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Biomedical subjects

G R Johnson

Publications and source records attributed to G R Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Technique for the measurement of hindfoot inversion and eversion and its use to study a normal population.

Following earlier work identifying the difficulties of defining the subtalar neutral position, the authors have developed new techniques to measure the ranges of inversion and eversion in normal subjects. A test rig has been designed and constructed to apply a known torque about an anterior posterior axis and an electrogoniometer has been used to measure the resulting movements. The neutral position was defined as that position corresponding to the footplate being horizontal and the leg vertical. In a study of 100 normal subjects (50 female/50 male), it has been shown that the average overall range of motion decreased from 53.2 degrees in 20-year-olds to 44.3 degrees in 60-year-olds. It was also demonstrated that females had a greater range of motion than males, but that this difference reduced with age. This fact was largely accounted for by a decrease in the range of eversion in female subjects. RELEVANCE:--Hindfoot motion is essential for human walking, but accurate measurement is difficult because of the structure of the joints involved. This paper describes the development of a technique using electrogoniometry, for carrying out measurement of passive inversion and eversion of the hindfoot in a sample of healthy adults. It further highlights the difficulties in carrying out an accurate evaluation of hindfoot motion on which to base clinical decisions.

Journal Article↗
PubMed1996

Distribution of potential intermediate hosts for Fasciola hepatica and Fascioloides magna in Montana, USA.

A collection of lymnaeid snails in Montana was made over a 3 year period, in conjunction with a state-wide survey of the distribution of liver flukes in Montana. Collection areas were selected based on reports of infected cattle, sheep or wildlife, and with the intent of covering all geographic regions of the state. Snails were found at all 97 of the locations chosen for collections, with lymnaeids collected at 71 of the locations. The 97 sites were located in 28 of Montana's 56 counties. Nine lymnaeid species were collected, five of which have been reported either as natural or experimental intermediate hosts for Fasciola hepatica or Fascioloides magna. The two snail species most widely distributed over the areas enzootic for the flukes were Lymnaea modicella and Lymanaea caperata.

Animals↗
PubMed1996

Amphiregulin in lung branching morphogenesis: interaction with heparan sulfate proteoglycan modulates cell proliferation.

Epithelial and mesenchymal cells isolated from mouse embryonic lungs synthesized and responded to amphiregulin (AR) in a different fashion. Mesenchymal cells produced and deposited 3- to 4-fold more AR than epithelial cells, proliferated in the presence of exogenous AR, and their spontaneous growth was blocked by up to 85% by anti-AR antibodies. In contrast, epithelial cells exhibited a broad response to this growth regulator factor depending on whether they were supplemented with extracellular matrix (ECM) and whether this ECM was of epithelial or mesenchymal origin. AR-treated epithelial cells proliferated by up to 3-fold in the presence of mesenchymal-deposited ECM, remained unchanged in the presence of epithelial-deposited ECM, and decreased in their proliferation rate below controls in the absence of ECM supplementation. This effect was abolished by treatment with the glycosaminoglycan-degrading enzymes heparinase and heparitinase suggesting the specific involvement of heparan sulfate proteoglycan (HSPG) in AR-mediated cell proliferation. In whole lung explants, branching morphogenesis was inhibited by antibodies against the AR heparan sulfate binding site and stimulated by exogenous AR. Since during development, epithelial cells are in contact with mesenchymal ECM at the tips of the growing buds and alongside the basement membrane, focal variations in the proportion of epithelial and mesenchymal HSPG will focally affect epithelial proliferation rates. Therefore, AR-HSPG interaction may underlie the process of branching morphogenesis by inducing differential cell proliferation.

Amphiregulin↗
PubMed1996

Dynamics of the upper limb during performance of the tasks of everyday living--a review of the current knowledge base.

This paper provides a brief review of the published literature on the subject of kinematics and kinetics of the human arm and shoulder mechanism, specifically when performing the tasks of everyday living. Surprisingly, only a small number of papers covering functional analysis of the arm were found, and the majority of these were concerned only with the kinematics of the elbow and lower arm. Differences in experimental method and a lack of consensus as to how to model the joint axes of the human arm make the results difficult to compare. Results are normally only presented in the form of angular excursion of the arm segments, with only one paper providing data on angular velocities and accelerations. The results of the different analyses suggest that the human arm is adaptive (due to its inherent mechanical redundancy), showing the ability to perform the same tasks using differing kinematic strategies. Therefore, the principal interest for the designer of upper limb orthoses should be the work-space defined by the start and end points of the hand, and the maintenance of the desired hand orientation when performing these tasks.

Activities of Daily Living↗
PubMed1996

Development of an in vitro method for skin corrosion testing.

National and international regulations require that chemicals must be properly classified, labeled, packaged, and transported based on their ability to damage or destroy tissue, e.g., skin. Traditionally, skin corrosion assessments were based on tests involving topical application of test substances to the skin of rabbits. In the present work, an in vitro skin corrosion test based on the use of reconstructed human skin cultures was developed as a potential replacement for in vivo rabbit skin tests for corrosion. In the in vitro method, test substances were applied topically to the stratum corneum surface of human skin cultures. Skin culture damage or cytotoxicity was measured as decreased 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide (MTT) vital dye metabolism. In time-course experiments, the time (in minutes) of test material exposure eliciting a 50% reduction of MTT metabolism (i.e., t50 value) was calculated. Using this method we evaluated 24 chemicals and found that the 9 corrosive chemicals were accurately distinguished from 15 strong, moderate, or mild skin irritants, using an in vitro cutoff of t50 < 3 min. Histologic examination of the cultures indicated gradations of epidermal necrosis quantitated using a specially designed grading scale, which correlated well with the corrosivity of treatment chemicals and cytotoxicity measurements. The predictivity of the method was confirmed and was consistent in skin culture models from two suppliers. Thus, the utility of human skin equivalent cultures as a screening tool for prediction of skin corrosivity appears to be independent of the commercial source of the cultures. We conclude that the in vitro assay using human skin equivalent cultures is a promising alternative to in vivo rabbit skin corrosion tests for assessment of the corrosivity of chemicals to human skin.

Animal Testing Alternatives↗
PubMed1995

Murine hematopoietic stem and progenitor cells: I. Enrichment and biologic characterization.

Murine bone marrow cells were fractionated by fluorescence-activated cell sorting into Rh123lo Lin- c-kit+ Ly6A+, Rh123hi Lin-c-kit+ Ly6A+, and Lin- c-kit+ Ly6A- populations within which most, if not all, of the hematopoietic activities of the marrow resided. The Rh123lo Lin- c-kit+Ly6A+ cells, which consist exclusively of small- or medium-sized lymphocyte-like cells, are highly enriched for long-term hematopoietic in vivo repopulating cells. The enrichment factor for these cells from the marrow was estimated as 2,000-fold. The Rh123hi Lin- c-kit+ Ly6A+ cells, although also highly enriched for day-12 spleen colony-forming units, were relatively depleted of long-term in vivo repopulation capacity. Most, if not all Lin- c-kit+ Ly6A- cells were Rb123hi. In contrast to both Rh123lo and Rh123hi Lin- c-kit+ Ly6A+ stem cell populations, the Lin- c-kit+ Ly6A- cells can be stimulated to proliferate in vitro in the presence of single cytokines, which is a characteristic of committed progenitor cells. No marked synergistic interactions between individual cytokines were observed with this cell population. Both Rh123hi Lin- c-kit+ Ly6A+ mature stem cell and Lin- c-kit+ Ly6A- progenitor cell populations displayed in vivo repopulation kinetics resembling those of the putative short-term hematopoietic repopulating cells.

Animals↗
PubMed1995

mRNA phenotyping of the major ligands and receptors of the EGF supergene family in human ovarian epithelial cells.

mRNA amplification phenotyping (MAPPing) was used to determine the level of mRNA expression of the major EGF-related ligands (EGF, TGF-alpha, and Amphiregulin) and receptors (EGF-receptor and erbB-2) of the EGF supergene family in three ovarian carcinoma lines (OVCA 429 and 433, and NIH:OVCAR-8) under serum-supplemented and reduced serum (minimal medium with 2% fetuin) growth conditions. mRNA levels of TGF-alpha, EGF-R, and erbB-2 were particularly high, and increased approximately 2-3 orders of magnitude when grown in serum, consistent with an autocrine involvement of these genes in ovarian epithelial growth in vitro. Moreover, even when grown without serum, OVCA 429 and NIH:OVCAR-8 expressed elevated levels of mRNA for erbB-2.

Amphiregulin↗
PubMed1995

Detection and location of amphiregulin and Cripto-1 expression in the developing postnatal mouse mammary gland.

Amphiregulin (Ar) and Cripto-1 (Cr-1) are growth promoting peptides that share amino acid sequence homology with epidermal growth factor (EGF). The present study examined Ar and Cr-1 mRNA and protein expression during various stages of C57BL/6 mouse mammary morphogenesis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect transcripts for Ar and Cr-1 at all stages of mammary development. Immunocytochemical (ICC) localization demonstrated that in virgin 4-week to mature 12-week-old mouse fourth inguinal mammary gland, Ar and Cr-1 are expressed in the stromal cells, luminal epithelial cells, and myoepithelial cells of the branching ducts. Ar, and to lesser extent Cr-1, were also found in the epithelial cap cells and in the luminal epithelial cells of the advancing terminal end bud (TEB) from virgin 4-week and 6-week-old mice. Western blot analysis demonstrated that both Ar (28 and 26 kDa) and Cr-1 (90, 67, 56, and 21 kDa) proteins are expressed in virgin, 13.5 day midpregnant and in the 14 day lactating mammary gland. In addition, Ar and Cr-1 are associated with developing alveolar structures as determined by ICC. These results imply that together with EGF and transforming growth factor alpha (TGF alpha), Ar and Cr-1 may play salient roles as modifiers in the morphogenesis and differentiation of the mammary gland.

Amphiregulin↗
PubMed1995

Localization of amphiregulin in the human placenta and decidua throughout gestation: role in trophoblast growth.

Amphiregulin (AR) is a growth regulatory glycoprotein with significant amino acid homology to members of the epidermal growth factor (EGF) family. Its effects are mediated via the EGF receptor tyrosine kinase or through specific nuclear targeting sequences. In this study, the localization of immunoreactive AR was examined in paraformaldehyde-glutaraldehyde fixed, paraffin-embedded human placentae and decidua obtained at various stages from 11 weeks to term pregnancy using the avidin-biotin complex/peroxidase method. In addition, the effects of AR on trophoblast proliferation were evaluated from 3HTdR uptake by first trimester human trophoblast cells. Results revealed immunolocalization of AR to the nucleus as well as the cytoplasm of the syncytiotrophoblast cell layer of chorionic villi until approximately week 18 of gestation after which no immunostaining was detected. Villous and extravillous cytotrophoblast cells as well as decidual tissue were negative for AR at all gestational ages examined. In the presence of exogenous AR, there was a dose-dependent increase in proliferation of the trophoblast at AR concentrations ranging from 1-100 ng/ml. These results suggest that AR may be an important paracrine or juxtacrine growth stimulatory molecule for cytotrophoblast cells in situ early in gestation.

Amphiregulin↗
PubMed1995

Variability in measurement of abdominal aortic aneurysms. Abdominal Aortic Aneurysm Detection and Management Veterans Administration Cooperative Study Group.

PURPOSE: The purpose of this study was to report interobserver and intraobserver variability of computed tomography (CT) measurements of abdominal aortic aneurysm (AAA) diameter and agreement between CT and ultrasonography observed in the course of a large, multicenter, randomized trial on the management of small AAAs. METHODS: CT measurements of AAA diameter from participating centers were compared with measurements made from the same scan by a central laboratory. Blinded central remeasurement of a randomly selected subset of these CT scans was used to assess intraobserver variability. Agreement between AAA measurements by CT and ultrasonography done within 30 days of each other was also assessed. RESULTS: For interobserver pairs of local and central CT measurements of AAA diameter (n = 806), the difference was 0.2 cm or less in 65% of pairs, but 17% differed by at least 0.5 cm. For intraobserver pairs of central CT remeasurements (n = 70), 90% differed by 0.2 cm or less, 70% were within 0.1 cm, and only one differed by 0.5 cm. Of 258 ultrasound-measured and central CT pairs, the difference was 0.2 cm or less in 44% and at least 0.5 cm in 33%. Ultrasound measurements were smaller than central CT measurements by an average of 0.27 cm (p < 0.0001). Local CT and ultrasound measurements showed a marked preference for recording by half centimeter. CONCLUSIONS: A high degree of precision is possible in CT measurement of AAA diameter, but this precision may not be obtained in practice because of differences in measurement techniques. Differences between imaging modalities increase variability further. Variations in AAA measurement of 0.5 cm or more are not uncommon, and this should be taken into account in management decisions. Efforts to reduce variation in measurement are warranted and might include (1) seeking agreement between surgeons and radiologists on a precise definition of AAA diameter, (2) limiting the number of radiologists who measure AAAs, and (3) use of calipers and magnifying glass for CT measurements.

Aged↗
PubMed1995

Complementary therapies in nursing. Implications for practice using aromatherapy as an example.

This paper explores the use of aromatherapy within nursing. Beliefs and values which may influence nursing are explored and how these frequently parallel the philosophies that influence complementary therapies. Organisational and professional factors which may influence the use of aromatherapy are considered. The development of policies to guide aromatherapy practice plus identifying the most appropriate person to undertake this care is discussed. Justifying care is explored via the development of research based practice and the generation of appropriate knowledge to guide practice. Although the paper is based on aromatherapy many of the issues raised are relevant to other complementary therapies. Similarly, the word 'nurse' is used but the issues also relate to the practice of aromatherapy within midwifery and health visiting.

Aromatherapy↗
PubMed1995

Nucleotide sequence analysis of genes encoding a toluene/benzene-2-monooxygenase from Pseudomonas sp. strain JS150.

It was previously shown by others that Pseudomonas sp. strain JS150 metabolizes benzene and alkyl- and chloro-substituted benzenes by using dioxygenase-initiated pathways coupled with multiple downstream metabolic pathways to accommodate catechol metabolism. By cloning genes encoding benzene-degradative enzymes, we found that strain JS150 also carries genes for a toluene/benzene-2-monooxygenase. The gene cluster encoding a 2-monooxygenase and its cognate regulator was cloned from a plasmid carried by strain JS150. Oxygen (18O2) incorporation experiments using Pseudomonas aeruginosa strains that carried the cloned genes confirmed that toluene hydroxylation was catalyzed through an authentic monooxygenase reaction to yield ortho-cresol. Regions encoding the toluene-2-monooxygenase and regulatory gene product were localized in two regions of the cloned fragment. The nucleotide sequence of the toluene/benzene-2-monooxygenase locus was determined. Analysis of this sequence revealed six open reading frames that were then designated tbmA, tbmB, tbmC, tbmD, tbmE, and tbmF. The deduced amino acid sequences for these genes showed the presence of motifs similar to well-conserved functional domains of multicomponent oxygenases. This analysis allowed the tentative identification of two terminal oxygenase subunits (TbmB and TbmD) and an electron transport protein (TbmF) for the monooxygenase enzyme. In addition to these gene products, all the tbm polypeptides shared significant homology with protein components from other bacterial multicomponent monooxygenases. Overall, the tbm gene products shared greater similarity with polypeptides from the phenol hydroxylases of Pseudomonas putida CF600, P35X, and BH than with those from the toluene monooxygenases of Pseudomonas mendocina KR1 and Burkholderia (Pseudomonas) pickettii PKO1. The relationship found between the phenol hydroxylases and a toluene-2-monooxygenase, characterized in this study for the first time at the nucleotide sequence level, suggested that DNA probes used for surveys of environmental populations should be carefully selected to reflect DNA sequences corresponding to the metabolic pathway of interest.

Amino Acid Sequence↗
PubMed1995

Estrogen and phorbol esters regulate amphiregulin expression by two separate mechanisms in human breast cancer cell lines.

The actions of 17 beta-estradiol (E2) and protein kinase C (PKC) appear to converge in the regulation of expression of certain growth modulatory genes, such as the growth factor amphiregulin (AR). AR is known to modulate cell growth by binding to the epidermal growth factor receptor. In the current report we established the mechanisms of the PKC-activating phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the steroid hormone E2 on the induction of AR expression in human breast carcinoma cell lines. TPA (100 nM) and E2 (1 nM) induce AR messenger RNA (mRNA) expression by 6- to 8-fold and 3- to 6-fold, respectively, in a time- and dose-dependent manner. In addition, immunoreactive AR protein is induced by both TPA and E2 by 6- to 8-fold and 2- to 4-fold, respectively. The PKC-modulating drugs, bryostatin and H-7, and antiestrogens (ICI 164,384 and 4-hydroxytamoxifen) interfere with AR induction by TPA and estrogen, respectively. The effects of TPA and E2 on the induction of AR mRNA were both closely associated with enhanced transcription of the AR gene. However, TPA had an additional effect at the posttranscriptional level by stabilizing the AR mRNA. The protein synthesis inhibitor, cycloheximide, prevented AR induction by TPA, suggesting that a component of the TPA induction of AR is indirect and dependent upon protein synthesis. Conversely, the E2 induction of AR transcription was found to be a direct response, independent of protein synthesis. The results presented herein thus demonstrate that TPA and E2 are able to stimulate AR gene transcription by two separate mechanisms.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Winging of the scapula: the underlying biomechanics and an orthotic solution.

Winging of the scapula occurring in muscular disorders (muscular dystrophy and spinal muscular atrophy) or nerve injury has been investigated, resulting in a thorough understanding and presentation of the underlying biomechanics causing this occurrence. This includes a biomechanical explanation of the characteristic prominence of the medial border of the scapula upon attempted elevation, together with the biomechanical reasons for the rotation of the scapula in a direction contrary to the normal scapulohumeral rhythm. Based on these findings, a non-invasive alternative to the surgical technique for scapular stabilization has been devised, using an inflatable orthosis, placed between the scapula and an external restraint (such as a spinal jacket). The device has been tested on one subject using a 3SPACE Isotrak electromagnetic source and sensor system, and gave encouraging results. Elevation increased by up to 35 degrees (37 per cent), and functional improvement in the use of the hand around the head and face has been achieved. The technique needs no aftercare or physiotherapy and is therefore both economical and functionally effective.

Biomechanical Phenomena↗
PubMed1995

Syndrome of flank pain and acute renal failure after binge drinking and nonsteroidal anti-inflammatory drug ingestion.

The binge drinking of alcohol combined with the ingestion of a nonsteroidal anti-inflammatory drug (NSAID) is a recently described cause of reversible acute renal failure. The pathogenetic mechanisms leading to acute tubular necrosis in this setting include the initial compromise in renal perfusion due to alcohol-induced extracellular volume contraction and the superimposed renal hemodynamic alterations induced by the NSAID that interfere with the renal autoregulation. Although alcohol may also cause rhabdomyolysis leading to acute tubular necrosis, this is usually not apparent in these cases. Previously, only three such cases have been reported but the incidence is likely to be higher in view of the prevalence of alcohol and NSAID use. Herein is presented another patient in whom the features of flank pain and acute renal failure in association with binge drinking and NSAID ingestion constitute a characteristic syndrome.

Abdominal Pain↗
PubMed1995

Role of talectomy in the treatment of rigid talipes equinovarus deformities.

The authors provide a review of the principles of talectomy as a surgical treatment option for severe, rigid, and resistant clubfoot deformities. Such deformities are associated with a high recurrence rate and frequently involve a large number of surgical interventions to attain a satisfactory result. Talectomy has been successfully used as both a primary and salvage procedure to treat such deformities, often eliminating the need for subsequent surgeries. A discussion of the operative technique, indications, advantages, and common complications associated with the procedure is presented. In addition, a case report of talectomy used to treat a severe, bilateral clubfoot deformity in a 4-year-old boy is included.

Child, Preschool↗
PubMed1995

Lineage-restricted recruitment of immature hematopoietic progenitor cells in response to Epo after normal hematopoietic cell transfection with EpoR.

The receptor for erythropoietin (EpoR) is normally restricted in its expression to the relatively mature cells of the erythroid and megakaryocytic lineages. Using retrovirus-mediated gene transfer, the wild-type EpoR and a constitutively activated mutant of the EpoR, EpoRR129C, were expressed in primary hematopoietic cells. Retroviral infection of day-12 murine fetal liver, followed by stimulation with Epo as a single stimulus, generated day-8 erythroid colonies resembling colonies derived from burst-forming units-erythroid (BFU-E). Similarly, murine post-5 fluorouracil (5-FU) bone marrow cells or fetal liver cells, induced to express EpoR and stimulated by Epo, displayed a significant enhancement of megakaryocyte colony formation, particularly of the BFU-megakaryocyte (BFU-Mk) colony type. Cultures of bone marrow cells transduced with the EpoR retrovirus and stimulated by Epo contained macrophage colonies but very few granulocyte colonies. Experiments to culture single clones demonstrated direct action of Epo on megakaryocyte and macrophage clones but failed to demonstrate a direct action on granulocyte precursors. A similar pattern of lineage-restricted effects was demonstrated in unstimulated cultures of cells infected with the EpoRR129C retrovirus. In summary, we have demonstrated Epo-induced recruitment of immature erythroid and megakaryocyte precursors induced to express the EpoR. Furthermore, we have also demonstrated lineage-restricted cell proliferation in response to Epo by normal myeloid hematopoietic cells transduced with the EpoR.

Animals↗