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Biomedical subjects

C M Anderson

Publications and source records attributed to C M Anderson.

At least 19 recordsLinked to original sources

Predation as a cause of neurologic signs and acute mortality in a pheasant flock.

A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was evaluated for a sudden increase in mortality and acute neurological signs after having been previously diagnosed 3 wk earlier with a chronic respiratory disease of undetermined etiology. Approximately 25 live birds were displaying neurological signs including circling, ataxia, and obtunded behavior and 50 birds were dead. Three birds with neurological signs were submitted for evaluation. Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds through the skull and into the brain were found. Trauma from a wild predatory mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the pheasant house and expressed surplus killing behavior was determined to be the cause of the acute neurological signs and mortality. The relationship of the chronic respiratory disease to the predation episode was not determined but it is possible that pheasants with severe respiratory disease may have had increased susceptibility to predation.

Animals↗

Ectopic expression of the human adenine nucleotide translocase, isoform 3 (ANT-3). Characterization of ligand binding properties.

The adenine nucleotide translocase (ANT) is a key component in maintaining cellular energy homeostasis, and has also been implicated in formation of the mitochondrial permeability transition pore. Human ANT-3 was cloned from a human heart cDNA library and expressed as a histidine-tagged fusion protein in the mitochondria of the Trichoplusia ni. cell line. Overexpression resulted in a concomitant decrease in the endogenous ANT content, allowing for the characterization of binding of known ANT ligands to the human protein. Binding affinities for bongkrekic acid (BKA), ADP, and atractyloside (ATR) were measured in mitochondria from the human ANT-3 expressing cell line, and compared to similar preparations from bovine heart mitochondria by use of a novel radioiodinated derivative of ATR. Binding to ANT-3 by the high affinity inhibitors BKA and ATR, as well as the lower affinity natural ligand ADP, was similar to that measured in bovine heart mitochondria, and to that previously reported for mammalian heart mitochondria. Characterizations such as these of human ANT isoforms may lead to drug development for enhanced mitochondrial function and cellular viability.

Adenine Nucleotide Translocator 3↗

Brain T2 relaxation times correlate with regional cerebral blood volume.

We previously reported cerebellar and putaminal transverse relaxation time (T2) differences in children with ADHD and in adults with childhood trauma. As brain T2 can be altered by deoxyhemoglobin concentration ([dHb]) and because [dHb] is proportional to regional cerebral blood volume (rCBV), at steady state we attributed those differences to rCBV changes. Studies in other species have established a correlation between T2 and rCBV; however this has yet to be demonstrated in human brain. Echo planar imaging (EPI) T2 relaxometry and dynamic susceptibility-contrast (DSC) MRI were used to measure T2 and rCBV in 11 healthy adults. Significant T2-rCBV correlations were observed in both cerebellar vermis and putamen (r = 0.759,p = 0.007;r = 0.782,p = 0.004, respectively). These correlations predict 9 +/- 3% and 10 +/- 3% rCBV changes, respectively, for each 1-msec change in T2. Consequently, brain T2 measurements may be useful for estimating steady-state rCBV.

Adolescent↗

The invariance of directional tuning with contrast and coherence.

The responses of motion mechanisms depend not only on the direction of a stimulus, but also on its contrast, coherence and speed. We examined how contrast, coherence and directional selectivity interact by measuring directional tuning psychophysically across a wide range of coherence and contrast levels. We fit data with a simple model that estimated directional tuning bandwidth using contrast and coherence gain parameters that were based on neurophysiological estimates. This model estimated a bandwidth of approximately 90 degrees for directionally selective mechanisms. Bandwidth was invariant across a wide range of contrasts and coherences, as predicted by models of contrast normalization.

Contrast Sensitivity↗

The use of a hemoglobin-based oxygen-carrying solution (HBOC-201) for extracorporeal membrane oxygenation in a porcine model with acute respiratory distress syndrome.

OBJECTIVE: To evaluate whether hemoglobin-based oxygen-carrying solution (HBOC)-201 (Biopure) is an effective alternative to donor blood for extracorporeal membrane oxygenation support in a porcine model of acute respiratory distress syndrome (ARDS). DESIGN: Randomized animal clinical trial. SETTING: Animal surgical research laboratory. SUBJECTS: Immature Yorkshire swine were assigned to one of three groups: 1, noninjured animals, donor porcine blood primed circuit; 2, ARDS-injured, HBOC-201 primed circuit; or 3, ARDS-injured, donor blood primed. INTERVENTIONS: ARDS injury was induced in groups 2 and 3 with oleic acid infusion before bypass. All animals were placed on full venoarterial extracorporeal membrane oxygenation support for 8 hrs. MEASUREMENTS AND MAIN RESULTS: Physiologic variables and laboratory samples were measured at baseline and hourly for 8 hrs. Data analysis consisted of repeated-measures analysis of variance with post hoc analysis. We found that 100% of animals survived on extracorporeal membrane oxygenation for the duration of the study period. HBOC-supported animals had comparable oxygen delivery to both donor blood groups. Mean pulmonary artery pressure, heart rate, and lactate concentrations were higher in the injury groups. Blood pressure was mildly increased in HBOC animals (p <.05 vs. control animals). Methemoglobin concentrations in the HBOC group were elevated and increased over time on extracorporeal membrane oxygenation (p <.001). CONCLUSIONS: HBOC-201 appears to be an effective alternative circuit-priming agent for use during extracorporeal membrane oxygenation. HBOC offers the advantages of rapid availability and diminished donor blood cell exposure. The efficacy of HBOC in longer duration bypass, and its associated methemoglobinemia, need to be further investigated.

Analysis of Variance↗

Variable association between genetic variation in the CYP7 gene promoter and plasma lipoproteins in three Canadian populations.

The promoter sequence variant -278A in the CYP7 gene, which encodes cholesterol 7-alpha hydroxylase, was previously reported to be associated with reduced plasma low density lipoprotein (LDL) cholesterol concentration. We tested for association of CYP7-278A with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 594 Alberta Hutterites, 325 Ontario Oji-Cree and 190 Keewatin Inuit. The CYP7-278A allele frequencies in these three groups were 0.708, 0.466 and 0.490, respectively. The frequencies of CYP7-278A/A homozygotes were 0.481, 0.215 and 0.247, respectively. In the Hutterites, CYP7-278A was associated with reduced plasma HDL-cholesterol and apolipoprotein AI concentration. In the Oji-Cree, CYP7-278A was not significantly associated with any plasma lipoprotein trait. In the Inuit CYP7-278A was associated with elevated plasma total and LDL-cholesterol. There was no consistent relationship between the population mean plasma LDL-cholesterol concentration and the population CYP7-278A frequency. Our findings suggest that the common -278A promoter variant of CYP7 was inconsistently associated with variation in plasma LDL- and HDL-cholesterol in samples from three independent populations. The inconsistencies could be due to differences in genetic background or to unspecified environmental or genetic factors.

Adult↗

Development of psychophysically-derived detection contours in L- and M-cone contrast space.

In order to investigate the development of color mechanisms in infants we fitted elliptical detection contours to psychophysically-derived contrast thresholds plotted in L- and M-cone contrast space. Detection ellipses were obtained for 47 infants (ages 2-5 months of age), and were compared to those of six adults tested under nearly identical conditions. The parameters of the fitted ellipses allowed us to address several aspects of color development. First, the lengths and widths were used to assess the relative development of chromatic, with respect to luminance, sensitivity. The results of these analyses revealed a sharp increase in chromatic sensitivity between 3 and 4 months of age, suggesting an accelerated development of chromatic mechanisms around this time. Second, the angles of the ellipses provided estimates of individual red/green isoluminance points. In line with previous reports, we found that isoluminance points do not vary significantly with age. Finally, our ellipse-fitting procedures were used to assess whether color sensitivity is best described by a model that assumes independence between post-receptoral chromatic and luminance mechanisms. Similar to previous results of Kelly and Chang [Kelly, J. P. & Chang, S. (2000). Vision Research 40, 1887-1906] obtained using steady-state visually evoked potentials, only a proportion (approximately half) of our infants exhibited detection contours that were consistent with independent mechanisms, a finding that most likely results from statistical noise in the infant data sets.

Adolescent↗

Differing effects of substrate and non-substrate transport inhibitors on glutamate uptake reversal.

Na(+)-dependent excitatory amino acid transporters (EAATs) normally function to remove extracellular glutamate from brain extracellular space, but EAATs can also increase extracellular glutamate by reversal of uptake. Effects of inhibitors on EAATs can be complex, depending on cell type, whether conditions favor glutamate uptake or uptake reversal and whether the inhibitor itself is a substrate for the transporters. The present study assessed EAAT inhibitors for their ability to inhibit glutamate uptake, act as transporter substrates and block uptake reversal in astrocyte and neuron cultures. L-threo-beta-hydroxyaspartate (L-TBHA), DL-threo-beta-benzyloxyaspartate (DL-TBOA), L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-2,4-PDC) (+/-)-cis-4-methy-trans-pyrrolidine-2,4-dicarboxylic acid (cis-4-methy-trans-2,4-PDC) and L-antiendo-3,4-methanopyrrolidine-2,4-dicarboxylic acid (L-antiendo-3,4-MPDC) inhibited L-[14C]glutamate uptake in astrocytes with equilibrium binding constants ranging from 17 microM (DL-TBOA and L-TBHA) - 43 microM (cis-4-methy-trans-2,4-PDC). Transportability of inhibitors was assessed in astrocytes and neurons. While L-TBHA, L-trans-2,4-PDC, cis-4-methy-trans-2,4-PDC and L-antiendo-3,4-MPDC displayed significant transporter substrate activities in neurons and astrocytes, DL-TBOA was a substrate only in astrocytes. This effect of DL-TBOA was concentration-dependent, leading to complex effects on glutamate uptake reversal. At concentrations low enough to produce minimal DL-TBOA uptake velocity (< or = 10 microM), DL-TBOA blocked uptake reversal in ATP-depleted astrocytes; this blockade was negated at concentrations that drove substantial DL-TBOA uptake (> 10 microM). These findings indicate that the net effects of EAAT inhibitors can vary with cell type and exposure conditions.

ATP-Binding Cassette Transporters↗

Evidence for the biosynthesis of bryostatins by the bacterial symbiont "Candidatus Endobugula sertula" of the bryozoan Bugula neritina.

The marine bryozoan, Bugula neritina, is the source of the bryostatins, a family of macrocyclic lactones with anticancer activity. Bryostatins have long been suspected to be bacterial products. B. neritina harbors the uncultivated gamma proteobacterial symbiont "Candidatus Endobugula sertula." In this work several lines of evidence are presented that show that the symbiont is the most likely source of bryostatins. Bryostatins are complex polyketides similar to bacterial secondary metabolites synthesized by modular type I polyketide synthases (PKS-I). PKS-I gene fragments were cloned from DNA extracted from the B. neritina-"E. sertula" association, and then primers specific to one of these clones, KSa, were shown to amplify the KSa gene specifically and universally from total B. neritina DNA. In addition, a KSa RNA probe was shown to bind specifically to the symbiotic bacteria located in the pallial sinus of the larvae of B. neritina and not to B. neritina cells or to other bacteria. Finally, B. neritina colonies grown in the laboratory were treated with antibiotics to reduce the numbers of bacterial symbionts. Decreased symbiont levels resulted in the reduction of the KSa signal as well as the bryostatin content. These data provide evidence that the symbiont E. sertula has the genetic potential to make bryostatins and is necessary in full complement for the host bryozoan to produce normal levels of bryostatins. This study demonstrates that it may be possible to clone bryostatin genes from B. neritina directly and use these to produce bryostatins in heterologous host bacteria.

Amino Acid Sequence↗

The effect of incentive spirometry on postoperative pulmonary complications: a systematic review.

OBJECTIVE: To systematically review the evidence examining the use of incentive spirometry (IS) for the prevention of postoperative pulmonary complications (PPCs). METHODS: We searched MEDLINE, CINAHL, HealthSTAR, and Current Contents databases from their inception until June 2000. Key terms included "incentive spirometry," "breathing exercises," "chest physical therapy," and "pulmonary complications." Articles were limited to human studies in English. A secondary search of the reference lists of all identified articles also was conducted. A critical appraisal form was developed to extract and assess information. Each study was reviewed independently by one of three pairs of group members. The pair then met to reach consensus before presenting the report to the entire review group for final agreement. RESULTS: The search yielded 85 articles. Studies dealing with the use of IS for preventing PPCs (n = 46) were accepted for systematic review. In 35 of these studies, we were unable to accept the stated conclusions due to flaws in methodology. Critical appraisal of the 11 remaining studies indicated 10 studies in which there was no positive short-term effect or treatment effect of IS following cardiac or abdominal surgery. The only supportive study reported that IS, deep breathing, and intermittent positive-pressure breathing were equally more effective than no treatment in preventing PPCs following abdominal surgery. CONCLUSIONS: Presently, the evidence does not support the use of IS for decreasing the incidence of PPCs following cardiac or upper abdominal surgery.

Abdomen↗

Parental use of escape extinctionand differential reinforcement to treat food selectivity.

Escape extinction combined with differential reinforcement for acceptance has been demonstrated to be an effective treatment for food selectivity when implemented by trained professionals in clinic settings. This study evaluated the efficacy of parent-implemented escape extinction in the child's natural environment using video monitoring to train parents and assess intervention efficacy. Parents were able to use intervention to significantly increase bites accepted and decrease problem behavior.

Behavior Therapy↗

Corticosteroids in advanced cancer.

Despite the fact that there are only a few controlled trials demonstrating the benefits associated with the use of corticosteroids in specific situations, these agents are administered frequently to patients with advanced cancer. Corticosteroids may be used alone or as adjuvants in combination with other palliative or antineoplastic treatments. For example, corticosteroids may help prevent nausea, vomiting, and hypersensitivity reactions to treatment with chemotherapy or radiation. They are also commonly used as appetite stimulants in patients with advanced cancer. In the adjuvant setting, corticosteroids help to alleviate pain in advanced cancer patients, including specific situations such as back pain related to epidural compression. This article reviews the evidence supporting the use of corticosteroids in a broad range of situations seen in patients with advanced cancer.

Adrenal Cortex Hormones↗

WAKs: cell wall-associated kinases linking the cytoplasm to the extracellular matrix.

There are only a few proteins identified at the cell surface that could directly regulate plant cell wall functions. The cell wall-associated kinases (WAKs) of angiosperms physically link the plasma membrane to the carbohydrate matrix and are unique in that they have the potential to directly signal cellular events through their cytoplasmic kinase domain. In Arabidopsis there are five WAKs and each has a cytoplasmic serine/threonine protein kinase domain, spans the plasma membrane, and extends a domain into the cell wall. The WAK extracellular domain is variable among the five isoforms, and collectively the family is expressed in most vegetative tissues. WAK1 and WAK2 are the most ubiquitously and abundantly expressed of the five tandemly arrayed genes, and their messages are present in vegetative meristems, junctions of organ types, and areas of cell expansion. They are also induced by pathogen infection and wounding. Recent experiments demonstrate that antisense WAK expression leads to a reduction in WAK protein levels and the loss of cell expansion. A large amount of WAK is covalently linked to pectin, and most WAK that is bound to pectin is also phosphorylated. In addition, one WAK isoform binds to a secreted glycine-rich protein (GRP). The data support a model where WAK is bound to GRP as a phosphorylated kinase, and also binds to pectin. How WAKs are involved in signaling from the pectin extracellular matrix in coordination with GRPs will be key to our understanding of the cell wall's role in cell growth.

Arabidopsis↗

Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians.

We previously showed that a rare mutation in LMNA, which encodes lamins A and C, underlies autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD). Because FPLD is an extreme example of genetically disturbed adipocyte differentiation, it is possible that common variation in LMNA is associated with obesity-related phenotypes. We therefore analyzed the relationships between the common LMNA 1908T/C single nucleotide polymorphism (SNP) and plasma leptin and anthropometric indices in 306 nondiabetic Canadian Oji-Cree. We found that subjects with the LMNA 1908T/1908T genotype had significantly higher plasma leptin than the subjects with either the 1908C/1908T or 1908C/1908C genotypes, after adjustment for age and sex. Physical indices of obesity, such as body mass index, percent body fat, and ratio of waist-to-hip circumference, were also higher among Oji-Cree subjects with the LMNA 1908T/1908T genotype than the subjects with either the 1908C/1908T or 1908C/1908C genotypes. The results suggest that common genetic variation in LMNA may be an important determinant of plasma leptin and obesity-related quantitative traits.

Adult↗

Structural requirements for activity of the pheromones of Ustilago hordei.

Ustilago hordei, the cause of barley-covered smut, initiates mating with pheromones. Gene sequence analysis suggested that these pheromones, Uhmfa1 and Uhmfa2, would be farnesylated peptides. Although isolation of mating-type-specific activity was rarely possible, chromatographic separations of culture supernatants yielded fractions that stimulated or inhibited mating. Based on predicted amino acid sequences and mass spectra of stimulating fractions, a series of pheromone analogs were synthesized and their activities were determined. Underivatized Uhmfa1 (PGKSGSGLGYSTC) or Uhmfa2 (EGKGEPAPYC) peptides were inactive, while peptides that were farnesylated and/or methyl esterified specifically induced conjugation tubes by cells of the opposite mating type. Uhmfa1 truncated from the amino terminus beyond the lysine lost activity, while truncated Uhmfa2 remained partially active. In mating bioassays, a pheromone concentration-dependent default mating response was observed. In competition studies, shorter Uhmfa1 peptides lacking pheromone activity inhibited activity of full-length peptides most effectively when both had the same functional groups.

Chromatography, High Pressure Liquid↗

Functional phenotype in transgenic mice expressing mutant human presenilin-1.

Mutations in the presenilin-1 (PS1) gene cause approximately 50% of cases of early onset familial Alzheimer's disease. The function of this protein remains unknown. We have made an electrophysiological study of hippocampal slices from transgenic mice expressing either a normal human PS1 transgene (WT) or one of two human PS1 transgenes bearing pathogenic mutations at codon M146 (M146L and M146V). Medium and late afterhyperpolarizations in CA3 pyramidal cells were larger in mice expressing either mutant form compared with WT and nontransgenic controls. Calcium responses to depolarization were larger in M146L mice compared with nontransgenic littermates; synaptic potentiation of the CA3 to CA1 projection was also stronger. These results demonstrate disruption of the control of intracellular calcium and electrophysiological dysfunction in PS1 mutant mice.

Alzheimer Disease↗