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Biomedical subjects

T R Anderson

Publications and source records attributed to T R Anderson.

At least 19 recordsLinked to original sources
PubMed2007

Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence.

To identify sequence variants in genes that may have roles in neuronal responses to alcohol, we resequenced the 5' region of tyrosine kinase B neurotrophin receptor gene (NTRK2) and determined linkage disequilibrium (LD) values, haplotype structure, and performed association analyses using 43 single nucleotide polymorphisms (SNPs) covering the entire NTRK2 region in a Finnish Caucasian sample of 229 alcohol-dependent subjects with antisocial personality disorder (ASPD) and 287 healthy controls. Individually, three SNPs were associated with alcohol dependence and alcohol abuse (AD) (P-value from 0.0019 to 0.0059, significance level was set at P<or=0.01 corrected for multiple testing), whereas a common 18 locus haplotype within the largest LD block of NTRK2, a 119-kb region containing the 5' flanking region and exons 1-15, was marginally overrepresented in control subjects compared to AD individuals (global P=0.057). Taken together, these results support a role for the NTRK2 gene in addiction in a Caucasian population with AD and a subtype of ASPD.

5' Flanking Region↗
PubMed2005

Genomics and variation of ionotropic glutamate receptors: implications for neuroplasticity.

We used two approaches to identify sequence variants in ionotropic glutamate receptor (IGR) genes: high-throughput screening and resequencing techniques, and "information mining" of public (e.g. dbSNP, ENSEMBL) and private (i.e. Celera Discovery System) sequence databases. Each of the 16 known IGRs is represented in these databases, their positions on a canonical physical map are established. Comparisons of mouse, rat, and human sequences revealed substantial conservation among these genes, which are located on different chromosomes but found within syntenic groups of genes. The IGRs are members of a phylogenetically ancient gene family, sharing similarities with glutamate-like receptors in plants. Parsimony analysis of amino acid sequences groups the IGRs into three distinct clades based on ligand-binding specificity and structural features, such as the channel pore and membrane spanning domains. A collection of 38 variants with amino acid changes was obtained by combining screening, resequencing, and informatics approaches for several of the IGR genes. This represents only a fraction of the sequence variation across these genes, but in fact these may constitute a large fraction of the common polymorphisms at these genes and these polymorphisms are a starting point for understanding the role of these variants in function. Genetically influenced human neurobehavioral phenotypes are likely to be linked to IGR genetic variants. Because ionotropic glutamate receptor activation leads to calcium entry, which is fundamental in brain development and in forms of synaptic plasticity essential for learning and memory and is essential for neuronal survival, it is likely that sequence variants in IGR genes may have profound functional roles in neuronal activation and survival mechanisms.

Amino Acid Substitution↗
PubMed2001

Anoxic depolarization mediates acute damage independent of glutamate in neocortical brain slices.

An important but poorly understood event associated with ischemia is anoxic depolarization (AD), a sudden and profound depolarization of neurons and glia in cortical and subcortical gray matter. Leao first measured the AD as a wave of electrical silence moving across the cerebral cortex in 1947 and noted its similarity to spreading depression (SD). SD is harmless when coursing through normoxic cortical tissue as during migraine aura. However for 3-4 h following focal ischemia, the additional metabolic stress arising from recurring SD in the penumbra expands the ischemic core, so SD blockade is potentially beneficial therapeutically. In the present study, we measured intrinsic optical signals (IOSs) to monitor anoxic depolarization in submerged rat neocortical slices during O2/glucose deprivation (OGD). After approximately 6 min of OGD, the AD was imaged as a focal increase in light transmittance which then propagated across neocortical gray at approximately 2 mm/min. Although the slice was globally stressed, the AD always initiated focally, sometimes at multiple sites. Its propagation was coincident with a transient negative shift in the extracellular potential, the electrical signature of AD. Acute damage to neocortex (measured as a delayed decrease in LT and as a loss of the evoked field potential) followed only where the AD had propagated, so it is the combined metabolic demands of AD and OGD that acutely damages all layers of the neocortex. Glutamate receptor antagonists (2 mM kynurenate or 25 microM AP-5/10 microM CNQX) did not block AD initiation, slow its propagation or prevent post-AD damage. This study shows that acute ischemic damage is greatly exacerberated by AD during metabolic stress and that glutamate receptor antagonists are not protective. Using this slice model, therapeutically tolerable drugs that block the AD and SD can be investigated.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Epitope tagging: general method for tracking recombinant proteins.

Epitope tagging has provided a useful experimental strategy with widespread applicability. The ample variety of epitope tag systems that have been put to use to date provide a collection of attributes relevant to virtually any experimental system. As a consequence, epitope tagging will continue to be a valuable tool for molecular biologists long into the future.

Animals↗
PubMed1999

Children and adolescents in the psychiatric emergency setting.

Emergencies in child and adolescent psychiatry are not uncommon, occur in a variety of settings, and require referral to resources offering different levels of care. Clinicians must be familiar with basic tenets of emergency assessment and treatment whether practicing alone in a rural area or as part of an interdisciplinary team in a busy urban hospital. Recommendations for future research include gathering more extensive epidemiologic data and data regarding practice patterns nationwide and conducting more psychopharmacologic research into the management of patients with acute agitation, aggression, and violence. In addition, outcome data to support provision of necessary inpatient and outpatient services must be collected. The development of successful strategies to prevent psychiatric emergencies in children and adolescents is equally important.

Adolescent↗
PubMed1998

Female voice communications in high levels of aircraft cockpit noises--Part I: spectra, levels, and microphones.

HYPOTHESIS: Female produced speech, although more intelligible than male speech in some noise spectra, may be more vulnerable to degradation by high levels of some military aircraft cockpit noises. The acoustic features of female speech are higher in frequency, lower in power, and appear more susceptible than male speech to masking by some of these military noises. Current military aircraft voice communication systems were optimized for the male voice and may not adequately accommodate the female voice in these high level noises. METHODS: This applied study investigated the intelligibility of female and male speech produced in the noise spectra of four military aircraft cockpits at levels ranging from 95 dB to 115 dB. The experimental subjects used standard flight helmets and headsets, noise-canceling microphones, and military aircraft voice communications systems during the measurements. RESULTS: The intelligibility of female speech was lower than that of male speech for all experimental conditions; however, differences were small and insignificant except at the highest levels of the cockpit noises. Intelligibility for both genders varied with aircraft noise spectrum and level. Speech intelligibility of both genders was acceptable during normal cruise noises of all four aircraft, but improvements are required in the higher levels of noise created during aircraft maximum operating conditions. CONCLUSIONS: The intelligibility of female speech was unacceptable at the highest measured noise level of 115 dB and may constitute a problem for other military aviators. The intelligibility degradation due to the noise can be neutralized by use of an available, improved noise-canceling microphone, by the application of current active noise reduction technology to the personal communication equipment, and by the development of a voice communications system to accommodate the speech produced by both female and male aviators.

Adult↗
PubMed1993

Immunocytochemical and immunogold localization of two prolactin isoforms in the same pituitary cells and in the same granules in the tilapia (Oreochromis mossambicus).

The tilapia pituitary secretes two forms of prolactin (tPRL) and a single growth hormone (tGH). The tPRLs share only 69% sequence identity and are designated tPRL177 and tPRL188 to indicate the number of amino acid residues in each isoform. Our aim was to develop specific antisera for detection of these three related polypeptides. Ten peptides corresponding to unique epitopes on the tPRLs and two peptides of tGH were synthesized using solid-phase methods, conjugated to carrier proteins, and used as immunogens for antibody production in rabbits. Select antisera for the tPRLs were highly specific, exhibiting only 1% cross-reactivity to the alternate tPRL under noncompetitive ELISA conditions at dilutions used in immunocytochemical analysis. The anti-tGH specifically bound to cells in the proximal pars distalis. Production of both tPRLs by a single cell type was indicated by the binding of both anti-tPRL177 and anti-tPRL188 to the same cells in the rostral pars distalis. Ultrastructural analysis of PRL-producing cells stained sequentially using the two different anti-tPRL antibodies labeled with immunogold of two size classes indicated that both tPRLs appear in the same granules. These findings suggest that the biological significance of two forms of PRL in the adult tilapia is not a function of differential regulation of two different classes of PRL cells or differential release of unique secretory granules.

Amino Acid Sequence↗
PubMed1992

Induction by beta-estradiol of vitellogenin in striped bass (Morone saxatilis): characterization and quantification in plasma and mucus.

Striped bass (Morone saxatilis) were implanted with beta-estradiol to induce the production of vitellogenin, the egg yolk precursor produced by the liver. Electrophoretic analysis revealed that beta-estradiol caused marked production of a plasma protein of apparent molecular mass 170 kDa. Size exclusion chromatography suggested that the estradiol-induced protein circulated as a dimer. This protein was purified from the plasma of estradiol-treated fish by DEAE-agarose column chromatography and used to induce antibodies in rabbits and goats. Western blots revealed that the antiserum bound to the putative vitellogenin in plasma from estradiol-treated fish and adult females, but not with any proteins in male plasma. Western blot of ovarian extract revealed several smaller immunoreactive protein bands and supported the identity of the purified protein as vitellogenin. A competitive ELISA was developed with sensitivity in a range from 8 to 1000 ng/ml. Plasma concentrations of adult females during their spawning migration ranged from 100 to 600 micrograms/ml. Western blot of mucus extract revealed the presence of a 170-kDa protein in vitellogenic female fish along with several minor bands ranging from 50 to 110 kDa. Positive immunoreactivity was present in the surface mucus of all females and in none of the males collected during a spawning migration in the Hudson River.

Animals↗
PubMed1989

Ultrastructural localization of tartrate-resistant, purple acid phosphatase in rat osteoclasts by histochemistry and immunocytochemistry.

The intracellular localization of the tartrate-resistant purple acid phosphatase in osteoclasts of developing rat bone has been determined immunocytochemically using an antiserum to the purified bone-derived purple acid phosphatase. The localization of the immunoreactivity was compared with the results of enzyme histochemistry using p-nitrophenylphosphate as substrate and 10 mM tartrate. Both methods revealed the presence of the enzyme in numerous vesicles of various sizes up to 2-3 microns in diameter and in granules. There was no immunoreactivity in the Golgi apparatus, and tartrate completely inhibited the histochemical activity of this organelle. No consistent extracellular activity could be detected, nor was any reaction product observed at the ruffled border. The localization of the tartrate-resistant purple acid phosphatase in osteoclasts is consistent with an intracellular function for this enzyme.

Acid Phosphatase↗
PubMed1989

Pseudomonas aeruginosa flagellar antibodies in patients with cystic fibrosis.

An enzyme-linked immunosorbent assay specific for flagellum type (a or b) of Pseudomonas aeruginosa was used to detect serum immunoglobulin antibodies in 98 random outpatients and 14 colonized cystic fibrosis patients. Antibodies were detected to both types of flagella in addition to M-2 lipopolysaccharide. Titers to both flagellar antigens (FlAg) were 10 to 100 times higher in cystic fibrosis patients than in random outpatients of a comparable age group. Mean antibody titers against b-type FlAg were 454 for outpatients (ages newborn to 21 years), whereas the mean titer for cystic fibrosis patients (ages 6 to 21 years) was 51,520. Titers against a-type FlAg were generally lower, with mean outpatient titers of 68 and mean cystic fibrosis patient titers of 34,323. Differences were also seen in antibody titer against M-2 lipopolysaccharide, but these differences did not correspond to M-2 FlAg titers. In 98 random outpatients (ages newborn to 86 years), FlAg titers generally increased with age. To demonstrate further specificity of the enzyme-linked immunosorbent assay for flagellum antibody, Western blots were performed with selected high-titer cystic fibrosis patient sera. Sera that had a high titer (greater than 25,600) for b- or a-type FlAg showed a corresponding reactive band. These results demonstrate that flagellum antibodies are produced in humans in response to P. aeruginosa infection.

Adolescent↗
PubMed1989

Flagellar antibody stimulated opsonophagocytosis of Pseudomonas aeruginosa associated with response to either a- or b-type flagellar antigen.

Pseudomonas aeruginosa exhibit one of two flagella types: a homogeneous b type, with molecular weight of 53,000, or a heterogeneous a type (subtypes a0, a1, a2, a3, and a4), with molecular weights ranging from 45,000 to 52,000. Pseudomonas aeruginosa flagellar antiserum was shown to promote uptake of radiolabeled bacteria by mouse polymorphonuclear leukocytes. Bacteria were detected directly associated with washed leukocytes and visualized, by electron microscopy, internalized in polymorphonuclear leukocytes. Phagocytosis was specific for the flagella type (a or b) in that homologous flagella serum enhanced uptake three to four times greater than heterologous serum or normal rabbit serum. An a-type antiserum was shown to enhance phagocytosis of four different a-type strains with varying subantigen types, indicating the presence of a common cross-reactive a0 antigen in this flagella type. Phagocytic killing of internalized bacteria was not seen with the addition of only flagellar antiserum.

Animals↗
PubMed1988

Enzyme-linked immunosorbent assay for detection of Pseudomonas aeruginosa H (flagellar) antigen.

An enzyme-linked immunosorbent assay (ELISA) with goat anti-rabbit IgG conjugated to peroxidase was used to test for the two antigen types of Pseudomonas aeruginosa: b (homogeneous) and a (heterogeneous) which contains the common subantigen (a0) and combinations of subtypes (a, a2 a3 a4). Preparations of b-type flagellar antigen could be distinguished from a-type by using b-adsorbed antisera titers as reciprocals of endpoint dilutions exceeding one million. Extracts from nonflagellated bacteria or purified lipopolysaccharides from the same strain were used as controls, which showed only background activity. Unknown flagellar antigen was determined using both isolated antigen preparations and formalin-killed bacterial cells. The ELISA procedure proved much more sensitive than the slide agglutination procedure: whereas nine of 18 strains tested did not react in the slide agglutination procedure all 18 strains were definitively typed as a or b strains with the ELISA. The ELISA also revealed the presence of a dominant, cross-reacting epitope (a0) in the heterogeneous a-type flagella using either isolated antigen or intact cells.

Agglutination Tests↗
PubMed1987

Interactions among prolactin, epidermal growth factor, and proinsulin on the growth and morphology of the pigeon crop-sac mucosal epithelium in vivo.

The local pigeon crop-sac assay was used to test the direct effects of epidermal growth factor (EGF) and several other growth factors and hormones on the growth of mucosal epithelial cells in vivo. Insulin, relaxin, multiplication-stimulating activity, proinsulin, and platelet-derived or fibroblast growth factors had no direct stimulatory activity by themselves. Human insulin-like growth factor I and EGF caused dose-related stimulation, but were less effective than ovine (o) PRL. Insulin, platelet-derived growth factor, fibroblast growth factor, and multiplication-stimulating activity did not affect the proliferative response to oPRL when injected along with the hormone. Proinsulin augmented the direct mitogenic action of oPRL, but not that of EGF. When EGF was injected locally with PRL no interaction occurred even though both hormones were independently mitogenic. A single sc injection of a high dose of oPRL (0.5 mg) given at a site distant from the crop-sac had no effect on the mucosal epithelial cells, but it caused a significant increase in their response to the direct action of oPRL. However, the systemically acting PRL did not affect the direct local effect of EGF. The gross pattern of mucosal cell proliferation induced by PRL (parallel ridges resembling gastric rugae) differed from that produced by EGF (usually irregular patches), and PRL, but not EGF, promoted the accumulation of lipid droplets in the stimulated mucosal epithelial cells. Furthermore, the crop mucosal cells in the midline of the organ are unresponsive to PRL, but were highly responsive to EGF. These results indicate that although EGF and PRL are both mitogenic to crop mucosal epithelial cells, the former does not mimic the latter. They produce a different growth pattern, and EGF fails to promote differentiation of the resultant daughter cells. Moreover, EGF is a less specific mitogen than is PRL, and the two hormones do not interact in their mitogenic effects.

Animals↗
PubMed1986

The human growth hormone gene is negatively regulated by triiodothyronine when transfected into rat pituitary tumor cells.

Human growth hormone (hGH) gene expression and regulation by thyroid and glucocorticoid hormones were examined after its stable introduction into rat anterior pituitary tumor cells. Transcripts from the hGH gene were correctly initiated and could be positively regulated by glucocorticoids. In contrast to the endogenous rat GH gene and a transfected, modified rat GH gene, the hGH gene was negatively regulated by triiodothyronine. Analysis of hGH gene 5'-flanking deletions indicated that a distal regulatory element is required for efficient transcription. Thus promoter, glucocorticoid, and thyroid hormone control elements are present on the transfected hGH gene, whose expression may be negatively controlled by thyroid hormone.

Animals↗
PubMed1986

Purification and characterization of purple acid phosphatase from developing rat bone.

Tartrate-resistant acid phosphatase active on nucleoside di- and triphosphate substrates was isolated from developing rat bone and purified 2500-fold. The enzyme concentration had a purple coloration and activity that was sensitive to reducing agents. Mild reducing agents such as ferrous ion and ascorbic acid caused loss of purple color and increased activity toward substrates severalfold; however, a strong reductant such as dithionite caused loss of both color and activity which were partially restored by addition of ferrous ion and ascorbic acid. Enzyme activity was homogeneous with protein during the final gel permeation steps of chromatography and gave an apparent molecular size of about 40,000 Da. Determination of iron in the most pure preparation revealed the presence of 1.3 atoms of iron per molecule of the tartrate-resistant enzyme E2. Other properties of the purified enzyme include a pI of approximately 9.5 and sensitivity to inhibition by ions of copper, zinc, fluoride, and molybdate. Antibody prepared to the pre-concanavalin A (Con A)-Sepharose purified enzyme reacted with all protein from the Con A step, but it did not react with tartrate-sensitive acid phosphatase from rat bone or with potato acid phosphatase. Purple acid phosphatase from rat bone has many properties that parallel the iron-containing purple acid phosphatases from rat spleen, bovine spleen, and pig uterine secretions.

Acid Phosphatase↗
PubMed1986

The 5'-flanking sequences of the human growth hormone gene contain a cell-specific control element.

The 5'-flanking sequences of the human growth hormone (hGH) gene contain a cell-specific control element. Hybrid genes containing truncated 5'-flanking DNA fragments from the hGH gene fused to the chloramphenicol acetyl transferase (cat) gene were examined using transient transfection of rat anterior pituitary (GC) and nonpituitary cell lines (HeLa, Rat 2, and KB); preferential expression of these gene hybrids was only observed in GC cells. Deletions through the 5'-flanking sequences of the hGH gene revealed that the region containing nucleotides -230 to -180 is required for efficient cat gene expression in GC cells. This region of DNA is highly homologous to a region of the rGH gene that contains a tissue-specific control element. A hybrid gene containing the tissue-specific control element, but lacking the proximal promoter elements, of the hGH gene upstream from the promoter of the thymidine kinase gene (TKp) from herpes simplex virus ligated to the cat gene produced more CAT activity than the TKp.cat gene in GC cells but not in HeLa cells. These data suggest that the tissue-specific control element located in the 5'-region of the hGH gene can act in the presence of a heterologous promoter and is specific for expression in pituitary cells.

Acetyltransferases↗