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Biomedical subjects

B Sager

Publications and source records attributed to B Sager.

9 recordsLinked to original sources

Effect of lifestyle changes on whole-body protein turnover in obese adolescents.

OBJECTIVE: To investigate the effect of lifestyle changes on whole-body protein turnover (WBPT) in obese adolescents. DESIGN/METHODS: Randomized and controlled nonpharmacological intervention study of WBPT in obese adolescents using stable isotope dilution techniques. SUBJECTS AND MEASUREMENTS: We studied a total of 21 adolescents (11 boys and 10 girls, matched for their pubertal status) of which 15 were obese (age=15.8+/-0.4 y old and BMI=38.6+/-3.3 kg/m(2)) and six were lean controls (age=16.0+/-0.4 y old and BMI=21.3+/-1.2 kg/m(2)). The obese subjects were subjected to a randomized controlled lifestyle intervention program that involved moderate physical activity and diet changes for 3 months. A group of lean age-matched subjects was also studied at baseline to compare the WBPT in obese and lean adolescents. The studies were performed during a primed, continuous infusion of L-[1-(13)C]leucine. Leucine appearance rate (Leu Ra) was used as an index of whole protein breakdown and the nonoxidative portion of leucine disposal (NOLD) as an index of whole-body protein synthesis. RESULTS: The obese groups showed significantly higher body mass index (BMI), fat mass (FM), percent body fat (%BF), fat-free mass (FFM), resting energy expenditure (REE) and WBPT compared to the lean controls. The intervention program resulted in a redistribution of the parameters of body composition without apparent changes in BMI or body weight. There was a significant decrease in WBPT in the obese intervention group, but not in the obese control group. Insulin levels also decreased significantly in the obese group after intervention but not in the obese control group, whereas the glucose concentrations remained normal in all groups at baseline and also after intervention/or control. CONCLUSIONS: Results from the current study suggest: (i). abonormalities of protein metabolism occur early in the clinical course of obesity and (ii). these abnormalities are modifiable by moderate lifestyle changes in obese adolescents. The mechanism for these changes in WBPT in obese adolescents as well as their impact on specific cardiovascular risk factors and turnover of specific proteins will require further investigation.

Adolescent↗

Disease management: a practitioner's perspective.

Disease management focuses on the patient throughout the entire course of a disease, measuring desired outcomes related to the patient and each intervention. Traditional health care based on cost component management does little to reduce the long-term costs of chronic illness. Hypertension is an appropriate target for disease management. Successful disease management will require integrated information systems and third party payer support.

Cost-Benefit Analysis↗

Intercellular C-signaling and the traveling waves of Myxococcus.

Early in their development into fruiting bodies, Myxococcus xanthus cells organize themselves into dense bands that move as trains of traveling waves. C-factor, a 20-kD cell-surface bound protein, is a short-range developmental signal molecule required for these waves. What is the role of C-factor in the wave pattern? It is proposed that oriented collisions between cells initiate C-signaling, which, in turn, causes individual cells to reverse their direction of gliding. Cells would move about one wavelength and then reverse. Several lines of experimental evidence support these proposals: (1) Cells that suffered a mutation in the signal transduction pathway that controls the spontaneous reversal frequency lost the ability to form waves; (2) presentation of developing cells with detergent-solubilized C-factor increased the mean frequency of single cell reversal by three-fold; and (3) fluorescently labeled cells in the waves were tracked, and it was found that they moved and reversed on linear paths along the axis of wave propagation. Similar numbers of cells were found moving in the direction of ripple propagation, and in the reverse direction, as expected. (4) Dilution of C-signaling-competent cells with C-factor-deficient cells increased the wavelength as the probability of productive collision decreased. The waves exemplify a way that a multicellular pattern of stripes can be produced de novo, one that maintains a uniform 50-microns separation between stripes over a distance as large as 1 cm.

Bacterial Proteins↗

Beta-galactosidase activity in single differentiating bacterial cells.

Myxococcus xanthus strains containing transcriptional fusions to lacZ were analyzed and fractionated by differences in their levels of beta-galactosidase expression. The fluorogenic substrate for beta-galactosidase, fluorescein di-beta-galactopyranoside, was introduced into M. xanthus cells during a rapid decrease in osmolarity of the medium followed by a return to isoosmolarity. Fluorescein, the product of hydrolysis, was retained within the cells and their viability was preserved. Fluorescence increased linearly with time and was proportional to beta-galactosidase activity. beta-Galactosidase expression in most fusion strains, though beginning at different phases of growth or development, was distributed unimodally amongst cells. However, fusion strain Tn5 lac omega 4473 was shown to be heterogeneous at 9 hr of development. It was possible to separate physically cells that expressed beta-galactosidase at a high level from other, still viable, cells with no expression. The approach described here could be adapted to study differentiation in plants and animals as well, where transcriptional fusions and fluorogenic substrates for enzyme probes of gene expression also can be used.

DNA Transposable Elements↗

Two cell-density domains within the Myxococcus xanthus fruiting body.

Myxococcus xanthus, one of the simplest of multicellular organisms, develops into an organized, multicellular aggregate, called a fruiting body. Examination of the internal structure of the nascent fruiting body showed it to consist of a hemispherical outer domain of densely packed and ordered cells. Inside this dense shell is an inner domain of less ordered cells at 3-fold lower cell density. Single cells move in a bidirectional stream in the outer domain, orbiting the fruiting body throughout development, whereas in the inner domain, cell movement ceases as the fruiting body matures. The fruiting body thus consists of two domains, distinguished from each other by differential cell density, cell arrangements, and cell movements.

Cell Movement↗

Spatial restriction of cellular differentiation.

Myxococcus xanthus cells differentiate into myxospores within a fruiting body, an aggregate of approximately 10(5) cells. Previous work had discerned an inner and outer domain within the fruiting body differentiated by cell density and cell alignment. To test whether the two domains might play different roles in spore differentiation, developmentally regulated gene fusions were screened for expression restricted to one domain or the other. Transcriptional lacZ fusions to 80 developmentally regulated genes were examined and eight fusions were found that restricted expression to the inner domain, while one fusion, omega 7621, showed initial expression in the outer domain. Initial omega 7621 expression coincided with patches of spore precursors evident in bright-field microscopy. Later in development, both omega 7621 expression and the patches expanded inward, eventually filling both the inner and outer domains. Previous work had also shown that high cell density and cell alignment are required for transmission of the C-signal, which is needed to initiate spore differentiation. Evidence is presented for a novel morphogenetic mechanism in which C-signaling in the outer (high density) domain initiates spore differentiation. It is proposed that spore precursors are passively transported from the outer to the inner domain by the movements of undifferentiated rod cells. Reconstruction experiments showed that developing rod cells move with sufficient force to displace spores. Spore precursors thus accumulate in the inner domain where they express spore-specific genes at high levels and account for inner domain specific expression.

Biological Transport↗