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Biomedical subjects

D C Anderson

Publications and source records attributed to D C Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Postinoculation PMPA treatment, but not preinoculation immunomodulatory therapy, protects against development of acute disease induced by the unique simian immunodeficiency virus SIVsmmPBj.

The fatal disease induced by SIVsmmPBj4 clinically resembles endotoxic shock, with the development of severe gastrointestinal disease. While the exact mechanism of disease induction has not been fully elucidated, aspects of virus biology suggest that immune activation contributes to pathogenesis. These biological characteristics include induction of peripheral blood mononuclear cell (PBMC) proliferation, upregulation of activation markers and Fas ligand expression, and increased levels of apoptosis. To investigate the role of immune activation and viral replication on disease induction, animals infected with SIVsmmPBj14 were treated with one of two drugs: FK-506, a potent immunosuppressive agent, or PMPA, a potent antiretroviral agent. While PBMC proliferation was blocked in vitro with FK-506, pig-tailed macaques treated preinoculation with FK-506 were not protected from acutely lethal disease. However, these animals did show some evidence of modulation of immune activation, including reduced levels of CD25 antigen and FasL expression, as well as lower tissue viral loads. In contrast, macaques treated postinoculation with PMPA were completely protected from the development of acutely lethal disease. Treatment with PMPA beginning as late as 5 days postinfection was able to prevent the PBj syndrome. Plasma and cellular viral loads in PMPA-treated animals were significantly lower than those in untreated controls. Although PMPA-treated animals showed acute lymphopenia due to SIVsmmPBj14 infection, cell subset levels subsequently recovered and returned to normal. Based upon subsequent CD4(+) cell counts, the results suggest that very early treatment following retroviral infection can have a significant effect on modifying the subsequent course of disease. These results also suggest that viral replication is an important factor involved in PBJ-induced disease. These studies reinforce the idea that the SIVsmmPBj model system is useful for therapy and vaccine testing.

Animals↗
PubMed1999

Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds.

BACKGROUND: Inflammatory bowel diseases (IBD) are characterised by an intense infiltration of leucocytes that is mediated by adhesion molecules expressed on the surface of activated endothelial cells. AIMS: To determine whether drugs used in the treatment of IBD, specifically dexamethasone (DEX), 5-aminosalicylic acid (5-ASA), methotrexate (MTX), and 6-mercaptopurine (6-MP), alter the expression of endothelial cell adhesion molecules (ECAMs). METHODS: The expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular CAM 1 (VCAM-1) in different vascular beds of C57Bl/6J mice was measured using the dual radiolabelled monoclonal antibody technique. RESULTS: Lipopolysaccharide (LPS) elicited a profound increase in the expression of all ECAMs in the mesentery, small intestine, caecum, and distal colon. The LPS induced increase in CAM expression was not significantly affected by prior treatment with either MTX or 6-MP. However, pretreatment with either DEX or 5-ASA significantly attenuated LPS induced increases in expression of P- and E-selectin, and VCAM-1 in the majority of tissues evaluated. DEX also blunted the LPS induced increase in ICAM-1 expression in the caecum and distal colon. DEX, but not 5-ASA, largely abolished the rise in plasma tumour necrosis factor alpha elicited by LPS. CONCLUSIONS: These findings suggest that DEX and 5-ASA may exert their beneficial therapeutic action in IBD, at least in part, by inhibiting the expression of ECAMs which mediate leucocyte adhesion and transmigration in the microvasculature.

Animals↗
PubMed1999

Indomethacin induced gastropathy in CD18, intercellular adhesion molecule 1, or P-selectin deficient mice.

BACKGROUND: Neutrophil-endothelial cell interactions are thought to play a critical role in the pathophysiology of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy. AIMS: To optimise a mouse model of NSAID induced gastropathy and to evaluate the importance of adhesion molecules using adhesion molecule deficient mice. METHODS: Gastropathy was induced in C57BL/6 mice or their adhesion molecule deficient counterparts via oral administration of indomethacin (20 mg/kg). Lesion scores, mucosal permeability, and histopathology were used to assess gastric mucosal injury. RESULTS: Intragastric administration of indomethacin induced linear haemorrhagic mucosal lesions, primarily in the corpus of the stomach that were first observed at six hours. These lesions continued to develop over the next six hours with maximal lesion scores and mucosal permeabilities at 12 hours. When indomethacin was administered to mice deficient in CD18, intercellular adhesion molecule 1 (ICAM-1), or P-selectin, there were significant decreases in lesion scores compared with their C57BL/6 controls. In addition, mucosal permeabilities were found to be significantly lower in CD18 or ICAM-1 deficient mice observed at 12 hours. CONCLUSION: Certain leucocyte and endothelial cell adhesion molecules are important determinants for full expression of indomethacin induced gastropathy. It is proposed that this modification of the mouse model may be useful for the investigation of other pathophysiological mechanisms of NSAID induced gastropathy.

Animals↗
PubMed1999

Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor.

Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a negative feedback mechanism to modulate peripheral inflammatory responses. We investigated whether central CRF attenuates endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during endotoxemia in rats and determined its mechanisms of action. As measured by intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was associated with upregulation of endothelial ICAM-1 expression. Intracisternal injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte recruitment. Intravenous injection of the specific CRF receptor antagonist astressin did not modify leukocyte-endothelial cell interactions induced by a high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade of endogenous glucocorticoids but not alpha-melanocyte-stimulating hormone (alpha-MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial cell interactions during endotoxemia. In conclusion, cerebral CRF blunts endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes during endotoxemia. The anti-inflammatory effects of CRF are mediated by adrenocortical activation and additional mechanisms independent of alpha-MSH.

Adrenalectomy↗
PubMed1998

P-selectin antibody reduces hemorrhage and infarct volume resulting from MCA occlusion in the rat.

We investigated the effect of an anti-P-selectin antibody (RMP-1) on ischemic cell damage and hemorrhage after transient middle cerebral artery occlusion (MCAo) in the rat. Animals were divided into four groups: (1) antibody (Ab) 1 group (n = 14) RMP-1 (2 mg/kg) was administered to rats 1 h prior to induction of 2 h of MCA occlusion; (2) control-vehicle group Ab2 (n = 12) rats were subjected to the same experimental protocol, except that an isotype-matched control antibody was administered; (3) Abl group (n = 10) rats were subjected to 2 h of MCA occlusion and RMP-1 (2 mg/kg) was administered upon reperfusion; (4) control-vehicle group Ab2 (n = 10) rats were subjected to the same experimental protocol, except that an isotype-matched control antibody was administered. Animals were sacrificed 48 h after onset of the MCAo for histological evaluation of infarction and hemorrhage, and to quantify number of neutrophils. The lesion volume was significantly smaller only in pretreated rats (RMP-1 group, 18.7+/-3.1%) compared to the vehicle-treated (31.6+/-2.6%) group (P<0.01). Total area of hemorrhage (5.94 x 10(3)+/-2.86 x 10(3) microm2) in the pre MCAo RMP-1 treated group animals was significantly reduced (P<0.02) compared to the vehicle group (6.1 x 10(4)+/-3.42 x 10(4) microm2), respectively. Our data demonstrate that administration of the anti-P-selectin antibody before transient focal cerebral ischemia in rat brain reduces ischemic cell damage and petechial hemorrhage.

Animals↗
PubMed1998

Detection of programmed cell death using fluorescence energy transfer.

Fluorescence energy transfer (FRET) can be generated when green fluorescent protein (GFP) and blue fluorescent protein (BFP) are covalently linked together by a short peptide. Cleavage of this linkage by protease completely eliminates FRET effect. Caspase-3 (CPP32) is an important cellular protease activated during programmed cell death. An 18 amino acid peptide containing CPP32 recognition sequence, DEVD, was used to link GFP and BFP together. CPP32 activation can be monitored by FRET assay during the apoptosis process.

Amino Acid Sequence↗
PubMed1998

Primary and secondary stroke prevention in atrial fibrillation.

Atrial fibrillation, with a prevalence of 6% in those over 65 years, is responsible for 75-100 x 10(3) strokes each year in the United States. These strokes are more severe and have less favorable long-term prognosis than strokes due to other mechanisms. Modern trials show that warfarin reduces stroke rate by about 70% and aspirin by about 20%. Although average annual stroke rate among atrial fibrillation patients is about 4-5%, considerable risk heterogeneity exists. The goal of risk stratification is to differentiate patients with risk high enough to justify warfarin from those whose risk is so low that they are better off on aspirin or even no antithrombotic therapy. Ideal antithrombotic therapy is individualized, balancing risks of thromboembolism versus bleeding on antithrombotic therapy, and considering patient preferences. Although the science has advanced significantly in the past decade, application has lagged behind. Much benefit will potentially accrue from broad education efforts.

Atrial Fibrillation↗
PubMed1998

Isolation and characterization of a neuropathogenic simian immunodeficiency virus derived from a sooty mangabey.

Transfusion of blood from a simian immunodeficiency virus (SIV)- and simian T-cell lymphotropic virus-infected sooty mangabey (designated FGb) to rhesus and pig-tailed macaques resulted in the development of neurologic disease in addition to AIDS. To investigate the role of SIV in neurologic disease, virus was isolated from a lymph node of a pig-tailed macaque (designated PGm) and the cerebrospinal fluid of a rhesus macaque (designated ROn2) and passaged to additional macaques. SIV-related neuropathogenic effects were observed in 100% of the pig-tailed macaques inoculated with either virus. Lesions in these animals included extensive formation of SIV RNA-positive giant cells in the brain parenchyma and meninges. Based upon morphology, the majority of infected cells in both lymphoid and brain tissue appeared to be of macrophage lineage. The virus isolates replicated very well in pig-tailed and rhesus macaque peripheral blood mononuclear cells (PBMC) with rapid kinetics. Differential replicative abilities were observed in both PBMC and macrophage populations, with viruses growing to higher titers in pig-tailed macaque cells than in rhesus macaque cells. An infectious molecular clone of virus derived from the isolate from macaque PGm (PGm5.3) was generated and was shown to have in vitro replication characteristics similar to those of the uncloned virus stock. While molecular analyses of this virus revealed its similarity to SIV isolates from sooty mangabeys, significant amino acid differences in Env and Nef were observed. This virus should provide an excellent system for investigating the mechanism of lentivirus-induced neurologic disease.

AIDS Dementia Complex↗
PubMed1998

Nitric oxide modulates gut ischemia-reperfusion-induced P-selectin expression in murine liver.

Reperfusion of ischemic intestine is associated with P-selectin-dependent adhesion of leukocytes in the liver microcirculation. The objective of this study was to define the contribution of nitric oxide (NO) to the enhanced P-selectin expression and increased leukocyte rolling elicited by gut ischemia-reperfusion (I/R). Leukocyte rolling (monitored by intravital microscopy) in the terminal hepatic venules (THV) and P-selectin expression (measured using the dual-radiolabeled monoclonal antibody technique) were determined in mice after 15 min of superior mesenteric artery occlusion and 30 min of reperfusion. After 30 min of reperfusion, P-selectin expression was significantly increased in the liver, intestine, and lung, with a corresponding increase in the number of rolling leukocytes (in THV). The NO synthase inhibitor NG-monomethyl-L-arginine exaggerated the gut I/R-induced increases in both rolling leukocytes and P-selectin expression (in liver and intestine), responses that were not detected with coadministration of L-arginine or in P-selectin-deficient mice. The NO donor diethylenetriamine/NO and L-arginine were both effective in attenuating the gut I/R-induced increases in rolling leukocytes (in THV) and P-selectin expression (in liver, intestine, and lung). These findings indicate that NO modulates gut I/R-induced recruitment of rolling leukocytes in THV via an action on P-selectin expression.

Animals↗
PubMed1998

Mechanisms responsible for enhanced inflammatory response to ischemia-reperfusion in diabetes.

The objective of the present study was to assess the role of lipid mediators and adhesion molecule expression in exacerbation of ischemia-reperfusion-induced inflammatory response in diabetes. Leukocyte-endothelial cell interactions were studied in mesenteric venules by intravital microscopy. Endothelial expression of intercellular adhesion molecule (ICAM)-1 was measured by the double-radiolabeled monoclonal antibody technique, and beta2-integrin expression was measured by flow cytometry. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration in diabetic rats that were prevented by a platelet-activating factor (PAF)-receptor antagonist or a leukotriene synthesis inhibitor. Leukotriene B4 (LTB4) superfusion induced similar leukocyte recruitment in diabetic and control rats, whereas PAF elicited larger increases in diabetic rats. CD11a, but not CD11b, expression was higher in leukocytes from diabetic animals. Endothelial ICAM-1 in mesentery and in intestine did not differ between diabetic and control rats. These results indicate that diabetes is associated with an enhanced response to ischemia-reperfusion that depends on both PAF and leukotrienes. An increased sensitivity to PAF, along with an increased CD11a expression, may account for the exaggerated inflammatory response to ischemia-reperfusion in diabetes.

Animals↗
PubMed1998

Coronary endothelial P-selectin in pathogenesis of myocardial ischemia-reperfusion injury.

We investigated in vivo coronary P-selectin expression and its pathophysiological consequences in a murine model of myocardial ischemia-reperfusion (MI/R) using wild-type and P-selectin deficient (-/-) mice. Coronary P-selectin expression [microgram monoclonal antibody (MAb)/g tissue] was measured using a radiolabeled MAb method after 30 min of myocardial ischemia and 20 min of reperfusion. P-selectin expression in wild-type mice was significantly (P < 0. 01) elevated in the ischemic zone (0.070 +/- 0.010) compared with the nonischemic zone (0.037 +/- 0.008). Myocardial P-selectin expression was nearly undetectable in P-selectin -/- mice after MI/R. Furthermore, myocardial infarct size (% of area at risk) after 30 min of myocardial ischemia and 120 min of reperfusion was 42.5 +/- 4. 4 in wild-type mice and 24.4 +/- 4.0 in P-selectin -/- mice (P < 0. 05). In additional experiments of prolonged myocardial ischemia (60 min) and reperfusion (120 min), myocardial infarct size was similar in P-selectin -/- mice and wild-type mice. Our results clearly demonstrate the involvement of coronary P-selectin in the development of myocardial infarction after MI/R.

Animals↗
PubMed1998

Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice.

Previous studies have demonstrated that circulating neutrophils (PMNs) contribute to the pathophysiology of myocardial ischemia-reperfusion (MI/R) injury. PMN-endothelial cell interactions are highly regulated by adhesive interactions between PMN CD11/CD18 and coronary endothelial cell intercellular adhesion molecule-1 (ICAM-1). We investigated the effects of MI/R in wild-type, CD18-, and ICAM-1-deficient (-/-) mice. Wild-type (n = 6), CD18 -/- (n = 6), and ICAM-1 -/- (n = 6) mice were subjected to 30 min of myocardial ischemia and 120 min of reperfusion to determine the extent of PMN infiltration and myocardial cell necrosis. Myocardial infarction (% of the area at risk) was 45.1 +/- 5.9 in wild-type mouse hearts. In contrast, the extent of myocardial infarction was significantly (P < 0.05) reduced in the CD18 (19.3 +/- 5.1%)- and ICAM-1 (17.9 +/- 3.2%)-deficient mice. Similarly, PMN infiltration into the ischemic-reperfused myocardium was attenuated by 54% in the CD18 -/- mice and by 32% in ICAM-1 -/- mice compared with wild-type hearts. Deficiency in either CD18 or ICAM-1 expression results in a marked reduction in PMN accumulation and myocardial necrosis after acute MI/R.

Animals↗
PubMed1998

Chest radiography as a predictor of outcome in posttransplantation lymphoproliferative disorder in lung allograft recipients.

OBJECTIVE: The radiologic findings of posttransplantation lymphoproliferative disorder in lung transplant recipients have received little attention compared with the findings for recipients of other solid organ transplants. We describe the intrathoracic findings and explore whether the radiographic presentation can predict outcome. MATERIALS AND METHODS: Twenty-six patients (mean age, 32 years; range, 2-63 years; 18 female, eight male) with histologically proven lymphoproliferative disorder were identified from 518 lung transplantation patients, a 5.0% frequency. Chest radiographs, obtained within 1 week of diagnosis, were compared with baseline posttransplantation radiographs for all 26 patients and with chest CT scans for 20 patients. RESULTS: The interval between transplantation and diagnosis ranged from 6 weeks to 7 years (mean, 16 months; median, 6 months). The thorax was involved in 18 (69%) of 26 patients. A new chest radiographic abnormality was present in all 18 patients and provided the first indication of disease in 14 (78%) of 18 patients. The most common finding was a solitary pulmonary nodule, seen in nine (50%) of 18 patients. Other findings included multiple nodules, multifocal alveolar infiltrates, and hilar and mediastinal adenopathy. CT scans detected additional nodules and lymph nodes but did not show occult disease in any case that appeared normal on radiography. Eight (89%) of nine patients with solitary pulmonary nodules at presentation were alive 1 year after diagnosis, compared with six (35%) of 17 patients with other presentations (p < .01). CONCLUSION: Thoracic manifestations are present in most lung transplant recipients with lymphoproliferative disorder. Patients with solitary nodules have a better outcome in the first year after diagnosis than do patients with other presentations.

Adolescent↗
PubMed1998

Heterosis and breed additive effects for Hereford, Tarentaise, and the reciprocal crosses for calf traits.

Records from 595 straightbred Hereford (HH), straightbred Tarentaise (TT), and reciprocal-cross (HT) females, randomly mated to HH, TT, or HT bulls, were analyzed for estimates of heterosis and breed additive effects for calf traits that included birth weight (BWT), calving difficulty (DIFF), prebreeding (PRE) and postbreeding (PST) weight, weaning weight (WWT), weaning condition score (WCS), weaning hip height (WHH), and preweaning average daily gain (ADG). The statistical model included year, age of dam, sex, regression on age at time of measurement, and regressions for the genetic effects of breed individual, breed maternal, breed grandmaternal, individual heterosis, and maternal heterosis. Breed effects were coded to reflect TT- HH differences. Age at the time of measurement, year, age of dam, and sex were significant for most traits. Individual breed effects were important (P < .05) for BWT, PRE, PST, WCS, and WHH but not for WWT, resulting in lower weights, less condition, and taller animals for TT. Maternal breed effects did not influence BWT, but they were important ( P < .05) for PRE, PST, WWT, WCS, WHH, and ADG. Grandmaternal effects were only important for BWT and ADG. Individual and maternal heterosis were important (P < .05) for most traits measured, resulting in increased calf size, weight, and body condition.

Animal Feed↗
PubMed1998

Intravenous thrombolytic therapy for acute ischemic stroke. Weighing the risks and benefits of tissue plasminogen activator.

The use of intravenous tPA within 3 hours after acute ischemic stroke has been proved to increase the number of good outcomes. However, tPA is a toxic therapy that carries a substantial risk of intracerebral hemorrhage. To decrease the risk, tPA use must be restricted to a carefully selected patient population. Treatment must be administered in an intensive care setting and directed by physicians with expertise in diagnosing and managing stroke.

Acute Disease↗
PubMed1998

Ultrastructure of atypical (teratoid) sporogonial stages of Enterocytozoon bieneusi (Microsporidia) in naturally infected rhesus monkeys (Macacca mulatta).

OBJECTIVE: To demonstrate the ultrastructural features of normal and atypical (teratoid) developmental stages of Enterocytozoon bieneusi in naturally infected rhesus monkeys (Macacca mulatta). DESIGN AND METHODS: Two rhesus monkeys with chronic simian immunodeficiency virus infection developed naturally acquired microsporidian infections. The gallbladder had a high parasite burden and was evaluated by transmission electron microscopy. The microsporidian agent was confirmed as E bieneusi by polymerase chain reaction. RESULTS: In addition to normal sporogonial plasmodia and spores of E bieneusi, abnormal teratoid structures were noted. These structures were greatly enlarged (up to 10 microm) and were surrounded by an electron-dense exospore and electron-lucent endospore typical of mature spores. Unlike mature spores, the abnormal structures contained multiple nuclei and polar tubes in varying proportions, which were reminiscent of sporogonial plasmodia. CONCLUSIONS: These teratoid structures represent aberrant sporogonial stages, a result of defective maturation in which abnormal cytokinetic replication of organelles occurs, and normal development into uninucleate sporoblasts and spores is inhibited. This leads to the development of teratoid stages having mature spore walls, but containing multiple sets of nuclei and polar tubes, unusual polyribosomal arrays and vacuoles, or persistent cleavage. The biological significance of these atypical spores is unknown, but it is evident that they develop in the absence of antimicrosporidian drugs in extraintestinal tissues from nonhuman primates. Teratoid spores of E bieneusi should not be misinterpreted as another microsporidian species or confused with other pathogenic protozoa, nor should their presence be misconstrued as evidence of antimicrosporidian drug efficacy or toxicity.

Animals↗
PubMed1998

Differential expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) in murine tissues.

OBJECTIVE: To characterize and compare the expression of PECAM-1 in unstimulated and tumor necrosis factor alpha-(TNF-alpha)-stimulated tissues of mice. METHODS: Binding and non-binding monoclonal antibodies (mAb) were radiolabeled and injected into wild-type mice and mice deficient of P-selectin, CD18, or ICAM-1. The relative accumulation of binding mAb (PECAM-1 mAb) was determined in wild-type mice following a 25 micrograms/kg i.p. injection of TNF-alpha and in mutant mice under basal conditions. RESULTS: Under unstimulated conditions, PECAM-1 was significantly expressed in all tissues examined, with no changes occurring after TNF-alpha stimulation. An equivalence of PECAM-1 expression was observed in unstimulated tissues among wild-type mice and mice that are genetically deficient in either CD18, ICAM-1, or P-selectin. The level of PECAM-1 expression in different vascular beds was highly correlated to published values of endothelial surface area. Normalization of previously published values of ICAM-1, VCAM-1, E- and P-selectin expression relative to PECAM-1 expression in the same tissues revealed a diminished organ-to-organ variability in expression of the different adhesion molecules. Estimates of adhesion molecule expression in lung and brain were most profoundly affected by normalization to PECAM-1 expression. CONCLUSIONS: These findings support the use of PECAM-1 expression in regional vascular beds as an indicator of endothelial cell surface area.

Animals↗