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D C Anderson

Publications and source records attributed to D C Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1995

The temporal profiles of ICAM-1 protein and mRNA expression after transient MCA occlusion in the rat.

Leukocytes may contribute to ischemic cell damage. ICAM-1 expression on endothelial cells facilitates the migration of leukocytes into tissue. Therefore, we measured the temporal profiles of ICAM-1 mRNA and protein in rat brain after transient (1 or 2 h) of middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 86) were subjected to 1 or 2 h MCA of occlusion, or 2 h of MCA occlusion followed by reperfusion for a variety of durations ranging from 1 h to 1 week. 10 additional control animals were employed. ICAM-1 mRNA and protein were measured during ischemia and reperfusion, and immunohistochemical methods were used to identify specific cell types expressing ICAM-1. ICAM-1 mRNA was detected 1 h after the onset of ischemia. mRNA maximized at 10 h of reperfusion and persisted out to 1 week of reperfusion. ICAM-1 significantly increased in microvascular endothelial cells at 2 h of reperfusion, maximized at 46 h and persisted out to 1 week of reperfusion (P < 0.05). ICAM-1 mRNA and protein are present in ischemic brain early after the onset of ischemia and reperfusion, respectively. These data provide support for the role of ICAM-1 in mediating leukocyte-endothelial adhesion after transient MCA occlusion in the rat.

Animals↗
PubMed1995

C1q triggers neutrophil superoxide production by a unique CD18-dependent mechanism.

Complement protein C1q induces the production of superoxide (O2-) by neutrophils via an as yet unidentified receptor or receptor complex. Several strategies were therefore used to identify cell surface molecules involved in the response of neutrophils to C1q and its collagen-like domain (C1q-CLR). Treatment of neutrophils with phosphatidylinositol-specific phospholipase C effectively removed the phosphatidylinositol-linked surface molecules CD14 and CD16, yet did not reduce O2- production in response to C1q. Next, 17 monoclonal antibodies (mAbs) recognizing various neutrophil surface antigens were tested for their ability to inhibit C1q-CLR-mediated O2- production. Only two of the mAbs, 44a and IB4, which recognize CD11b/CD18 (complement receptor 3 or Mac-1), were inhibitory. In addition, neutrophils from a patient with leukocyte adhesion deficiency, which are CD18 deficient, did not produce O2- in response to C1q or C1q-CLR. Because CD11b/CD18 is recognized to play a role in cell adhesion, the role of adherence in C1q-mediated O2- production was explored. Adherence of neutrophils to C1q-CLR-coated surfaces occurred with kinetics, which usually paralleled those of O2- production, and was invariably abolished by the anti-CD11b mAb 44a. However, this mAb often only partially inhibited O2- production, indicating that an avid attachment of neutrophils to the C1q-CLR-coated surface is not required for O2- production.

Antibodies, Monoclonal↗
PubMed1995

Effects of 5-benzylacyclouridine, an inhibitor of uridine phosphorylase, on the pharmacokinetics of uridine in rhesus monkeys: implications for chemotherapy.

The effects of subcutaneous administration of 5-benzylacyclouridine (BAU), a uridine phosphorylase (UrdPase, EC 2.4.2.3) inhibitor, on uridine concentration in plasma and urine were evaluated in rhesus monkeys. Administration of BAU at 50, 100 and 250 mg/kg increased the plasma uridine baseline concentration 1.5-, 2.9-, and 3.2-fold, respectively. The basis for this moderate perturbation of plasma uridine by BAU was investigated using a tracer dose of 500 microCi 3H-uridine. Administration of 3H-uridine alone led to its rapid catabolism to uracil and dihydrouracil. Administration of 83.3 mg/kg BAU with 500 microCi 3H-uridine resulted in a 2.5-fold enhancement of 3H-uridine plasma levels and a substantial decrease in the plasma levels of uridine catabolites, suggesting inhibition of UrdPase activity by BAU in rhesus monkeys. Coadministration of 83.3 mg/kg BAU with 83.3 mg/kg uridine also reduced the plasma concentration of uracil and dihydrouracil, but it did not increase plasma uridine concentration above that of control animals receiving 83.3 mg/kg uridine alone. In animals receiving uridine alone at 83.3 or 25 mg/kg, approximately 10% of the administered dose was recovered in the urine within 6 h, with unchanged uridine being the major component. In contrast, administration of 83.3 mg/kg BAU increased the excretion of unchanged uridine to more than 32% of the total dose administered, even when the urinary excretion ratio of uracil to uridine was reduced ten-fold. Administration of multiple doses (three times per day) of BAU alone (83.3 mg/kg) or in the presence of uridine (83.3 mg/kg) did not enhance plasma uridine concentration further. In addition, uridine pharmacokinetics were associated with a time-dependent relationship as evidenced by an increased total plasma clearance, renal clearance and volume of distribution, resulting in a substantial decrease in uridine peak concentration with time. These results indicate that administration of BAU inhibits UrdPase activity in rhesus monkeys as manifested by decreased uracil and dihydrouracil plasma levels, as well as a lower urinary excretion ratio of uracil to uridine, as compared to control animals. However, plasma levels of unchanged uridine were not substantially enhanced by BAU in spite of the large increase in urinary excretion of unchanged uridine. This phenomenon was also observed when uridine was coadministered with BAU, suggesting that plasma uridine concentration in monkeys may be strongly regulated by the renal system as evidenced by the "spillover" of excess plasma uridine into urine. In addition, the pharmacokinetics of uridine were dose-independent, but time-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Aspirin-induced, neutrophil-mediated injury to vascular endothelium.

Previous studies indicate that aspirin can promote neutrophil (PMN) adhesion to endothelial cells and neutrophil-mediated endothelial cell detachment. The objectives of the present study were to determine whether PMN adhesion is a prerequisite for aspirin-induced, PMN-mediated endothelial cell detachment and whether neutrophil-derived oxidants and/or proteases are responsible for the cell detachment. Human PMNs were added to confluent monolayers of human umbilical vein endothelial cells (HUVEC) and coincubated with or without aspirin at a clinically relevant concentration (300 micrograms/ml). Aspirin-activated PMNs induced endothelial cell detachment, but not cell lysis. Endothelial cell detachment was always preceded by retraction of endothelial cells within the monolayer. The aspirin-induced, neutrophil-mediated cell detachment was prevented by a monoclonal antibody directed against CD11/CD18 adhesion integrins on PMNs. Elastase inhibitors, but not superoxide dismutase or catalase, prevented both endothelial cell retraction and detachment. If aspirin-activated neutrophils were allowed to migrate across the monolayers, endothelial cell retraction or detachment did not occur. These studies indicate that aspirin-induced, PMN-mediated endothelial cell retraction and detachment requires PMN adhesion to the target cells and is due to neutrophil-derived elastase. Endothelial cell retraction, induced by activated neutrophils, may represent an exaggeration of a normal physiologic event, i.e., neutrophil emigration.

Adult↗
PubMed1995

Role of leukocyte-endothelial cell adhesion in radiation-induced microvascular dysfunction in rats.

BACKGROUND/AIMS: Recent evidence suggests an active role of endothelial cells and inflammatory cells in radiation-induced vascular dysfunction and organ damage. The aim of this study was to characterize the endothelial cell-leukocyte interactions, their molecular mechanisms, and the associated microvascular dysfunction in postcapillary venules exposed to ionizing radiation. METHODS: Leukocyte rolling, adherence, and emigration and leakage of fluorescein isothiocyanate albumin in rat mesenteric venules were measured in control conditions and at 2, 4, and 6 hours after abdominal irradiation. Some animals were treated with monoclonal antibodies against leukocyte (CD18) or endothelial cell (intercellular adhesion molecule 1, P-selectin) adhesion molecules before radiation and 5 hours thereafter. RESULTS: In comparison with controls, irradiated animals had a marked increase in the number of rolling leukocytes at 2 hours after radiation. In animals studied 6 hours after radiation, a significant increment in the number of adherent and emigrated leukocytes was observed. This was associated with an increased permeability to fluorescein isothiocyanate albumin. Treatment with antibodies against either CD18 or intercellular adhesion molecule 1, but not P-selectin, significantly attenuated leukocyte adherence, emigration, and the increase in permeability induced by radiation. CONCLUSIONS: Radiation-induced leukocyte adherence and emigration involves an interaction between CD11/CD18 on leukocytes and intercellular adhesion molecule 1 on vascular endothelium. These interactions are implicated in the early increase in vascular permeability after irradiation.

Animals↗
PubMed1995

An audit of oestradiol levels and implant frequency in women undergoing subcutaneous implant therapy.

OBJECTIVES: The aim of the study was to review our long-term use of subcutaneous oestradiol (E2) implant therapy for the treatment of climacteric symptoms in post-menopausal women. On the grounds that the aim is to restore premenopausal serum E2 levels, our declared clinical policy is not to repeat implants even in the presence of symptoms if serum E2 levels are > 400 pmol/l. Therapy was with 50 mg E2 implants inserted subcutaneously in the lower abdominal wall. DESIGN: All women who had attended the gynaecological/endocrinological clinic who had received subcutaneous E2 implants for the relief of climacteric symptoms between December 1981 and 1992 were included. RESULTS: Between December 1981 and December 1992, 275 women received a total of 759 50 mg E2 implants. The median length of implant therapy was 34.2 months (range 3.7-109.5 months), and the median number of implants per patient was 4 and ranged from 1 to 13. One hundred and twenty-nine women had more than four implants and their mean recorded serum E2 level was 425 +/- 187 (mean +/- SD) pmol/l; the mean level over the first 24 months of therapy was 408 +/- 157 pmol/l. This was not different from the mean value of the remaining period of therapy (439 +/- 168 pmol/l). Following the second implant there was no significant progressive rise in serum E2 with time and implant number and the mean E2 level per patient was no higher in those patients who received implants more frequently. The mean time between the first two implants was 9.7 +/- 0.4 months and between subsequent ones was 11.7 +/- 0.5 months. After the first two implants there was no progressive change in this interval with time. CONCLUSION: This study shows that effective, safe and sympathetic management of women with oestrogen deficient symptoms may be achieved by use of two criteria to determine re-treatment; the return of symptoms, and a serum E2 level no higher than 400 pmol/l. Once therapy is established, E2 implants may need to be prescribed only on an annual basis. There appears to be no justification for giving E2 implants more frequently as this policy achieves satisfactory (physiological) premenopausal E2 levels and good symptomatic relief without any evidence for accumulation of E2 or 'tachyphylaxis'.

Adolescent↗
PubMed1995

Chemotherapy-induced hemolytic uremic syndrome: description of a potential animal model.

Hemolytic uremic syndrome (HUS) is an uncommon complication of chemotherapy that contributes to the morbidity of oncology and bone marrow transplant patients. The pathogenesis is not well understood and no established clinical animal model exists. We studied four rhesus monkeys (RM) that developed fatal HUS following high-dose chemotherapy. Microangiopathic hemolytic anemia (pre-Hct 40% and day 5-8 Hct 31% (P < .05), increased BUN (168 mg/dl), creatinine (8.2 mg/dl), and lactate dehydrogenase (1458 IU/L) (mean day 5-8 measurements) were observed. Platelets counts decreased to 39 +/- 15 x 10(9)/l from a mean of 397 +/- 31 x 10(9)/L (P < .0001). vWF, ATIII, thrombin:anti-thrombin complex (T:AT) and prothrombin fragment F1.2 levels were not different from a control group (N = 2). The data presented describe chemotherapy-induced HUS with typical clinical and laboratory features which may provide an animal model for the study of this important syndrome.

Animals↗
PubMed1995

Leucocyte-endothelial cell adhesion in a model of intestinal inflammation.

Leucocyte-endothelial cell adhesion is modulated by a variety of adhesion glycoprotein expressed on the surface of leucocytes and endothelial cells. Although in vitro studies show that these adhesion molecules mediate the decrease in leucocyte rolling velocity and the increase in leucocyte adherence and emigration associated with inflammation, there are few in vivo data to support this hypothesis. The aim of this study was to assess the role of leucocyte (CD11b/CD18) and endothelial cell (P- and E-selectin) adhesion molecules in mediating the leucocyte-endothelial cell adhesion elicited in rat mesenteric venules during a model of longlasting intestinal inflammation. Indomethacin was injected 48 and 24 hours before the experiment. The mesenteric microcirculation was observed by intravital microscopy in animals treated with monoclonal antibodies (MAb) directed against either P-selectin, E-selectin, or CD11b/CD18. Leucocyte rolling velocity, and the number of adherent and emigrated leucocytes as well as vessel diameter and erythrocyte velocity were monitored in roughly 30 micron diameter postcapillary venules. Indomethacin treatment resulted in mucosal ulceration and granulocyte infiltration, and a corresponding inflammatory response in the mesentery, which was characterised by an increase in the number of adherent (eightfold) and emigrated (sixfold) leucocytes and a reduction (80%) in leucocyte rolling velocity. The indomethacin induced leucocyte-endothelial cell adhesion in mesenteric venules was significantly reduced by treatment with MAbs against either CD11b/CD18 or E-selectin, but not by the P-selectin MAb. These results suggest that both leukocyte (CD11b/CD18) and endothelial cell (E-selectin) adhesion molecules contribute to the granulocyte accumulation in a chronic model of intestinal inflammation.

Animals↗
PubMed1995

Bronchial dehiscence in lung transplantation: CT evaluation.

PURPOSE: To determine the signs of bronchial dehiscence on computed tomographic (CT) scans in a select subset of lung transplant recipients. MATERIALS AND METHODS: In 23 patients who underwent single or bilateral sequential lung transplantations, CT scans were obtained for suspected or known diagnosis of bronchial dehiscence. Dehiscence was identified at bronchoscopy in 17 of the 23 patients. In four patients, the dehiscence was bilateral, resulting in 21 anastomotic dehiscences. RESULTS: CT allowed identification of a bronchial defect in 100% of the bronchoscopically proved dehiscences but only one (5%) of the 18 bronchoscopically proved intact anastomoses. CT also demonstrated extraluminal air in 100% of the bronchoscopically proved dehiscences. Only a very small amount of extraluminal air (without associated bronchial defect) was identified on CT scans in the early postoperative period in four additional patients with bronchoscopically proved intact anastomoses. CONCLUSION: CT is an easily performed and well-tolerated technique that has a high degree of sensitivity and specificity for depicting bronchial dehiscence.

Adolescent↗
PubMed1995

Lung transplant edema: chest radiography after lung transplantation--the first 10 days.

PURPOSE: To determine the imaging spectrum and clinical correlates of lung transplant edema within the first 10 days after lung transplantation. MATERIALS AND METHODS: The study group consisted of 105 consecutive lung transplant recipients. Lung infiltrates on chest radiographs were scored and characterized. Findings that satisfied the accepted description of reperfusion edema were identified. Lung ischemia times and the clinical or biopsy diagnosis of acute rejection were correlated with radiographic findings. RESULTS: Lung infiltrates compatible with reperfusion edema were seen in 97% of transplanted lungs without a demonstrable correlation with lung ischemia times. Lung scores between groups of patients treated and not treated for acute rejection were not statistically significantly different. CONCLUSION: The spectrum of findings attributable to lung transplantation or reperfusion edema is variable and diminishes the use of chest radiography as an early postoperative modality for monitoring acute rejection.

Adult↗
PubMed1995

Mechanisms of oxidized chylomicron-induced leukocyte-endothelial cell adhesion.

The objectives of this study were to determine whether oxidatively modified chylomicrons (oxCM) can elicit leukocyte-endothelial cell adhesion in the mesenteric microcirculation and to define the mechanisms underlying the oxCM-induced adhesive interactions. Oxidation of chylomicrons (CM) with the peroxyl radical generator 2,2'-azobis(2-amidinopropane)hydrochloride was associated with the formation of thiobarbituric acid-reactive substances and lipid hydroperoxides. Leukocyte rolling, adherence, and emigration as well as erythrocyte velocity were monitored in rat mesenteric venules infused with either native CM or oxCM. oxCM, but not native CM, increased the numbers of rolling, adherent, and emigrated leukocytes. The oxCM-induced leukocyte adherence was significantly blunted by pretreating the animals with either superoxide dismutase, a platelet-activating factor (PAF) receptor antagonist, or monoclonal antibodies (MAb) directed against either CD11/CD18 or intracellular adhesion molecule 1. A MAb against P-selectin reduced oxCM-induced leukocyte rolling but not adherence. These findings suggest that the increased plasma oxCM levels associated with ingestion of oxidized lipids may promote leukocyte adhesion through a mechanism that involves the superoxide anion, PAF, and adhesion receptors on leukocytes and endothelial cells.

Animals↗
PubMed1995

Regional differences in constitutive and induced ICAM-1 expression in vivo.

The aim of the present study was to characterize and compare the expression of intercellular adhesion molecule 1 (ICAM-1) on unstimulated and endotoxin-challenged endothelial cells in different tissues of the rat. ICAM-1 expression was measured using 125I-labeled anti-rat ICAM-1 monoclonal antibody (MAb) and an isotype-matched control MAb labeled with 131I (to correct for nonspecific accumulation of the binding MAb). Under baseline conditions, ICAM-1 MAb binding was observed in all organs. The binding of 125I-ICAM-1 MAb varied widely among organs, with the largest accumulation (per g tissue) in the lung, followed by heart (1/30th of lung activity), splanchnic organs (1/50th of lung activity), thymus (1/100th of lung activity), testes (1/300th of lung activity), and skeletal muscle (1/800th of lung activity). Endotoxin induced an increase in ICAM-1 MAb binding in all organs except the spleen. Endotoxin-induced upregulation of ICAM-1 was greatest in heart and skeletal muscle (5- to 10-fold), whereas the remaining organs exhibited a two- to fourfold increase in ICAM-1 expression. Maximal upregulation of ICAM-1 occurred at 9-12 h after endotoxin administration. A dose-dependent increase in ICAM-1 expression was elicited by 0.1-10 microgram/kg, with higher doses (up to 5 mg/kg) producing no further increment. Induction of ICAM-1 mRNA after endotoxin was observed in all tissues examined (lung, heart, intestine), peaked at 3 h, and then rapidly returned to control levels. These findings indicate that ICAM-1 is constitutively expressed on vascular endothelium in all organs of the rat and that there are significant regional differences in the magnitude and time course of endotoxin-induced ICAM-1 expression.

Animals↗
PubMed1995

Sneddon's syndrome with granulomatous leptomeningeal infiltration.

BACKGROUND: There is limited neuropathologic information available from cases of Sneddon's syndrome in which strokes are associated with livedo reticularis. Pathogenesis of the syndrome is controversial, although current opinion favors a coagulopathy, often with antiphospholipid antibodies. We describe a case lacking antiphospholipid antibodies but having a granulomatous infiltration of the leptomeninges. CASE DESCRIPTION: The patient presented at age 29 with stroke, livedo reticularis, essential hypertension, and Raynaud's phenomenon. Assessment uncovered no underlying disease, including absent antiphospholipid antibodies. A leptomeningeal biopsy showed granulomatous infiltration. CONCLUSIONS: The findings suggest that an inflammatory process plays a role in at least some cases of Sneddon's syndrome.

Adult↗
PubMed1995

Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat.

BACKGROUND AND PURPOSE: Postischemic cerebral inflammation may contribute to ischemic cell damage. Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on endothelial cells that facilitates leukocyte adhesion. We investigated the effect of administration of an anti-ICAM-1 antibody (1A29) on ischemic cell damage after transient (2-hour) or permanent middle cerebral artery (MCA) occlusion in the Wistar rat. METHODS: Groups studied were as follows: (1) transient MCA occlusion: rats were subjected to 2 hours of MCA occlusion, and after 1 hour of reperfusion they were treated with 1A29 (n = 11) or an isotype control antibody (n = 9); and (2) permanent MCA occlusion: rats were treated with 1A29 (n = 9) or an isotype control antibody (n = 7) 2 hours after onset of MCA occlusion. All animals were killed 1 week after onset of ischemia. Brain sections were stained with hematoxylin and eosin for histological evaluation. RESULTS: Significant reductions (P < .05) in both volume (44%) of the ischemic lesion and weight loss were found in animals subjected to transient MCA occlusion and treated with 1A29 compared with vehicle-treated animals. In contrast, in animals subjected to permanent MCA occlusion the lesion and the temporal profile of body weight were not altered by 1A29 administration. CONCLUSIONS: Ischemic cell damage is promoted by postischemic inflammatory response after 2 hours of transient MCA occlusion, and ischemic cell damage is reduced by administration of an anti-ICAM-1 antibody during reperfusion.

Animals↗
PubMed1995

Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses.

BACKGROUND: Intracranial hemorrhage is the most feared and lethal complication of oral anticoagulation. We review the frequency, predictors, and prognosis of this most common neurological complication of oral anticoagulation. SUMMARY OF REVIEW: Anticoagulation to conventional intensities increases the risk of intracranial hemorrhage 7- to 10-fold, to an absolute rate of nearly 1%/y for many stroke-prone patients. Most (70%) anticoagulant-related intracranial hemorrhages are intracerebral hematomas (approximately 60% are fatal); the bulk of the remainder are subdural hematomas. Predictors of anticoagulant-related intracerebral hematoma are advanced patient age, prior ischemic stroke, hypertension, and intensity of anticoagulation. In approximately half of anticoagulated patients with intracerebral hematoma the bleeding evolves slowly over 12 to 24 hours, and emergency reversal of anticoagulation is crucial. CONCLUSION: Both patient factors and anticoagulation intensity importantly influence the rate of anticoagulation-related intracranial hemorrhage. Patient-related risk factors for this complication overlap with those for ischemic stroke. The risk/benefit equation of anticoagulation for elderly, stroke-prone patients is complex and differs from that for younger patients. The absolute rate reduction (not the relative risk reduction) of ischemic stroke by anticoagulation is the critical issue and must offset accentuation of often lethal brain hemorrhage.

Age Factors↗
PubMed1995

A nursing survey to determine the characteristics of medication administration through enteral feeding catheters.

A statewide survey was designed to develop a better understanding of the current practices and problems encountered with medication administration through enteral feeding catheters (EFCs). The sample of 223 registered nurses and licensed practical nurses estimated that a median of 10% of patients received medications through an EFC. EFC obstruction was estimated to have occurred a median of 1.5 times per week, with 50% of obstructions estimated to be due to medication administration. Nine of 14 specific medications reported as "most frequently contributing to" feeding catheter obstruction available in liquid form, yet tablets were crushed and given. When nurses perceived the pharmacy department as helping them insure that liquid dosage form was used, there was greater use of liquid forms, less use of crushed forms, and less medication-associated catheter obstruction. In this sample, the majority of nurses did not follow consistently the few recommendations available.

Drug Therapy↗
PubMed1995

Tarentaise and Hereford breed effects on cow and calf traits and estimates of individual heterosis.

Preweaning and weaning records on 457 calves and weights and milk production of their dams were used to evaluate breed of dam effects, breed of sire effects, and individual heterosis effects. Hereford and Tarentaise dams were mated to Hereford and Tarentaise sires and calves were born from 1987 to 1991. Calf traits were birth weight, proportion calving difficulty, weaning weight, weaning height, weaning weight:height ratio, and condition score at weaning. Cow traits were milk production four weights during the year, weight changes, height at weaning, condition score, ratio of calf weight:cow weight, proportion calved and weaned, and calf weaning weight per cow exposed to breeding. Breed of sire was nonsignificant for all traits except calf hip height, but breed of dam was significant for calf weaning weight and condition score, late milk production, change in milk production, and the cow traits of all weights, condition score, weight:height ratio, and ratio of calf weight:cow weight. Least squares means for Hereford and Tarentaise dams, respectively, were 216 and 236 kg for calf weaning weight, 6.2 and 9.3 kg for late milk production, 559 and 507 kg for cow weight at weaning, 6.0 and 4.9 for cow condition score, and .39 and .47 for ratio of calf weight at weaning:cow weight at weaning. Heterosis was significant for birth weight (1.05 kg, 3%, P = .01), weaning weight (11.0 kg, 5%, P = .01), and condition score (.13, 2%, P = .06). Thus, Hereford dams weighted more and had higher levels of condition, whereas Tarentaise dams produced more milk late in lactation and weaned heavier calves.

Analysis of Variance↗