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K Nixon

Publications and source records attributed to K Nixon.

9 recordsLinked to original sources
PubMed2005

Neurogenesis in adolescent brain is potently inhibited by ethanol.

Adolescence is a period of progressive changes in brain that likely contribute to the maturation of behavior. Human adolescents consume large amounts of ethanol. To investigate the effects of ethanol on adolescent neural progenitor cells, male rats (35-40 days old) were treated with an acute dose of ethanol (1.0, 2.5 or 5.0 g/kg, i.g.) or vehicle that resulted in peak blood levels of 33, 72, and 131 mg/dl, respectively. Bromodeoxyuridine (300 mg/kg i.p.) was administered to label dividing cells and rats were killed at 5 h to assess proliferation or at 28 days to assess cell survival and differentiation. After 5 h, bromodeoxyuridine-immunoreactivity was reduced by 63, 97 and 99% in the rostral migratory stream and 34, 71 and 99% in the subventricular zone by 1.0, 2.5 and 5.0 g/kg of ethanol respectively. In the dentate gyrus, ethanol reduced bromodeoxyuridine-immunoreactivity by 29, 40, and 78% at the three doses respectively. The density of doublecortin immunoreactivity was decreased after 3 days and the number of bromodeoxyuridine+ cells remained decreased at 28 days when most hippocampal bromodeoxyuridine+ cells coexpressed neuronal nuclei, a neuronal marker. These studies indicate that the adolescent brain is very sensitive to acute ethanol inhibition of neurogenesis.

Aging↗
PubMed2000

Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys.

PURPOSE: The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS: Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharmacokinetics and toxicological properties of NX1838 were determined following six biweekly bilateral injections of 0.25 or 0.50 mg/eye or following four biweekly bilateral injections of 0.10 mg per eye followed by two biweekly bilateral injections of 1.0 mg per eye. RESULTS: Plasma and vitreous humor NX1838 concentrations were linearly related to the dose administered. NX1838 was cleared intact from the vitreous humor into the plasma with a half-life of approximately 94 h, which was in agreement with the plasma terminal half-life. Vascular endothelial growth factor (VEGF)-binding assays demonstrated that the NX1838 remaining in the vitreous humor after 28 days was fully active. No toxicological effects or antibody responses were evident. CONCLUSIONS: The no observable effect level was greater than six biweekly bilateral 0.50 mg/eye doses or two biweekly bilateral 1.0 mg/eye doses. These pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regimens in human clinical trials.

Animals↗
PubMed1999

Stable expression of human glycine alpha1 and alpha2 homomeric receptors in mouse L(tk-) cells.

We report the development of two mouse fibroblast-like stably-transfected cell lines (alpha1-62-4 and alpha2-B36-1) that express human alpha1 or alpha2 glycine receptor subunits, respectively. Transfected cDNAs were cloned into the pMSGneo expression vector, for which transcription is controlled by the dexamethasone-inducible MMTV promoter. Patch-clamp electrophysiological recordings revealed that the alpha1 or alpha2 glycine receptor subunits expressed in these cells form functional glycine receptors that are inhibited by strychnine and picrotoxin. Glycine activated currents in these cells with EC50s of 101+/-7 or 112+/-23 microM for cells stably expressing alpha1 or alpha2 receptors, respectively. As indicated by assays of glycine-stimulated 36Cl-- uptake, these cells express glycine receptors only after treatment with dexamethasone. In order to measure expression of the glycine alpha1 or alpha2 receptor protein, we produced a new anti-alpha1/alpha2 glycine receptor antibody (anti-alpha GR). Western blot analysis with this antibody showed a band of approximately 48 kDa only in homogenates from cells which had been transfected with the glycine alpha1 or alpha2 receptor cDNAs. Thus, through use of this stable expression system, we successfully produced cell lines expressing strychnine-sensitive glycine receptors that display similar functional characteristics to homomeric glycine receptors expressed in other systems. These stably transfected cells should provide a useful in vitro system for the study of the physiology and pharmacology of strychnine-sensitive glycine receptors.

Animals↗
PubMed1999

Near infra-red interactance for nutritional assessment of dialysis patients.

BACKGROUND: Malnutrition is a common problem in dialysis patients and may affect up to one-third of patients. Near-infrared interactance (NIR) is a novel approach to estimate body composition and per cent total body fat. METHODS: We used near-infrared interactance (Futrex 5000) to estimate the body composition including body fat percentage, as well as subjective global assessment (SGA), anthropometric measurements including mid-arm circumference (MAC), triceps and biceps skinfold thickness, calculated mid-arm muscle circumference (MAMC), body mass index (BMI), and laboratory values. NIR score, SGA assessment and anthropometric parameters were measured shortly after the end of a dialysis session. NIR measurement was made by placing a Futrex sensor on the nonaccess upper arm for several seconds. Serum albumin, transferrin (reflected by total iron binding capacity), and total cholesterol concentrations were performed as well. RESULTS: Thirty-four patients (20 men and 14 women) were selected from a pool of 120 haemodialysis patients. Their ages ranged from 26 to 86 years (58+/-14 years). Time on dialysis ranged from 8 months to 19 years (4.5+/-4.6 years). NIR scores were significantly different in three SGA groups: (A) well-nourished, 32.5+/-6.9%; (B) mildly to moderately malnourished, 29.2+/-5.3%; and (C) severely malnourished, 23.2+/-10.2% (P<0.001). Pearson correlation coefficients (r) between the NIR score and nutritionally relevant parameters were significant (P<0.001) for body mass index (r=+0.81), mid-arm circumference (r=+0.74), triceps skin fold (r=+0.54), biceps skin fold (r=+0.55), and mid-arm muscle circumference (r=+0.54). An inverse correlation was also found between NIR and years dialysed (r=-0.49, P=0.004), denoting a lesser body fat percentage according to NIR for patients dialysed longer. NIR was correlated with serum transferrin (r=+0.41, P=0.016) and cholesterol (r=+0.39, P=0.022) and marginally with serum albumin (r=+0.29, P=0.097). CONCLUSIONS: We conclude that NIR, which can be performed within seconds, may serve as an objective indicator of nutritional status in haemodialysis patients. More comparative and longitudinal studies are needed to confirm the validity of NIR measurements in nutritional evaluation of dialysis patients.

Adipose Tissue↗
PubMed1996

The NMDA antagonist MK-801 affects nonspatial learning in preweanling rats.

The N-methyl-D-aspartate (NMDA) subtype of the excitatory amino acid receptor has been implicated in several kinds of learning and memory, as well as in long-term potentiation (LTP), a putative cellular mechanism for learning and memory. This experiment examined the role of the NMDA receptor in patterned single-alternation (PSA) learning in preweanling rats following intraperitoneal injections of 0.05 mg/kg MK-801, a selective NMDA antagonist. MK-801 significantly inhibited PSA at both 60-s and 30-s intertrial intervals (ITIs), and attenuated, but did not block, learning at 8-s ITI. These results are compared with effects on PSA, a form of nonspatial, memory-based learning, observed after early postnatal exposure to alcohol, infant hippocampal lesions, and infant exposure to X-irradiation, and they add strongly to these earlier demonstrations of the role of the hippocampus in learning and memory that is clearly nonspatial and non-cognitive-map-related.

Animals↗
PubMed1991

Induction of opsonic antibodies to Pseudomonas aeruginosa mucoid exopolysaccharide by an anti-idiotypic monoclonal antibody.

Mucoid strains of Pseudomonas aeruginosa are the major pulmonary pathogens for cystic fibrosis patients. Opsonizing antibodies to the mucoid exopolysaccharide (MEP) antigen may protect animals and some cystic fibrosis patients from infection. However, MEP does not readily elicit opsonic antibodies either during chronic infection or after vaccination. To evaluate alternative means to induce opsonic antibodies, a murine monoclonal anti-idiotypic antibody directed to an opsonic monoclonal antibody specific to MEP was produced. The anti-idiotypic antibody bound to F(ab')2 fragments of the opsonic antibody, blocked binding to MEP, bound to cross-reactive idiotopes on human opsonic antibodies to MEP, and elicited MEP-specific antibodies in syngeneic and allogeneic mice. These anti-idiotype-induced, MEP-specific antibodies fixed complement to mucoid P. aeruginosa cells and opsonized them for phagocytic killing by human leukocytes. These studies demonstrate the potential utility of anti-idiotypic monoclonal antibody for generating protective immunity against bacterial polysaccharides.

Animals↗