentaCDE and 2,3,3',4,4',5-hexaCDE analogs, respectively, and similar results were also observed for their enzyme induction potencies. For the corresponding polychlorinated biphenyls (PCB) congeners the coplanar compounds were significantly more active than their monoortho analogs. In addition, two diortho-substituted compounds, namely, 2,2',4,5,5'-pentaCDE and 2,2',4,4',5,5'-hexaCDE, were also immunotoxic at a dose of 400 mumols/kg whereas, their PCB analogs were inactive. These studies clearly demonstrate that for the polyCDE congeners, increasing ortho-chloro substitution is less effective in reducing the activity of these congeners compared to the well-recognized ortho effects reported for the PCBs. The differences in the structure-activity relationships between polyCDEs and PCBs are related to the ether bridge in the polyCDEs in which the resultant increased bond length between the two phenyl rings thereby diminishes the effects of ortho substituents on the biochemical and toxic potencies of these compounds.

Animals↗
PubMed1990

Photoinduced electron transfer within complexes between plastocyanin and ruthenium bisbipyridine dicarboxybipyridine cytochrome c derivatives.

A new technique has been developed to measure intracomplex electron transfer between cytochrome c and its redox partners. Cytochrome c derivatives labeled at single lysine amino groups with ruthenium bisbipyridine dicarboxybipyridine were prepared as previously described [Pan, L.P., Durham, B., Wolinska, J., & Millett, F. (1988) Biochemistry 27, 7180-7184]. Excitation of RuII with a short light pulse resulted in the formation of the excited-state RuII*, which rapidly transferred an electron to the ferric heme group to form FeII and RuIII. Aniline was included in the buffer to reduce RuIII to RuII, leaving the heme group in the ferrous state. This process was complete within the lifetime of the light pulse. When plastocyanin was present in the solution, electron transfer from the ferrous heme of cytochrome c to CuII in plastocyanin was observed. All of the ruthenium cytochrome c derivatives formed electrostatic complexes with plastocyanin at low ionic strength, allowing intracomplex electron-transfer rate constants to be measured. The rate constants for derivatives modified at the indicated lysines were as follows: Lys 13, 1920 s-1; Lys 8, 1480 s-1; Lys 7, 1340 s-1; Lys 86, 1020 s-1; Lys 25, 820 s-1; Lys 72, 800 s-1; Lys 27, 530 s-1. It is interesting that the derivative modified at lysine 13 at the top of the heme crevice had the largest rate constant, while lysine 27 at the right side of the heme crevice had the smallest.(ABSTRACT TRUNCATED AT 250 WORDS)

2,2'-Dipyridyl↗
PubMed1990

The structure-dependent effects of heptachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction.

The dose-response effects of the 1,2,3,4,6,7,8-, 1,2,3,4,7,8,9-, 1,2,3,4,6,8,9-, and 1,2,3,4,6,7,9-heptachlorodibenzofurans (HpCDFs) on the splenic plaque-forming cell (PFC) response to sheep erythrocytes and on the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) activities were determined in male C57BL/6 mice. The ED50 values for the decrease in the PFCs/spleen, the number of PFCs/10(6) viable cells, and the induction of AHH and EROD activities were 1,2,3,4,6,7,8-HpCDF, 0.011, 0.018, 0.11, and 0.315 mumol/kg, respectively; 1,2,3,4,7,8,9-HpCDF, 0.012, 0.054, 0.70, and 0.20 mumol/kg, respectively; 1,2,3,4,6,7,9-HpCDF, 1.2, 1.3, greater than 43, and greater than 43 mumol/kg, respectively; 1,2,3,4,6,8,9-HpCDF, 1.5, 3.4, 22, and 22 mumol/kg, respectively. It was apparent from these studies that the 2,3,7,8-substituted HpCDF isomers (1,2,3,4,6,7,8- and 1,2,3,4,7,8,9-) were significantly more potent than the compounds which contained only three lateral C1 groups. These results were obtained using a multiple dosing regimen in which 10 separate doses of the HpCDF isomers were administered to the mice by intraperitoneal injection over a period of 12 days. However, when the mice were treated with a single dose of an HpCDF congener, which was equivalent to the total dose used in the multiple dose study, the responses were comparable. A comparison of the relative immunotoxic potencies of the 2,3,7,8-substituted HpCDFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin showed that the latter compound was approximately 10 times more active than the HpCDFs.

Animals↗
PubMed1990

Immunosuppressive activities of polychlorinated biphenyls in C57BL/6N mice: structure-activity relationships as Ah receptor agonists and partial antagonists.

The immunosuppressive activity of polychlorinated biphenyl (PCB) congeners is structure-dependent and 2 classes of compounds, namely the coplanar (class I) and monoortho coplanar (class II) congeners exhibit immunotoxicity. This study extends the structure-immunotoxicity relationships for PCBs by investigating representative congeners from the following structural classes of PCBs: monoortho coplanar (2,3,3',4,4',5-hexachlorobiphenyl, class II); monoortho coplanar minus a single parachloro group (2,3,3',4,5,5'-hexachlorobiphenyl and 2,3,3',4,5'-pentachlorobiphenyl, class III); diortho coplanar (2,3',4,4',5',6-hexachlorobiphenyl, class IV); triortho coplanar (2,2',4,4',5,6'-hexachlorobiphenyl, class V) and a tetraortho-substituted PCB (2,2',4,4',6,6'-hexachlorobiphenyl, class VI). The effects of these compounds on the splenic plaque forming cell response to sheep red blood cells was determined in 7-8 week old male C57BL/6N mice. The results showed that the class II-IV congeners were immunotoxic and with only one exception these compounds also induced hepatic microsomal aryl hydrocarbon hydroxylase and ethoxyresorufin O-deethylase activities and displaced [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from the cytosolic aryl hydrocarbon (Ah) receptor in competitive binding assays. These results thus extend the structure-activity relationships for PCBs as Ah receptor agonists. The interaction of these PCB congeners with an ED70-90 dose of TCDD (3.7 nmol/kg) showed that only one structural class of compounds, namely class III, partially antagonized TCDD-mediated immunotoxicity.

Animals↗
PubMed1990

A bi-national perspective on continuing medical education.

This paper presents a review and comparison of qualitative improvements in the organization, needs assessment, educational methodology, evaluation, and research in continuing medical education (CME) in the United States and Canada. Although accreditation now establishes minimal standards for CME and reduces the chances of irresponsible programs, some organizational issues (such as commercial sponsorship) and educational issues (how to "accredit" journal reading) remain unresolved. There are many examples of excellent, innovative CME programs offered by medical schools, and specialty societies have been instrumental in upgrading CME by serving as sponsors of accreditation and special projects. There is some evidence that the national health system of Canada has influenced the organization and content of Canadian CME, and these changes may soon affect U.S. programs as well. CME research has grown, with two types of research evident: the biomedical model, which assesses the efficacy of CME interventions by quantitative methods; and a model that uses grounded, ethnographic, methods to assess physician learning and performance change. Given the improvements of the past 20 years, the criticisms that focus exclusively on the lack of ideal educational planning for all CME programs are not so much wrong as dated and perhaps irrelevant. In developing their programs, CME leaders can begin to emphasize the physician learner and the clinical and social environment in which learning occurs.

Accreditation↗
PubMed1990

Patterns of care in general hospitals for patients with psychiatric diagnoses. Some findings and some cautions.

Patients with psychiatric diagnoses in general hospitals in New Jersey in 1985 with and without dedicated psychiatric units are compared. Unit and nonunit bed occupants are compared also in hospitals having dedicated units. Types of referral, case-mix, length of stay, co-morbidity, transfer to other settings, and social characteristics of patients vary by type of bed. Patients in scatter beds have relatively low lengths of stay, rarely are attended by a psychiatrist and have more CAT scans and EEGs for almost every diagnostic group. These data suggest the critical need for clinical studies of quality of care in varying psychiatric inpatient settings.

Affective Disorders, Psychotic↗
PubMed1990

Glycosylation governs the binding of antipeptide antibodies to regions of hypervariable amino acid sequence within recombinant gp120 of human immunodeficiency virus type 1.

Antibodies raised to an overlapping series of peptides following the amino acid sequence of the external envelope glycoprotein (gp 120) of human immunodeficiency virus type 1 (HIV-1) recognize eight regions in recombinant gp 120 molecules. If the recombinant molecules are glycosylated, three of these regions show a reduced capacity to bind antibody. Of the other five regions, two are strain-specific and carbohydrate restricts antibody binding to their N-terminal flanks, and three can be recognized by antibodies in recombinant gp 120 from an unrelated strain of HIV-1. Antibodies in sera from HIV-1-infected patients bind at high levels to peptides from five regions of gp 120. Of these regions, two coincide with those recognized by antibodies raised to peptides. Four of the five epitopes recognized by the rat antipeptide sera whose ability to bind antibody is influenced most by glycosylation, and three of the five regions which induce high levels of antibodies in patients' sera, contain putative glycosylation sites which are variable between strains of HIV-1. Such sites flank the putative neutralization and CD4-binding regions of gp 120. It is suggested that changes in the number and position of carbohydrate moieties following mutation can alternately mask and reveal epitopes. Masking an epitope can render a virus resistant to neutralization, whereas virus which binds antibody without being neutralized is able to gain entry to cells bearing antibody and complement receptors. Changes in the glycosylation pattern of gp 120 may therefore contribute to the control of HIV-1 spread within its host.

Amino Acid Sequence↗
PubMed1990

The immunodominance of epitopes within the transmembrane protein (gp41) of human immunodeficiency virus type 1 may be determined by the host's previous exposure to similar epitopes on unrelated antigens.

Six major epitopes have been recognized within the transmembrane gp41 molecule of human immunodeficiency virus type 1 (HIV-1). The immunodominant epitope is also recognized by antibodies in sera from laboratory personnel and is similar to a linear sequence of amino acids in the genome protein of two rhinovirus serotypes. The hypothesis is presented that immunodominance is produced by multiple priming of the host, following repeated infections with viruses unrelated to HIV-1, which share similar epitopes.

Amino Acid Sequence↗
PubMed1990

Interferon alpha-2b injections used as an adjuvant therapy to carbon dioxide laser vaporization of recalcitrant ano-genital condylomata acuminata.

We retrospectively analyzed our treatment of men with anogenital condylomata acuminata (CA) at Hennepin County Medical Center and the University of Minnesota. Between October 1985 and August 1989, 48 patients with CA were treated with laser vaporization, and 27 were treated with laser vaporization followed by a series of intralesional interferon (IFN) alpha-2b injections. The patients in the IFN group were more likely to have perianal CA (44% vs 24%), had larger numbers of CA, and were more likely to have had previous treatment, including previous laser vaporization. The CA in the laser group were more likely to be on the penis alone (67% vs 45%) and had a longer mean duration. The laser-treated group experienced a 38.2% rate of recurrence or reinfection with a mean follow-up period of 13 weeks. The laser and IFN group had an 18.5% rate of recurrence or reinfection with the same follow-up. We conclude that intralesional injections of alpha-2b interferon following carbon dioxide laser vaporization of recalcitrant ano-genital condylomata substantially reduce the risk of recurrence or reinfection.

Anus Neoplasms↗
PubMed1990

Effects of desipramine on norepinephrine clearance in congestive heart failure.

Elevated plasma norepinephrine (NE) in congestive heart failure (CHF) is caused by increased NE spillover and decreased NE clearance. To evaluate the effects of neuronal uptake blockade on NE clearance, we studied NE kinetics during steady-state infusions of [3H]NE, before and after oral desipramine (DMI, 50 mg) in 11 patients with CHF and 8 normal volunteers. Baseline plasma NE was greater in the CHF group (637 +/- 56 vs. 271 +/- 32 pg/ml; P less than 0.001), NE clearance was lower in CHF (1.31 +/- 0.21 vs. 1.94 +/- 0.17 l.min-1.m-2; P = 0.026), and NE spillover was greater in CHF (4.71 +/- 0.78 vs. 3.04 +/- 0.35 nmol.min-1.m-2, P = 0.054). After DMI, plasma NE rose significantly in CHF (778 +/- 67; P = 0.008), and NE clearance decreased further in CHF (0.97 +/- 0.16; P = 0.024), but neither changed in normal subjects. NE spillover did not change in either group. There appears to be an enhanced effect of DMI on NE clearance in CHF patients. Two general mechanisms may be responsible for this finding, an increased concentration of drug, possibly caused by a decreased volume of distribution, and an increased sensitivity of neuronal amine pumps to DMI. Both mechanisms may reflect a more general abnormality of clearance of drugs and hormones related to abnormalities of tissue perfusion in CHF.

Adult↗
PubMed1990

A controlled trial of colchicine to reduce the elastase load in the lungs of cigarette smokers with chronic obstructive pulmonary disease.

Current data suggest that emphysema in smokers is caused at least in part by the unrestrained action of neutrophil elastase on pulmonary tissues. Since colchicine reduces the secretion of enzymes from stimulated neutrophils, we designed a clinical trial to determine if colchicine could reduce the elastase load in the lungs or several putative indicators of elastin destruction. We carried out a prospective, double-blind, randomized, and placebo-controlled clinical trial. Outpatients seeking treatment for chronic obstructive pulmonary disease at the University of Texas Health Center at Tyler who met specific criteria were recruited into the study. A group of 46 cigarette smokers between 45 and 75 yr of age with chronic obstructive pulmonary disease (COPD) were studied. Colchicine or placebo was given orally in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of Theodur orally and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization. The patients were then randomized and treated for 14 days with colchicine, and the measurements were repeated. Modifications in plasma elastin peptides and neutrophil elastase-generated fibrinopeptide A, urinary desmosines, and bronchoalveolar lavage fluid neutrophils or neutrophil elastase were the indicators of success or failure of the treatment. Pre- and posttreatment measurements in each patient and the difference between colchicine-treated and placebo-treated groups were compared. There were no statistically significant differences in either of the two types of analyses in any of the variables. We conclude that variables related to elastase load in the lungs were not modified by colchicine treatment. If a drug can be identified that is successful in modifying one of these variables, it would then have to be tested in a large-scale clinical trial in which the rate of decline in the FEV1.0 or mortality would be measured. The data presented here may provide useful information about the variability of key measurements of elastase load in the lungs and the breakdown of elastin and may aid investigators in designing similar trials in the future.

Aged↗
PubMed1990

Choosing among health insurance options: a study of new employees.

This study examines how 296 new university employees selected among alternative health care options. Those selecting a traditional Blue Cross and Blue Shield (BC&BS) plan attributed greater importance to freedom of choice of physician, while those selecting an HMO were more likely to give priority to cost considerations in seeing a doctor and to having services at a single location. Better educated respondents and those with more recent experience with the medical care system were more accurate in objectively appraising alternative choices. Respondents, whether choosing a BC&BS plan or an HMO, tended to deny the gatekeeper roles of physicians in HMOs, although the BC&BS plan enrollees were somewhat better informed.

Attitude↗
PubMed1987

Termination of sustained tachycardia by external noninvasive pacing.

Invasive cardiac pacing has proved useful in the induction and termination of reentrant sustained tachycardias. In one of our two cases, programmed ventricular extra-stimulation was used to induce sustained ventricular tachycardia from the endocardial surface of the right ventricle. Induced ventricular tachycardia was terminated by burst ventricular pacing with an external cardiac pacemaker. In our second patient, external pacing was effective at inducing and terminating sustained supraventricular tachycardia. These patients illustrate that the principles of terminating sustained reentrant tachycardia with invasive pacing may also apply to noninvasive external pacing. The usefulness of this approach in treating reentrant tachycardias needs further evaluation.

Adult↗
PubMed1979

Atypical patterns of retrograde conduction over accessory atrioventricular pathways in the Wolff-Parkinson-White syndrome.

Patterns of ventriculoatrial conduction have been used to distinguish retrograde conduction over an accessory atrioventricular pathway from that over the normal atrioventricular conduction system. Ventriculoatrial conduction at a constant interval during incremental ventricular pacing and during progressive prematurity of ventricular extrastimuli has been considered characteristic of conduction over an accessory pathway. We describe three patients with the Wolff-Parkinson-White syndrome who had progressive or sudden increments in ventriculoatrial conduction over an accessory pathway during fixed-rate ventricular pacing or during introduction of ventricular extrastimuli. Such properties have been considered characteristic of conduction over the normal atrioventricular conduction system. We conclude that retrograde conduction over accessory pathways may resemble conduction over the normal atrioventricular conduction system.

Adult↗