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Biomedical subjects

L Bacon

Publications and source records attributed to L Bacon.

At least 19 recordsLinked to original sources

Evaluating a 'non-diet' wellness intervention for improvement of metabolic fitness, psychological well-being and eating and activity behaviors.

CONTEXT: Current public health policy recommends weight loss for obese individuals, and encourages energy-restricted diets. Others advocate an alternative, 'non-diet' approach which emphasizes eating in response to physiological cues (eg hunger and satiety) and enhancing body acceptance. OBJECTIVE: To evaluate the effects of a 'health-centered' non-diet wellness program, and to compare this program to a traditional 'weight loss-centered' diet program. DESIGN: Six-month, randomized clinical trial. SETTING: Free-living, general community. PARTICIPANTS: Obese, Caucasian, female, chronic dieters, ages 30-45 y (n=78). INTERVENTIONS: Six months of weekly group intervention in a non-diet wellness program or a traditional diet program, followed by 6 months of monthly after-care group support. OUTCOME MEASURES: Anthropometry (weight, body mass index); metabolic fitness (blood pressure, blood lipids); energy expenditure; eating behavior (restraint, eating disorder pathology); psychology (self-esteem, depression, body image); attrition and attendance; and participant evaluations of treatment helpfulness. Measures obtained at baseline, 3 months, 6 months and 1 y. RESULTS: (1 y after program initiation): Cognitive restraint increased in the diet group and decreased in the non-diet group. Both groups demonstrated significant improvement in many metabolic fitness, psychological and eating behavior variables. There was high attrition in the diet group (41%), compared to 8% in the non-diet group. Weight significantly decreased in the diet group (5.9+/-6.3 kg) while there was no significant change in the non-diet group (-0.1+/-4.8 kg). CONCLUSIONS: Over a 1 y period, a diet approach results in weight loss for those who complete the intervention, while a non-diet approach does not. However, a non-diet approach can produce similar improvements in metabolic fitness, psychology and eating behavior, while at the same time effectively minimizing the attrition common in diet programs.

Adult↗

A fully human antibody neutralising biologically active human TGFbeta2 for use in therapy.

Phage display provides a methodology for obtaining fully human antibodies directed against human transforming growth factor-beta (TGFbeta) suitable for the treatment of fibrotic disorders. The strategy employed was to isolate a human single chain Fv (scFv) fragment that neutralises human TGFbeta2 from a phage display repertoire, convert it into a human IgG4 and then determine its TGFbeta binding and neutralisation properties and its physical characteristics. Several scFv fragments binding to TGFbeta2 were isolated by panning of an antibody phage display repertoire, and subsequent chain shuffling of the selected V(H) domains with a library of V(L) domains. The three most potent neutralising antibodies were chosen for conversion to IgG4 format. The IgG4 antibodies were ranked for their ability to neutralise TGFbeta2 and the most potent, 6B1 IgG4, was chosen for further characterisation. 6B1 IgG4 has a high affinity for TGFbeta2 with a dissociation constant of 0.89 nM as determined using the BIAcore biosensor and only 9% cross-reactivity with TGFbeta3 (dissociation constant, 10 nM). There was no detectable binding to TGFbeta1. 6B1 IgG4 strongly neutralises (IC50 = 2 nM) the anti-proliferative effect of TGFbeta2 in bioassays using TF1 human erythroleukaemia cells. Similarly, there was strong inhibition of binding of TGFbeta2 to cell surface receptors in a radioreceptor assay using A549 cells. 6B1 IgG4 shows no detectable cross-reactivity with related or unrelated antigens by immunocytochemistry or ELISA. The 6B1 V(L) domain has entirely germline framework regions and the V(H) domain has only three non-germline framework amino acids. This, together with its fully human nature, should minimise any potential immunogenicity of 6B1 IgG4 when used in therapy of fibrotic diseases mediated by TGFbeta2.

Amino Acid Sequence↗

Evaluating a test protocol for predicting maximum lactate steady state.

BACKGROUND: Maximum lactate steady state (MLSS) is defined as the highest steady state exercise level one can maintain while also maintaining an equilibrium between the elimination of blood lactate and the diffusion of lactate into the blood. MLSS is an excellent tool for assessing fitness level, predicting endurance performance, and designing training programs. METHODS: This investigation assesses the validity of the Lactate Minimum Test (LMT), which consists of inducing lactic acidosis through a VO2peak test, followed by an eight-minute walking recovery and an incremental exercise test, to determine if the running velocity associated with the minimum lactate value predicts the MLSS velocity. Following this LMT, two constant velocity 28-minute runs were performed, one at the predicted MLSS velocity (trial 1) and the other 0.13 m sec-1 (4-8%) above the predicted MLSS velocity (trial 2). Ten active female subjects participated (32 +/- 7 yrs (mean +/- SD); 65.7 +/- 16.4 kg; VO2peak 40.0 +/- 7.5 ml.kg-1.min-1). RESULTS: During trial 1, there was a -0.6 +/- 0.3 mmol l-1 (mean +/- SE) change in lactate. Based on a definition of lactate steady state (LSS) as less than a 0.5 mmol.l-1 increase, this value signified LSS. A similar comparison during trial 2 revealed a 1.8 +/- 0.3 mmol.l-1 increase in lactate, signifying a workload above LSS and therefore confirming trial 1 as the maximum LSS (MLSS). CONCLUSIONS: These results suggest that the test protocol accurately predicted the MLSS velocity.

Adult↗

Antigen specificity and tumour targeting efficiency of a human carcinoembryonic antigen-specific scFv and affinity-matured derivatives.

We have examined the biological properties of CEA6, a human carcinoembryonic antigen (CEA)-specific single-chain Fv (scFv) isolated by phage display, and five related clones derived by affinity maturation and selected for improved off-rate (Koff). All clones bind strongly and specifically to CEA-positive human tumours by immunocytochemistry and show negligible cross-reactivity with normal colon. Flow cytometry of scFv on human liver cells indicates a shift in fine epitope specificity resulting from mutagenesis. All monomeric scFv have been radioiodinated, retaining effectively full binding activity. A single intravenous injection into nude mice bearing human colon tumour xenografts confirms tumour targeting in all cases. As reported in other studies, the kidney is the main route of elimination of scFv at early time points. Tumour binding of the parental antibody CEA6 consistently gives the highest tumour-blood ratios at 24 h (mean 16:1). Clone TO6D11, which has a sevenfold reduced Koff relative to CEA6, showed no difference in tumour uptake at 24 h but persisted at the tumour site for longer than CEA6. This study demonstrates a possible correlation between binding affinity and tumour residence time when examined in this model.

Animals↗

Age modulates the long-term but not the acute effects of the serotonergic neurotoxicant 3,4-methylenedioxymethamphetamine.

Tissue levels of serotonin (5-HT), levels of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and populations of 5-HT reuptake sites were measured in the brains of rats exposed to 3,4-methylenedioxymethamphetamine (MDMA) at selected developmental ages. MDMA exposure at postnatal day (PND) 10 did not result in altered 5-HT or 5-HIAA levels 1 week after administration in any brain region examined. However, MDMA exposure at PND 40 and PND 70 resulted in dose-dependent reductions in 5-HT and 5-HIAA levels at 1 week in all brain regions examined. Time course studies revealed that at PND 10, MDMA acutely (< or = 24 hr) reduced 5-HT levels and that these levels later recovered to control levels. MDMA also acutely reduced 5-HT levels at PND 40 and PND 70, but at these ages the 5-HT levels were persistently depressed ( > or = 72 hr). Time course studies also revealed that MDMA acutely elevated dopamine levels in caudate putamen at PND 40 and PND 70, but no alterations in dopamine levels were observed at PND 10. Analysis of 5-HT reuptake site populations revealed that at PND 10 and PND 40, MDMA had little effect on reuptake site populations. At PND 70, however, MDMA reduced 5-HT reuptake site populations as early as 24 hr after administration. These experiments demonstrate not only that the biochemical effects of MDMA exposure are altered by the developmental status of the experimental animal, but also that each individual biochemical component may show differing sensitivities to alteration by MDMA at different developmental ages.

Age Factors↗

Use of indium-111 in antibody-dependent complement-mediated cytotoxicity assay for detection of B locus alloantigens on chicken lymphocytes.

An antibody-dependent complement-mediated cytotoxicity assay has been devised to detect B locus alloantigens on the surface of peripheral blood lymphocytes. The assay utilizes unheated chicken antiserum and guinea pig complement, which cooperate to yield specific lysis of 111In-labeled target cells. Specific cell lysis appears to be mediated by the classical complement pathway and can be inhibited by heat inactivation of the guinea pig complement. Heat inactivation of the chicken antiserum results in partial inhibition of cell lysis which can be restored by the addition of a small amount of unheated normal chicken serum. The use of a 111In-oxine chelate was found to be a quick and efficient way to label chicken cells. It has a high labeling efficiency, localizes primarily in the cytoplasm, and is released specifically from dead cells in a form that cannot be reutilized. The highly sensitive detection of B locus alloantigens with this assay strongly suggest that it will be of equal value in the detection of other alloantigens, tumor-specific (transplantation) antigens, and differentiation antigens on the surface of chicken cells.

Animals↗

A review of two safety factors in the use of paraldehyde.

Clinical observations and laboratory tests suggest that, contrary to normal practice, paraldehyde can be used with certain plastic syringes and has been safely used when well over six months old. This may make its use as an anticonvulsant in primary care more widely acceptable.

Child↗

Plasma estrogen response to dehydroepiandrosterone sulphate injection in normal and complicated late pregnancy.

Dehydroepiandrosterone sulphate (DHAS) was administered intravenously to 70 women in the third trimester of pregnancy. By measuring the increase in the concentrations of estrogens in maternal plasma, it was hoped to assess the reserve capacity of the placenta. In normal pregnancies, unconjugated estradiol invariably showed a marked increase within 60 minutes of the injection of DHAS, reaching 174 to 478% above basal levels. Changes in unconjugated estrone were more variable, but significant increases usually occurred 2 to 3 hours after the peak concentration of estradiol. The concentrations of unconjugated estriol showed no significant change. Patients with preeclampsia, essential hypertension, retarded intrauterine growth, diabetes, and twin pregnancies did not show any major differences in response compared to the normal pregnancies. Two patients with intrauterine deaths had low basal concentrations of estrogens but responded to the DHAS injection by having significantly increased concentrations of unconjugated estradiol after 60 minutes. The only patient who did not show any increase in unconjugated estradiol levels after DHAS was thought to have a placental sulphatase deficiency. This test does not appear to have any advantage over existing methods of assessing the endocrine function of the placenta except in confirmation of placental sulphatase deficiency.

Dehydroepiandrosterone↗

Characterization of different B-F (MHC class I) molecules in the chicken.

B-F alloantisera recognized distinct 45-Kd molecules on peripheral red blood cells (RBC) from embryonic chickens and heterogeneous molecules of approximately 40 to 44 Kd on peripheral RBC from adult chickens, provisionally referred to as type 1 and type 2, respectively. Type 2 molecules migrated to the basic end of isoelectric focusing gels, exhibited multiple isomorphic variants, and were associated with a smaller polypeptide of approximately 11 to 12 Kd assumed to be beta-2-microglobulin. Type 1 molecules migrated to the acidic end of isoelectric focusing gels, exhibited limited heterogeneity, and were not associated with a smaller polypeptide. Type 1 and type 2 molecules were also shown to be distinct by peptide mapping and serological analyses. In addition, two distinct molecular-weight forms of the type 2 molecules were distinguished, provisionally referred to as 2A (45 Kd) and 2B (42 Kd). In vivo-derived avian erythroblastosis virus (AEV)-transformed erythroleukemia cells expressed type 2A molecules. In vitro-derived AEV-transformed erythroleukemia cells expressed very low levels of B-F molecules; however, they expressed type 2B molecules when induced to differentiate. Normal bursa-derived lymphoid cells expressed type 2A molecules, whereas normal thymus-derived lymphoid cells expressed type 2B molecules. Cloned reticuloendotheliosis virus (REV)-transformed immature lymphoid cells expressed either type 2A or type 2B molecules.

Animals↗