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Biomedical subjects

R Cotter

Publications and source records attributed to R Cotter.

At least 19 recordsLinked to original sources
PubMed2002

Fractalkine (CX3CL1) and brain inflammation: Implications for HIV-1-associated dementia.

Leukocyte migration and activation play an important role in immune surveillance and the pathogenesis of a variety of neurodegenerative disorders, including human immunodeficiency virus (HIV)-1-associated dementia (HAD). A novel chemokine named fractalkine (FKN, CX3CL1), which exists in both membrane-anchored and soluble isoforms, has been proposed to participate in the generation and progression of inflammatory brain disorders. Upon binding to the CX3C receptor one (CX3CR1), FKN induces adhesion, chemoattraction, and activation of leukocytes, including brain macrophages and microglia (MP). Constitutively expressed in the central nervous system (CNS), mainly by neurons, FKN is up-regulated and released in response to proinflammatory stimuli. Importantly, FKN is up-regulated in the brain tissue and cerebrospinal fluid (CSF) of HAD patients. Together, these observations suggest that FKN and its receptor have a unique role in regulating the neuroinflammatory events underlying disease. This review will examine how FKN contributes to the recruitment and activation of CX3CR1-expressing MP, which are critical events in the neuropathogenesis of HAD.

AIDS Dementia Complex↗
PubMed2001

A leucine-rich repeat region is conserved in pollen extensin-like (Pex) proteins in monocots and dicots.

We previously isolated a pollen-specific gene encoding a pollen tube wall-associated glycoprotein with a globular domain and an extensin domain from maize (mPex1). To evaluate which protein domains might be important for function, we isolated a second monocot gene (mPex2) and a dicot gene (tPex). Each gene encodes a signal sequence, an N-terminal globular domain comprised of a variable region, a leucine-rich repeat (LRR) with an adjacent cysteine-rich region, a transition region and an extensin-like C-terminal domain. The LRRs of the maize and tomato Pex proteins are highly conserved. Although the extensin domains in the maize and tomato proteins vary in length and in amino acid sequence, they are likely to be structurally conserved. Additional putative Pex gene sequences were identified by either GenBank search (Arabidopsis) or PCR (sorghum and potato): all encode conserved LRRs. The presence of a conserved LRR in the known and potential Pex proteins strongly suggests that this motif is involved in the binding of a specific ligand during pollen tube growth. Gene expression studies using RNA and protein blotting as well as promoter-reporter gene fusions in transient and stable transformation indicate that the tomato Pex gene is pollen-specific.

Amino Acid Sequence↗
PubMed1999

Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia.

The mechanism(s) by which HIV-1 affects neural injury in HIV-1-associated dementia (HAD) remains unknown. To ascertain the role that cellular and viral macrophage products play in HAD neurotoxicity, we explored one potential route for neuronal demise, CXCR4. CXCR4, expressed on lymphocytes and neurons, is both a part of neural development and a co-receptor for HIV-1. Its ligand, stromal cell-derived factor-1alpha (SDF-1alpha), affects neuronal viability. GTP binding protein (G-protein) linked signaling after neuronal exposure to SDF-1alpha, virus-infected monocyte-derived macrophage (MDM) secretory products, and virus was determined. In both human and rat neurons, CXCR4 was expressed at high levels. SDF-1alpha/beta was detected predominantly in astrocytes and at low levels in MDM. SDF-1beta/beta was expressed in HAD brain tissue and upregulated in astrocytes exposed to virus infected and/or immune activated MDM conditioned media (fluids). HIV-1-infected MDM secretions, virus and SDF-1beta induced a G inhibitory (Gi) protein-linked decrease in cyclic AMP (cAMP) and increase inositol 1,4, 5-trisphosphate (IP3) and intracellular calcium. Such effects were partially blocked by antibodies to CXCR4 or removal of virus from MDM fluids. Changes in G-protein-coupled signaling correlated, but were not directly linked, to increased neuronal synaptic transmission, Caspase 3 activation and apoptosis. These data, taken together, suggest that CXCR4-mediated signal transduction may be a potential mechanism for neuronal dysfunction during HAD.

AIDS Dementia Complex↗
PubMed1998

A low-viscosity soluble-fiber fruit juice supplement fails to lower cholesterol in hypercholesterolemic men and women.

This study was designed to determine whether a soluble dietary fiber supplement containing gum arabic and pectin in apple juice would lower serum lipids in 110 hypercholesterolemic men and women. Subjects were stabilized on an American Heart Association Phase I Diet for 8 wk. Those with elevated low density lipoprotein cholesterol levels, despite dietary modification, continued to follow the diet and were randomly assigned to receive 720 mL/d of apple juice containing 0 (control), 5, 9 or 15 g of gum arabic and pectin (4:1 ratio) for 12 wk, followed by a 6-wk apple juice-only washout phase. Serum lipid profiles, body weight and 3-day diet records were collected at 3-wk intervals. No significant differences among groups were observed in serum lipid responses during treatment or washout. During the treatment phase, mean serum total cholesterol and triglyceride concentrations increased by 3.5 and 28.5%, respectively (all groups combined, P < 0.0001). The high density lipoprotein cholesterol level did not change significantly from baseline in any group. During washout, mean total cholesterol concentration rose by an additional 2.4% (P < 0.05) compared with the value at the end of the treatment period, suggesting that the apple juice used to deliver the fiber supplement may have contributed to the adverse changes observed in the serum lipid profile. These findings do not support the hypothesized hypocholesterolemic effect of the gum arabic/pectin (4:1) mixture studied, but do underline the importance of selecting appropriate vehicles for delivery of dietary fiber mixtures.

Adult↗
PubMed1998

Long-term memory of an operantly conditioned respiratory behaviour pattern in lymnaea stagnalis

The freshwater snail Lymnaea stagnalis breaths bimodally either through its skin (cutaneous respiration) or via a rudimentary lung opening called the pneumostome (aerial respiration). Aerial respiratory behaviour can be operantly conditioned. Animals placed in an aquatic, hypoxic environment received a tactile stimulus to the pneumostome area every time they attempted to breathe. Over a period of five training sessions (2.5 days), the animals learned not to breathe, and the number of stimuli received in the fifth session was significantly lower than in the first session. These changes in the respiratory behaviour following the operant paradigm were shown to persist for at least 24 h. We aimed to determine whether the changes in the learned behaviour would persist for longer. We obtained direct evidence that the behavioural changes following operant conditioning persisted for at least 4 weeks following the last training session. However, we found that the persistence of this memory was dependent upon the training procedure used. Memory persisted longer following a spaced training procedure (4 weeks) as opposed to a massed training procedure (2 weeks). Yoked control animals showed no changes in their respiratory behaviour over the same time periods. However, if these yoked control animals were subjected to an operant conditioning procedure, their ability to learn was not impeded. This study demonstrated that operant conditioning of a behaviour pattern in a molluscan preparation can result in long-term memory and that the persistence of the memory is contingent on the training procedure used.

Journal Article↗
PubMed1997

Longitudinal study of nutrient and food intakes of infants aged 2 to 24 months.

OBJECTIVE: To determine the nutrient and food intakes of healthy, white infants from families of middle and upper socioeconomic status and to compare intakes to current recommendations. DESIGN: Using an incomplete random block design, we interviewed 98 mother-infant pairs longitudinally when infants were 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 months old. Data obtained included 24-hour dietary recalls, usual food intake, and food likes and dislikes. SETTING: Interviews were conducted in the mother's home by registered dietitians. Subjects resided in two urban areas of Tennessee. SUBJECTS: Of the original 98 subjects, 94 completed the 2-year study. RESULTS: Mean energy and nutrient intakes generally met or exceeded the Recommended Dietary Allowance (RDA). Exceptions were zinc and vitamin D, which were each below 100% of the RDA at 9 of the 10 data points, and vitamin E, which was below the RDA in the infants' second year. Fat intake decreased from more than 40% of energy in the first 6 months to 30% to 32% from 10 to 24 months. One third of the infants drank reduced-fat milks at 12 months and more than half drank them at 24 months. Although infants ate a variety of foods, vegetables often were the least favorite foods. A variety of dairy products provided calcium for the infant but lacked vitamin D. CONCLUSIONS: Several nutritional issues about infant feeding before 2 years of age arose. Low intakes of zinc, vitamin D, and vitamin E were observed. In the second year, low fat intake, use of reduced-fat milks, and dislike of vegetables were areas of concern.

Age Factors↗
PubMed1997

Transitions in infant feeding during the first year of life.

OBJECTIVE: To document ages at which transitions in infant feeding occur, to compare these transitions to literature reports from the 1970s and 80s, and to identify maternal characteristics related to the age of the infant when solid food was first introduced. METHODS: Ninety-eight mother/infant pairs (middle and upper socioeconomic status) participated in the longitudinal study. Using a randomized, incomplete block design, in-home interviews were conducted by trained personnel when infants were 2, 3, 4, 6, 8, 10, and 12 months of age; each mother/infant pair was seen four or five times. Information on food intake, including breast milk/formula, was collected at each interview. Means +/- SD and frequencies were calculated, and least squares analysis of variance was used to develop a predictive model related to the introduction of cereal. RESULTS: Most mothers decided on the initial feeding mode (breastfeeding or formula) prior to pregnancy; 83% breastfed initially although most (76%) totally discontinued breastfeeding by 6 months. Infants' ages varied greatly when each of the seven categories of food was introduced, cereal was added to the infants' diets at a mean age of 3.8 +/- 1.4 (SD) months, juice 4.7 +/- 2.2, fruit 4.9 +/- 1.6, vegetables 5.2 +/- 1.3, mixed foods 7.8 +/- 2.1, table foods 8.2 +/- 2.1, and meat 8.2 +/- 2.1. The multivariate model explained 59% of the variability in ages of infants when cereal (generally the first solid food) was added. Significant variables (p < or = 0.05) were feeding mode, recommendation by the physician, and the interaction between feeding mode and education of the mother. Mother's employment and sibling rank of the infant contributed to the model (p = 0.06 and p = 0.09, respectively). Infants' age when cereal was added was not related to the variables of gender or birth weight. CONCLUSIONS: The finding that the mothers' decision whether or not to breastfeed was made prior to conception supports the importance of population-based education aimed at women in the child-bearing years as well as patient instruction early in the pregnancy. However, the duration of breastfeeding was shorter than was reported in the 1980s. Infants varied greatly in ages when the seven categories of complementary foods were added to their diets. Although recommendations for delaying introduction of solid foods until the infant is 4 to 6 months of age have been in place for more than a decade, about half the mothers in this study did so earlier. Characteristics of mothers who introduced cereal earliest (i.e., mean age of infants < 4 months) were more likely to be formula feeding when cereal was added, to feed cereal via the bottle, to be primiparous, to be employed outside the home, and/or not to cite the physician as a source for guiding the infant's transition to supplemental food.

Adult↗
PubMed1996

The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product.

Tumors express peptide antigens capable of being recognized by tumor-specific cytotoxic T lymphocytes (CTL). Immunization of mice with a carcinogen-induced colorectal tumor, CT26, engineered to secrete granulocyte/macrophage colony-stimulating factor, routinely generated both short-term and long-term CTL lines that not only lysed the parental tumor in vitro, but also cured mice of established tumor following adoptive transfer in vivo. When either short-term or long-term CTL lines were used to screen peptides isolated from CT26, one reverse-phase high performance liquid chromatography peptide fraction consistently sensitized a surrogate target for specific lysis. The bioactivity remained localized within one fraction following multiple purification procedures, indicating that virtually all of the CT26-specific CTL recognized a single peptide. This result contrasts with other tumor systems, where multiple bioactive peptide fractions have been detected. The bioactive peptide was identified as a nonmutated nonamer derived from the envelope protein (gp70) of an endogenous ecotropic murine leukemia provirus. Adoptive transfer with CTL lines specific for this antigen demonstrated that this epitope represents a potent tumor rejection antigen. The selective expression of this antigen in multiple non-viral-induced tumors provides evidence for a unique class of shared immunodominant tumor associated antigens as targets for antitumor immunity.

Animals↗
PubMed1991

Investigation of the structure of lipid A from Actinobacillus actinomycetemcomitans strain Y4 and human clinical isolate PO 1021-7.

The lipopolysaccharides of Actinobacillus actinomycetemcomitans strain Y4 and a human clinical isolate PO 1021-7 were examined by SDS/PAGE, deoxycholate/PAGE and mass spectrometry. PAGE analysis revealed an electrophoretic pattern similar to the SR-type lipopolysaccharide (LPS) of Salmonella. Deoxycholate/PAGE indicated the LPS of A. actinomycetemcomitans to consist of short sugar chains. Chemical analysis revealed the presence of thiobarbituric-acid-positive material (3-deoxy-D-manno-octulosonic acid equivalents) and four neutral sugars: glucose, galactose, D-glycero-D-manno-heptose and L-glycero-D-manno-heptose. Phosphate, glucosamine, glycine, and the fatty acids, 3-hydroxymyristic acid, myristic acid and palmitic acid, comprised the remainder of the molecule. The structure of the free lipid A revealed it to consist of a 1,6-glucosamine disaccharide esterified at C4' by a phosphomonoester. The hydroxyl group at C3 and the amide group of the non-reducing glucosamine were both acylated by 3-myristoylmyristic acid; analogous sites on the reducing glucosamine were acylated by 3-hydroxymyristic acid. Hydroxyl groups at C4 and C6' in the free lipid A were unsubstituted, with C6 being the proposed attachment site of the polysaccharide moiety. Chemical analysis revealed the presence of glycine in the intact LPS; its exact location in the A. actinomycetemcomitans LPS is still to be determined. Both intact LPS and free lipid A were highly lethal to galactosamine-sensitized mice, comparable to that of Salmonella.

Actinobacillus↗
PubMed1991

Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis.

Scrapie prion infectivity can be enriched from hamster brain homogenates by using limited proteolysis and detergent extraction. Purified fractions contain both scrapie infectivity and the protein PrP 27-30, which is aggregated in the form of prion rods. During purification, PrP 27-30 is produced from a larger membrane protein, PrPSc, by limited proteolysis with proteinase K. Brain homogenates from scrapie-infected hamsters do not contain prion rods prior to exposure to detergents and proteases. To determine whether both detergent extraction and limited proteolysis are required for the formation of prion rods, microsomal membranes were prepared from infected brains in the presence of protease inhibitors. The isolated membranes were then detergent extracted as well as protease digested to evaluate the effects of these treatments on the formation of prion rods. Neither detergent (2% Sarkosyl) extraction nor limited proteinase K digestion of scrapie microsomes produced recognizable prion amyloid rods. Only after combining detergent extraction with limited proteolysis were numerous prion rods observed. Rod formation was influenced by the protease concentration, the specificity of the protease, and the duration of digestion. Rod formation also depended upon the detergent; some combinations of protease and detergent did not produce prion amyloid rods. Similar results were obtained with purified PrPSc fractions prepared by repeated detergent extractions in the presence of protease inhibitors. These fractions contained amorphous structures but not rods; however, prion rods were produced upon conversion of PrPSc to PrP 27-30 by limited proteolysis. We conclude that the formation of prion amyloid rods in vitro requires both detergent extraction and limited proteolysis. In vivo, amyloid filaments found in the brains of animals with scrapie resemble prion rods in their width and their labeling with prion protein (PrP) antisera; however, filaments are typically longer than rods. Whether limited proteolysis and some process equivalent to detergent extraction are required for amyloid filament formation in vivo remains to be established.

Animals↗
PubMed1990

Medium-chain-triglyceride lipid emulsion: metabolism and tissue distribution.

The utilization and distribution of radioactively labeled lipid emulsions were evaluated in Sprague-Dawley rats. Animals received one of three lipid emulsions. Group 1 received [14C]medium-chain-triglyceride (MCT) lipid emulsion, group 2 received a 75%:25% (vol:vol) admixture of [14C]MCT: unlabeled long-chain-triglyceride (LCT) lipid emulsion, and group 3 received only [14C]LCT. The radioactive dose appearing in expired carbon dioxide and various body tissues was monitored over a 24-h period. Results indicate that MCT is oxidized more rapidly and completely than in LCT; approximately 90% of the MCT is converted to carbon dioxide with in 24 h compared with 45% for LCT. When MCT and LCT are administered together, the metabolism of MCT is slowed but remains more rapid than that of LCT. Removal of MCT from the blood was more rapid than was removal of LCT, and tissue radioactivity was lower.

Animals↗
PubMed1989

Characterization of novel glycolipids from the giant cockroach (Blaberus colosseus).

A novel class of glycolipids, assigned the trivial name blaberosides, was isolated from whole head tissues of the giant cockroach (Blaberus colosseus). The class consists of two closely related families, blaberoside I and blaberoside II, each containing species differing by 26 atomic mass units. The structure of these gentiobiose-based glycoglycerolipids was elucidated by chromatographic behavior, nuclear magnetic resonance spectroscopy, mass spectrometry, and analysis of chemical degradation products and derivatives. Species in the blaberoside I family have been identified as 2-O-[6'-O-(6"-O-3-hydroxy-11-eicosenoyl-beta-D-glucopyranosyl)-bet a-D- glucopyranosyl]-3-(hexadecyloxy)-1-(3-hydroxy-11-eicosenoyl)-1,2-p ropanediol (blaberoside Ia) and 2-O-[6'-O-(6"-O-3-hydroxy-11-eicosenoyl-beta-D-glucopyranosyl)-bet a- D-glucopyranosyl]-3-(6-octadeceloxy)-1-(3-hydroxy-11-eicosenoyl )-1,2- propanediol (blaberoside Ib). Two smaller homologs of the blaberoside II family were discerned to be 2-O-[6'-O-(6"-O-3-hydroxy-11- eicosenoyl-beta-D-glucopyranosyl)-beta-D-glucopyranosyl]-3-(hex ade cyloxy)- 1,2-propanediol (blaberoside IIa), and 2-O-[6'-O-(6"-O-3-hydroxy-11-eicosenoyl-beta-D- glucopyranosyl)-beta-D-glucopyranosyl]-3-(4-octadeceloxy)-1,2-prop anediol (blaberoside IIb). These compounds are unique because they are animal origin glyceroglycolipids with a highly flexible gentiobiose backbone, and a beta-linkage of the carbohydrate to the glycerol ether at the 2 position rather than the usual 1 position.

Animals↗
PubMed1989

Fasting plasma amino acids in elderly men.

The fasting amino acid profile in 22 healthy young men aged 25-35 y (group A) was compared with the fasting profile in 21 healthy independent men aged 65-85 y (group B), in 23 orally-fed nursing home men with dementia aged 65-92 y (group C), and in 17 tube-fed nursing home men with dementia aged 65-88 y (group D). Groups B, C, and D had significantly (p less than 0.05) lower levels of methionine and branched-chain amino acids than group A. Methionine was significantly lower in groups C and D than in group B. The ratio of essential to nonessential amino acids was significantly lower in groups B, C, and D than in group A. The data suggest that the intake of essential amino acids may often be suboptimal in both independent and institutionalized elderly men.

Aged↗
PubMed1989

Competitive effects of long-chain-triglyceride emulsion on the metabolism of medium-chain-triglyceride emulsions.

This study was conducted to assess the potential metabolic competitive interactions of intravenous medium-chain-triglyceride (MCT) and long-chain-triglyceride (LCT) lipid emulsions. To assess this competition increasing concentrations of LCT emulsion were added to an intravenous dose of MCT emulsion of 3.0 g/kg body wt up to a maximum dose of 3.0 g LCTs/kg body wt. Blood samples were assessed for competitive interactions by analyzing the following metabolites: glucose, insulin, lactate, pyruvate, ketones (acetoacetate, beta-hydroxybutyrate), elimination of triglycerides, and free fatty acids. Evaluation of the data showed a strong competitive interaction between the MCT and LCT emulsions. This competition was evident as soon as LCTs were added to the MCT infusions and appeared to favor LCTs for removal and metabolism over MCTs. This appears to indicate that there is a peripheral, strong affinity site for LCT removal and metabolism and a shared peripheral site and specific visceral site for MCT removal and metabolism.

Animals↗
PubMed1987

A metabolic comparison of a pure long-chain triglyceride lipid emulsion (LCT) and various medium-chain triglyceride (MCT)-LCT combination emulsions in dogs.

Two 20% lipid emulsions containing mixtures of long-(LCT) and medium-chain triglycerides (MCT) were compared with a 20% LCT lipid emulsion. Beagles were infused with emulsions containing either 100% LCT, 75% LCT-25% MCT, or 50% LCT-50% MCT. The emulsions were part of a total parenteral nutrition (TPN) regimen that included 10% dextrose and 5.5% amino acids. Basic nutritional parameters as well as elimination kinetics were monitored. Plasma linoleic acid, ketone, lactate, pyruvate, insulin, glucose, and carnitine were analyzed. The 75% LCT-25% MCT emulsion offers little advantage over 100% LCT as a metabolic substrate. The 50% LCT-50% MCT combination proved to be a potentially better caloric source due to rapid elimination kinetics, increased ketone production, lack of deposition, and no interference with linoleic acid metabolism.

Animals↗
PubMed1986

Dietary supplementation of undernourished rats with soy or safflower oil: effects on myelin polyunsaturated fatty acids.

Undernourished suckling rats were administered, by gastric intubation, either soy oil (which is rich in both linoleic and linolenic acids) or safflower oil (which is rich in linoleic acid but deficient in linolenic acid) to determine (1) if dietary supplementation would offset the hypomyelination characteristic of the undernourished, developing brain and (2) to compare myelin fatty acids in normal, undernourished, and oil-supplemented rats. Myelin recovery was not increased by supplementation with either oil. The proportions of C22:4 and C22:6 fatty acids were reduced in myelin of the undernourished rats. Undernourished rats supplemented with either soy or safflower oil had higher than normal proportions of polyunsaturated fatty acids (C20:4 and C22:6). The triene-tetraene ratio in the oil-supplemented rats was lower than in normal controls, indicating that the oil-supplemented rats were not deficient in essential fatty acids. No significant differences were observed between the oil-supplemented groups.

Animals↗