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Biomedical subjects

R L Johnson

Publications and source records attributed to R L Johnson.

At least 19 recordsLinked to original sources
PubMed2004

Characterization of migration behavior of myogenic precursor cells in the limb bud with respect to Lmx1b expression.

Limb buds develop from lateral plate-derived stationary mesenchyme and are invaded by cells from extrinsic regions. The largest populations of these cells are myogenic precursor cells that originate from the lateral dermomyotomes. After detachment under the influence of SF/HGF, myogenic precursor cells migrate in a proximo-distal direction and populate a dorsal and ventral zone. The patterning mechanism leading to the segregation of dorsal and ventral myogenic cells is at present not understood. Lmx1b, a LIM homeodomain transcription factor expressed in the dorsal mesenchyme of the developing limb bud, forms a sharp dorso-ventral boundary of expression within the limb. We have investigated the mechanisms of dorso-ventral patterning of muscle precursor cells in the limb buds with respect to Lmx1b expression using quail-chick chimeras and transgenic mice. Although cells appeared to be capable of migrating either ventrally or dorsally, their migration was restricted to the position they had attained during normal development or in the experimental situation. They were never found to cross the dorso-ventral boundary. Immunohistochemistry and histological analysis of mice carrying a LacZ reporter gene under the control of the endogenous Lmx1b locus confirmed that myogenic precursors in the limb bud were devoid of Lmx1b expression. In addition, it was shown that Lmx1b is not only expressed at early stages of limb development but maintains its pattern, at least until after birth. The present study provides new insights into migratory pathways of myogenic precursor cells and reveals details of Lmx1b expression on a cellular basis within the limb.

Animals↗
PubMed2004

Estimate of pulmonary diffusing capacity for oxygen during exercise in humans from routine O(2) and CO(2) measurements.

A method to estimate pulmonary diffusing capacity for O(2) (D(LO2)) during exercise based on routine O(2) and CO(2) transport variables is presented. It is based on the fitting of a mathematical model to gas exchange data. The model includes heterogeneity (described as two exchanging compartments), diffusion limitation and right-to-left shunt. Mass conservation equations and Bohr integration were solved to calculate partial pressures in each compartment. Diffusion was distributed with perfusion. Two-compartment ventilation and perfusion distributions were estimated at rest during conditions of negligible diffusion limitation. These distributions were used during hypoxic and normoxic exercise to obtain the D(LO2) from the model computations (D(LO2)2C) compatible with experimental data. Three normals, four sarcoid patients and four patients after lung resection were studied. An independent technique for carbon monoxide was used to provide experimental estimates of DLo2 (D(LO2)EXP, rebreathing technique for sarcoid patients and single breath for lung resection). D(LO2)2C was highly correlated with D(LO2)EXP (r2 = 0.95, P<0.001) and the slope of the regression line was not statistically different from 1. The mean (D(LO2)EXP - D(LO2)2C) difference was -1.0 +/- 7.4 ml min-1 mmHg-1. The results suggest that use of a refined analytical procedure allows for assessment of D(LO2) from routine O(2) and CO(2) measurements comparable with those obtained from independent carbon monoxide techniques. The method may be an alternative for estimates of D(LO2) during exercise.

Adult↗
PubMed2003

Air distribution in the Borden aquifer during in situ air sparging.

A field experiment was conducted at Canadian Forces Base Borden (CFB Borden) to assess the air distribution from a single in situ air sparging injection point. This aquifer consists of fine to medium sand deposited in horizontal layers. The permeability at the study location varied from 10(-10) to 10(-14) m2 and distinct low permeability horizons were present at approximately 1.2, 2.0, and 2.9 m below the water table. Prior to air injection, a 15x15-m portion of the vadose zone was excavated to the water table (approximately 1 m below ground surface) in order to visually observe air release distribution at the water table. The water table was actively maintained 5 cm above the excavated surface. The sparging system operated for a period of 7 days with an injection flow rate of 200 m3/days (5 scfm). The resulting subsurface air distribution was assessed using a variety of techniques including neutron logging, borehole and surface ground penetrating radar, piezometric head measurements, surface visualization, and hydraulic testing. Through this combination of tests, it was demonstrated that variations in permeability and, hence, capillary pressure at the site were sufficient to cause the injected air to spread laterally, forming stratigraphically trapped air pockets beneath the low permeability horizons. The formation of these air pockets eventually resulted in a buildup of capillary pressure that exceeded the air entry pressure and allowed some air to migrate up through the lower permeability layers. Each of the assessment techniques employed generated information at different spatial scales that prevented a direct comparison of the results from the various techniques; however, the results from all techniques proved to be critical in the interpretation of the experimental data. As a consequence, the different assessment techniques should not be viewed as alternatives, but rather as complimentary techniques.

Air↗
PubMed2003

Pro-Leu-glycinamide and its peptidomimetic, PAOPA, attenuate haloperidol induced vacuous chewing movements in rat: A model of human tardive dyskinesia.

In the present experimental paradigm, we examine the effect of L-prolyl-L-leucyl-glycinamide (PLG) co-administration with haloperidol on vacuous chewing movements (VCM) in rats-a model of tardive dyskinesia (TD) in humans. We examined the dose dependent induction of VCM through both injected and orally administered PLG (MIF-1). Our results show significant levels of VCM attenuation (P<0.05) in rats treated with 10mg/kg of PLG. Doses of 1 and 100mg/kg were ineffective. Reductions were present in both orally treated and injected rats. We also examined the therapeutic effect of a peptidomimetic of PLG-PAOPA. PAOPA was able to produce similar behavioral effects to PLG at a dose, which was 100-fold lower than the effective dose of PLG. These results suggest that PLG may play a role in D2 receptor expression and function, as well as providing a therapy for neuroleptic induced TD.

Administration, Oral↗
PubMed2001

Sharper images by focusing soft X-rays with photon sieves.

Fresnel zone plates consisting of alternating transmissive and opaque circular rings can be used to focus X-rays. The spatial resolution that can be achieved with these devices is of the order of the width of the outermost zone and is therefore limited by the smallest structure (20-40 nm) that can be fabricated by lithography today. Here we show that a large number of pinholes distributed appropriately over the Fresnel zones make it possible to focus soft X-rays to spot sizes smaller than the diameter of the smallest pinhole. In addition, higher orders of diffraction and secondary maxima can be suppressed by several orders of magnitude. In combination with the next generation of synchrotron light sources (free-electron lasers) these 'photon sieves' offer new opportunities for high-resolution X-ray microscopy and spectroscopy in physical and life sciences.

Journal Article↗
PubMed2001

Subsurface dimerization in III-V semiconductor (001) surfaces.

We present the atomic structure of the c(8 x 2) reconstructions of InSb-, InAs-, and GaAs-(001) surfaces as determined by surface x-ray diffraction using direct methods. Contrary to common belief, group III dimers are not prominent on the surface, instead subsurface dimerization of group III atoms takes place in the second bilayer, accompanied by a major rearrangement of the surface atoms above the dimers to form linear arrays. By varying the occupancies of four surface sites the (001)-c(8 x 2) reconstructions of III-V semiconductors can be described in a unified model.

Journal Article↗
PubMed2001

Requirement for math5 in the development of retinal ganglion cells.

math5 is a murine orthologue of atonal, a bHLH proneural gene essential for the formation of photoreceptors and chordotonal organs in Drosophila. The expression of math5 coincides with the onset of retinal ganglion cell (RGC) differentiation. Targeted deletion of math5 blocks the initial differentiation of 80% of RGCs and results in an increase in differentiated amacrine cells. Furthermore, the absence of math5 abolishes the retinal expression of brn-3b and the formation of virtually all brn-3b-expressing RGCs. These results imply that math5 is a proneural gene essential for RGC differentiation and that math5 acts upstream to activate brn-3b-dependent differentiation processes in RGCs.

Animals↗
PubMed2001

Phylogenetics of freshwater black basses (Centrarchidae: Micropterus) inferred from restriction endonuclease analysis of mitochondrial DNA.

Geographic isolation and habitat specialization has aided in the evolution and genetic integrity of the micropterid bass species of North America. Members of the genus Micropterus form a close natural unit with little morphologic and meristic variation. Our goals were to measure the genetic characteristics of and distances between six black bass species by using mitochondrial DNA analysis. Mitochondrial DNA restriction fragment length polymorphisms were examined in Guadalupe bass (M. treculi), largemouth bass (M. salmoides), shoal bass (M. cataractae), smallmouth bass (M. dolomieu), spotted bass (M. punctulatus), and Suwannee bass (M. notius), using 15 restriction endonucleases. The bluegill (Lepomis macrochirus) was used as an outgroup. The phylogeny inferred from Dollo parsimony cladistic analysis concurred with published results from allozyme analyses, yet it was inconsistent with published meristic analyses. Genetic distances between species ranged from 0.0659 to 0.2145, with the largemouth and Suwannee basses showing the greatest divergence from the other black basses. The Guadalupe, smallmouth, and spotted basses were most diverged from the bluegill. The black basses diverged over a broad time frame, with estimated black bass speciation occurring during late Miocene-early Pliocene (3.30-10.73 MYA).

Animals↗
PubMed2001

Targeted Disruption of the Myocilin Gene (Myoc) Suggests that Human Glaucoma-Causing Mutations Are Gain of Function.

Glaucoma is a heterogeneous eye disease and a major cause of blindness worldwide. Recently, primary open angle glaucoma (POAG)-associated mutations have been found in the trabecular meshwork inducible glucocorticoid response gene (TIGR), also known as the myocilin gene (MYOC), at the GLC1A locus on chromosome 1q21-q31. These mutations occurred in a subset of patients with juvenile- and adult-onset POAG and exhibited autosomal dominant inheritance. Ocular expression and its involvement in POAG suggest that TIGR/MYOC may have a role(s) in regulating intraocular pressure (IOP). Here, we report the generation and analysis of mice heterozygous and homozygous for a targeted null mutation in Myoc. Our study shows that Myoc mutant mice are both viable and fertile. Our in vivo findings further demonstrate that Myoc is not required for normal IOP or normal ocular morphology. The lack of a discernable phenotype in both Myoc-heterozygous and Myoc-null mice suggests that haploinsufficiency is not a critical mechanism for POAG in individuals with mutations in MYOC. Instead, disease-causing mutations in humans likely act by gain of function.

Animals↗
PubMed2001

The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos.

The winged-helix or forkhead class of transcription factors has been shown to play important roles in cell specification and lineage segregation. We have cloned the chicken homolog of FoxD3, a member of the winged-helix class of transcription factors, and analyzed its expression. Based on its expression in the dorsal neural tube and in all neural crest lineages except the late-emigrating melanoblasts, we predicted that FoxD3 might be important in the segregation of the neural crest lineage from the neural epithelium, and for repressing melanogenesis in early-migrating neural crest cells. Misexpression of FoxD3 by electroporation in the lateral neural epithelium early in neural crest development produced an expansion of HNK1 immunoreactivity throughout the neural epithelium, although these cells did not undergo an epithelial/mesenchymal transformation. To test whether FoxD3 represses melanogenesis in early migrating neural crest cells, we knocked down expression in cultured neural crest with antisense oligonucleotides and in vivo by treatment with morpholino antisense oligonucleotides. Both experimental approaches resulted in an expansion of the melanoblast lineage, probably at the expense of neuronal and glial lineages. Conversely, persistent expression of FoxD3 in late-migrating neural crest cells using RCAS viruses resulted in the failure of melanoblasts to develop. We suggest that FoxD3 plays two important roles in neural crest development. First, it is involved in the segregation of the neural crest lineage from the neuroepithelium. Second, it represses melanogenesis, thereby allowing other neural crest derivatives to differentiate during the early stages of neural crest patterning.

Alpharetrovirus↗
PubMed2001

Pulmonary membrane diffusing capacity and capillary blood volume measured during exercise from nitric oxide uptake.

STUDY OBJECTIVES: To validate lung diffusing capacity for nitric oxide (DLNO) as an index of conductance of the alveolar-capillary membrane during exercise, we compared DLNO to lung diffusing capacity for carbon monoxide (DLCO) and pulmonary membrane diffusing capacity for carbon monoxide (DMCO), and compared pulmonary capillary blood volume (Vc) calculated by two methods. SETTING AND PARTICIPANTS: The study was performed at a university medical center involving 12 nonsmoking healthy volunteers (age range, 23 to 79 years). DLCO, DLNO, cardiac output (c), and lung volume were measured simultaneously at rest and during graded ergometer exercise by a rebreathing technique. Pulmonary membrane diffusing capacity and Vc were compared by (1) the classic technique of Roughton and Forster from DLCO measured at two alveolar oxygen tension (PAO(2)) levels, and (2) from DLNO and DLCO assuming negligible erythrocyte resistance to nitric oxide (NO) uptake, ie, DLNO approximately equal to pulmonary membrane diffusing capacity for nitric oxide. RESULTS: In all subjects, DLNO increased linearly from rest to exercise; age, c, and lung volume were the major determinants of DLNO by stepwise regression analysis. The DLNO/DLCO ratio averaged 3.98 +/- 0.38 (+/- SD) and the DLNO/DMCO ratio averaged 2.49 +/- 0.28 irrespective of exercise intensity. Changing PAO(2) did not alter DLNO. Brief exposure to 40 ppm of inhaled NO during 16 s of rebreathing did not alter either DLCO or c. Estimates of pulmonary membrane diffusing capacity and Vc by the two methods showed a strong correlation. CONCLUSION: Results support DLNO as a direct measure of pulmonary membrane diffusing capacity, allowing the estimation of Vc in a single rebreathing maneuver during exercise. The DLNO-DLCO rebreathing technique can be applied clinically in the investigation of pulmonary microvascular regulation.

Adult↗
PubMed2001

Abnormal superior popliteomeniscal fascicle and posterior pericapsular edema: indirect MR imaging signs of a lateral meniscal tear.

OBJECTIVE: Because MR diagnosis of lateral meniscal tears can be difficult, indirect signs may be useful when a tear is suspected. We studied whether an abnormality of the superior popliteomeniscal fascicle or pericapsular edema was associated with lateral meniscal tears and thus may be an indirect MR imaging sign of a lateral meniscal tear. MATERIALS AND METHODS: We identified 59 consecutive patients who underwent both knee MR imaging examinations and knee arthroscopy. Thirty patients had lateral meniscal tears, and 29 had intact lateral menisci. We reviewed paired sagittal proton density- and T2-weighted MR images from these 59 patients for abnormal superior popliteomeniscal fascicles and edema surrounding the posterolateral capsule. RESULTS: The superior popliteomeniscal fascicles were abnormal in nine of the 30 patients with torn lateral menisci but were normal in all 29 patients with intact menisci (p = 0.001). Abnormal fascicles were apparent only when the lateral meniscal tear involved the posterior horn. Posterior pericapsular edema was seen in 10 patients with a torn posterior horn and in one patient with an anterior horn tear of the lateral meniscus, but in only two patients with intact menisci (p = 0.006). CONCLUSION: The presence of superior popliteomeniscal fascicle abnormalities and of posterior pericapsular edema is significantly associated with a tear of the lateral meniscus, most commonly in the posterior horn. Noting the presence of these findings may help improve the accuracy of MR diagnosis of lateral meniscal tears.

Adolescent↗
PubMed2001

High-risk sexual behaviors among adolescents engaged through a street-based peer outreach program--(the Adolescent HIV Project).

On-the-street peer based programs can overcome barriers and successfully engage teens in HIV counseling and testing. This initiative combines on-the-street peer outreach with on-the-street HIV testing in a mobile counseling and testing van. A survey was conducted to measure HIV risk behaviors concern about HIV infection. In year one, the program engaged 1550 youth. Of these, 666 completed HIV counseling and testing. Only 18% indicated that they had not had unprotected sexual intercourse in the preceding year. Thirty-nine percent of the males and 52% of the females had caused or been pregnant. Sixty-six percent of the males and 53% of the females believed that they could become HIV infected. Fifty-three percent of the male and 75% of the female respondents had had a previous HIV test. However concern about HIV did not significantly decrease the prevalence of HIV risk behaviors. Peer outreach and on-the-street counseling and testing is a successful method of increasing HIV testing among high risk youth. Youth are concerned about HIV infection but that concern does not translated into a change in risk behaviors.

Adolescent↗
PubMed2000

Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb.

Motor neurons extend axons along specific trajectories, but the molecules that control their pathfinding remain poorly defined. We show that two LIM homeodomain transcription factors, Lim1 and Lmx1b, control the initial trajectory of motor axons in the developing mammalian limb. The expression of Lim1 by a lateral set of lateral motor column (LMC) neurons ensures that their axons select a dorsal trajectory in the limb. In a complementary manner, the expression of Lmx1b by dorsal limb mesenchymal cells controls the dorsal and ventral axonal trajectories of medial and lateral LMC neurons. In the absence of these two proteins, motor axons appear to select dorsal and ventral trajectories at random. Thus, LIM homeodomain proteins act within motor neurons and cells that guide motor axons to establish the fidelity of a binary choice in axonal trajectory.

Animals↗