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Biomedical subjects

David E Anderson

Publications and source records attributed to David E Anderson.

At least 19 recordsLinked to original sources
PubMed2007

Humerus fractures in llamas and alpacas: seven cases (1998-2004).

OBJECTIVE: To describe treatment and outcome of humerus fractures in llamas and alpacas. STUDY DESIGN: Retrospective study. ANIMALS: Llamas (n=4) and alpacas (3) with humerus fracture. METHODS: Medical records (January 1, 1998-August 1, 2004) were reviewed for small camelids with a humeral fracture. Retrieved data were signalment, history, physical examination and radiographic findings, surgical and medical treatment, and outcome. RESULTS: Humeral fracture occurred in 7 of 38 (18%) camelids admitted with fractures. Affected animals were aged from 1 month to 3 years old. Fracture configuration included long-oblique (n=4), short-oblique (2), and Salter-Harris Type II fracture of the proximal physis (1). One adult llama was managed by stall confinement and surgical repair was attempted in the other camelids: fixation by screws inserted in lag fashion (n=3), intramedullary pinning and fixation by screws inserted in lag fashion (1), rush pinning (1), and bone plating (1). A Velpeau sling was used for additional support in 3 animals. All fractures healed but temporary radial nerve paresis occurred in 3 animals. Limb shortening and permanent lameness occurred in the llama managed conservatively. CONCLUSIONS: Humerus fractures in small camelids are amenable to surgical repair which may offer better long-term outcome than medical treatment alone. CLINICAL RELEVANCE: Surgical treatment of humerus fractures should have a good prognosis in llamas and alpacas. In select cases, minimally invasive techniques, such as rush pinning or fixation by screws inserted in lag fashion are sufficient for fracture healing.

Age Factors↗
PubMed2006

Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters.

BACKGROUND: One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters. RESULTS: We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E CONCLUSION: Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity.

AIDS Vaccines↗
PubMed2006

TIM-3 in autoimmunity.

T cell immunoglobulin and mucin domain (TIM)-3 is a molecule expressed on terminally differentiated murine Th1 cells but not on Th2 cells. Identification of galectin-9 as a ligand for TIM-3 has now firmly established the TIM-3-galectin-9 pathway as an important regulator of Th1 immunity and tolerance induction. TIM-3 is similarly expressed on human Th1 cells and not on Th2 cells, which suggests that TIM-3 might also contribute to Th1 regulation in humans. In addition, genetic data associate the TIM locus and specific TIM-3 polymorphisms with various immune-mediated diseases. Most importantly, recent data suggest a novel paradigm in which dysregulation of the TIM-3-galectin-9 pathway could underlie chronic autoimmune disease states, such as multiple sclerosis.

Animals↗
PubMed2006

Dysregulated T cell expression of TIM3 in multiple sclerosis.

T cell immunoglobulin- and mucin domain-containing molecule (TIM)3 is a T helper cell (Th)1-associated cell surface molecule that regulates Th1 responses and promotes tolerance in mice, but its expression and function in human T cells is unknown. We generated 104 T cell clones from the cerebrospinal fluid (CSF) of six patients with multiple sclerosis (MS) (n = 72) and four control subjects (n = 32) and assessed their cytokine profiles and expression levels of TIM3 and related molecules. MS CSF clones secreted higher amounts of interferon (IFN)-gamma than did those from control subjects, but paradoxically expressed lower levels of TIM3 and T-bet. Interleukin 12-mediated polarization of CSF clones induced substantially higher amounts of IFN-gamma secretion but lower levels of TIM3 in MS clones relative to control clones, demonstrating that TIM3 expression is dysregulated in MS CSF clones. Reduced levels of TIM3 on MS CSF clones correlated with resistance to tolerance induced by costimulatory blockade. Finally, reduction of TIM3 on ex vivo CD4+ T cells using small interfering (si)RNA enhanced proliferation and IFN-gamma secretion, directly demonstrating that TIM3 expression on human T cells regulates proliferation and IFN-gamma secretion. Failure to up-regulate T cell expression of TIM3 in inflammatory sites may represent a novel, intrinsic defect that contributes to the pathogenesis of MS and other human autoimmune diseases.

Clone Cells↗
PubMed2006

Immune regulation in tumor-bearing hosts.

A wealth of data indicates that tumor immunity directed against a wide variety of malignancies is suppressed in cancer patients. Recent studies have explored the role of 'natural' CD4(+)CD25(+) regulatory T cells (Tregs) in the suppression of tumor immunity in cancer patients. It is now clear, using multiple phenotypic and functional criteria, that the frequency of Tregs is increased in the peripheral blood of cancer patients as well as within the tumor microenvironment. Human Tregs with specificity for tumor-associated antigens have recently been identified, and murine studies have demonstrated that vaccination with tumor-associated antigens can expand Tregs, posing a challenge to cancer vaccine strategies. However, a variety of approaches, including depletion of Tregs or modulation of their activity in vivo, might soon enhance the efficacy of existing cancer vaccines directed against a variety of malignancies.

Animals↗
PubMed2006

Suppressed anger is associated with increased carotid arterial stiffness in older adults.

BACKGROUND: Anger and hostility have been implicated in the pathogenesis of heart disease, but the extent to which the large conduit arteries play an intermediate role in this relationship remains to be clarified. The present study investigated associations of anger frequency and expression style with carotid artery intima-media thickness (IMT) and stiffness in healthy adults older than 50 years. METHODS: Two hundred participants (95 men) in the Baltimore Longitudinal Study of Aging completed the Spielberger Anger Expression Inventory, which assesses anger frequency (trait anger), anger expression (anger-out), and anger suppression (anger-in). The carotid artery IMT was assessed by ultrasonography. Carotid stiffness was determined from the log of systolic over diastolic blood pressure (BP) as a function of carotid distensibility. RESULTS: In univariate correlational analysis, a significant positive association of anger-in with stiffness was observed (P < .01), together with a less significant association of anger-in with carotid artery IMT (P < .05). Neither anger-out nor trait anger was significantly associated with carotid artery IMT or stiffness. Moreover, none of the anger measures was significantly associated with resting BP in this normotensive sample. As expected, carotid artery IMT, stiffness, and systolic BP were all positively associated. In multivariate analysis, anger-in remained a determinant of stiffness independent of BP, and a marginally significant determinant of carotid artery IMT. CONCLUSIONS: This is the first known finding that high anger-in is a significant independent determinant of carotid artery stiffness. These results suggest that high anger-in can potentiate the effects of age on stiffening of the central arteries.

Aged↗
PubMed2006

Short- and long-term outcome and factors predicting survival after surgical tube cystostomy for treatment of obstructive urolithiasis in small ruminants.

OBJECTIVE: To evaluate outcome of small ruminants after tube cystostomy without urethral flushing. STUDY DESIGN: Retrospective clinical study. ANIMALS: Small ruminants (n=63; 50 goats, 13 sheep). METHODS: Medical records (January 1996-October 2003) for all small ruminants undergoing tube cystostomy were analyzed. Signalment, laboratory data, intraoperative findings, urolith type, and postoperative outcome were compared. Long-term follow-up was obtained at 6 and > or= 12 months postoperatively. RESULTS: Most animals were castrated males. Pygmy goats were overrepresented. Mean time to normal urination after tube cystostomy was 11 days, and mean hospitalization was 14 days. Seventy-six percent of animals were successfully treated with tube cystostomy (90% of those discharged from hospital). Short- and long-term survival was good for those animals with follow-up data. Reobstruction occurred in <20% of animals at 6 and 12 months. Goats, castrated males, and animals with normal serum potassium, no fluid in the abdomen, or no urethral process amputation were more likely to survive. Stone type, bladder appearance, and age at castration were not associated with outcome. CONCLUSION: Surgical tube cystostomy without urethral flushing is an effective technique for resolution of obstructive urolithiasis in small ruminants. CLINICAL RELEVANCE: Goats, small ruminants with an intact urethral process, absence of abdominal fluid, and serum potassium concentration <5.2 mEq/L at admission were all associated with survival after tube cystostomy. Castrated males may also be more likely to survive. These factors should be considered in management of small ruminants with urolithiasis.

Animals↗
PubMed2006

Pharmacokinetics of intravenously administered caffeine in healthy alpacas (Lama pacos) and llamas (Lama glama).

OBJECTIVE: To determine the pharmacokinetic disposition of IV administered caffeine in healthy Lama spp camelids. ANIMALS: 4 adult male alpacas and 4 adult female llamas. PROCEDURES: Caffeine (3 mg/kg) was administered as an IV bolus. Plasma caffeine concentrations were determined by use of high-performance liquid chromatography in 6 animals and by use of liquid chromatography-mass spectrometry in 2 llamas. RESULTS: Median elimination half-life was 11 hours (range, 9.3 to 29.8 hours) in alpacas and 16 hours (range, 5.4 to 17 hours) in llamas. The volume of distribution at steady state was 0.60 L/kg (range, 0.45 to 0.93 L/kg) in alpacas and 0.75 L/kg (range, 0.68 to 1.15 L/kg) in llamas. Total plasma clearance was 44 mL/h/kg (range, 24 to 56 mL/h/kg) in alpacas and 42 mL/h/kg (range, 30 to 109 mL/h/kg) in llamas. CONCLUSIONS AND CLINICAL RELEVANCE: High-performance liquid chromatography and liquid chromatography-mass spectrometry were suitable methods for determination of plasma caffeine concentrations in alpacas and llamas. Plasma caffeine concentration-time curves were best described by a 2-compartment model. Elimination half-lives, plasma clearance, volume of distribution at steady state, and mean residence time were not significantly different between alpacas and llamas. Intravenous administration of caffeine at a dose of 3 mg/kg did not induce clinical signs of excitement.

Animals↗
PubMed2006

Development of a technique for serial bilateral renal biopsy in steers.

A biopsy procedure was developed to provide serial kidney samples from standing steers. Ten clinically normal steers were given intramuscular injections of gentamicin sulfate, 4 mg/kg body weight. Renal biopsy was performed at 5 separate times. After feed was withheld for 24 h, laparoscopic surgery was performed in standing stocks. Acepromazine, xylazine, and butorphanol were used for sedation and analgesia, and 2% lidocaine was used for local anesthesia. Two incisions approximately 2 cm long were made in the paralumbar fossa to allow for trocar introduction. The abdomen was insufflated with CO2 and, with endoscopic guidance, a biopsy forceps used to remove a kidney sample 2 to 3 mm in diameter, by either a left or a right abdominal approach. Each operation was recorded on videotape, and images were also captured with a digital medical device system. Respiration, heart rate, temperature, appetite, attitude, and postural positions were evaluated at 12, 24, 48, and 72 h after surgery. The 51 laparoscopic procedures provided 48 renal samples (approximately 100 mg each). The 1st and 2nd samples were from the right kidney, and the 3rd sample was from either the left or the right kidney; the 4th and 5th samples were from the left kidney. Adhesions made an approach from the right side difficult for the 3rd sample. No clinical changes were observed in 9 steers after the procedure. One steer died after the 3rd procedure owing to hemorrhage.

Anesthesia, Local↗
PubMed2005

Regulatory cells and human cancer.

While there is now little debate about the existence or relevance of regulatory populations of T cells to a variety of human diseases, including cancer, there is considerable debate about the ontogeny, phenotype, and mechanisms of action of given regulatory T cell populations. This review will limit itself to discussion to two distinct populations of CD4+ regulatory T cells: T cells co-expressing the CD25 receptor (Tregs), and type 1 regulatory (Tr1) T cells. Attention will be focused on the definition and role of these regulatory T cell populations in human cancers.

Humans↗
PubMed2005

One-step laparoscopic abomasopexy for correction of left-sided displacement of the abomasum in dairy cows.

Four adult dairy cows in which a diagnosis of left-displaced abomasum (LDA) had been made underwent a 1-step laparoscopic abomasopexy (LA). The technique was performed with each cow positioned in dorsal recumbency. Two laparoscopic portals were created in the right paramedian area to identify the abomasum and direct insertion of the steel trocar and cannula into the abomasal lumen. A stainless steel toggle pin (with 2 lengths of suture attached to its midpoint) was inserted via the cannula into the abomasal lumen while the excess suture material remained exterior to the abdomen. The abomasum was deflated, and the excess suture material was withdrawn up to a preset marker on the suture to position the abomasum adjacent to the body wall. The suture was then tied to secure the abomasum in place. By use of this 1-step LA technique, LDA was successfully corrected in all 4 cows. The procedure is minimally invasive and allows viewing of the abomasum for correct positioning and fixation; it can be accomplished with the speed associated with the blind roll-and-tack technique. The 1-step LA technique may reduce the incidence of complications associated with traditional laparotomy and the blind roll-and-tack technique and could be a useful alternative procedure for the treatment of LDA in dairy cows.

Abomasum↗
PubMed2005

Kar3 interaction with Cik1 alters motor structure and function.

Kar3, a kinesin-14 motor of Saccharomyces cerevisiae required for mitosis and karyogamy, reportedly interacts with Cik1, a nonmotor protein, via its central, predicted coiled coil. Despite this, neither Kar3 nor Cik1 homodimers have been observed in vivo. Here we show that Kar3 is a dimer in vitro by analytical ultracentrifugation. The motor domains appear as paired particles by rotary-shadow electron microscopy (EM) and circular dichroism (CD) spectroscopy of the nonmotor region shows characteristics of helical structure, typical of coiled coils. Remarkably, the Kar3/Cik1 nonmotor region shows greater helicity by CD analysis and rotary-shadow EM reveals a stalk joined to one large or two smaller particles. The highly helical Kar3/Cik1 nonmotor region and visible stalk indicate that dimerization with Cik1 causes structural changes in Kar3. The Cik1 and Kar3 stalk regions preferentially associate with one another rather than forming homodimers. Kar3/Cik1 moves on microtubules at 2-2.4 microm min(-1), 2-5-fold faster than Kar3, and destabilizes microtubules at the lagging ends. Thus, structural changes in Kar3 upon dimerization with Cik1 alter the motor velocity and likely regulate Kar3 activity in vivo.

Circular Dichroism↗
PubMed2005

Cesarean section in cows.

The goals of the cesarean section are preservation of the dam and calf and the future reproductive efficiency of the dam. The outcome of the cesarean section is a self-fulfilling prophecy. Numerous variables may affect the successful outcome of this procedure. Case selection is the most important and often overlooked variable. In addition, skin preparation,surgical technique, calf viability at the time of surgery, and exteriorizing the uterus can affect outcome. Minimizing excessive adhesion formation is equally important because it may affect reproductive efficiency adversely. Good surgical technique, including gentle tissue handling, appropriate suture materials and patterns, and adequate infolding of the uterine incision to prevent leakage, combined with antibiotics and anti-inflammatories when indicated can help minimize detrimental adhesions that may affect adversely the future reproductive efficiency of the cow. When dealing with anemphysematous fetus, intensive medical management perioperatively isa crucial determining factor of cow survival. Anti-inflammatories, high doses of intravenous antibiotics, and a ventral midline approach that permits adequate uterine exteriorization and reduces abdominal contamination also are likely key elements that contribute to the high survival rates of cows with emphysematous fetuses.

Animals↗
PubMed2005

Pain management in ruminants.

Based on the available literature, the most important tool available in modern veterinary medicine is preemptive analgesia. Veterinarians must capture "opportunities" to prevent the onset of pain, prevent noxious stimuli or their perception, and limit the pain-stress-distress cascade that results in altered behavior and deviation from physiologic norms. Rational treatment of pain requires an appreciation of its consequences, a fundamental understanding of the mechanisms that are responsible for its production,and a practical appreciation of the analgesic drugs that are available. The goal of pain treatment should be to restore normal (physiologic) pain responses and to eliminate pathologic pain processes. In this context, pain therapy should be directed at the multiple mechanisms (multimodal therapy)responsible for its production, and analgesic therapies should be instituted before (preemptive therapy) pain is initiated (eg, surgery) whenever possible.

Analgesia↗
PubMed2005

Intestinal surgery of adult cattle.

Surgical disorders of the gastrointestinal tract of cattle occur occasionally, and veterinarians are challenged to determine an accurate diagnosis and treatment for these conditions. Although surgical diseases most commonly occur in the forestomachs (dislocated abomasum, reticuloperitonitis) and the colons (cecal dilation), this article focuses n lesions in the small intestine (duodenum, jejunum, ileum).

Animals↗
PubMed2005

Timing of retroviral infection influences anamnestic immune response in vaccinated primates.

Using simian immunodeficiency virus (SIV) infection of rhesus macaques to model human immunodeficiency virus (HIV) infection of humans, we assessed whether broadly reactive vaccine-induced humoral immunity would remain broadly reactive after viral challenge, and whether there would be significant differences in anamnestic antibody responses if animals were challenged when predominately effector or memory lymphocyte populations were present. Animals immunized over a prolonged period and challenged 11 months after vaccination mounted more broadly reactive and stronger humoral immunity than those rapidly vaccinated and challenged 2 weeks after their final vaccinations. These data suggest that vaccination schedule and the timing of virus challenge should be considered when evaluating future candidate HIV vaccines.

AIDS Vaccines↗
PubMed2005

Multiple sclerosis.

Multiple sclerosis (MS) is a complex genetic disease associated with inflammation in the central nervous system (CNS) white matter and is thought to be mediated by autoimmune processes. Clonal expansion of B cells, their antibody products, and T cells, hallmarks of inflammation in the CNS, are found in MS. The association of the disease with major histocompatibility complex genes, the inflammatory white matter infiltrates, similarities with animal models, and the observation that MS can be treated with immunomodulatory and immunosuppressive therapies support the hypothesis that autoimmunity plays a major role in the disease pathology. This review discusses the immunopathology of MS with particular focus given to regulatory T cells and the role of B cells and antibodies, immunomodulatory therapeutics, and finally new directions in MS research, particularly new methods to define the molecular pathology of human disease with high-throughput examination of germline DNA haplotypes, RNA expression, and protein structures that will allow the generation of a new series of hypotheses that can be tested to develop better understandings and therapies for this disease.

Animals↗