Search PubMed⌕ Search

Biomedical subjects

R M Bennett

Publications and source records attributed to R M Bennett.

At least 91 records · Page 5Linked to original sources

Lactoferrin binds to neutrophilic membrane DNA.

Lactoferrin (LF) binding to the surface of human neutrophils was shown to be dependent upon the presence of cell surface DNA by (i) an abrogation of LF binding after treatment of whole cells with DNAse; (ii) an abrogation of LF binding to a purified cell membrane suspension after DNAse digestion, (iii) a restoration of LF binding, after initial treatment of cells with DNAse, by the addition of exogenous DNA. Using a biotinylated LF probe, no other binding molecules were found after SDS PAGE of neutrophil cell membrane proteins. Further evidence of a DNA-LF interaction was obtained by the co-isolation of LF with DNA by both gel chromatography and affinity chromatography using Heparin Sepharose CL 6B. The interaction of LF with neutrophils was a saturable phenomenon with a Kd of 6.2 X 10(-6) M and a maximum binding of 9.2 X 10(6) molecules per cell. These results suggest that cell membrane DNA may have a novel role as a receptor for LF, and indicates the need for further experiments to determine whether the functional effects of LF are modified by the DNAse treatment of LF responsive cells.

Cell Membrane↗

Anti-DNA antibodies react with DNA expressed on the surface of monocytes and B lymphocytes.

It is becoming increasingly apparent that nuclear antigens can be expressed on the surfaces of certain cells. We provide evidence that anti-DNA antibodies are reactive with DNA on the surface of monocytes and B lymphocytes. The DNA isolated from monocytes sedimented in a 17.8S position, corresponding to a molecular weight of 4.6 X 10(6); it was mainly double-stranded with many short single stranded regions. In one patient with active systemic lupus erythematosus experiments indicated that anti-DNA antibodies had interacted in vivo with the cell surface DNA on monocytes. The functional significance, if any, of these findings remains to be determined.

Antigen-Antibody Reactions↗

A 12-week, double-blind, multicenter study comparing diflunisal twice daily and ibuprofen four times daily in the treatment of rheumatoid arthritis.

Diflunisal, a nonacetylated salicylate preparation with a prolonged duration of action, was compared with ibuprofen for the treatment of rheumatoid arthritis in a multicenter trial comprising 210 patients. Diflunisal was administered twice a day (500 to 750 mg/day) and ibuprofen was administered four times a day (1,600 to 2,400 mg/day). To maintain double-blind conditions, all patients ostensibly followed the same regimen, ingesting their assigned drug and a matching placebo of their nonassigned drug. Disease activity assessments and laboratory tests were done periodically throughout the 12 weeks of the study, and results were compared with pretreatment findings. Efficacy evaluations in 187 patients showed that both treatments were similarly efficacious. Safety and tolerability also were similar in the two groups. Diflunisal, however, offers a more acceptable BID treatment schedule.

Adult↗

Complete heart block in a fetus associated with maternal Sjögren's syndrome.

This report illustrates the case of a fetus who was diagnosed by M-mode echocardiography, at the twentieth week of gestation, as having a complete heart block. The mother had a positive antinuclear antibody test result with antibodies directed against the Ro (SSA) and La (SSB) antigen system consistent with the diagnosis of Sjögren's syndrome. Management and outcome of the pregnancy are discussed.

Adult↗

Clinical characteristics of fibrositis. II. A "blinded," controlled study using standard psychological tests.

Twenty-two patients with fibrositis and 22 control patients selected from a general medical outpatient population were given 3 standardized psychological questionnaires: the Beck Depression Inventory, the Spielberger State and Trait Anxiety Inventory, and the SCL-90-R. There were no statistically significant differences between fibrositis patients and control patients on any of these tests, a finding at variance with a commonly held belief that patients with fibrositis have an underlying psychological disorder. While psychological factors may be important in some patients with fibrositis, these results indicate that the presence of a psychopathologic condition is not mandatory for the persistence of fibrositis.

Adult↗

Angiographic findings in mixed connective tissue disease. Correlation with fingernail capillary photomicroscopy and digital photoplethysmography findings.

Thirteen patients with mixed connective tissue disease underwent hand angiography to assess the degree of vascular abnormalities and their correlation to nailfold capillary microscopy and digital photoplethysmography findings. Organic obstruction was found in 60% of ulnar arteries, 87% of superficial arches, 13% of deep arches, and 65% of digital arteries. Fingernail capillary abnormalities were seen in 90% of patients. Normal photoplethysmography results had a predictive value of 91% for identifying digits without bilateral occlusions. These findings indicate a hitherto unrecognized propensity for disease of both small and medium-sized vessels in patients with mixed connective tissue disease.

Adult↗

DNA binding to human leukocytes. Evidence for a receptor-mediated association, internalization, and degradation of DNA.

Previous studies have indicated that white blood cells possess DNA on their outer membranes. In this study we set out to determine whether exogenous DNA bound to cells in a fashion compatible with a ligand receptor union. Purified populations of white blood cells; neutrophils (polymorphonuclear leukocytes, PMN), adherent mononuclear cells (ADMC), rosetting lymphocytes (E+ cells), and nonrosetting lymphocytes (E- cells) were incubated with radiolabeled lambda phage DNA in increasing concentrations. Binding of [3H]DNA was a saturable process and was inhibited by excess cold DNA and prior trypsinization of the cells. Rate zonal density centrifugation of purified cell membrane preparations confirmed that DNA was binding to the outer cell surface. The dissociation constant for all four cell types was approximately 10(-9) M, and from 0.81 X 10(3) to 2.6 X 10(3) molecules of lambda phage DNA bound to each cell depending upon cell type. Binding was not competitively inhibited by RNA, polydeoxyadenylic acid-polydeoxythymidylic acid (poly [d(A).d(T)]), or mononucleotides. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE)-separated proteins from PMN, ADMC, E+, and E- cells were electrophoretically blotted onto nitrocellulose sheets; a probe of biotin-labeled DNA indicated a single species of DNA-binding molecule migrating in a position consistent with a molecular weight of 30,000. Isotopic and immunofluorescent studies indicate that DNA is internalized and degraded to oligonucleotides; this process is inhibited by cycloheximide. These results support the notion that there is a common binding site for DNA on white blood cells, that the stoichiometry of the association is compatible with a ligand receptor relationship, and that this apparent receptor is responsible for the endocytosis and degradation of exogenous DNA.

Biological Transport↗

A double blind crossover trial of prednisone versus placebo in the treatment of fibrositis.

Twenty patients with a diagnosis of fibrositis were entered into a double blinded crossover study to compare the effects of prednisone versus placebo. Each patient was randomly assigned to either prednisone 15 mg/day or placebo for 14 days of therapy and then therapy was switched for a further 14 days. The following measurements were assessed at baseline, end of Week 2 and end of Week 4: analogue scores for pain, sleep disturbance, morning stiffness and fatiguability, and dolorimetry readings of pain tolerance over 14 representative tender points. Overall there was no improvement while taking prednisone, indeed most measured variables showed a trend towards deterioration with this therapy.

Adult↗

Biotin-labelled DNA: a novel approach for the recognition of a DNA binding site on cell membranes.

There have been several independent observations over the last decade attesting to the association of deoxyribonucleic acid with the surface membranes of certain mammalian cells. In general these findings have generated little interest as it has usually been assumed that this association is a non-specific epiphenomenon. In this study, we show that the isolated cell membranes of human neutrophils possess a DNA binding molecule with a molecular weight of 30,000. The techniques used to demonstrate this DNA binding molecule, namely the use of biotinylated DNA to probe proteins that have been electrophoretically separated and blotted onto nitrocellulose, should find a general applicability in identifying putative cell surface receptors.

Bacteriophage lambda↗

Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus.

Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment, major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.

Adolescent↗

Menses induction in rhesus monkeys using a controlled-release vaginal delivery system containing (15S) 15-methyl prostaglandin F2 alpha methyl ester.

Polymeric controlled-release vaginal delivery systems were designed for (15S)15-methyl prostaglandin (PG)F2 alpha methyl ester (carboprost methyl). The drug was incorporated into a highly permeable reservoir membrane that was bound to a relatively nonpermeable support membrane. The rate of drug release was controlled by coating the reservoir membrane with a less permeable rate-controlling membrane. Vaginal devices were prepared with in vitro steady-state release rates from 5 to 180 microgram/hour. The release curves were characterized by an initial, transient rapid release of the drug, followed by a linear zero-order release phase. Pregnancy was terminated in rhesus monkeys following a 24-hour treatment with vaginal devices having release rates of carboprost methyl of 45 microgram/hour or greater. Successful menses induction was associated with peripheral plasma concentrations of (15S)15-methyl PGF2 alpha between 2000 and 3000 pg/ml. Peripheral plasma concentrations of progesterone declined very rapidly to less than 1.0 ng/ml in monkeys in which pregnancy was terminated. These studies demonstrate the feasibility of manufacturing controlled-release vaginal delivery systems containing carboprost methyl for use in early pregnancy termination.

Abortion, Induced↗

Myelopathy in Reiter's disease.

A 21-year-old male presented with fevers, polyarthritis, dysuria and rash. Neurologic examination indicated myelopathic changes below the T12 spinal cord level. These changes were present during the acute course of his illness but were not evident after 8 weeks of treatment. We are unaware of reports of myelopathy associated with Reiter's disease.

Adult↗

Clinical characteristics of fibrositis. I. A "blinded," controlled study of symptoms and tender points.

Twenty-two patients with fibrositis, selected from a general medical outpatient population by a screening questionnaire and subsequent evaluation, were compared with age-, sex-, and clinic-matched patients without fibrositis. Although there was a high prevalence of musculoskeletal complaints in both groups, the fibrositis patients had a uniform constellation of symptoms, including axial pain, severe aching and stiffness, morning fatigue, and modulation by specific factors. They also had a higher incidence of tension headache and irritable bowel syndrome. The use of a dolorimeter demonstrated that fibrositis patients had many more areas of localized tenderness than control patients, but also that fibrositis patients did not have diffusely diminished pain threshold and tolerance. Using the criteria of this study, fibrositis appears to be a common and readily definable syndrome within the spectrum of soft tissue rheumatism.

Adolescent↗