Biomedical subjects

D E Anderson

Publications and source records attributed to D E Anderson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Resting rectal temperature of Vietnamese potbellied pigs.

OBJECTIVE: To determine resting rectal temperatures of Vietnamese potbellied pigs. DESIGN: Prospective clinical trial. ANIMALS: 85 potbellied pigs on a single farm and 27 potbellied pigs examined at a veterinary teaching hospital for routine veterinary care. PROCEDURE: Rectal temperatures of the potbellied pigs on a farm were measured during the morning, afternoon, and evening. Rectal temperatures at the time of initial examination were obtained from medical records for the potbellied pigs examined at the hospital. RESULTS: Mean rectal temperatures for both groups of potbellied pigs were the same. Overall unadjusted mean +/- SD rectal temperature was 37.6 +/- 0.8 C (99.7 +/- 1.5 F; range, 35.1 to 39.6 C [95.2 to 103.3 F]). However, diurnal variation in rectal temperature was found among the farm population of potbellied pigs. After adjustment for age and repeated sampling, rectal temperatures recorded during the morning were found to be significantly lower than temperatures recorded during the afternoon and evening (mean difference, 0.5 and 0.9 C [0.9 and 1.6 F], respectively), and rectal temperatures recorded during the afternoon were found to be significantly lower than temperatures recorded during the evening (mean difference, 0.4 C [0.7 F]). There was a significant inverse linear relationship between age and rectal temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Rectal temperatures of Vietnamese potbellied pigs may be lower than the lower limit of the reference range reported for domestic pigs. Because of diurnal variation in rectal temperatures, it is important to compare temperatures obtained at the same time of day when assessing patients.

Age Factors↗

PubMed1999

Ileocecocolic intussusception in a one-month-old llama.

A 1-month-old female llama was examined because of signs of acute abdominal pain. Physical and ultrasonographic examination revealed a cylindrical mass in the left caudal quadrant of the abdomen. Results of serum biochemical analyses and CBC were within reference ranges. Exploratory laparotomy revealed an ileocecocolic intussusception. Ileocecal resection and end-to-end ileocolic anastomosis were performed. After surgery, fecal examination revealed many coccidial oocysts, although a direct association between coccidiosis and intussusception could not be determined. The cria recovered without serious complications.

Abdomen, Acute↗

PubMed1999

Combination antiretroviral therapy improves psychomotor speed performance in HIV-seropositive homosexual men. Multicenter AIDS Cohort Study (MACS).

BACKGROUND: Combination antiretroviral therapy including protease inhibitors (combo+PI) is effective in suppressing systemic viral load in HIV infection, but its impact on HIV-associated cognitive impairment is unclear. OBJECTIVE: To determine whether psychomotor speed, a sensitive measure of impairment in HIV dementia, improves with combo+PI compared with other antiretroviral treatments. METHODS: A total of 411 HIV-seropositive (HIV+) homosexual men (with longitudinal neuropsychological testing) in the Multicenter AIDS Cohort Study and, in a separate analysis, 282 HIV+ homosexual men with psychomotor slowing at baseline were classified by treatment into four groups: antiretroviral naive (no antiretroviral medication treatment), monotherapy, combination antiretroviral therapy without protease inhibitors (combo-noPI), and combo+PI. We compared longitudinal performance on three tests of psychomotor speed: the Grooved Pegboard (GP) (nondominant and dominant hands), Trail Making Test B, and the Symbol Digit Modalities Test (SDMT). RESULTS: Relative to antiretroviral-naïve and monotherapy participants, on the GP nondominant hand test, combo+PI participants with abnormal baseline neuropsychological testing showed improved performance (difference = +0.63 standard deviation [SD], p = 0.02). For the SDMT, both combo+PI participants (difference = +0.26 SD, p = 0.03) and combo-noPI participants (difference = +0.29 SD, p = 0.01) with abnormal baseline neuropsychological testing improved compared with antiretroviral-naïve and monotherapy groups. CONCLUSION: Combo+PI and combo-noPI are associated with improved psychomotor speed performance in HIV+ homosexual men with abnormal neuropsychological testing.

Adult↗

PubMed1999

alpha-lytic protease precursor: characterization of a structured folding intermediate.

The bacterial alpha-lytic protease (alphaLP) is synthesized as a precursor containing a large N-terminal pro region (Pro) transiently required for correct folding of the protease [Silen, J. L., and Agard, D. A. (1989) Nature 341, 462-464]. Upon folding, the precursor is autocatalyticly cleaved to yield a tight-binding inhibitory complex of the pro region and the fully folded protease (Pro/alphaLP). An in vitro purification and refolding protocol has been developed for production of the disulfide-bonded precursor. A combination of spectroscopic approaches have been used to compare the structure and stability of the precursor with either the Pro/alphaLP complex or isolated Pro. The precursor and complex have significant similarities in secondary structure but some differences in tertiary structure, as well as a dramatic difference in stability. Correlations with isolated Pro suggest that the pro region part of the precursor is fully folded and acts to stabilize and structure the alphaLP region. Precursor folding is shown to be biphasic with the fast phase matching the rate of pro region folding. Further, the rate-limiting step in oxidative folding is formation of the disulfide bonds and autocatalytic processing occurs rapidly thereafter. These studies suggests a model in which the pro region folds first and catalyzes folding of the protease domain, forming the active site and finally causing autocatalytic cleavage of the bond separating pro region and protease. This last processing step is critical as it allows the protease N-terminus to rearrange, providing the majority of net stabilization of the product Pro/alphaLP complex.

Circular Dichroism↗

PubMed1999

Molecular pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is best understood as an inflammatory disease of the central nervous system (CNS) white matter characterized by demyelination, focal T cell and macrophage infiltrates, axonal injury and loss of neurological function. Our current understanding invokes proinflammatory cells and mediators that may be triggered by environmental factors to mediate disease in a genetically susceptible host. Five major themes which have been associated with the pathogenesis of MS lesions will be discussed: (1) The differential activation states of myelin-reactive T cells from MS patients vs. normal individuals, (2) the selective expression of chemokines, adhesion molecules and matrix metalloproteinases, (3) the proposed roles of the B7 costimulatory pathway, (4) the proinflammatory cytokines and (5) the role of molecular mimicry.

Autoimmunity↗

PubMed1999

The B7-CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system.

The past year has seen significant advances in our understanding of the role of the B7-CD28/CTLA-4 pathway in regulating the responses of self-reactive T cells, giving impetus to manipulation of this pathway for treating human autoimmune diseases. Recent studies have demonstrated that B7-CD28 costimulation has critical roles in stimulating both the initiation and effector phases of autoimmunity and that CD28 regulates the threshold for activation of self-reactive T cells. Recent work has also revealed critical roles for CTLA-4 in limiting the extent of Th1/Th2 cell differentiation and in downregulating the responses of self-reactive T cells during both the initiation and progression of autoimmune disease.

Abatacept↗

PubMed1999

Dalmeny disease in an alpaca (Lama pacos): sarcocystosis, eosinophilic myositis and abortion.

Disseminated eosinophilic myositis was diagnosed in an alpaca that had been imported to the USA from Peru 5 years earlier. The myositis was associated with macroscopically visible large sarcocysts that were characterized histologically by septate compartments containing bradyzoites, and ultrastructurally by cyst walls composed of anastomosing villous protrusions. Two hours before death, the alpaca aborted an 8-month-gestation fetus, but no lesions were found in the uterus, placenta or fetus. Additional macroscopical findings included haemoabdomen and myofibre haemorrhage, degeneration and necrosis. It is believed that this is the first described case of clinical disease associated with a Sarcocystis sp. (probably S. aucheniae) in camelids.

Abortion, Veterinary↗

PubMed1999

The effect of short duration transportation on serum cortisol response in alpacas (Llama pacos).

This research project evaluated the changes in serum cortisol in six male and six female alpacas in response to transportation of short duration. All alpacas were subjected to trailer transportation for 30 min. Serum samples were obtained prior to transportation, immediately after transportation, and after a 4-h recovery period. Heart rate was recorded at each time interval and observations of individual behavioural characteristics were recorded. Data were analysed using analysis of variance. Heart rate was not significantly changed by transportation stress. Serum cortisol concentration was significantly higher after transportation, but head returned to baseline concentration after the 4-h recovery period. Behavioural characteristics were not associated with changes in serum cortisol concentration.

Animals↗

PubMed1999

Tick paralysis: 33 human cases in Washington State, 1946-1996.

Tick paralysis is a preventable cause of illness and death that, when diagnosed promptly, requires simple, low-cost intervention (tick removal). We reviewed information on cases of tick paralysis that were reported to the Washington State Department of Health (Seattle) during 1946-1996. Thirty-three cases of tick paralysis were identified, including 2 in children who died. Most of the patients were female (76%), and most cases (82%) occurred in children aged <8 years. Nearly all cases with information on site of probable exposure indicated exposure east of the Cascade Mountains. Onset of illness occurred from March 14 to June 22. Of the 28 patients for whom information regarding hospitalization was available, 54% were hospitalized. Dermacentor andersoni was consistently identified when information on the tick species was reported. This large series of cases of tick paralysis demonstrates the predictable epidemiology of this disease. Improving health care provider awareness of tick paralysis could help limit morbidity and mortality due to this disease.

Aged↗

PubMed1999

Simian retrovirus receptor and neutralization mechanism by antibodies to the envelope glycoprotein.

Type D simian retroviruses (SRV) cause an acquired immunodeficiency syndrome (AIDS) in monkeys. Results of infection with SRV range from complete recovery with absence of viremia to a viremic state, which produces AIDS-like symptoms and culminates in death. These varied outcomes render the interaction of the host and SRV an attractive model for the study of immunosuppressive retrovirus resulting in different pathologic consequences. We describe here the isolation and determination of the molecular weight of the receptor for SRV. We demonstrate that a cell receptor with the same molecular weight is bound by the envelope protein of all five serotypes of SRV. We also show that the receptor recognizes a region containing amino acids 142-167 of the envelope protein of SRV serotype 1 (SRV-1). In addition, we show that a different region of SRV serotype 2 (SRV-2) envelope protein containing amino acids 93-106, interacts with a cell receptor of identical molecular weight. Furthermore, polyclonal and monoclonal antibodies that are directed to envelope epitopes 142-167 of SRV-1 or to 93-106 of SRV-2, specifically neutralize only the respective viral serotype. Our results indicate that the neutralization of SRV infectivity by antibodies is achieved through blocking the interaction between the virus and its cell receptor.

Antibodies, Viral↗

PubMed1999

End tidal CO2 is an independent determinant of systolic blood pressure in women.

OBJECTIVE: Recent studies have shown that high resting end tidal CO2 (PECO2) is a marker for blood pressure sensitivity to high sodium intake by normotensive humans. The present study investigated the association of resting PECO2 with resting blood pressure in participants in the Baltimore Longitudinal Study on Aging (BLSA). DESIGN: PECO2 of 314 healthy participants (153 men and 161 women, aged 21-79 years) was measured by a respiratory gas monitor during 25 min of seated rest, and blood pressure every 5 min by an automated oscillometric system. The independent associations of PECO2 and other variables with systolic (SBP) and diastolic (DBP) blood pressure were analysed via multiple regression. Sex differences in age-associated changes in PECO2 and in the role of pulmonary capacity in the PECO2 -blood pressure relationships were also studied. RESULTS: Resting PECO2 was an independent predictor of SBP in women (beta = 0.215; P<0.0015; overall r2 = 0.27; P<0.0001), and accounted for more than 10% of the variance in SBP in women over age 50 years. No such associations of PECO2 with SBP of men, or with DBP of men or women, were observed. PECO2 was lower in younger women (36.0+/-0.9 mm Hg) than in younger men (40.4+/-2.0), but higher in older women (37.1+/-0.5) than in older men (35.5+/-0.4). CONCLUSIONS: PECO2 is an independent determinant of resting SBP in women, especially those aged 50 years or more. The origin of individual differences in resting PECO2 and its possible role in the development of chronic hypertension remain to be clarified.

Adult↗

PubMed1999

Intraoperative electromyographic assessment of recurrent laryngeal nerve stress and pharyngeal injury during anterior cervical spine surgery with Caspar instrumentation.

OBJECT: Recurrent laryngeal nerve (RLN) injury occurs after anterior cervical spine procedures. In this study the authors used intraoperative electromyographic (EMG) monitoring of the posterior pharynx as a surrogate for RLN function and monitored endotracheal tube (ET) cuff pressure to determine if there was an association between these variables and clinical outcome. METHODS: Sixty patients in whom anterior cervical spine procedures were to be performed comprised the study population. After intubation, the ET cuff was adjusted to a just-seal volume and attached to a pressure monitor. A laryngeal surface electrode was placed in the posterior pharynx, and spontaneous EMG activity was monitored throughout the procedure. Cuff pressures and EMG activity were recorded during neck retraction and when EMG activity increased 20% above baseline. Patients were divided into two groups: those with sore throat/dysphonia and those without symptoms. Cuff pressures and EMG values were compared between groups, and the differences were correlated with clinical outcome. CONCLUSIONS: Hoarseness immediately after surgery was reported in 38% of patients whereas 15% exhibited severe symptoms. In symptomatic patients the period of intubation had been longer, and the ET cuff pressures had been elevated. In most patients EMG activity increased during insertion of the retractor and decreased after its removal. In these patients a greater number of episodes of elevated EMG activity during surgery were also noted. Two patients experienced prolonged hoarseness, and one required teflon injections of the vocal fold. This patient's EMG activity increased (15-18 times baseline) during surgery. In the few patients who were symptomatic with increased EMG activity, neither the timing nor direction of change could be associated with symptoms. Intubation time and elevated ET cuff pressure were the most important contributors to dysphonia and sore throat after anterior cervical spine surgery.

Analysis of Variance↗

PubMed1999

In vitro dose-dependent effects of enrofloxacin on equine articular cartilage.

OBJECTIVE: To determine whether enrofloxacin has detrimental, dose-dependent effects on equine articular cartilage in vitro. ANIMALS: Cartilage explants were developed from 6 healthy horses between 0 and 96 months old. PROCEDURE: Patellar cartilage explants were incubated in 5 concentrations of enrofloxacin (2 microg/ml, 10 microg/ml, 1,000 microg/ml, 10,000 microg/ml, and 50,000 microg/ml) for 72 hours. Proteoglycan synthesis (Na35SO4 incorporation for 24 hours), proteoglycan degradation (Na35SO4 release for 72 hours), endogenous proteoglycan content (dimethylmethlene blue assay), and total protein content were determined. Cartilage explants were evaluated by use of histomorphologic and histomorphometric techniques (toluidine blue stain) for cytologic and matrix characteristics. Quantitative data were analyzed with a one-way ANOVA to compare results among various enrofloxacin concentration groups and the control group. A general linear model was used to determine whether age had an effect. RESULT: Proteoglycan synthesis was excellent in control specimens and in specimens incubated in low concentrations of enrofloxacin (2 microg/ml and 10 microg/ml). High concentrations of enrofloxacin (> 1,000 microg/ml) effectively eliminated proteoglycan synthesis regardless of horse age. Proteoglycan degradation at low concentrations (2 microg/ml and 10 microg/ml) was not different than control. High concentrations of enrofloxacin (> 1,000 microg/ml) caused significant degradation. Different concentrations of enrofloxacin did not affect endogenous proteoglycan. High concentrations of enrofloxacin were associated with a significant increase in number of pyknotic nuclei. CONCLUSION: Concentrations of enrofloxacin that might be achieved following systemic administration did not suppress chondrocyte metabolism in vitro. High concentrations of enrofloxacin (> 1,000 microg/ml) were toxic to chondrocytes.

Analysis of Variance↗

PubMed1999

Effects of percutaneous liver biopsy in alpacas and llamas.

OBJECTIVE: To determine changes in results of selected serum biochemical tests after a single percutaneous liver biopsy and changes in results of hematologic and selected serum biochemical tests after multiple percutaneous liver biopsies in alpacas and llamas. ANIMALS: 5 llamas and 10 alpacas. PROCEDURE: A single percutaneous liver biopsy was performed in 5 llamas and 6 alpacas. Blood samples were collected before and 1, 2, and 3 days after liver biopsy, and submitted for serum biochemical analysis. In the other 4 alpacas, liver biopsy was performed on day 0 and then weekly for 4 weeks. Blood samples were collected at the time of each biopsy, and CBC and serum biochemical analyses were performed. Attitude and appetite of all animals were evaluated daily. RESULTS: None of the animals developed clinically apparent adverse effects. A mild decrease in sorbitol dehydrogenase activity was detected in animals that underwent a single liver biopsy, and mild decreases in plasma protein and albumin concentrations were detected in animals that underwent multiple biopsies. Other significant changes were not detected. CONCLUSIONS: Results of this study suggest that liver biopsy is safe in healthy llamas and alpacas and that, if necessary, multiple weekly liver biopsies can be performed safely in healthy alpacas.

Alkaline Phosphatase↗

PubMed1998

Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis.

The objective of this study was to determine whether autoreactive T cells in patients with multiple sclerosis (MS) are polarized and committed in their differentiation to a stable cytokine phenotype or whether the cytokine secretion can be altered. We examined the cytokines secreted by myelin basic protein (MBP) as compared to tetanus toxoid-reactive (TT) T cells in 12 patients with relapsing remitting MS (RR-MS), 9 patients with chronic progressive MS (CP-MS), and 14 normal individuals. A total of 5094 short term T cell lines to MBP and TT were generated in the presence of growth conditions promoting Th1 (IL-12/alpha-IL-4 mAb) or Th2 (IL-4/alpha-IL-12 mAb) cytokine secretion. Antigen-specific cytokine secretion from normals and MS patients could be shifted to a Th1 or Th2 type phenotype depending upon culture conditions, indicating that the phenotype of MBP reactive T cells can be altered even in longstanding chronic progressive MS. There were no significant differences in the cytokine patterns secreted by MBP reactive T cells in patients with MS as compared to normal individuals. However, CP-MS patients tended to have fewer MBP reactive T cells secreting IL-4 when cultured with IL-12/anti-IL-4 mAb and more IFN-gamma secreting MBP reactive T cells when cultured with IL-4/anti-IL-12 mAb as compared to both normal controls and RR-MS, suggesting that cells from these patients might be more polarized or that fewer undifferentiated MBP-reactive cells are present in these individuals. The most striking observation was that in contrast to the RR-MS patients and normal controls, almost none of the MBP reactive T cells secreting cytokines in CP-MS incorporated 3[H]thymidine. This may be due to chronic in vivo stimulation in the presence of IL-12, or because these T cells may have entered a terminally differentiated state. Nonetheless, the ability to alter the cytokine secretion of autoreactive T cell lines even in longstanding autoimmune disease indicates that cytokine therapy might have therapeutic benefits by switching the function of myelin reactive T cells such that they are non-pathogenic.

Antibodies, Monoclonal↗

PubMed1998

Pro region C-terminus:protease active site interactions are critical in catalyzing the folding of alpha-lytic protease.

alpha-Lytic protease is encoded with a large (166 amino acid) N-terminal pro region that is required transiently both in vivo and in vitro for the correct folding of the protease domain [Silen, J. L. , and Agard, D. A. (1989) Nature 341, 462-464; Baker, D., et al. (1992) Nature 356, 263-265]. The pro region also acts as a potent inhibitor of the mature enzyme [Baker, D., et al. (1992) Proteins: Struct.,Funct., Genet. 12, 339-344]. This inhibition is mediated through direct steric occlusion of the active site by the C-terminal residues of the pro region [Sohl, J. L., et al. (1997) Biochemistry 36, 3894-3904]. Through mutagenesis and structure-function analyses we have begun to investigate the mechanism by which the pro region acts as a single turnover catalyst to facilitate folding of the mature protease. Of central interest has been mapping the interface between the pro region and the protease and identifying interactions critical for stabilizing the rate-limiting folding transition state. Progressive C-terminal deletions of the pro region were found to have drastic effects on the rate at which the pro region folds the protease but surprisingly little effect on inhibition of protease activity. The observed kinetic data strongly support a model in which the detailed interactions between the pro region C-terminus and the protease are remarkably similar to those of known substrate/inhibitor complexes. Further, mutation of two protease residues near the active site have significant effects on stabilization of the folding transition state (kcat) or in binding to the folding intermediate (KM). Our results suggest a model for the alpha-lytic protease pro region-mediated folding reaction that may be generally applicable to other pro region-dependent folding reactions.

Amino Acid Sequence↗

PubMed1998

Hypervariable epitope constructs representing variability in envelope glycoprotein of SIV induce a broad humoral immune response in rabbits and rhesus macaques.

Using synthetic peptides, we developed an approach to account for protein epitope variability. We have prepared, in a single synthesis, a cocktail of peptides we have designated a hypervariable epitope construct (HEC), which collectively represents much of the in vivo variability seen in an epitope. Eight HECs representing the in vivo variability seen throughout the envelope glycoprotein of the simian immunodeficiency virus (SIV) were designed and synthesized. The constructs were collectively conjugated to KLH (HEC-KLH) or recombinant gp130 (HEC-rgp130) and used to immunize rabbits and rhesus macaques, respectively. Using sera collected from rabbits immunized with HEC-KLH, we demonstrated that individual components of the immunogen were recognized as antigen in ELISAs, and that the induced antibodies cross-reacted with several strains of SIV as well as with a strain of HIV-2. Following immunization of macaques with HEC-rgp130 antiviral antibodies were induced. These antibodies were still present 9.5 months after the last boost and were also capable of recognizing several different strains of SIV, including SIVmac239, SIVmac251, and SIVsmH3, as well as a strain of HIV-2 (HIV-2ROD). In addition, the antibodies were also capable of neutralizing SIV viral infectivity in vitro. Peripheral blood lymphocytes (PBLs) from immunized macaques proliferated in response to whole proteins and virus. Finally, sera from monkeys immunized with SIV, rgp130, and HIV-2 as well as sera from HIV-2-positive humans recognized HECs in ELISAs, demonstrating the relevance of these epitopes in vivo. This approach can be used as an effective method for generating a strong, broadly cross-reactive humoral response against HIV and can serve as an important component of combination vaccines against HIV and AIDS.

Amino Acid Sequence↗

PubMed1998

Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation.

Multiple sclerosis (MS) is an inflammatory disease of the myelinated central nervous system that is postulated to be induced by myelin-reactive CD4 T cells. T cell activation requires an antigen-specific signal through the TCR and a costimulatory signal, which can be mediated by B7-1 or B7-2 engagement of CD28. To directly examine the activation state of myelin-reactive T cells in MS, the costimulation requirements necessary to activate myelin basic protein (MBP) or tetanus toxoid (TT)-reactive CD4 T cells were compared between normal controls and MS patients. Peripheral blood T cells were stimulated with Chinese hamster ovary (CHO) cells transfected either with DRB1*1501/DRA0101 chains (t-DR2) alone, or in combination with, B7-1 or B7-2. In the absence of costimulation, T cells from normal subjects stimulated with the recall antigen TT p830-843 were induced to expand and proliferate, but stimulation with MBP p85-99 did not have this effect. In marked contrast, T cells from patients with MS stimulated with MBP p85-99 in the absence of B7-1 or B7-2 signals expanded and proliferated. Thus, MBP-reactive CD4 T cells in patients with MS are costimulation independent and have been previously activated in vivo. These experiments provide further direct evidence for a role of activated MBP-specific CD4 T cells in the pathogenesis of MS.

Abatacept↗