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Biomedical subjects

D L Gordon

Publications and source records attributed to D L Gordon.

At least 91 records · Page 5Linked to original sources
PubMed1990

Spontaneous improvement after acute ischemic stroke. A pilot study.

Recent clinical studies emphasize the importance of early (less than 12 hours after onset) treatment of patients with acute ischemic stroke. Therapies have been proposed as being effective because of early clinical improvement. The frequency and degree of spontaneous improvement in such patients, however, is unknown. We prospectively evaluated the course of 29 patients (19 men, 10 women) aged 33-82 years who were seen less than or equal to 12 hours after the onset of acute ischemic stroke. Seventeen patients were first evaluated less than or equal to 6 hours and the remaining patients at 6-12 hours after onset. All patients were examined using a modified National Institutes of Health Stroke Scale at baseline, 1, 2, 3, and 6 hours. No specific treatment for acute ischemic stroke was given during this time. Improvement (defined as a decrease of greater than or equal to 2 points from baseline score) was noted at 1 hour in seven patients (24%). By 6 hours 15 patients (52%) had improved, 12 (41%) were unchanged, and two (7%) were worse. Our results suggest that spontaneous, often dramatic improvement occurs in patients with acute ischemic stroke and should be taken into consideration in the design of any trial of acute treatment.

Adult↗
PubMed1989

Surface phagocytosis of Staphylococcus epidermidis and Escherichia coli by human neutrophils: serum requirements for opsonization and chemiluminescence.

We examined the serum requirements for surface phagocytosis of Staphylococcus epidermidis and Escherichia coli and for the subsequent chemiluminescent response of human neutrophils. Substantial surface phagocytosis of S. epidermidis occurred in the absence of opsonins, although the presence of 10% pooled or heat-inactivated serum significantly increased phagocytosis. There was no significant difference between these opsonins, indicating that surface phagocytosis of S. epidermidis did not require complement. Unopsonized E. coli were not as readily phagocytized as S. epidermidis (33% versus 57%). In contrast to S. epidermidis optimal phagocytosis of E. coli required complement as 10% heat inactivated donor serum (HHS) was significantly less effective as an opsonin than 10% pooled healthy donor serum (PHS). The time kinetics for phagocytosis of each organism were similar, with most of the phagocytosis occurring in the first 10 min. The chemiluminescent response of neutrophils produced discrepant results. Maximal chemiluminescence was observed when neutrophils were stimulated with bacteria opsonized in PHS. The response to HHS-opsonized bacteria was less, and chemiluminescence to unopsonized bacteria was only marginally higher than the control, even though there was relatively good phagocytosis. These results define the opsonic requirements for surface phagocytosis of S. epidermidis and E. coli and indicate that although complement may not be required for phagocytosis, it is necessary for generation of a maximal oxidative burst, and thus may be essential for efficient intracellular killing.

Blood Bactericidal Activity↗
PubMed1989

Regulation of human neutrophil type 3 complement receptor (iC3b receptor) expression during phagocytosis of Staphylococcus aureus and Escherichia coli.

Human neutrophils (PMN) express a receptor for iC3b, a cleavage product of C3b. CR3 is an important receptor for phagocytosis of opsonized bacteria and its expression is enhanced by cell activation. We examined PMN CR3 expression during phagocytosis using flow cytometry and a CR3-specific monoclonal antibody. After 30 min phagocytosis of opsonized S. aureus and E. coli, CR3 expression increased to 151% and 221% of controls, respectively. Unopsonized S. aureus had no effect on CR3; however, unopsonized E. coli enhanced CR3 expression despite not being phagocytosed. Time-kinetic studies indicated a rapid initial fall in CR3 after addition of bacteria to PMN, followed by enhanced expression within 5-10 min. The initial fall in CR3 probably represented CR3 internalization rather than receptor destruction, as superoxide dismutase, catalase and protease inhibitors had no effect on this. Correlation of CR3 expression with the PMN oxidative response, measured with the intracellular fluorescent probe DCF-DA, demonstrated a dichotomy. Opsonized S. aureus and E. coli caused an oxidative response from PMN but unopsonized E. coli, which caused significant CR3 up-regulation, did not. CR3 up-regulation with unopsonized and opsonized E. coli was markedly inhibited by Polymyxin B, suggesting a role for endotoxin. These experiments indicate that CR3 expression can be regulated during phagocytosis, and the mechanisms responsible are distinct from those involved in the oxidative burst. CR3 up-regulation following exposure to bacteria in vivo may enhance neutrophil function at sites of infection.

Escherichia coli↗
PubMed1988

Analysis of C3 deposition and degradation on bacterial surfaces after opsonization.

C3b and iC3b, opsonic fragments of C3, interact with specific receptors on phagocytic cells. After bacterial opsonization, C3 fragments were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, western blotting, and immunodetection. For bacteria opsonized in 50% pooled human serum (PHS), C3 deposition and cleavage to iC3b occurred rapidly. C3b, iC3b, and C3d made up 17%, 64%, and 19%, respectively, of the C3 on Staphylococcus aureus and 53%, 44%, and 2% respectively, on Escherichia coli. Residual C3b was refractory to factor I cleavage, an occurrence enabling alternative pathway activation to continue. C3 deposited was quantitated by enzyme-linked immunosorbent assay; with 50% PHS, greater than 50% and 90% of total C3 deposition occurred within 5 and 10 min, respectively. With a lower percentage of PHS, maximal deposition required up to 60 min and was not achieved in less than 10% PHS. Ester-bound fragments represented 34% and 82% of covalently bound C3 on S. aureus and E. coli, respectively.

Amides↗
PubMed1988

Serum bactericidal activity against Haemophilus influenzae.

The requirement for an intact thiolester bond in C3 for assembly of the membrane attack complex and bactericidal activity was demonstrated in a system permitting only alternative pathway activation. Serum depleted of C3 and C4 by treatment with potassium bromide was reconstituted with forms of C3 with an intact (native C3) or disrupted (NH3.C3) thiolester bond, and bactericidal activity against Haemophilus influenzae b was determined. For strain 885 in high-antibody-containing serum, reconstitution with native C3 was associated with marked bactericidal activity (log10 kill in 60 min 1.01 +/- 0.08) compared with reconstitution with NH3.C3 (log10 kill -0.04 +/- 0.19, p less than 0.001). Similar results were obtained with other strains of H. influenzae b. In serum lacking type-specific antibody no alternative pathway-mediated bactericidal activity was detected against any of the strains examined, even when native C3 was added to KBr serum. These experiments indicate how the biochemical structure of C3 directs its functions; only forms of C3 with an intact thiolester bond, which can covalently bind to bacterial surfaces, can serve as the C5 convertase and generate bacterial activity. In addition these experiments demonstrate an absolute antibody dependence for alternative pathway-mediated bactericidal activity against H. influenzae.

Antibodies, Bacterial↗
PubMed1988

Capnocytophaga species: a cause of amniotic fluid infection and preterm labour.

Subclinical amniotic fluid infection and subsequent preterm labour may occur with intact membranes. We report two cases of subclinical amniotic fluid infection with intact membranes presenting in preterm labour. Capnocytophaga species, fastidious Gram-negative bacilli normally found in oral flora, were isolated in pure culture from amniotic fluid obtained by transabdominal amniocentesis. The distinctive microbiological features and spectrum of infections associated with Capnocytophaga species, and the importance of recognition of subclinical amniotic fluid infection as a cause of preterm labour, are discussed.

Adult↗
PubMed1988

Opsonin-dependent and independent surface phagocytosis of S. aureus proceeds independently of complement and complement receptors.

We examined the mechanism of surface phagocytosis of Staphylococcus aureus by human polymorphonuclear leucocytes (PMN). Surface phagocytosis of unopsonized bacteria occurred, but was significantly enhanced by the presence of serum. The serum requirement was low, and a maximal effect occurred with serum concentrations of 0.25-0.5%. The opsonic effect of serum was not removed by heat inactivation of complement but was adsorbed, at low serum concentrations, by protein A, indicating that opsonin-dependent surface phagocytosis requires IgG but not C3. The requirement of opsonin-dependent surface phagocytosis for IgG was demonstrated further with purified IgG preparations as the sole opsonin. Activation of PMN by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA) increased opsonin-independent surface phagocytosis by 47% and 66%, respectively, but had no effect on opsonin-dependent surface phagocytosis. Blockade of the PMN iC3b receptor (CR3), which has lectin-like properties, by a panel of monoclonal antibodies against the alpha- and beta-chains of CR3 did not inhibit the surface phagocytosis of opsonized or unopsonized S. aureus, and one antibody (NIMP-R10) enhanced opsonin-independent surface phagocytosis. These results indicate that the mechanism of surface phagocytosis is quite different to that observed in suspension assays. Opsonin-independent surface phagocytosis occurs and is enhanced by PMN activation, opsonin-dependent surface phagocytosis is dependent on IgG and not complement, and neither opsonin-independent nor -dependent surface phagocytosis proceeds through CR3.

Antibodies, Monoclonal↗
PubMed1987

Characteristics of iC3b binding to human polymorphonuclear leucocytes.

We determined in binding assays using monomeric fluid-phase iC3b and Scatchard analysis that iC3b binds to human polymorphonuclear leucocyte type 3 complement receptor (CR3), a low-density/high-affinity receptor (28,200 binding sites, affinity constant (Ka) = 2.1 +/- 0.47 X 10(6) L/M), and to the C3b receptor (CR1), a high-density/low-affinity receptor (54,700 binding sites, Ka = 1.7 +/- 2.04 X 10(5) L/M. Binding of iC3b to CR1 was confirmed by blocking experiments with polyclonal F(ab')2 antibody against CR1, and competitive binding experiments with C3b. Binding of iC3b to CR3 was demonstrated by blocking experiments with the monoclonal antibody OKM10 against the ligand binding site of CR3. Inhibition of both CR1 and CR3 did not completely reduce iC3b binding, indicating the existence of additional iC3b-binding sites on PMN. Using flow cytometric analysis of receptor expression, no positive or negative co-operativity was observed between CR1 and CR3. Expression of both receptors increased in a dose-dependent manner after incubation with f-met-leu-phe or phorbol myristate acetate; however, only CR3 expression was enhanced at very low concentrations of these stimuli. iC3b/CR3 interactions probably play a central role in host defence against microorganisms.

Complement C3b↗
PubMed1986

Ligand-receptor interactions in the phagocytosis of virulent Streptococcus pneumoniae by polymorphonuclear leukocytes.

We used polyclonal and monoclonal antibodies to neutrophil complement receptors CR1 and CR3 to assess the role of these receptors in the phagocytosis of virulent Streptococcus pneumoniae serotypes 3, 6A, and 14, which bear accessible C3 ligands covalently bound to the polysaccharide capsule. When the iC3b receptor (CR3) on normal polymorphonuclear leukocytes (PMNLs) was blocked by the monoclonal antibody OKM10, phagocytosis of pneumococcal serotypes 6A and 14 (which bear exclusively iC3b) was inhibited 50%-80% in pooled human serum and completely in nonimmune serum. Blockade of the PMNL C3b receptor (CR1) failed to inhibit phagocytosis for serotypes 6A and 14. For serotype 3, which bears C3b and C3d (as well as iC3b) on the capsule, CR3-mediated phagocytosis accounted for only 20% of the uptake; again, there was no evidence for CR1-mediated phagocytosis. The iC3b ligand elicited consistently greater release of superoxide, myeloperoxidase, and lactoferrin than did C3b. The iC3b/CR3 interaction is thus the primary trigger for phagocytosis of iC3b-bearing pneumococci and for stimulation of intracellular bactericidal processes.

Complement C3b↗
PubMed1985

Amidation of C3 at the thiolester site: stimulation of chemiluminescence and phagocytosis by a new inflammatory mediator.

We studied the ability of particle-bound and fluid-phase C3b monomers and monomeric amidated C3 (prepared by treatment of purified human C3 with ammonium chloride or methylamine) to stimulate chemiluminescence of human polymorphonuclear leukocytes (PMN) and monocytes and to promote phagocytosis in the absence of antibody. Particle-bound C3b evoked chemiluminescence from both PMN and monocytes, and fluid-phase C3b (0.5 mg/ml) elicited significant chemiluminescence from PMN but not from monocytes. Amidated forms of C3, both particle bound and fluid phase, were potent stimulators of chemiluminescence from phagocytic cells and caused a significantly greater response than did C3b. The phagocytosis of 1-micron microspheres by PMN and monocytes was enhanced by coating them with purified C3b in an antibody-free system. Microspheres coated with amidated C3 were avidly phagocytized, and to a greater degree than were C3b-coated microspheres. In a direct binding assay with tritiated monomeric C3b and amidated C3, the affinity of the PMN complement receptor type 1 for C3b (Ka = 4.9 X 10(7) L/M) was similar to that for amidated C3 (Ka = 5.7 X 10(7) L/M). However, there was a fourfold increase in the number of apparent binding sites for amidated C3. This increase did not reflect binding of amidated C3 to the complement receptor type 3, because blocking of CR3 with the monoclonal antibody OKM 10 failed to decrease binding of amidated C3. In sites of increased ammoniagenesis, such as the kidney in chronic renal failure, amidated C3 may play a role as an inflammatory mediator by stimulating oxidative metabolism in phagocytic cells.

Ammonium Chloride↗
PubMed1983

Diagnostic criteria and natural history of catheter-associated urinary tract infections after prostatectomy.

Bacteriuria occurred postoperatively in 28 of 122 patients who had sterile urine before transurethral prostatectomy without antibiotic prophylaxis. Prospective monitoring of catheter bacteriuria indicated that a bacterial count of 10(3) colony-forming-units (cfu/ml progressed to significant infection except when the bacterium in the urine was Staphylococcus epidermidis. Bacteraemia developed in 4 bacteriuric patients, including 2 in whom the bacteria in the urine and blood were mixed. Catheter removal without antibiotic therapy resulted in spontaneous resolution of Staph epidermidis bacteriuria in 9 patients but infection persisted in 5 of 6 patients with other bacteria in the urine. This study indicates that a bacterial count of 10(3) cfu/ml in catheter urine is associated with pathological sequelae and that catheter removal does not result in resolution of bacteriuria caused by pathogenic bacteria.

Bacteria↗
PubMed1983

Plesiomonas shigelloides septic arthritis complicating rheumatoid arthritis.

A patient with severe seropositive rheumatoid arthritis and hepatic cirrhosis developed septic arthritis of his knees. Plesiomonas shigelloides was isolated from joint fluid, blood, and also from the gut. The patient's joint symptoms responded to treatment with oral trimethoprim-sulphamethoxazole, but he died of uncontrolled gastrointestinal bleeding five days later.

Aged↗
PubMed1982

Simultaneous primary hyperparathyroidism and nodular thyroid disease.

Of 351 patients treated for primary hyperparathyroidism from 1966 to 1981, 70 (20%) had grossly evident nodular thyroid disease at the time of subtotal parathyroidectomy. These patients have been reviewed to determine if prior radiation exposure may play a role in their coexistence and if combined subtotal parathyroidectomy and thyroidectomy are safe and efficacious. Thirty-three of the 70 patients (47%) had received prior radiation therapy for benign conditions of the head and neck. Nine of 15 patients with nonmedullary thyroid carcinoma had received previous irradiation. In addition to subtotal parathyroidectomy, 28 patients underwent total thyroidectomy, 14 underwent bilateral subtotal thyroidectomy, and 28 underwent unilateral lobectomy. There were no deaths and no permanent recurrent laryngeal nerve injury from combined subtotal parathyroidectomy and thyroidectomy. Two patients in whom parathyroid tissue was not autotransplanted required calcium and vitamin D supplementation. This study shows that (1) primary hyperparathyroidism and nodular thyroid disease occur simultaneously with sufficient frequency to warrant careful preoperative and intraoperative evaluation of both glands, (2) radiation probably does play a role in the pathogenesis of coexistent primary hyperparathyroidism and nodular thyroid disease, and (3) in experienced hands combined subtotal parathyroidectomy and thyroidectomy can be safely performed.

Adenoma↗