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Biomedical subjects

D J Hurley

Publications and source records attributed to D J Hurley.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of multiple immune parameters after vaccination with modified live or killed bovine viral diarrhea virus vaccines.

The development of immunity to vaccine antigen was examined using three prime/boost strategies and the progression of immune activities was evaluated over the course of 8 weeks. Calves were vaccinated and multiple immune parameters were evaluated using several methods to assess humoral or cellular immunity from the same samples in parallel. The three vaccination protocols used were a killed vaccine followed by a killed boost (killed/killed), MLV vaccine and boost (MLV/MLV), or a MLV vaccine and killed boost (MLV/killed). All the vaccines used included modified live IBR/PI3 viruses to make the bystander context as similar as possible. The Singer strain of BVDV was used as the source antigen in the killed vaccine, and the NADL strain of BVDV was used in the MLV vaccine. Controls received a vaccine containing only MLV IBR/PI3. The assessment panel measured SN titers, as well as lymphocyte proliferation, cytokine mRNA expression, intracellular cytokine production, and released IFN-gamma after in vitro stimulation with three strains of BVDV virus. MLV/MLV and MLV/killed groups developed significant SN titers to the type 1 BVDV virus strains, Singer and NADL, and low crossover titers were also seen to the type 2 strain, 890 over the evaluation period. These two groups showed significant proliferation in response to the NADL virus as compared to controls. Multiple immune assessments were conducted simultaneously to attempt to provide a broader, more in depth evaluation of immune response to these BVDV vaccination protocols. We observed that the correlation among most of the assays conducted were weak; the correlation between SN titers and cellular proliferation assays demonstrated a moderate correlation.

Animals↗
PubMed2005

Colostrum induced phenotypic and trafficking changes in maternal mononuclear cells in a peripheral blood leukocyte model for study of leukocyte transfer to the neonatal calf.

The relationship between the colostral environment and the function of leukocytes in colostrum is not clearly defined. This study examined the effects of defatted, acellular colostrum (AC) on the phenotype of peripheral blood mononuclear cells (PBMC) and their capacity to enter the circulation of neonatal calves after ingestion as a model of this relationship. Maternal PBMC were exposed to medium alone or medium supplemented with 25% AC. Expression of CD11a, CD11b, CD11c, CD43, CD49d, CD49e, and CD62L was assessed on freshly isolated and treated PBMC. Exposure to AC increased the percentage of cells expressing CD11a, CD11c and CD43, but decreased the percentage of cells expressing CD62L relative to freshly isolated PBMC. The density of expression of CD11b and CD11c was reduced, but increased for CD43 after exposure to AC relative to freshly isolated PBMC. Density of CD62L expression and percentage of cells expressing CD11a and CD43 were significantly different for cells treated with AC relative to medium alone. Further, these changes could not be attributed to occult bacterial contamination of the AC, as treatment of PBMC with LPS in the same medium yielded none of the observed changes. Maternal PBMC (treated as described) were labeled with the fluorescent tracer, PKH26-GL, and fed to neonatal calves within 6 h of birth. The circulation of these cells in the neonate was monitored by flow cytometry. We observed that: (1) cells exposed to AC, but not medium alone, entered the circulation; (2) peak trafficking occurred 12-24 h after ingestion; (3) a large fraction of labeled cells appeared in the neonatal circulation; and (4) labeled cells disappeared from circulation by 36 h after ingestion. This study indicates that exposure to the colostral environment induced phenotypic changes facilitating trafficking of colostral cells into the neonate.

Animals↗
PubMed2003

The role of acidogenic diets and beta-hydroxybutyate on lymphocyte proliferation and serum antibody response against bovine respiratory viruses in Holstein steers.

Acidogenic diets were evaluated for their effects on lymphocyte proliferation in response to Staphylococcus aureus exotoxin B (SEB), and specific lymphocyte proliferation and serum-neutralizing antibody titers to four bovine respiratory viruses in vitro. Four Holstein steer calves, with an average weight of 213 +/- 42 kg, were fed a basal (control) diet consisting of 49% forage and 51% concentrate (DM basis), with 15% CP (on a DM basis). Three additional treatment diets were used: 1) the basal diet supplemented with 700 mL/d of butylene glycol (BG) to induce ketoacidosis by increasing blood beta-hydroxybutyate (BHBA); 2) the basal diet supplemented with 1.2 +/- 0.1 kg/d of anionic salts (AS; Soychor 16.7, West Central Soy, Ralston, IA) to induce a metabolic acidosis; and 3) the basal diet with all forage replaced by finely ground corn and soybean meal blended to provide 15% CP (HG), to induce lactic acidosis. The calves were fed each diet for 21 d in a 4 x 4 Latin square design. Blood samples were collected on d 18, 19, and 20 of each 21-d period and analyzed for pH; concentrations of BHBA; in vitro lymphocyte proliferation to SEB, bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza-3 (PI-3), and bovine herpesvirus-1 (BHV-1); and titers of serum-neutralizing antibodies against the four viruses. Following treatment, the average pH of the serum samples was 7.38 for calves fed the control diet, 7.37 for the BG treatment, and 7.36 for the HG treatment, and was decreased (P < 0.05) to 7.33 for the AS treatment. All acidogenic diets decreased lymphocyte response to SEB (P < 0.05). The lymphocyte proliferative response, however, of each virus showed a different pattern of interaction with the three acidogenic diets tested. The AS diet was associated with increased lymphocyte proliferative response to BVDV and BRSV (P < 0.01) and increased serum neutralization titers to BHV-1 (P < 0.05). In calves fed the BHBA-inducing diet (BG), an increase in lymphocyte proliferation to BRSV was observed (P < 0.05). A similar relationship to blood BHBA concentration was not observed with the lymphocyte proliferation to BVDV, PI-3, or BHV-1. Titers of serum-neutralizing antibody against PI3 (P < 0.05) and BHV-1 (P < 0.01) were negatively correlated with blood pH, and titers of serum neutralizing antibodies to BHV-1 were negatively correlated to elevated circulating concentrations of BHBA (P < 0.05).

3-Hydroxybutyric Acid↗
PubMed2001

Detection of bovine herpesvirus-1 in peripheral blood mononuclear cells eight months postinfection.

Peripheral blood mononuclear cells (PBMCs) from 5 calves (3 controls and 2 vaccinates) used in a bovine herpesvirus 1 (BHV-1) vaccine study with a BHV-1 Cooper strain challenge were collected 6 months after challenge. The PBMCs from the control animals were positive by immunofluorescence for the BHV-1 glycoprotein D (gD) while the vaccinates were negative. The PBMC samples from 4 of the 5 animals were examined for BHV-1 DNA by polymerase chain reaction (PCR) and for gD immunofluorescence at 8 months after challenge. The BHV-1 DNA and viral antigen were detected in PBMC samples at 8 months postinfection, but no virus was isolated.

Animals↗
PubMed2000

A role for bovine herpesvirus 1 (BHV-1) glycoprotein E (gE) tyrosine phosphorylation in replication of BHV-1 wild-type virus but not BHV-1 gE deletion mutant virus.

Bovine herpesvirus 1 (BHV-1), an alphaherpesvirus, is a major pathogen that causes respiratory and reproductive infections. We observed tyrosine phosphorylation of a 95-kDa viral protein and dephosphorylation of 55- and 103-kDa cellular proteins during the course of BHV-1 infection. We demonstrated BHV-1 glycoprotein E (gE) to be the tyrosine phosphorylated viral protein by immunoprecipitation. Inhibition of phosphorylation of BHV-1 gE by tyrosine kinase inhibitors genistein and tyrphostin AG1478 substantially lowered the viral titer in Madin-Darby bovine kidney cells. The decrease in viral titer was directly proportional to the decrease in phosphorylation of the BHV-1 gE. Interestingly, these kinase inhibitors did not inhibit the replication of the BHV-1 gE deletion mutant virion (BHV-1gEDelta3.1). Our findings suggest that the wild-type BHV-1, with a functional gE protein, uses a different pathway of signaling events than the BHV-1 gE deletion mutant in replication. Our results indicate that the tyrosine phosphorylation of the cytoplasmic tail of BHV-1 gE is an important post-translational modification of the functional protein. An application of this study may be the use of tyrosine kinase inhibitors in controlling the BHV-1 infection.

Animals↗
PubMed1998

The effect of subclinical selenium toxicosis on pregnant beef cattle.

A field investigation conducted by the South Dakota Animal Disease Research and Diagnostic Laboratory suggested that subclinical selenium toxicosis in pregnant cows may have contributed to an outbreak of aborted/stillborn calves in a high-selenium region of South Dakota. This study was undertaken to evaluate the relationship between abortion and subclinical selenium toxicosis in the dam and to assess the effects of subclinical selenium toxicosis on the bovine immune system. Fifteen pregnant cows were fed diets containing 0.25 (control), 6.0, and 12.0 ppm selenium beginning at 80-110 days gestation. Although selenium toxicosis has been reported to cause abortion, this study failed to reproduce abortions. A single cow in the 12-ppm selenium treatment group gave birth to a weak calf, which subsequently died. This calf had myocardial lesions consistent with those described for selenium toxicosis and had hepatic selenium levels of 9.68 ppm (wet weight). Elevated dietary selenium resulted in the depression of several leukocyte function parameters in pregnant cows. A statistically significant depression in forced antibody response was identified in both selenium-supplemented groups. A significantly diminished mitogenic response to concanavalin A and pokeweed mitogen was also observed in the 12-ppm selenium group. Although a similar pattern of depression was also observed with phytohemagglutinin, differences were not significant. These findings indicate that even in the absence of clinical alkali disease, elevated selenium levels may adversely affect both pregnancy outcome and the bovine immune system.

Analysis of Variance↗
PubMed1997

Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease.

OBJECTIVE: To evaluate the therapeutic effects of selective cholinergic replacement with xanomeline tartrate, an m1 and m4 selective muscarinic receptor (mAChR) agonist in patients with probable Alzheimer disease (AD). DESIGN: A 6-month, randomized, double-blind, placebo-controlled, parallel-group trial followed by a 1-month, single-blind, placebo washout. SETTING: Outpatients at 17 centers in the United States and Canada. PARTICIPANTS: A total of 343 men and women at least 60 years of age with mild to moderate AD. INTERVENTIONS: Patients received 75, 150, or 225 mg (low, medium, and high doses) of xanomeline per day or placebo for 6 months. OUTCOME MEASURES: Scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the Clinician's Interview-Based Impression of Change (CIBIC+), the Alzheimer's Disease Symptomatology Scale (ADSS), and the Nurses' Observational Scale for Geriatric Patients (NOSGER). RESULTS: A significant treatment effect existed for ADAS-Cog (high dose vs placebo; P < or = .05), and CIBIC+ (high dose vs placebo; P < or = .02). Treatment Emergent Signs and Symptoms analysis of the ADSS, which assesses behavioral symptoms in patients with AD, disclosed significant (P < or = .002) dose-dependent reductions in vocal outbursts, suspiciousness, delusions, agitation, and hallucinations. On end-point analysis, NOSGER, which assesses memory, instrumental activities of daily living, self-care, mood, social behavior, and disturbing behavior in the elderly, also showed a significant dose-response relationship (P < or = .02). In the high-dose arm, 52% of patients discontinued treatment because of adverse events; dose-dependent adverse events were predominantly gastrointestinal in nature. Syncope, defined as loss of consciousness and muscle tone, occurred in 12.6% of patients in the high-dose group. CONCLUSIONS: The observed improvements in ADAS-Cog and CIBIC+ following treatment with xanomeline provide the first evidence, from a large-scale, placebo-controlled clinical trial, that a direct-acting muscarinic receptor agonist can improve cognitive function in patients with AD. Furthermore, the dramatic and favorable effects on disturbing behaviors in AD suggest a novel approach for treatment of noncognitive symptoms.

Alzheimer Disease↗
PubMed1995

The safety and tolerance of xanomeline tartrate in patients with Alzheimer's disease.

Xanomeline tartrate (active ingredient xanomeline) is a muscarinic agonist that has demonstrated specificity for the M1 receptor in preclinical studies and has been well tolerated at dosages up to 50 mg three times a day in healthy elderly subjects. To define the maximum tolerated dose (MTD) of xanomeline tartrate in patients with Alzheimer's disease, 48 patients (20 men, 28 women) with probable Alzheimer's disease were enrolled in a double-blind, placebo-controlled inpatient study to determine the safety and tolerability of 8 fixed dosages of xanomeline tartrate (25, 35, 50, 60, 75, 90, 100, and 115 mg, all three times a day) given for 7 days. For each dosage the treatment panel consisted of six patients (four taking xanomeline tartrate and two taking placebo). With the discontinuation of two patients because of severe intolerable adverse events, a minimum intolerated dose was reached at 115 mg three times a day, and 100 mg three times a day was defined as the MTD. This MTD in patients was two-fold greater than the MTD previously determined in healthy elderly volunteers.

Aged↗
PubMed1995

The utility of salivary amylase as an evaluation of M3 muscarinic agonist activity in Alzheimer's disease.

1. In this double-blind, placebo-controlled phase I study of the safety/tolerance of two doses of xanomeline tartrate (100 mg and 115 mg tid) given to 12 AD patients, the authors measured serum amylase, fractionated into pancreatic and salivary isoenzymes, as a potential marker for M3 activity associated with maximally tolerated dose (MTD). 2. MTD of xanomeline was determined to be 100 mg tid based on intolerable adverse events at 115 mg tid. One patient at the 115 mg tid level presented with moderate hypersalivation and salivary amylase levels 400% of baseline. 3. Overall amylase results were not significant, however a trend in the results for salivary amylase in the 115 mg panel suggests that salivary amylase may be a useful marker for M3 activity.

Aged↗
PubMed1994

Characterization of resting and phorbol ester or concanavalin A activated bovine lymph node cells with leukocyte specific monoclonal antibodies.

Bovine lymph node cells (LNC) have been used as a model to study cell activation and proliferation. Because monoclonal antibodies to bovine lymphoid-specific surface antigens have only recently become available, these cells have not been previously characterized in regard to subpopulations. Furthermore, it was not known how expression of lymphoid differentiation antigens and subset proportionalities might change following different modes of activation of LNC. Therefore, the distribution of cell-surface differentiation antigens in unstimulated LNC as well as in LNC incubated with the mitogen concanavalin A (Con A) or the phorbol ester, phorbol dibutyrate (PDBU), was measured using a series of leukocyte-specific monoclonal antibodies and flow cytometry. Unstimulated LNC were found to have similar proportions of T cells, B cells (sIgM positive), and MHC Class II positive cells similar to bovine peripheral blood mononuclear leukocytes (reviewed by Baldwin et al., 1988a). Treatment of the LNC with PDBU or mitogenic doses of Con A induced changes in the expression of surface antigens consistent with the changes observed with human and mouse cells after similar activation. However, these two compounds did not cause identical effects. After treatment with PDBU, the percentage of cells expressing CD4 as well as the density of surface expression decreased. An increase in the percentage of cells expressing and/or density of surface expression of the pan T cell antigens CD2, CD5, CD6, MHC Class II and J5, a T cell activation antigen, also occurred. PDBU treatment also increased the percentage of CD8 positive cells. The change in CD6 following PDBU treatment has not been reported previously. Con A treatment led to a significant increase in the percentage of cells bearing CD8, CD6, MHC Class II and J5, but it had no effect on the percentages of cells positive for the other T cell markers CD5, CD4, or CD2. Because Con A is a complete mitogen and PDBU is not, the changes observed following Con A stimulation probably reflected an expansion of a particular subpopulation. In contrast, PDBU most likely modifies surface antigen expression directly. Neither treatment affected the B cell subpopulation.

Animals↗
PubMed1993

Immunocompromise in gnotobiotic pigs induced by verotoxin-producing Escherichia coli (O111:NM).

A verotoxin-producing Escherichia coli serotype O111:NM strain (strain 10049; verotoxin 1 positive) persistently infected experimentally inoculated gnotobiotic pigs, causing attaching-effecting intestinal lesions and chronic diarrhea. Experiments were performed to determine whether persistent infection might be associated with immunocompromise of the host of this organism. Pigs inoculated with this strain had a significant reduction in peripheral blood lymphocytes and lower antibody titers to sheep erythrocytes compared with control pigs. Compared with pigs given a verotoxin-negative pathogenic strain of the same serotype (O111:NM, strain 2430), pigs inoculated with the verotoxin-positive strain had lower peripheral lymphocyte counts and proliferative responses to concanavalin A, phytohemagglutinin, and pokeweed mitogens. The results of this study suggest that strain 10049 has an immunocompromising effect on gnotobiotic pigs.

Animals↗
PubMed1991

Numbers and percent of T lymphocytes in bovine peripheral blood during the periparturient period.

To determine if periparturient immunosuppression in dairy cattle might be due to an alteration in total numbers of percent of T lymphocytes, we examined the numbers and percent of T lymphocyte subsets in peripheral blood from periparturient dairy cows, some of which received recombinant bovine granulocyte colony stimulating factor (rbG-CSF) during the study. Beginning 2 weeks preparatum through 4 weeks postpartum, peripheral blood mononuclear cells (PBMC) were collected and labeled with monoclonal antibodies to BoCD5, BoCD4, and BoCD8, and the percent of cells positive for each marker measured by flow cytometry. The percent of PBMC expressing BoCD5 (total T cells), and BoCD8 (T suppressor/cytotoxic cells) was not significantly different between the groups, or at different times before and after calving. The percent of PBMC expressing BoCD4 (T helper cells) was not significantly different between the groups, however, within both groups there was a higher percent of BoCD4+ cells after calving than during the prepartum period. In cows receiving rbG-CSF, total numbers of PBMC were significantly increased compared to controls during the postpartum treatment period.

Animals↗
PubMed1990

Culture conditions for blastogenic responses of bovine mammary mononuclear cells.

Several experimental parameters were examined to determine optimal conditions for proliferative responses of mammary mononuclear cells (MMC) obtained from six nonlactating dairy cows. These parameters were: pre-incubation of cells in medium prior to assay, mitogen concentration, assay incubation time, and type of culture medium. Response variables included viability of cells and the rate of proliferation as assessed by tritiated thymidine incorporation. Pre-incubation of cells in medium had no effect on the proliferative response of MMC. Whereas Concanavalin A (ConA; 3.3 or 6.6 micrograms/ml) and phytohemagglutinin (PHA; 1, 5, 10 micrograms/ml) did stimulate proliferation of MMC, the higher doses did not stimulate greater proliferation than the lower doses of mitogens. The greatest mitogenic response was obtained on days 2 and 3 of incubation. Proliferative responses were significantly higher at all mitogen levels tested in a 50-50 mixture of Rosewell Park Memorial Institute medium 1640 and Liebovitz-15 medium (RPMI/L-15) than in RPMI alone. Viability of MMC was also significantly higher in the RPMI/L-15 medium. To test whether the significant effect of media on blastogenesis was specific for mononuclear cells from the bovine mammary gland, peripheral blood lymphocytes (PBL) from four dairy cows were cultured with ConA and PHA in a mitogen assay in both RPMI and RPMI/L-15. Viability was measured on day of collection and on all culture days. PBL were stimulated equally in both media. PBL viability decreased significantly on day 1 in both RPMI and RPMI/L-15. These results suggest that the optimal culture conditions for blastogenic responses of mammary mononuclear cells and peripheral blood lymphocytes may differ.

Animals↗
PubMed1990

An evaluation of the mononuclear cells derived from bovine mammary gland dry secretions using leukocyte antigen specific monoclonal antibodies, light scattering properties and non-specific esterase staining.

The distribution of mononuclear cells isolated from the bovine mammary gland during the nonlactating (dry) period was examined using monoclonal antibodies against leukocyte cell surface antigens, cellular light scattering properties, and the presence of nonspecific esterase. Most of the mononuclear cells isolated during the dry period were lymphocytes. T cells predominated until about 1 week prior to parturition. During the week prior to calving, the percentage of B cells increased until it approximated T cells. The ratio of CD4:CD8 cells was 2-3:1 for mammary gland T cells. This was similar to the ratio found in peripheral blood. At dry-off, about 12% of mammary mononuclear cells were macrophages. The macrophage percentage increased (to about 30%) at mid-dry and remained at this levels until parturition. PMN's were isolated with the mononuclear cells during the first 2 weeks dry and the week prior to calving. Three methods were used to identify mammary macrophages. Esterase staining (as an enzymatic method), forward angle/90 degrees light scatter (based on size and internal complexity), and MHC class II/forward angle light scatter (based on size and surface markers) were compared. Each method yielded similar specificity for macrophage identification. Non-adherent cell fractions, obtained by passage of the cells over Sephadex G-10 columns, were enriched in CD4 positive T cells, somewhat depleted of B cells, and depleted of macrophages and PMN's. Cells eluted from G-10 columns, with lidocaine, were mostly lymphocytes, but reflected the cells loaded onto the column.

Animals↗
PubMed1990

Children's observations of violence: I. Critical issues in child development and intervention planning.

Children are often the unintended or indirect victims of wife abuse as witnesses of this violence in their family. Current research on these children and a conceptual framework to understand how this violence affects their development are outlined. The implications of this research are discussed in terms of several intervention strategies. The importance of primary prevention programs in school systems is stressed.

Canada↗
PubMed1990

Children's observations of violence: II. Clinical implications for children's mental health professionals.

This paper discusses the clinical implications of our current knowledge about children exposed to violence. It highlights a number of typical case scenarios in which mental health professionals have responded inadequately to the issue of violence. Alternative strategies for assessing and treating children exposed to violence are offered which have both therapeutic and preventative value. Finally, a family based assessment and treatment approach, which may be appropriate in a number of cases, is suggested.

Child↗