PubMed HealthSearch

Biomedical subjects

R Armstrong

Publications and source records attributed to R Armstrong.

At least 19 recordsLinked to original sources

In vitro sulfotransferase activity of NodH, a nodulation protein of Rhizobium meliloti required for host-specific nodulation.

Early stages of nodulation involve the exchange of signals between the bacterium and the host plant. Bacterial nodulation (nod) genes are required for Rhizobium spp. to synthesize lipooligosaccharide morphogens, termed Nod factors. The common nod genes encode enzymes that synthesize the factor core structure, which is modified by host-specific gene products. Here we show direct in vitro evidence that Rhizobium meliloti NodH, a host-specific nodulation gene, catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to the terminal 6-O position of Nod factors, and we show substrate requirements for the reaction. Our results indicate that polymerization of the chitooligosaccharide backbone likely precedes sulfation and that sulfation is not absolutely dependent on the presence or the particular structure of the N-acyl modification. NodH sulfation provides a tool for the enzymatic in vitro synthesis of novel Nod factors, or putative Nod factors intermediates, with high specific activity.

Bacterial Proteins

A refractory phase in cyclic AMP-responsive transcription requires down regulation of protein kinase A.

Cyclic AMP (cAMP) stimulates the expression of numerous genes through the protein kinase A (PK-A)-mediated phosphorylation of the nuclear factor CREB at Ser-133 (G. A. Gonzalez and M. R. Montminy, Cell 59:675-680, 1989). Like other signal transduction pathways, cAMP induces gene expression with burst-attenuation kinetics; cAMP-dependent transcription and CREB phosphorylation peak within 30 min and decline steadily over the next 4 to 6 h via the protein phosphatase 1-mediated dephosphorylation of CREB (M. Hagiwara, A. Alberts, P. Brindle, J. Meinkoth, J. Feramisco, T. Deng, M. Karin, S. Shenolikar, and M. Montminy, Cell 70:105-113, 1992). Here we characterize a third phase in cAMP-responsive transcription--a refractory period during which hormone-treated cells become transcriptionally unresponsive to subsequent stimulation by cAMP. This refractory period begins 6 to 8 h after stimulation and lasts 3 to 5 days after the removal of hormone. In contrast to the earlier attenuation phase, transcription of cAMP-responsive genes during the refractory period is not restored by inhibitors of protein phosphatase 1 activity. Rather, the establishment and maintenance of this phase rely on a marked reduction in PK-A catalytic subunit expression at the translational level. As overexpression of C-subunit protein can reactive transcription of cAMP-responsive genes during the refractory period, our results suggest that hormone-responsive cells may stimulate, attenuate, and then silence signal-dependent genes through distinct regulatory mechanisms.

Animals

Factors that contribute to spontaneous platelet aggregation and streptokinase-induced aggregation in whole blood.

When whole blood is stirred there is a "spontaneous" platelet aggregation (SPA) which is presumed to be caused by proaggregatory factors released from platelets and other blood cells. Adding streptokinase (SK) to stirred whole blood frequently increases the rate and extent of the platelet aggregation that occurs; this is likely to be via immune complex formation between SK and natural anti-SK antibodies leading to increased release of pro-aggregatory factors. In this investigation we have examined the effects of several inhibitors and antagonists in an attempt to identify the proaggregatory factors that contribute to both SPA and SK-induced aggregation (SKA) and to evaluate different means of inhibiting both processes. The effects of the inhibitors/antagonists were determined in vitro after adding them to citrated whole blood obtained from healthy volunteers. Platelet aggregation was measured using a platelet counting technique. Inhibition of both SPA and SKA by apyrase and by FPL 66096 (a P2T receptor antagonist) demonstrated the involvement of ADP in both processes. Inhibition by chlorpromazine indicated that the most likely source of the ADP is red cells. The effects of sulotroban (a TXA2 antagonist) indicated involvement of TXA2 in SKA but not in SPA. The lack of effect of specific antagonists at S2, alpha 2 and PAF receptors suggested lack of involvement of serotonin, catecholamines and platelet-activating factor in either SPA or SKA. Both SPA and SKA were potently inhibited by low concentrations of iloprost (a PGI2 analogue), but a high concentration of SIN-1 (a NO donor) was much less effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate

The relevance of health state utilities to lower third molar surgery.

A study of the attitudes of 102 arts and science undergraduate students was carried out to establish relative utility values, that is the participants own assessments, for possible outcomes of surgical intervention and non-intervention in lower third molar management. Using a standardised visual analogue scale, respondents were asked to rate 17 outcomes of treatment presented to them by means of short descriptions (vignettes). Ranking of mean utility values showed that post operative complications were considered to be a greater handicap than the sequelae of leaving third molars in situ. The respondents considered that the effects of irreversible lingual and inferior dental nerve damage reduced health to a major degree, and that normally encountered post operative complications such as moderate pain, swelling and trismus were a greater handicap than recurrent mild/moderate pericoronitis.

Adult

Regulation of somatostatin gene transcription by cAMP.

A number of hormones and growth factors stimulate target cells through receptors which are coupled to second messenger pathways. The second messenger cAMP, for example, mediates a wide variety of cellular responses to hormonal signals, including changes in intermediary metabolism, cellular proliferation and cellular motility. In mammalian cells, all of these biological responses are triggered by the activation of the cAMP-dependent protein kinase A, a heterotetramer consisting of paired catalytic and regulatory subunits. Upon hormonal stimulation, cAMP binds tightly to the regulatory subunits, thereby liberating catalytic subunits and promoting the phosphorylation of cellular substrates. In the liver, cAMP functions as a starvation state signal, mediating hormonal cues from the pancreas and adrenal gland to stimulate glucose production. cAMP stimulates glucose production, in part, by regulating transcription of the gene for phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis. Following hormonal stimulation, cAMP induces PEPCK gene expression 10-fold within 20-30 min. This induction appears to be independent of new protein synthesis.

Animals

Patients achieve accurate home blood pressure measurement following instruction.

This study evaluates the effects of an instruction program conducted by registered nurses on subjects' ability to achieve three blood pressure measurements that were within 2 mmHg of simultaneous readings taken by an instructor listening through a dual headed stethoscope. The sample comprised 30 subjects aged between 22 and 76 years who were referred to a Hypertension Unit over a two month period for home blood pressure instruction. After approximately 45 minutes of individual instruction and practice in the use of an aneroid home blood pressure machine, subjects' ability to measure their blood pressure was assessed by the accuracy of their readings, their responses to a multiple choice knowledge questionnaire, their self-reported confidence in their ability to measure their blood pressure at home and an instructor's evaluation of their technique. Twenty seven percent of subjects achieved three measurements that were the same as those of their instructor, 57% and 17% obtained readings that were within 2 mmHg and 4 mmHg of an instructor respectively. Ninety percent of subjects obtained perfect scores in the knowledge questionnaire, 93% obtained perfect scores in the technique competency checklist and 100% of subjects either strongly agreed or agreed with the statement 'I feel confident enough to measure my blood pressure at home'. The study demonstrates that patients can be taught to accurately measure their blood pressure at home and, herefore, to provide reliable data to assist in the diagnosis and treatment of hypertension and hypotension.

Adult

The self reported prevalence of asthma symptoms amongst adult New Zealanders.

AIMS: To examine the prevalence of asthma symptoms in a random population sample of New Zealand adults aged 20-44 years drawn from the general and Maori electoral rolls as phase I of an international study of asthma prevalence. METHODS: Subjects aged 20-44 years in Auckland, Hawkes Bay, Wellington and Christchurch, were selected randomly from the electoral rolls and sent a one page screening questionnaire, asking about respiratory symptoms, asthma attacks and asthma treatment. They were also asked to record their ethnic affiliation. Nonresponders were subsequently sent two written reminders followed by a telephone questionnaire where possible. RESULTS: A response rate of 84% was achieved. The study found a high prevalence of asthma symptoms, with 26% reporting wheezing in the last year, 8% experiencing an attack of asthma in the last year and 9% currently using asthma medication. Females were more likely to have had wheezing in the last year (26.6%) and be on treatment for asthma (9.8%) compared with males (24.7% and 7.5% respectively). Small regional differences were found with more reported symptoms and asthma treatment in Wellington and Christchurch, compared with Auckland and Hawkes Bay. Maori were more frequently symptomatic (35.2%) than nonPolynesian (24.8%) but were no more likely to report an attack of asthma (Maori 9.0%, nonPolynesian 7.7%) or be currently receiving asthma treatment (Maori 10.0%, nonPolynesian 8.6%). Asthma symptoms tended to decline with age in non Maori but increased with age in Maori. Adjustment of prevalence rates by two independent methods suggests that nonresponse bias has not significantly inflated these rates. CONCLUSIONS: The symptoms of asthma and their treatment are common in young New Zealanders, affecting one in three Maori and one in four nonMaori. One in ten of this adult population currently receive asthma treatment.

Adult

Purification and properties of virus particles, infectious subviral particles, cores and VP7 crystals of African horsesickness virus serotype 9.

Methods were developed for the purification, at high yield, of four different particle types of African horsesickness virus serotype 9 (AHSV-9). These products included virus particles purified on CsCl gradients which contain proteins apparently directly comparable to those of bluetongue virus (VP1 to VP7); virus particles purified on sucrose gradients which also contain, as a variable component, protein NS2; infectious subviral particles (ISVPs), containing chymotrypsin cleavage products of VP2; and cores, obtained by treating purified ISVPs with 1 M-MgCl2 to remove the components of the outer capsid layer (VP5 and VP2 cleavage products). Additional protein bands migrating with apparent M(r)s lower than that of VP5 were detected during SDS-PAGE analysis of virus particles. These appear to be conformational variants of VP5 and are identified as VP5' and VP5". BHK-21 cells infected with this strain of AHSV-9 produce large quantities of flat, usually hexagonal crystals of VP7, a major group antigen and core protein; these were also purified. Either 20 mg of virus particles, 20 mg of ISVPs or 10 mg of cores as well as 20 mg of VP7 crystals could be purified from approximately 8 x 10(9) infected cells. None of the preparations of particles or crystals showed any detectable contamination with BHK-21 cell proteins or antigens, as determined by SDS-PAGE or indirect ELISA. Virus particle and ISVP preparations had similar specific infectivities for BHK-21 cells (approximately 1 x 10(9) TCID50/A260 unit) but the infectivity of cores was approximately 10(5)-fold lower.

African Horse Sickness Virus

The topographic distribution of the magnetic P100M to full- and half-field stimulation.

Visual evoked magnetic responses were recorded to full-field and left and right half-field stimulation with three check sizes (70', 34' and 22') in five normal subjects. Recordings were made sequentially on a 20-position grid (4 x 5) based on the inion, by means of a single-channel direct current-Superconducting Quantum Interference Device second-order gradiometer. The topographic maps were consistent on the same subjects recorded 2 months apart. The half-field responses produced the strongest signals in the contralateral hemisphere and were consistent with the cruciform model of the calcarine fissure. Right half fields produced upper-left-quadrant outgoing fields and lower-left-quadrant ingoing fields, while the left half field produced the opposite response. The topographic maps also varied with check size, with the larger checks producing positive or negative maximum position more anteriorly than small checks. In addition, with large checks the full-field responses could be explained as the summation of the two half fields, whereas full-field responses to smaller checks were more unpredictable and may be due to sources located at the occipital pole or lateral surface. In addition, dipole sources were located as appropriate with the use of inverse problem solutions. Topographic data will be vital to the clinical use of the visual evoked field but, in addition, provides complementary information to visual evoked potentials, allowing detailed studies of the visual cortex.

Adult

Repeated measurements of tibia lead concentrations by in vivo x ray fluorescence in occupational exposure.

A group of workers occupationally exposed to lead have had measurements of their tibia lead concentrations made on two occasions separated by five years; on the second occasion calcaneus lead concentrations were also measured. The results serve to confirm the reliability of the measurement technique and to illustrate the improved precision achieved through technical improvements. More importantly, the relation between tibia lead concentration and cumulative blood lead found in this longitudinal study was entirely consistent with that previously reported, which had been based on cross sectional studies. Furthermore, the relation between lead concentrations in the tibia and in calcaneus found here was similar to that previously found in a larger cross sectional survey. It is concluded that this technique of measuring bone lead concentrations non-invasively is likely to be used increasingly as a biological monitor of cumulative exposure to lead.

Calcaneus

Longitudinal studies of exposure to cadmium.

Measurements of urinary proteins, blood and urinary cadmium, and in vivo kidney and liver cadmium have been made for a group of workers at several times between 1981 and 1990. The possibility of the introduction of measurement artifacts due to the use of different in vivo measurement systems has been assessed and is considered to be small. Changes in cadmium body burden with time have been studied in relation to kidney function. The results suggest several interesting patterns, although more data are needed to elucidate these further. They do, however, show the effectiveness of good hygiene in the workplace.

Body Burden

In vivo measurements of lead in bone at four anatomical sites: long term occupational and consequent endogenous exposure.

Measurements of bone lead concentrations in the tibia, wrist, sternum, and calcaneus were performed in vivo by x ray fluorescence on active and retired lead workers from two acid battery factories, office personnel in the two factories under study, and control subjects. Altogether 171 persons were included. Lead concentrations in the tibia and ulna (representative of cortical bone) appeared to behave similarly with respect to time but the ulnar measurement was much less precise. In an analogous fashion, lead in the calcaneus and sternum (representative of trabecular bone) behaved in the same way, but sternal measurement was less precise. Groups occupationally exposed to lead were well separated from the office workers and the controls on the basis of calculated skeletal lead burdens, whereas the differences in blood lead concentrations were not as great, suggesting that the use of concentrations of lead in blood might seriously underestimate lead body burden. The exposures encountered in the study were modest, however. The mean blood lead value among active lead workers was 1.45 mumol l-1 and the mean tibial lead concentration 21.1 micrograms (g bone mineral)-1. The kinetics of lead in the tibia appeared to be noticeably different from that in the calcaneus. Tibial lead concentration increased consistently both as a function of intensity of exposure and of duration of exposure. Calcaneal lead concentration, by contrast, was strongly dependent on the intensity rather than duration of exposure. This indicated that the biological half life of lead in calcaneus was less than the seven to eight year periods into which the duration of exposure was split. Findings for retired workers clearly showed that endogenous exposure to lead arising from skeletal burdens accumulated over a working lifetime can easily produce the dominant contribution to systemic lead concentrations once occupational exposure has ceased.

Adult

Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and acitretin alone.

UVB radiation is beneficial for the treatment of psoriasis vulgaris. Patients with recalcitrant disease, however, are slow to respond to UVB phototherapy with and without the use of coal tars or emollients. Etretinate and, more recently, acitretin have proved useful, but clinical improvement is slow when they are used as monotherapy in plaque psoriasis. Each drug also produces side effects, some of which are dose related. This study was designed to compare results of treatment with UVB combined with either acitretin (50 mg/day) or placebo to determine if psoriasis would respond faster and to less cumulative exposure to UVB and acitretin. The psoriatic disease cleared to a greater degree in patients treated with acitretin-UVB with fewer treatments and smaller amounts of UVB radiation than in patients treated with either placebo-UVB or acitretin alone.

Acitretin

Transforming growth factor-beta 2 enhances the osteoinductive activity of a bovine bone-derived fraction containing bone morphogenetic protein-2 and 3.

We previously identified a novel glycoprotein in an osteoinductive fraction from bovine bone (Bentz et al.: Amino acid sequence of bovine osteoinductive factor. J. Biol. Chem. 265: 5024-5029, 1990). We now find that this fraction also contained small amounts of bone morphogenetic protein-2 and 3 (BMP-2 + 3) previously identified by others (see Wozney, J.M.: Bone morphogenetic proteins. Prog. Growth Factor Res. 1: 267-280, 1990). Separation of BMP-2 + 3 from the glycoprotein was achieved with a modified reversed phase-high pressure liquid chromatographic procedure. When assayed in the rat subcutis using a collagen-ceramic carrier, the osteoinductive activity was found in the subfraction containing BMP-2 + 3. This activity was potentiated and the ratio of cartilage to bone was increased by transforming growth factor-beta 2. The glycoprotein, originally called osteoinductive factor, has been renamed osteoglycin. In its precursor form, osteoglycin is a member of the leucine-rich family of proteins showing the characteristic 24-residue internal homology. Its biological function is unknown.

Amino Acid Sequence

Comparison of a topical mixture of lidocaine and prilocaine (EMLA) versus 1% lidocaine infiltration on wound healing.

We compared a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pharmaceuticals, Inc) with 1% lidocaine infiltration to determine the effect on wound healing in a prospective single blind study using the rat model. Thirty-six wounds were assessed. No clinical or histologic evidence of infection or necrosis was present in any wound. Five wounds (two in the lidocaine and three in the EMLA group, P = 1.0) demonstrated a widened scar owing to healing by secondary intention following suture disruption. There was no significant difference between groups in the degree of inflammation (P = 0.08). We conclude that EMLA does not affect wound healing adversely and is comparable to 1% lidocaine infiltration in the animal model. Further study to determine its anesthetic effect in laceration repair is presently being undertaken.

Administration, Topical

The cellular and molecular events of central nervous system remyelination.

Central nervous system (CNS)* regeneration is a subject of great interest, particularly in diseases causing a dramatic loss of neurons. However, some CNS diseases do not affect neurons but damage other cells, such as the myelin-forming cells--called oligodendrocytes--which are also crucial to the harmonious function of the nervous system. Diseases in which oligodendrocytes and myelin are attacked can cause devastating neurological dysfunction which is sometimes followed by recovery and myelin repair or remyelination. The question of the regeneration potential of oligodendrocytes in experimental and human demyelinating diseases such as multiple sclerosis has been debated for a long time. Present evidence suggests that oligodendrocyte precursor cells persist in the adult CNS and that oligodendrocyte regeneration can occur but may be limited by ongoing disease processes. Here we will briefly review recent advances which have broadened our understanding of the cellular and molecular events of CNS remyelination.

Age Factors