Search PubMed⌕ Search

Biomedical subjects

R L Johnson

Publications and source records attributed to R L Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Goosecoid misexpression alters the morphology and Hox gene expression of the developing chick limb bud.

The homeobox-containing gene goosecoid (gsc) has been implicated in a variety of embryonic processes from gastrulation to rib patterning. We have analyzed the role it plays during chick limb development. Expression is initially observed at stage 20 in a proximal-anterior-ventral domain of the early limb bud which expands during subsequent stages. Later in limb development a second domain of expression appears distally which resolves to regions which surround the condensing cartilage. In order to understand the function of gsc in limb development, we have examined the effect of misexpressing gsc throughout the limb. Two striking phenotypes are observed. The first, evident at stage 24, is an alteration in the angle of femur outgrowth from the main body axis. The second, which can be detected at day 10 of development, is an overall decrease in the size of the limb with bones that are small, misshapen and bent. These phenotypes correlate with a decrease in levels of Hox gene expression in gsc-infected limb buds. From these results we suggest that gsc may normally function to regulate growth and patterning of the limb, perhaps through regulation of Hox gene expression.

Animals↗
PubMed1997

Nutritional adequacy of diets reported at baseline and during trial years 1-6 by the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter addresses whether a fat-modified diet as implemented by special intervention participants in the Multiple Risk Factor Intervention Trial affected intake of vitamins and minerals, and whether nutritional adequacy was altered by this dietary intervention. Despite likely underreporting of intake, for men in the special intervention group, most mean intakes of 15 micronutrients estimated from 24-h recalls were above established recommended dietary allowances. A few means were slightly below; lowest was zinc at 77% (from 98% at baseline) followed by calcium at 79% (from 102% at baseline). Calculated as nutrient densities (per 1000 kcal), nutrients that were below indexes of nutritional quality (the corresponding standard based on nutrient density) during follow-up, although not reduced below baseline by this measure, were vitamin D, calcium, iron (marginally), and zinc. Analyses by food groups indicated that intake of these nutrients might have been improved by greater replacement of high- and medium-fat dairy products with low-fat dairy products (for vitamin D and calcium) and of high-fat meats with low-fat meats, fish, or poultry (for iron and zinc), or (because iron was adequate) by increasing consumption of vegetables and whole-grain products. The safety of the eating pattern was further confirmed by more favorable micronutrient profiles in men who adhered best to the intervention program, as measured by degree of serum cholesterol reduction and weight loss.

Body Weight↗
PubMed1997

Conformational analysis of homochiral and heterochiral diprolines as beta-turn-forming peptidomimetics: unsubstituted and substituted models.

The effect of replacing one of the proline residues in either unsubstituted homochiral or heterochiral diproline segments with either a 2- or a 3-substituted prolyl residue on the allowed conformational of the diproline template has been examined. In heterochiral (L-D) diprolines, placement of a 2-methyl-D-proline residue in the i + 2 position and placement of either a cis- or trans-3-methyl-L-proline residue in the i + 1 position results in substituted diproline peptides that adopt the same type II beta-turn conformation as that defined experimentally for the unsubstituted diproline peptides. In contrast, placement of a cis-3-methyl-D-proline residue in the i + 1 position of a homochiral (D-D) diproline peptide seems to promote a different conformation than that seen in the unsubstituted case, whereas the trans-3-methyl-D-proline residue seems to provide a stabilizing influence for the predicted type VI' beta-turn. The demonstrated ability of certain substituted diproline templates to adopt predictable conformations coupled with the development of asymmetric synthetic routes to both 2- and 3-substituted prolyl residues, capable of mimicking a variety of side chains should make these templates useful tools in designing specific turn mimics of biologically active molecules.

Crystallography, X-Ray↗
PubMed1997

The effects of gamma-oryzanol supplementation during resistance exercise training.

To determine the effectiveness of gamma-oryzanol supplementation, weight-trained males were randomly divided into supplemented (G-O) and control placebo (Con) groups. The G-O group ingested 500 mg.day-1 of gamma-oryzanol according to manufacturer's instructions. Test batteries were administered before (T1), after 4 weeks (T2), and after 9 weeks (T3) of a periodized resistance exercise program. Both groups demonstrated significant increases in 1 repetition maximum muscular strength (bench press and squat) and vertical jump power, with no differences between the groups. No differences between groups were observed for measures of circulating concentrations of hormones (testosterone, cortisol, estradiol, growth hormone, insulin, beta-endorphin), minerals (calcium, magnesium), binding protein (albumin), or blood lipids (total cholesterol, triglycerides, HDL-cholesterol). Resting cardiovascular variables decreased similarly for both groups. These data suggest that 9 weeks of 500 mg.day-1 of gamma-oryzanol supplementation does not influence performance or related physiological parameters in moderately weight-trained males.

Adult↗
PubMed1997

Source of error on A-aDO2 calculated from blood stored in plastic and glass syringes.

We studied the effects of time delay on blood gases, pH, and base excess in blood stored in glass and plastic syringes on ice and the effects of resulting errors on calculated alveolar-to-arterial PO2 difference (A-aDO2). Matched samples of dog whole blood were tonometered with gas mixtures of 5% CO2-12% )2-83% N2 (mixture A), 10% CO2-5% O2-85% N2 (mixture B), and 2.88% CO2-4% O2-93.12% N2 (mixture C). Tonometered blood samples were transferred to 5-ml glass (5G), 5-ml plastic (5P), and 3-ml plastic (3P) syringes and stored on ice. Blood gases were measured every 1 h up to 6 h. In 5G, PO2 progressively decreased in blood tonometered with mixture A but rose in blood tonometered with mixtures B and C. O2 saturation progressively fell in all cases. In 5G, blood PCO2 progressively rose regardless of which gas mixture was used, and pH as well as base excess progressively fell. The rise in PO2 was faster in plastic than in glass syringes, and O2 saturation always rose in plastic syringes. Differences between storage in plastic and glass syringes on PO2 change were greatest when initial blood PO2 was highest (mixture A). At the highest PO2, O2 exchange was faster in 3P than in 5P. The rise of PCo2 was just as fast in plastic as in glass syringes, but in both the rise in PCO2 was faster at a higher initial PCO2 (mixture B) than in lower initial PCO2 (mixtures B and C). Rates of PO2 and PCO2 change in matched samples were significantly faster in 3P than in 5P. Errors due to rises in PCO2 and PO2 cause additive errors in calculated A-aDO2, and when blood is stored in plastic syringes for > 1 h significant errors result. Errors are greater in normoxic blood, in which estimated A-aDO2 decreased by > 10 Torr after 6 h on ice in plastic syringes, than in hypoxic blood.

Animals↗
PubMed1997

A finite-element model of oxygen diffusion in the pulmonary capillaries.

We determined the overall pulmonary diffusing capacity (DL) and the diffusing capacities of the alveolar membrane (Dm) and the red blood cell (RBC) segments (De) of the diffusional pathway for O2 by using a two-dimensional finite-element model developed to represent the sheet-flow characteristics of pulmonary capillaries. An axisymmetric model was also considered to assess the effect of geometric configuration. Results showed the membrane segment contributing the major resistance, with the RBC segment resistance increasing as O2 saturation (SO2) rises during the RBC transit: RBC contributed 7% of the total resistance at the capillary inlet (SO2 = 75%) and 30% toward the capillary end (SO2 = 95%) for a 45% hematocrit (Hct). Both Dm and DL increased as the Hct increased but began approaching a plateau near an Hct of 35%, due to competition between RBCs for O2 influx. Both Dm and DL were found to be relatively insensitive (2-4%) to changes in plasma protein concentration (28-45%). Axisymmetric results showed similar trends for all Hct and protein concentrations but consistently overestimated the diffusing capacities (approximately 2.2 times), primarily because of an exaggerated air-tissue barrier surface area. The two-dimensional model correlated reasonably well with experimental data and can better represent the O2 uptake of the pulmonary capillary bed.

Blood Proteins↗
PubMed1997

Patterns of shortening and thickening of the human diaphragm.

To study how the human diaphragm changes configuration during inspiration, we simultaneously measured diaphragm thickening using ultrasound and inspired volumes using a pneumotachograph. Diaphragm length was assessed by chest radiography. We found that thickening and shortening were greatest during a breath taken primarily with the abdomen. However, the degree of thickening was greater than expected for fiber shortening, assuming parallel muscle fibers and no shear. So, to clarify this unexpected finding, we considered geometric models of the diaphragm. How a muscle thickens as its fibers shorten is critically dependent on geometry. Thus, if a flat rectangular sheet of muscle shortens along one dimension, surface area-to-length ratio along this dimension should remain constant, and thickness would be inversely proportional to length during shortening. The simplest model of the diaphragm, however, is a cylindrical sheet of muscle in the zone of apposition capped by a dome; the ratio of surface area to radial fiber length in the dome is substantially less than the ratio of area to length of the cylindrical zone of apposition; hence, as the zone of apposition shortens while the dome radius remains constant, the ratio of total surface area to combined length (i.e., dome + zone of apposition) must decrease and thickening of the muscle correspondingly must increase more than expected for a simple rectangular strip. A similar relationship can be derived between thickening and length in a muscle sheet with a wedge-shaped insertion into a thin flat tendon. Comparison of calculations with these types of models to data from human subjects indicates that the unexpected thickening in the zone of apposition is explained by the peculiar geometry of the diaphragm. The greater thickening of the diaphragm in the zone of apposition suggests that more of the muscle mass and more sarcomeres are retained in the zone of apposition as the dome descends. Physiologically, this greater thickening may have importance by reducing wall stress in the zone of apposition and reducing the work or energy requirements per sarcomere.

Adult↗
PubMed1997

Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis.

To understand the effects of dynamic shape distortion of red blood cells (RBCs) as it develops under high-flow conditions on the standard physiological and morphometric methods of estimating pulmonary diffusing capacity, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of equally spaced RBCs. RBCs are circular or parachute shaped, with the same perimeter length. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DMCO) were calculated by a finite element method. DLCO calculated at two levels of alveolar PO2 were used to estimate DMCO by the Roughton-Forster (RF) technique. The same capillary model was subjected to morphometric analysis by the random linear intercept method to obtain morphometric estimates of DMCO. Results show that shape distortion of RBCs significantly reduces capillary diffusive gas uptake. Shape distortion exaggerates the conceptual errors inherent in the RF technique (J. Appl. Physiol. 79: 1039-1047, 1995); errors are exaggerated at a high capillary hematocrit. Shape distortion also introduces additional error in morphometric estimates of DMCO caused by a biased sampling distribution of random linear intercepts; errors are exaggerated at a low capillary hematocrit.

Algorithms↗
PubMed1997

Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants.

Classical embryological experiments have demonstrated that dorsal-ventral patterning of the vertebrate limb is dependent upon ectodermal signals. One such factor is Wnt-7a, a member of the Wnt family of secreted proteins, which is expressed in the dorsal ectoderm. Loss of Wnt-7a results in the appearance of ventral characteristics in the dorsal half of the distal limb. Conversely, En-1, a homeodomain transcription factor, is expressed exclusively in the ventral ectoderm, where it represses Wnt-7a. En-1 mutants have dorsal characteristics in the ventral half of the distal limb. Experiments in the chick suggest that the dorsalizing activity of Wnt-7a in the mesenchyme is mediated through the regulation of the LIM-homeodomain transcription factor Lmx-1. Here we have examined the relationship between Wnt-7a, En-1 and Lmx-1b, a mouse homolog of chick Lmx-1, in patterning the mammalian limb. We find that Wnt-7a is required for Lmx-1b expression in distal limb mesenchyme, and that Lmx-1b activation in the ventral mesenchyme of En-1 mutants requires Wnt-7a. Consistent with Lmx-1b playing a primary role in dorsalization of the limb, we find a direct correlation between regions of the anterior distal limb in which Lmx-lb is misregulated during limb development and the localization of dorsal-ventral patterning defects in Wnt-7a and En-1 mutant adults. Thus, ectopic Wnt-7a expression and Lmx-1b activation underlie the dorsalized En-1 phenotype, although our analysis also reveals a Wnt-7a-independent activity for En-1 in the repression of pigmentation in the ventral epidermis. Finally, we demonstrate that ectopic expression of Wnt-7a in the ventral limb ectoderm of En-1 mutants results in the formation of a second, ventral apical ectodermal ridge (AER) at the junction between Wnt-7a-expressing and nonexpressing ectoderm. Unlike the normal AER, ectopic AER formation is dependent upon Wnt-7a activity, indicating that distinct genetic mechanisms may be involved in primary and secondary AER formation.

Animals↗
PubMed1997

Relationship between body image and percent body fat among male and female college students enrolled in an introductory 14-week weight-training course.

Students (39 men and 27 women) from a southern university, who were enrolled in a 14-wk. introductory weight-training course, were administered a 20-item body-image questionnaire and subsequently underwent skinfold measurements to assess percent body fat. Mean scores were correlated with percent body fat. For men, women, and both sexes combined correlations were significant and inverse (rs = -.68, -.41, -.66, respectively). Body image as measured was inversely related to percent body fat among these college students. Researchers should examine how dietary and exercise-induced changes in adiposity (pre-post design) influence scores on body image.

Adipose Tissue↗
PubMed1997

Newborn hearing screening in Hawaii.

Hawaii has been a pioneer and national leader in implementing universal newborn hearing screening. In fact, Hawaii is one of only two states (Rhode Island is the other) which have a statewide newborn hearing screening program in which 95% or more of all newborns are screened. Hawaii is the best example of a truly integrated system of services to provide effective intervention for all infants and toddlers who are identified as having a hearing loss. The success of the newborn hearing screening program is measurable in two ways: 1) all available information indicates that not a single infant with hearing loss has been missed by the screening process and not a single infant has been misdiagnosed as having a hearing loss; and 2) many of the children identified with hearing loss by the newborn hearing screening program have transitioned out of the early intervention program with age-appropriate developmental and communication skills. The success of Hawaii's program is a tribute to the enthusiastic support and collaboration of legislators, pediatricians, hospital staff, and DOH personnel.

Hawaii↗
PubMed1996

Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development.

Sonic hedgehog is a secreted factor regulating patterning of the anterior-posterior axis in the developing limb. The signaling pathway mediating the transduction of the signal is still poorly understood. In Drosophila several genes are known to act downstream of hedgehog, the fly homolog of Sonic hedgehog. An important gene epistatic to hedgehog is cubitus interruptus, which encodes the fly homolog of a family of vertebrate putative transcription factors, the GLI genes. We have isolated two members of the GLI family from chick, called GLI and GLI3. Their expression patterns in a variety of tissues during embryogenesis suggest that these genes may be targets of the Sonic hedgehog signal. We demonstrate that the two GLI genes are differentially regulated by Sonic hedgehog during limb development. Sonic hedgehog up-regulates GLI transcription, while down-regulating GLI3 expression in the mesenchymal cells of the developing limb bud. Finally, we demonstrate that an activated form of GLI can induce expression of Patched, a known target of Sonic hedgehog, thus implicating GLI as a key transcription factor in the vertebrate hedgehog signaling pathway. In conjunction with evidence from a mouse Gli3 mutant, our data suggest that GLI and GLI3 may have taken two different functions of their Drosophila homolog cubitus interruptus.

Animals↗
PubMed1996

The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.

The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development. Here we demonstrate that it binds Patched (vPtc), which has been identified as a tumour-suppressor protein in basal cell carcinoma, with high affinity. We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened (vSmo), and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly. These findings, combined with available genetic evidence from Drosophila, support the hypothesis that Ptc is a receptor for Shh, and that vSmo could be a signalling component that is linked to Ptc.

Amino Acid Sequence↗