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Biomedical subjects

D C Anderson

Publications and source records attributed to D C Anderson.

At least 271 records · Page 15Linked to original sources
PubMed1990

Nonhuman primate models for evaluation of AIDS therapy.

Infection of macaque monkeys with simian immunodeficiency virus (SIV) has been established as an excellent animal model system for studying the pathogenesis of an HIV-like virus and for evaluating newly developed antiretroviral drugs and vaccines. Based on their genetic, antigenic, and biologic properties, the simian immunodeficiency viruses are the closest known relatives of the human AIDS viruses, and experimental infection of macaque monkeys results in a disease that is remarkably similar to human AIDS. Infected macaques show diarrhea, weight loss, hematologic abnormalities including lymphopenia and thrombocytopenia, lymphadenopathy/lymphoid hyperplasia that progresses to lymphoid depletion, immunosuppression with marked reduction in CD4+ cells and in the CD4+/CD8+ cell ratio, and opportunistic infections. A majority of such macaques die from an AIDS-like disease within one to three years of infection. An acutely lethal variant of SIV has been identified that results in death in susceptible macaques within 7-12 days of infection. Preliminary prophylactic treatment trials with AZT in macaque monkeys exposed to the acutely lethal SIV variant indicate that some protection is provided when AZT treatment is initiated within 24 hours of virus exposure. Other studies with the more chronic SIV infection model, however, failed to show any prophylactic efficacy of CS-87, AZT, D4T, or FDT.

Animals↗
PubMed1990

Transfection of cells from patients with leukocyte adhesion deficiency with an integrin beta subunit (CD18) restores lymphocyte function-associated antigen-1 expression and function.

Leukocyte adhesion deficiency (LAD) is an inherited immunodeficiency disease that is characterized by the deficient expression of the leukocyte adhesion glycoproteins lymphocyte function-associated antigen-1 (LFA-1), Mac-1, and p150,95. This loss of expression is attributed to heterogeneous defects in the common beta subunit shared by these glycoproteins. Here we demonstrate that expression of the LFA-1 alpha beta heterodimer in EBV-transformed B lymphoblastoid cells from LAD patients can be recovered after transfection with the beta subunit cDNA contained in an EBV-based vector. Four patients with differing severities of LAD comprising three distinct classes of mutations were studied. Flow cytometry analysis of stably transfected patient cells revealed near normal levels of expression of both the alpha and beta chains of LFA-1, and immunoprecipitation studies confirmed that fully processed alpha and beta chains were being expressed at the cell surface. In addition, Northern analysis of mRNA expression also demonstrated that the transfected LAD patient cells were expressing high quantities of exogenous beta subunit mRNA. Functional studies such as homotypic adhesion and adhesion to a purified counterreceptor for LFA-1, intracellular adhesion molecule-1, demonstrated that LFA-1 function had been restored in the stably transfected LAD patient cell lines. These studies unequivocally show that the defect in cells from patients with LAD is in the leukocyte integrin beta subunit.

Animals↗
PubMed1990

Cocaine-induced seizures.

We retrospectively studied 474 patients seen at Hennepin County Medical Center because of medical complications related to acute cocaine intoxication. Of the 474, 403 had no history of seizures. Seizures within 90 minutes of cocaine use was the primary diagnosis in 32 (7.9%) of the 403. The majority of seizures were single, generalized, induced by intravenous or "crack" cocaine, and not associated with any lasting neurologic deficits. Most that were focal, multiple, or induced by nasal cocaine were associated with an acute intracerebral complication or concurrent use of other drugs. Of 71 patients with a history of non-cocaine-related seizures, 12 (16.9%) presented with cocaine-induced seizures; most of these were multiple, of the same type as those in their history, and induced by even nasal cocaine. In the 44 cocaine-induced seizure patients, a pattern of habitual cocaine abuse was associated with diffuse brain atrophy on CT and diffuse slowing on EEG.

Adult↗
PubMed1990

Performance of crosses among Hereford, Angus and Simmental cattle with different levels of Simmental breeding: IV. Maternal heterosis and calf production by two-year-old dams.

The performance of 264 contemporary 2-yr-old straightbred and crossbred dams during 1978 to 1981 was studied and maternal heterosis was estimated. Dam breed groups were Hereford (HH), Angus-Hereford (AH), 25% Simmental-75% Hereford (1S3H), 50% Simmental-50% Hereford (1S1H) and 75% Simmental-25% Hereford (3S1H). Differences among dam breed groups were nonsignificant for length of gestation, calving difficulty and late milk production but were important (P less than .01) for calf weights (birth, early and late milking periods and weaning), calf average daily gains during various intervals from conception to weaning, early milk production and other calf traits at weaning (height, weight/height and visual condition score). Dam breed group means (HH, AH, 1S3H, 1S1H and 3S1H, respectively) for representative calf traits were .37, .39, .39, .42 and .42 kg/d for estimated average daily gain the last 3 mo of gestation; 33.6, 34.7, 35.7, 37.6 and 37.1 kg for birth weight; 191, 205, 209, 228 and 228 kg for weaning and 7.5, 8.4, 8.3, 9.5 and 10.0 kg for 24-h early milk production. Therefore, 2-yr-old crossbred dams raised calves that were generally larger for the preweaning gain traits than HH dams. Differences among dam breed groups were significant for traits involving reproduction; means (HH, AH, 1S3H, 1S1H and 3S1H, respectively) were .58, .92, .72, .91 and .79 for proportion calving and 105, 179, 126, 182 and 154 kg for actual calf weaning weight per cow exposed to breeding. Estimates of percentage maternal heterosis were 6.3, 12.9, 9.0 and 7.6% for calf weights at birth, 40 d, 130 d and weaning, respectively; 1.8, 5.7 and 5.7% for calf hip height, height/weight and condition score at weaning, respectively; and 43.1 and 34.6% for proportion calving and actual calf weaning weight per cow exposed to breeding. The dominance model explained most (greater than 95%) of the variation observed among dam breed group means for most traits.

Animals↗
PubMed1990

Performance of crosses among Hereford, Angus and Simmental cattle with different levels of Simmental breeding: V. Calf production, milk production and reproduction of three- to eight-year-old dams.

Measures of maternal productivity and reproduction of Hereford (HH), Angus-Hereford (AH), 25% Simmental-75% Hereford (1S3H), 50% Simmental-50% Hereford (1S1H) and 75% Simmental-25% Hereford (3S1H) dams were studied. Half of each dam breed group was bred to Tartentaise and half to Charolais sires to produce 706 calves at weaning from 930 exposures to breeding in a Montana range environment. Data were analyzed according to a model that included the fixed effects of year, dam breed group, dam age, calf sex, calf sire breed, plus appropriate two-way interactions, linear partial regression on calf birth date and random effects of sire within dam breed group (maternal grandsire of the calf) and sire within calf sire breed. Calf sex interacted with calf sire breed for several traits, but interactions were due to changes of magnitude of differences between sexes. There were no significant interactions of dam breed group with other main effects for calf growth traits, except for the interaction with calf sire breed for some calf growth traits. This interaction was due to a change in magnitude; it suggested that larger sire breeds should be matched to larger dam breeds with greater potential for milk production. The only significant interaction for traits that included reproduction of the dam was dam breed group X age of dam. Ranking of dam breed groups depended on age at measurement. Differences among dam breed groups were significant for most traits. Calf weaning weights for HH, AH, 1S3H, 1S1H and 3S1H dams were 211, 223, 227, 237 and 243 kg, respectively; calf weaning weights per cow exposed were 157, 163, 179, 189 and 169 kg; calf weaning weights per unit of dam weight were .40, .41, .43, .44 and .42, respectively. Thus, dam breed groups that weaned the largest calves were not necessarily the most productive under Montana range conditions.

Animals↗
PubMed1990

Eosinophilic meningoencephalitis due to Angiostrongylus cantonensis as the cause of death in captive non-human primates.

Fatal eosinophilic meningoencephalitis due to Angiostrongylus cantonensis is reported in captive non-human primates. A howler monkey (Alouatta caraya) at the Audubon Park and Zoological Gardens, New Orleans, LA, died 21 days after initial clinical symptoms. A white-handed gibbon (Hylobates lar) died at the Ardastra Gardens and Zoo, Nassau, Bahamas, 17 days after onset of symptoms. Both had access to free-ranging gastropods within the zoos. These are the first reported cases of natural infection by A. cantonensis in non-human primates in the western hemisphere.

Alouatta↗
PubMed1990

Humoral response to SIV/SMM infection in macaque and mangabey monkeys.

Natural infection of sooty mangabey monkeys with simian immunodeficiency virus, designated SIV/SMM, results in long-term persistent infections with little or no disease. In contrast, experimental infection of macaques with isolates of SIV/SMM induces chronic and progressive disease that terminates in an AIDS-like illness and death in most animals. To determine whether antibodies might be important in preventing the development of disease in mangabeys or progression of disease in macaques, humoral immune responses to SIV/SMM were compared in 13 macaques infected for up to 43 months and in infected and uninfected mangabeys selected at random from among a breeding colony. Total SIV/SMM-specific antibody titers, profiles of antibodies to specific viral proteins, neutralizing antibodies that inhibited infectivity of cell-free virus or syncytia formation, antibodies that inhibited reverse transcriptase activity, and antibodies to lymphocyte cell-surface antigens were assessed. The results indicated that in macaques the magnitude of the SIV/SMM-specific antibody response and progression of disease were functions of virus load. Surprisingly, asymptomatic mangabeys also had high virus loads with, on average, lower antibody titers than macaques. In both species, the presence of neutralizing antibodies or antibodies that inhibited SIV/SMM reverse transcriptase activity did not correlate with protection from clinical disease. A correlation was observed, however, between the development of disease and the presence of antibodies to an 18-kDa protein that is found on the surface of activated lymphocytes and appears to be related to histone H2B. A similar correlation has been observed in association with HIV infection in humans, suggesting that some manifestations of both human and simian AIDS may result from autoimmune reactions.

Animals↗
PubMed1990

Molecular definition of the bovine granulocytopathy syndrome: identification of deficiency of the Mac-1 (CD11b/CD18) glycoprotein.

Leukocytosis (34,600 WBC/microliter of blood) was detected in an apparently healthy 7-day-old Holstein heifer. Analysis of blood samples obtained over the next 41 days revealed chronic progressive neutrophilia, which peaked at greater than 85% neutrophils and exceeded 100,000 WBC/microliter. In vitro assessment of isolated blood neutrophils obtained from the heifer at 38 and 45 days of age revealed selected functional abnormalities. Endocytosis of immunoglobulin-opsonized Staphylococcus aureus and killing of this test organism by the calf's neutrophils were significantly diminished, as were phagocytosis-associated superoxide generation, chemiluminescence activity, and myeloperoxidase-catalyzed iodination. Diminished H2O2 elaboration by the calf's neutrophils was evident during ingestion of opsonized zymosan or on exposure to phorbol myristate acetate. Extracellular release (secretion) of elastase during ingestion of zymosan was also diminished, although total cell content of elastase was normal, compared with that of neutrophils from age-matched calves, and granular or other morphologic abnormalities of the calf's neutrophils were not evident by ultrastructural examination. Abnormalities of random migration were inconsistently detected, and normal or high degree of antibody-dependent cytotoxicity or natural killing by the calf's neutrophils was observed. Similar in vitro assessment of neutrophils obtained from the calf's dam revealed no functional abnormalities. The calf died at 48 days of age, with persistent fever and chronic diarrhea, despite administration of antibiotics. Histologic examination at necropsy revealed large numbers of intravascular neutrophils in most tissues, including massive neutrophil sequestration in spleen. However, a striking lack of extravascular neutrophils was evident in inflamed submucosa adjacent to intestinal ulcers heavily contaminated with enteric microorganisms. Bone marrow examination revealed diffuse myeloid hyperplasia, but no other abnormalities.

Animals↗
PubMed1990

SIVsmm infection of macaque and mangabey monkeys: correlation between in vivo and in vitro properties of different isolates.

Simian immunodeficiency virus from sooty mangabey monkeys (SIVsmm), a lentivirus closely related to SIV from macaques and the human immunodeficiency virus type 2 (HIV-2), is pathogenic for various species of macaques but is nonpathogenic for mangabeys. Comparison of in vivo and in vitro responses of macaques and mangabeys or their lymphocytes, respectively, to SIVsmm infection indicated that lack of disease in mangabeys apparently was not due to effective control of virus expression by the immune system because SIVsmm-infected, asymptomatic mangabeys have high viral loads. Failure of mangabeys to develop disease may be related to the fact that the prototype SIVsmm (SMM-9) replicated in, but was not cytopathic for, mangabey CD4+ cells. In contrast, replication of SMM-9 in peripheral blood mononuclear cells from pigtailed macaques resulted in specific loss of CD4+ cells and induction of an AIDS-like disease. A variant of SMM-9, designated SMM-PBj14, was identified, however, that was extremely cytopathic for mangabey CD4+ cells and also induced acute lethal disease in both macaques and mangabeys. Acute disease was associated with extensive lymphoid hyperplasia, which was correlated in vitro with induction of proliferation of PBMC in SMM-PBj14-infected cultures. Infectious molecular clones of SMM-PBj14 exhibited the same in vitro and in vivo properties as SMM-PBj14. Future analysis of chimeric viruses may lead to the identification of specific regions of the viral genome that influence the various in vivo and in vitro properties of these SIVsmm isolates.

Animals↗
PubMed1990

A psychometric evaluation of adult patients with type 1 (insulin-dependent) diabetes mellitus: prevalence of psychological dysfunction and relationship to demographic variables, metabolic control and complications.

The relationship between psychosocial traits and glycaemic control and complications was examined in 130 adults (83 men, 47 women) with insulin-dependent diabetes mellitus. Abnormal depression ratings were observed in more women (19.1%) than men (12.0%), p less than 0.01, whilst obsessive symptoms were recorded more frequently in men (41.0 v 21.3%, p less than 0.01). Abnormal anxiety ratings were present in roughly 8-13% of men and women, although a notably low feeling of insecurity rating was observed more frequently in men (56.5%) than in women (38.3% of cases), p less than 0.05. Psychological scores were related to age, employment status and social class, but not to duration of diabetes or glycaemic control. The anxiety, depression and obsessive ratings correlated with one another (rs range 0.24-0.62, all p less than 0.001). Higher anxiety and depression ratings or overt psychological dysfunction was recorded in patients with neuropathic symptoms and signs, impotence, macrovascular disease or proliferative retinopathy. It is concluded that the presence of diabetic complications and adverse social circumstances are more relevant to psychological status than glycaemic control.

Adolescent↗
PubMed1990

Comparison of antioxidant and nonantioxidant lipoxygenase inhibitors on neutrophil function. Implications for pathogenesis of myocardial reperfusion injury.

The activation and accumulation of leukocytes during inflammatory processes such as that initiated by myocardial ischemia and reflow appear to be major determinants of irreversible tissue injury. Myocardial salvage by dual cyclooxygenase/lipoxygenase inhibitors and selective 5-lipoxygenase inhibitors has suggested a role for lipoxygenase (LOX) products, such as the potent chemotactic factor leukotriene B4, in ischemia-reflow injury. However, many LOX inhibitors are antioxidants and several have been shown to directly inhibit neutrophil function in vitro, thereby questioning the role of LOX products in reperfusion injury. To clarify further the protective mechanism of lipoxygenase inhibitors, we have examined the effects of two nonantioxidant inhibitors, SK&F 86002 and REV-5901, on human neutrophil activation and function in vitro. The antioxidant LOX inhibitor nordihydroguiaretic acid, which served as a positive control, exhibited a concentration-dependent inhibition of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and recombinant C5a-induced neutrophil bipolarization, fMLP-induced upregulation of the adherence glycoprotein Mac-1 (CD11b/CD18), fMLP-induced aggregation and neutrophil adherence to and migration through interleukin-1-stimulated human endothelial monolayers. In contrast, neither SK&F 86002 nor REV-5901 (in concentrations up to 50 microM) had any effect on these functions, nor did they inhibit neutrophil oxidative metabolism (phorbol myristate acetate-induced chemiluminescence). Inasmuch as both of these agents have been observed to reduce myocardial ischemia-reflow injury in vivo, their failure to directly inhibit neutrophil function further supports an important role for chemotactic LOX products in the pathogenesis of reperfusion injury.

Antigens, Differentiation↗
PubMed1990

Lymphocyte transformation in elderly non-insulin-dependent diabetics before and after improved glycaemic control.

Mitogen-induced lymphocyte transformation was examined in 23 elderly patients with poorly controlled Type II diabetes before and after achieving improved glycaemic control with sulphonylureas and compared with 11 healthy controls of similar age. No difference between groups was seen after incubation of lymphocytes with phytohaemagglutinin (PHA). Lymphocyte transformation after 10 micrograms/ml concanavalin A (con A) was significantly greater in diabetic patients after improved control and when compared to healthy controls (p less than 0.025). The response to 5 micrograms/ml and 10 micrograms/ml pokeweed mitogen (PWM) was greatest in diabetic patients after effective metabolic control.

Aged↗
PubMed1990

Progress report of the Stroke Prevention in Atrial Fibrillation Study.

The Stroke Prevention in Atrial Fibrillation Study recently found and reported (SPAF Investigators, N Engl J Med, 1990;322:863-868) a beneficial effect of both warfarin and aspirin compared with placebo in the primary prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Among warfarin-eligible patients, the event rates were 1.6%/yr for those receiving active antithrombotic therapy (warfarin or aspirin) and 8.3%/yr for those receiving placebo (p less than 0.00005) (risk reduction 81%, 95% confidence interval 56-91). Ironically, we did not find a beneficial effect of aspirin in warfarin-ineligible patients. On the basis of these results, the study has been reshaped to directly compare these two antithrombotic agents. Insight into the apparent aspirin unresponsiveness noted in some patients also is being sought. Interpretation of the preliminary results and the reshaping of the study have been made more complex by the continued blinding of the investigators to certain portions of the data. Presented is an account of the study from its inception through its recent redesign.

Aspirin↗
PubMed1990

Epidemiologic features of asymptomatic cerebral infarction in patients with nonvalvular atrial fibrillation.

We performed unenhanced computed tomographic scans on 141 asymptomatic patients with nonvalvular atrial fibrillation. Thirty-six patients (26%) had hypodense areas consistent with cerebral infarction. The majority of these were small deep infarcts, seen in 29 patients (21%), but 13 patients (9%) had cortical or large deep infarctions. Twelve patients had more than one infarct on computed tomographic scan. Increasing age and increased left atrial diameter were the only clinical features associated with asymptomatic infarction. Patients older than 65 years with a left atrial diameter greater than 5.0 cm (n = 23) had a 52% prevalence of asymptomatic infarction. Patients younger than 65 years with a left atrial diameter less than 5.0 cm (n = 38) had an 11% prevalence of silent infarction. Patients with only one of these risk factors (n = 72) had a 24% prevalence of silent infarction. Infarction was more common in those with chronic (34%) as opposed to intermittent (22%) nonvalvular atrial fibrillation, but this difference was not significant. Hypertension, diabetes, duration of atrial fibrillation, congestive heart failure, history of myocardial infarction, and echocardiographic evidence of left ventricular dysfunction were not associated with asymptomatic infarction. A history of hypertension was present in only 35% of our patients with small-deep asymptomatic infarction, similar to the percentage in patients without stroke. Asymptomatic cerebral infarction is common in nonvalvular atrial fibrillation. The association with enlarged left atria and the lack of correlation with major cerebrovascular risk factors suggests a cardioembolic mechanism. Further study is needed to determine the functional and prognostic significance of these strokes.

Aged↗
PubMed1990

Accessory lateral rectus orbital geometry in normal and naturally strabismic monkeys.

We conducted anatomic dissections of macaque monkey orbits and made a quantitative assessment of the orbital geometry of the accessory lateral rectus muscle. Our results show that the expected effect of this muscle on rotations of the globe is to produce elevation and abduction. The abducting component could counteract nasal drifts, and thus our findings provide support for the hypothesis that this muscle could render monkeys resistant to the development of esodeviations. Dissections of the orbits from two naturally esotropic monkeys also are consistent with this hypothesis. The accessory lateral rectus muscle was absent in one of them and abnormally small in the other. Humans do not have an accessory lateral rectus muscle, and we speculate that the high prevalence of esodeviations in humans may be related to an evolutionary loss of this muscle system.

Animals↗
PubMed1989

Suppression of human lymphocyte chemotaxis and transendothelial migration by anti-LFA-1 antibody.

The role of lymphocyte function-associated antigen 1 (LFA-1) in human T cell chemotaxis was investigated by using mAb specific to the beta-chain (TS1/18) (CD18) and alpha-chain (TS1/22) (CD11a) of LFA-1. T cell chemotaxis in response to IL-2 and to lymphocyte chemotactic factor (LCF) was markedly suppressed by the addition of TS1/18. TS1/22 was a less effective inhibitor than TS1/18 with only LCF stimulated responses showing significant inhibition when compared in seven different T cell preparations. Neither TS1/18 nor TS1/22 antibody inhibited random T cell migration. Control mAb to CD4 T cells failed to inhibit T cell random migration or chemotaxis. Additional studies to evaluate the adherence and migration of T cells through IL-1-stimulated human umbilical vein endothelial cell (HUVEC) monolayers showed that both TS1/22 and TS1/18 suppressed T cell migration through HUVEC, but failed to inhibit adherence of T cells to these cells. These studies indicate that LFA-1 plays a role in the migration of T cells through HUVEC and in the in vitro chemotactic response of T lymphocytes to IL-2 and LCF.

Animals↗