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Biomedical subjects

David E Anderson

Publications and source records attributed to David E Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2005

Positive emotions: exploring the other hemisphere in behavioral medicine.

The search for the psychological antecedents of medical disorders has focused on the role of stress and negative emotional states. Previous research in this area has investigated relations between negative emotions and physiological adaptations (e.g., blood pressure elevations), adverse health behaviors (e.g., smoking), and social conditions (e.g., social isolation). In this discussion, we argue that more attention is needed to understand the effects of positive emotional states on health enhancement and disease prevention. In each of the areas cited previously, evidence is beginning to emerge that indicates that positive emotions can be associated with health promoting conditions. Interventions using cognitive behavioral strategies or meditation can increase positive emotional states that are maintained over time and that may benefit health and well-being. Implications for behavioral medicine are discussed.

Adaptation, Physiological↗
PubMed2005

Determination of the effect of single abomasal or jejunal inoculation of Clostridium perfringens type A in dairy cows.

A randomized study was conducted to determine if inoculation of the abomasum or jejunum with Clostridium perfringens Type A would induce jejunal hemorrhage syndrome in healthy cows. Twelve adult nonlactating dairy cows were inoculated with 10 mL of pure culture broth of C. perfringens type A (beta2 toxin positive) into the abomasum (n = 6) or jejunum (n = 6). On day 6, the cows were euthanized and samples for culture were taken from the abomasum, jejunum, and feces. No cows developed clinical signs of jejunal hemorrhage syndrome during the course of the study. Five of 6 abomasal samples and 1 of 6 jejunal samples were positive for C. perfringens Type A (beta2 negative) prior to inoculation. Eight of 12 abomasal samples, 11 of 12 fecal samples, and 10 of 12 jejunal samples were positive for C. perfringens Type A (beta2 negative) after inoculation. Intraluminal inoculation of C. perfringens Type A alone at this dose and under these conditions did not induce clinical signs of jejunal hemorrhage syndrome in adult dairy cows. The multifactorial nature of the disease likely contributed to our inability to reproduce the disease in this study.

Abomasum↗
PubMed2004

Infection with Corynebacterium pseudotuberculosis in five alpacas.

Among the population of an alpaca breeding farm, 5 alpacas (22 days to 14 months old) developed focal swellings in the subcutaneous tissues of the head or neck. Infection with Corynebacterium pseudotuberculosis was confirmed on the basis of results of microbial culture of abscess material and a serum hemolysis inhibition assay to detect C. pseudotuberculosis toxin. The dams of the affected alpacas were seronegative for C. pseudotuberculosis toxin. The affected alpacas underwent surgical excision of the abscesses and were isolated from herdmates for 90 days; treatment was successful, and no other alpacas in the herd became infected. Common risk factors for sources of infection in the affected alpacas included housing in a maternity barn and a pasture. Also, the infection potentially originated from new alpacas introduced into the herd during the preceding 3 months. Infection with C. pseudotuberculosis should be considered as a differential diagnosis for camelids with peripheral lymphadenopathy or abscesses in subcutaneous tissues.

Abscess↗
PubMed2004

Cross-reactive TCR responses to self antigens presented by different MHC class II molecules.

Autoreactive T cells represent a natural repertoire of T cells in both diseased patients and healthy individuals. The mechanisms regulating the function of these autoreactive T cells are still unknown. Ob1A12 is a myelin basic protein (MBP)-reactive Th cell clone derived from a patient with relapsing-remitting multiple sclerosis. Mice transgenic for this human TCR and DRA and DRB1*1501 chains develop spontaneous experimental autoimmune encephalomyelitis. The reactivity of Ob1A12 is reported to be restricted to recognition of MBP peptide 85-99 in the context of DRB1*1501. DRA/DRB1*1501 and the patient's other restriction element, DRA/DRB1*0401, differ significantly in their amino acid sequences. In this study we describe an altered peptide ligand derived from MBP(85-99) with a single amino acid substitution at position 88 (Val to Lys; 88V-->K), that could stimulate the Ob1A12.TCR in the context of both DRA/DRB1*1501 and DRA/DRB1*0401. Analysis of a panel of transfected T cell hybridomas expressing Ob1A12.TCR and CD4 indicated that Ob1A12.TCR cross-reactivity in the context of DRA/DRB1*0401 is critically dependent on the presence of the CD4 coreceptor. Furthermore, we found that activation of Ob1A12.TCR with MBP altered peptide ligand 85-99 88V-->K presented by DRB1*1501 or DRB1*0401 resulted in significant differences in TCR zeta phosphorylation. Our data indicate that injection of altered peptide ligand into patients heterozygous for MHC class II molecules may result in unexpected cross-reactivities, leading to activation of autoreactive T cells.

Amino Acid Sequence↗
PubMed2004

Humoral immunity to immunodominant epitopes of Hepatitis C virus in individuals infected with genotypes 1a or 1b.

Cellular immunity against multiple Hepatitis C virus (HCV) proteins is observed in patients acutely infected with HCV most of whom later resolve infection. We wished to assess humoral immunity in patients infected with HCV 1a or 1b genotypes in relation to viral load using plasma samples from HCV-infected individuals and a panel of peptides representing immunodominant epitopes of HCV structural and nonstructural proteins. Plasma from HCV 1a- and 1b-infected patients, respectively, were divided into two groups: patients with low viral load (<==100,000 RNA copies/ml) and patients with high viral load (>/=10,000,000 RNA copies/ml). The antigens were peptides representing epitopes from immunodominant regions of HCV core, E2, NS3, and NS4 proteins, as well as the hypervariable (HVR) epitopes in E2 from genotypes 1a and 1b. Individuals infected with HCV 1a evoked a stronger immune response to many immunodominant epitopes of HCV relative to individuals infected with HCV 1b. Moreover, among individuals infected with HCV 1a, those with low viral loads mounted significantly greater responses against these epitopes than did individuals with high viral loads. Our observations demonstrate that quantitatively different antibody responses are elicited against HCV depending on the genotype of infecting virus, and suggest that humoral immunity directed against multiple immunodominant epitopes in HCV 1a-infected individuals may help lower viral load in vivo.

Antibody Formation↗
PubMed2004

Humoral immunity and the evolution of HIV-2.

Human immunodeficiency virus type 2 (HIV-2) evolved from the zoonotic transmission of simian immunodeficiency virus (SIV) that naturally infects sooty mangabeys found in West Africa. Using sera from HIV-2-infected humans, we discovered that an hypervariable region (the V4 loop) of HIV-2 induces antibody responses only weakly reactive against itself but strongly reactive against analogous sequences from the V4 loop of strains of SIV. Available sequence data indicates that all strains of HIV-2 have large deletions in the V4 region that truncate an immunodominant neutralizing B cell epitope among strains of SIV. Infection of a macaque with a sequenced clone of HIV-2 similarly elicited antibodies that poorly recognized the V4 loop of HIV-2 but readily bound to analogous SIV sequences. Our data are consistent with a scenario whereby a disparate antibody response directed against the V4 loop may have influenced the selective expansion and survival of HIV-2 in humans.

Biological Evolution↗
PubMed2004

Induction of immune responses against human papillomaviruses by hypervariable epitope constructs.

An ideal prophylactic vaccine against human papillomaviruses (HPV) would be one that can induce broadly reactive antibody titres to at least the major oncogenic strains of HPV. It has been previously shown that HPV structural proteins are highly immunogenic but fail to elicit cross-reactive immune responses against heterologous strains of HPV. Recent studies have demonstrated that the immunity induced by virus-like particles is mostly type specific. In the present study, we determined the breadth of reactivity of antibodies induced in mice immunized with hypervariable epitope constructs (HECs), which represent sequence variants of immunodominant B-cell epitopes of the major capsid protein L1 of HPV. In order to test the breadth of reactivity, sera from immunized mice were tested against peptides representing analogous sequences of HPV types 16, 18, 31 and 45. Mice immunized with HECs based on two epitopes mounted antibody responses that cross-reacted with two different analogues, 16 and 18. Significantly, antibodies from mice immunized with HECs also inhibited haemagglutination mediated by HPV-16 L1 VLPs, suggesting that immunization resulted in the development of antibodies that could bind to viral capsid proteins in their native conformation. Our observations suggest that HECs may overcome the restriction of type specific immunity against HPV.

Animals↗
PubMed2004

Assembly dynamics of FtsZ rings in Bacillus subtilis and Escherichia coli and effects of FtsZ-regulating proteins.

FtsZ is the major cytoskeletal component of the bacterial cell division machinery. It forms a ring-shaped structure (the Z ring) that constricts as the bacterium divides. Previous in vivo experiments with green fluorescent protein-labeled FtsZ and fluorescence recovery after photobleaching have shown that the Escherichia coli Z ring is extremely dynamic, continually remodeling itself with a half time of 30 s, similar to microtubules in the mitotic spindle. In the present work, under different experimental conditions, we have found that the half time for fluorescence recovery of E. coli Z rings is even shorter (approximately 9 s). As before, the turnover appears to be coupled to GTP hydrolysis, since the mutant FtsZ84 protein, with reduced GTPase in vitro, showed an approximately 3-fold longer half time. We have also extended the studies to Bacillus subtilis and found that this species exhibits equally rapid dynamics of the Z ring (half time, approximately 8 s). Interestingly, null mutations of the FtsZ-regulating proteins ZapA, EzrA, and MinCD had only modest effects on the assembly dynamics. This suggests that these proteins do not directly regulate FtsZ subunit exchange in and out of polymers. In B. subtilis, only 30 to 35% of the FtsZ protein was in the Z ring, from which we conclude that a Z ring only 2 or 3 protofilaments thick can function for cell division.

Adenosine Triphosphatases↗
PubMed2004

Determination of electrocardiographic parameters in healthy llamas and alpacas.

OBJECTIVE: To determine electrocardiographic parameters in healthy llamas and alpacas. ANIMALS: 23 llamas and 12 alpacas. PROCEDURE: Electrocardiography was performed in nonsedated standing llamas and alpacas by use of multiple simultaneous lead recording (bipolar limb, unipolar augmented limb, and unipolar precordial leads). RESULTS: Common features of ECGs of llamas and alpacas included low voltage of QRS complexes, variable morphology of QRS complexes among camelids, and mean depolarization vectors (mean electrical axes) that were directed dorsocranially and to the right. Durations of the QT interval and ST segment were negatively correlated with heart rate. CONCLUSIONS AND CLINICAL RELEVANCE: ECGs of acceptable quality can be consistently recorded in nonsedated standing llamas and alpacas. Features of ECGs in llamas and alpacas are similar to those of other ruminants. Changes in the morphology of the QRS complexes and mean electrical axis are unlikely to be sensitive indicators of ventricular enlargement in llamas and alpacas.

Animals↗
PubMed2003

CTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, thought to be mediated in part by an autoimmune response of T cells to protein components of the myelin sheath. The reaction of naïve T cells against these antigens requires co-stimulation through CD28. However, the proliferative response of peripheral blood mononuclear cells isolated from patients with MS and stimulated with myelin basic protein (MBP) has been shown to be relatively independent of B7-CD28 co-stimulation, suggesting that dysregulation of co-stimulatory pathways may be involved in the pathogenesis of MS. Here, the role of CTLA-4 engagement was investigated. As expected, blocking CTLA-4-mediated signaling during stimulation of MBP-reactive T cells from healthy controls enhanced the proliferative and cytokine responses. In contrast, CTLA-4 blockade had less effect in patients with MS, suggesting that at least two regulatory mechanisms may be impaired in these individuals. Understanding how co-stimulatory signals may be dysregulated in patients with MS is important at a time when targeting of these pathways is being developed.

Adult↗
PubMed2003

Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women.

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO), which plays an important role in natriuresis. We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW). METHODS: In 15 normotensive PMW (age 50-60 years), not receiving estrogen, ambulatory 24-h BP, plasma lipids, and ADMA were measured after 4 days of a low-salt diet (70 mEq/day) and following 7 days of high-salt intake (260 mEq/day). Brachial artery diameter at rest, during reactive hyperemia, i.e. EDD, and after sublingual nitroglycerin, i.e. non-EDD, were measured by ultrasound. The 24-h urinary NO metabolite (NOx) was measured by Griess reaction. Plasma ADMA was measured by high-pressure liquid chromatography. RESULTS: During low-salt, 24-h BP levels averaged 121 +/- 11 and 69 +/- 7 mmHg for systolic BP (SBP) and diastolic BP (DBP), respectively. After salt loading, average 24-h BP increases were: 7.6 mmHg for SBP, 2.2 mmHg for DBP, and 5.5 mmHg for pulse pressure (PP). Increases of 24-h SBP and 24-h PP after salt loading correlated directly with changes in ADMA (partial R2 = 0.16 for 24-h SBP and 0.17 for 24-h PP, P < 0.05 for both) and inversely with changes in EDD (partial R2 = 0.13, P = 0.09 for 24 h SBP and partial R2 = 0.15, P = 0.07 for 24-h PP), after adjustment for age and cholesterol. CONCLUSIONS: Inhibition of NO bioavailability by ADMA and a subsequent reduction in EDD contribute to the increase in BP during high-salt intake in normotensive PMW not receiving estrogen.

Arginine↗
PubMed2002

Portosystemic shunt in an alpaca cria.

A 5-month-old alpaca cria was examined for chronic poor growth and repeated episodes of diarrhea. Examination of feces for parasites yielded negative results. Serum bile acid and blood ammonia concentrations were high. Subsequent examination by ultrasonography, percutaneous splenic portography, and colonic scintigraphy did not reveal evidence of a portosystemic vascular anomaly. Exploratory celiotomy with mesenteric vein portography revealed a colonic vein shunt in the caudal portion of the abdomen from the caudal vena cava to the portal vein. The shunt vessel was ligated without incident. Following surgery, the cria began to gain weight and was more alert. Eighteen months after surgery, the cria was doing well, although it had loose feces and was slightly small for its age. Portosystemic shunts are rare in cattle and horses but should be considered in alpacas with chronic poor growth when parasitism has been ruled out.

Animals↗
PubMed2002

Diagnosis, surgical treatment, and performance after unilateral castration in breeding bulls: 21 cases (1989-1999).

OBJECTIVE: To evaluate signalment, surgical treatment, postoperative complications, and future breeding success or semen production in a group of bulls with naturally occurring disease of the scrotum or testis. STUDY DESIGN: Retrospective study. ANIMALS: 21 bulls that underwent unilateral castration after evaluation for scrotal swelling. PROCEDURE: A computer-assisted search of medical records at 2 veterinary teaching hospitals was performed. Historical, diagnostic, surgical, and follow-up data were collected and analyzed for those bulls with scrotal swelling that underwent unilateral castration. RESULTS: Four of 5 pasture breeding bulls and 9 of 10 semen collection-center bulls successfully bred cows or produced viable semen within 6 months of surgery. Fourteen of 21 surgical procedures were performed after induction of general anesthesia. Sixty-six percent of procedures were performed as open castrations. Seventy-one percent of bulls developed postoperative complications, most of which were mild swellings. Unilateral castration returned 13 of 15 bulls with unilateral disease of the scrotum or testis to productive service by 6 months after surgery. CONCLUSION AND CLINICAL RELEVANCE: Unilateral castration is an effective treatment for unilateral disease of the,scrotum or testis in bulls, allowing return to reproductive function.

Animals↗
PubMed2002

Condensin and cohesin display different arm conformations with characteristic hinge angles.

Structural maintenance of chromosomes (SMC) proteins play central roles in higher-order chromosome dynamics from bacteria to humans. In eukaryotes, two different SMC protein complexes, condensin and cohesin, regulate chromosome condensation and sister chromatid cohesion, respectively. Each of the complexes consists of a heterodimeric pair of SMC subunits and two or three non-SMC subunits. Previous studies have shown that a bacterial SMC homodimer has a symmetrical structure in which two long coiled-coil arms are connected by a flexible hinge. A catalytic domain with DNA- and ATP-binding activities is located at the distal end of each arm. We report here the visualization of vertebrate condensin and cohesin by electron microscopy. Both complexes display the two-armed structure characteristic of SMC proteins, but their conformations are remarkably different. The hinge of condensin is closed and the coiled-coil arms are placed close together. In contrast, the hinge of cohesin is wide open and the coiled-coils are spread apart from each other. The non-SMC subunits of both condensin and cohesin form a globular complex bound to the catalytic domains of the SMC heterodimers. We propose that the "closed" conformation of condensin and the "open" conformation of cohesin are important structural properties that contribute to their specialized biochemical and physiological functions.

Adenosine Triphosphatases↗
PubMed2002

Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro.

Although immunotherapeutic strategies against glioblastomas have been promising both in vitro and in animal models, similar successes have not been realized in human clinical trials. One reason may be that immunotherapeutic strategies are based on prior studies that primarily have used human glioblastoma cell lines passaged in vitro, which may not accurately reflect the in vivo properties of glioblastoma cells. In this report, we used flow cytometry to quantify the expression of immunological cell surface molecules on human glioblastomas directly ex vivo (prior to any in vitro culturing) and after varying passages in vitro. Furthermore, we used ELISA to quantitate cytokine secretion after various passages in vitro. We demonstrate that in vitro culturing of established cell lines led to increases in the cell surface expression of MHC class I and ICAM-1 and secretion of IL-6 and TGF-beta(2). Furthermore, there were significant changes in the expression of MHC class I, MHC class II, B7-2, ICAM-1, and FasL when comparing ex vivo tumor cells to those after a single passage in vitro. After passaging once in vitro, there were also significant changes in the secretion of TGF-beta(2) and IL-10. This report indicates that in vitro culturing leads to significant changes in both cell surface molecules and secreted cytokines, which are known to affect the ability of immune cells to initiate an anti-tumor immune response. These changes in the immunological phenotype of glioblastomas after in vitro culturing may in part explain the limited success of immunotherapeutic strategies against glioblastomas in human clinical trials.

Antigens, CD↗
PubMed2002

Gender-specific association of perceived stress and inhibited breathing pattern.

Stress can potentiate the development of hypertension via inhibition of renal excretory function. One potential mediating mechanism is an inhibited breathing pattern, because hypoventilation can decrease renal sodium excretion acutely via effects on pCO2 and acid-base balance. Large individual differences in resting breathing patterns have been well-documented, with some individuals maintaining slow frequency and high pCO2. Whether this breathing pattern is related to chronic stress has not been investigated. This study reports that high perceived stress over the past month was associated with significantly lower frequency breathing at rest, independently of age, race, or body mass index. This finding was more marked in women than in men. In addition, slow breathing frequency was independently associated with higher resting end tidal CO2 in both men and women. This is the first known report of an association of sustained stress with an inhibited breathing pattern in humans, and points to a pathway by which chronic stress might contribute to the development of hypertension, especially in women.

Blood Pressure↗
PubMed2002

Density of corneal endothelial cells, corneal thickness, and corneal diameters in normal eyes of llamas and alpacas.

OBJECTIVE: To determine density of corneal endothelial cells, corneal thickness, and corneal diameters in normal eyes of llamas and alpacas. ANIMALS: 36 llamas and 20 alpacas. PROCEDURE: Both eyes were examined in each camelid. Noncontact specular microscopy was used to determine density of corneal endothelial cells. Corneal thickness was measured, using ultrasonographic pachymetry. Vertical and horizontal corneal diameters were measured, using Jameson calipers. RESULTS: Values did not differ significantly between the right and left eyes from the same camelid. There was no significant effect of sex on density of corneal endothelial cells or corneal thickness in either species. Mean density of endothelial cells was 2,669 cells/mm2 in llamas and 2,275 cells/mm2 in alpacas. Density of endothelial cells decreased with age in llamas. Polymegathism was observed frequently in both species. Mean corneal thickness was 608 microm for llamas and 595 microm for alpacas. Corneal thickness and density of endothelial cells were negatively correlated in llamas. Older (> 36 months old) llamas had significantly larger horizontal and vertical corneal diameters than younger llamas, and older alpacas had a significantly larger vertical corneal diameter than younger alpacas. CONCLUSIONS AND CLINICAL RELEVANCE: Density of corneal endothelial cells is only slightly lower in camelids than other domestic species. Density of endothelial cells decreases with age in llamas. Age or sex does not significantly affect corneal thickness in normal eyes of llamas and alpacas. Specular microscopy is useful for determining density of corneal endothelial cells in normal eyes of camelids.

Age Factors↗