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Biomedical subjects

A Wood

Publications and source records attributed to A Wood.

At least 19 recordsLinked to original sources
PubMed1992

Segregation and early dispersal of neural crest cells in the embryonic zebrafish.

We have exploited our ability to visualize and follow individual cells in situ, in the living embryo, to study the development of trunk neural crest in the embryonic zebrafish. In most respects, the development of zebrafish trunk neural crest is similar to the development of trunk neural crest in other species: zebrafish trunk neural crest cells segregate from the dorsal neural keel in a rostrocaudal sequence, migrate ventrally along two pathways, and give rise to neurons of the peripheral nervous system, Schwann cells, and pigment cells. However, some aspects of the development of zebrafish trunk neural crest differ from those of other vertebrates: zebrafish trunk neural crest cells are significantly larger and fewer in number than those in avian embryos and the locations of their migratory pathways are slightly different. This initial description of neural crest development in the zebrafish embryo provides the foundation for future experimental studies.

Animals↗
PubMed1991

Differential effects of concanavalin A, serum and cytokines on proteoglycan elaboration and DNA synthesis by mononuclear cells from human peripheral blood.

Human blood derived mononuclear cell (MC) cultures required concanavalin A (Con A) stimulation to synthesize and secrete into the medium high levels of a protease-resistant proteoglycan (PG) containing predominantly chondroitin sulfate (CS), which was elaborated largely by T-cells in culture. PG and DNA synthesis were studied in MC cultures in the absence and presence of Con A as well as serum and some biologically active polypeptide factors. In the presence of Con A, stimulation of PG synthesis was substantially greater in T-cell enriched cultures than in B-cell enriched cultures. DNA synthesis was also stimulated in the presence of Con A. This stimulation was concentration-dependent, but required the presence of serum for additional responses. DNA and cell proliferation were stimulated by interleukin-2 (IL-2), but PG production was not stimulated by conditioned media, IL-1, IL-2, IL-3, or transforming growth factor-beta (TGF-beta). Our results indicate that the elaboration of PG from T-cells of human MC is independent of the effects of regulatory peptides on cell proliferation and DNA synthesis.

B-Lymphocytes↗
PubMed1991

A synthetic peptide corresponding to a sequence in the GTPase activating protein inhibits p21ras stimulation and promotes guanine nucleotide exchange.

Amino acid sequence homology between the GTPase Activating Protein (GAP) and the GTP-binding regulatory protein, Gs alpha, suggests that a specific region of GAP primary structure (residues 891-898) may be involved in its stimulation of p21ras GTP hydrolytic activity (McCormick, F. [1989] Nature 340, 678-679). A peptide, designated p891, corresponding to GAP residues 891-906 (M891RTRVVSGFVFLRLIC906) was synthesized and tested for its ability to inhibit GAP-stimulated p21ras GTPase activity. At a concentration of 25 microM, p891 inhibited GAP activity approximately 50%. Unexpectedly, p891 also stimulated GTP binding to p21N-ras independent of GAP. This stimulation correlated with an enhancement of p21N-ras.GDP dissociation; an approximate 15-fold increase in the presence of 10 microM p891. In contrast, dissociation of the p21N-ras.GTP gamma S complex was unaffected by 10 microM p891. The p21N-ras.GDP complex was unresponsive to 100 microM mastoparan, a peptide toxin shown previously to accelerate GDP dissociation from the guanine nucleotide regulatory proteins, Gi and Go. p21H-ras, as well as the two p21H-ras effector mutants, Ala-38, and Ala-35, Leu-36, also exhibited increased rates of GDP dissociation in the presence of p891. Also tested were three ras-related GTP-binding proteins; rap, G25K and rac. The rap.-GDP complex was unaffected by 10 microM p891. Dissociation of the G25K- and rac.GDP complexes were enhanced slightly; approximately 1.3- and 1.8-fold over control, respectively. Thus, the inhibitory effect of p891 on GAP stimulation of p21ras suggests that amino acids within the region 891-906 of GAP may be essential for interaction with p21ras. In addition, p891 independently affects the nucleotide exchange properties of p21ras.

Amino Acid Sequence↗
PubMed1991

The transient expression of type II collagen at tissue interfaces during mammalian craniofacial development.

Using immunocytochemical techniques, the spatiotemporal distribution of the major collagen isoform of cartilage, type II collagen, has been investigated during early craniofacial development in the mouse embryo. Early and transient expression was associated with the otic and optic vesicles, the ventrolateral surfaces of the developing brain, olfactory conchi, endocardial and mesocardial tissues, the lateral and basal surfaces of the pharyngeal endoderm and beneath the ectoderm of the branchial arches. A number of these locations are sites of epithelial-mesenchymal tissue interaction believed to generate the component parts of the chondrocranium; here, type II collagen appears transiently in advance of overt chondrogenesis in the mesenchyme. At such sites, immunofluorescence is typically localised along the basal surface of the epithelial partner, with the strongest reaction detected between the basal aspects of the otic and rhombencephalic epithelia. Immunoelectron microscopy, using pre-embedding immunostaining and a protein G-gold technique, reveals that the type II collagen is adjacent to, but not integral with, the basal laminae. Gold particles are clearly associated with 10-15 nm fibrils of the extracellular matrix in the reticulate lamina region. The pattern of type II collagen expression in the mouse closely correlates with that demonstrated previously in the quail, indicating a high degree of phylogenetic conservation between these two vertebrate species. These findings are consistent with the hypothesis that the pattern of epithelial secretion of type II collagen, or a coexpressed matrix molecule, constitutes a morphogenetic signal, realised as a matrix-mediated tissue interaction, and specifying the form of the vertebrate chondrocranium. Three-dimensional reconstruction of early type II collagen distribution, and of the subsequent chondrocranial cartilages, reveals that chondrocranial form can be derived from a 'pre-pattern' of epithelially derived type II collagen expressed at epithelial-mesenchymal tissue interfaces.

Animals↗
PubMed1990

Recurrent symptoms after ventricular pacing in unexplained syncope.

We report clinical and hemodynamic data in two cases of recurrent syncope. Both patients received permanent demand ventricular pacing (VVI) for unexplained syncope. Both patients experienced recurrent syncope after pacemaker implantation. They later underwent 60 degrees head-up tilt testing, initially noninvasively and then with hemodynamic profile. A vasovagal response to tilt occurred with bradycardia and was complicated by the onset of ventricular pacing and retrograde atrioventricular conduction (RAVC) with hemodynamic deterioration and rapid reproduction of syncope. Limited intracardiac electrophysiological study (EPS) excluded atrioventricular (AV) conduction disease, sinus node disease, and carotid sinus syndrome, and confirmed RAVC. Both patients were upgraded to dual chamber pacing, DDI mode, with 50/80 rate hysteresis. One patient was asymptomatic at repeat tilt testing; the other experienced continued symptoms due to the vasodepressor component of vasovagal syncope. Cardiac pacing alone is ineffective treatment for this phenomenon, and no proven therapy is presently available. Ventricular pacing applied to patients with unexplained syncope may lead to an increase in or continuation of symptoms rather than an amelioration. There is a need for full investigation of such patients, which must include tilt testing, to allow for the most accurate diagnosis possible and guide the most appropriate therapy.

Aged↗
PubMed1990

Cardiac surgery in Down syndrome.

Between January 1976 and December 1987 42 children with Down syndrome and congenital heart disease underwent cardiac surgery. Four children had two operations. Age at the time of surgery ranged from 11 days to 14 years. The commonest operative procedure was repair of a patent ductus arteriosus. Four patients died post-operatively, two following repair of a complete atrio-ventricular canal defect (CAVD), one following correction of tetralogy of Fallot in association with a CAVD, and a fourth following closure of ventricular septal defect and atrial septal defect. The mortality for those who had open heart surgery was 13.3% and for the series as a whole the mortality was 6.6% over a period of follow-up ranging from two months to four years. A relatively conservative approach has been adopted with regard to surgery, based on the shorter natural expectation of life in Down syndrome, the complexity of many of the cardiac lesions involved and the recognition of the frequency of early intellectual deterioration in Down patients.

Adolescent↗
PubMed1989

Hepatitis B vaccination and GPs.

Doctors seem ambivalent to their own health needs even though, when it comes to infectious diseases, their families are also at risk. This study looks at GPs' attitudes to getting themselves vaccinated against hepatitis B. Despite the risk, 21 per cent of GPs have no intention of being vaccinated.

Attitude of Health Personnel↗
PubMed1989

Estradiol binding to plasma proteins after changing to a low-fat diet.

Breast cancer development is believed to be associated with both dietary fat consumption and the proportion of biologically available estradiol in the serum. A study was undertaken to determine if a reduction in fat consumption would influence the binding, and thus the bioavailability, of estradiol. Groups of pre- and postmenopausal women were randomized to begin either a standard western diet (40% energy from fat) or a low-fat diet (20% energy from fat). After two months, each woman changed over to the alternate diet. Blood samples were taken at the end of each dietary period. Change of diet made no significant difference to the proportions of nonprotein-bound (free), albumin-bound, or sex hormone binding globulin-bound estradiol in this study. However, the number of women studied and the duration of change were relatively small.

Adult↗
PubMed1989

Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation.

Bioelectrical potential difference (PD) across the respiratory mucosa is raised in cystic fibrosis (CF). We have recorded airway potentials from seven patients with CF who had undergone heart-lung transplantation and from eight patients without CF who had had transplants for cardiovascular disease; comparison of these populations controls for the effects of denervation and immunosuppressive treatment. Six patients without CF who had not had transplants formed an additional control. PD was recorded during routine fiberoptic bronchoscopy, using a Ringer's-perfused exploring bridge connected across a high impedance amplifier to an intravenous reference bridge. Bronchial lavage and sputum culture revealed no evidence of infection. Bronchial PD was similar in all three groups of patients at equivalent sites. However, nasal PD was raised in the CF group (mean value, 44 mV +/- 3.9 SE) compared with the patients who had transplants for cardiovascular disease (mean, 18 mV +/- 1.1 SE), and the control patients (mean, 15 mV +/- 1.2 SE). We conclude that the epithelial defects that result in raised airway potentials in CF do not recur in the transplanted lung.

Adolescent↗
PubMed1989

Depressed activities of purine enzymes in lymphocytes of patients infected with human immunodeficiency virus.

Enzyme activities were studied in peripheral blood lymphocytes from patients infected with, or at risk for, infection with human immunodeficiency virus (HIV). No significant differences were observed in the HIV-infected and HIV-seronegative high-risk patients with regard to enzyme activities of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) and purine nucleoside phosphorylase (EC 2.4.2.1) in peripheral blood. Adenosine deaminase (EC 3.5.4.4) was significantly (P less than 0.02) depressed in asymptomatic HIV-seropositive patients and HIV-seronegative patients at high risk of HIV infection as compared with a healthy HIV-seronegative population. Adenosine kinase (AK, EC 2.7.1.20) was significantly increased in the asymptomatic seropositive (P less than 0.02) and also in the HIV-seronegative high-risk groups (P = 0.01) compared with the normal controls. AK activity was significantly lower in subjects with AIDS than in the asymptomatic (P less than 0.002) and high-risk groups (P less than 0.01). Taken together, these results indicate that adenosine deaminase and AK activities are influenced by the health of the patient, and that measurement of AK activity may prove useful in monitoring the clinical progress of patients with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Accurate measurement of airway thermal challenge.

Rapid and accurate measurement of air temperature is needed to determine both heat and water losses from the respiratory tract during breathing. We have designed, constructed and validated a low dead-space, two-channel valve/mouthpiece which prevents mixing of inspired and expired air outside the body. The effects of airflow on the thermocouple response time and of thermocouple position within the airstream on the temperature measured were assessed. The 63% thermocouple response time fell from 159 to 78.8 ms as airflow rose from 23.7 to 297 1 min-1, a range including the peak flows observed while breathing at rest and during exercise. Measurement of temperature profiles across the valve/mouthpiece at different flows indicated that thermocouples were best positioned at the centre of the airstream, though small deviations did not adversely affect accuracy.

Body Temperature Regulation↗
PubMed1988

Contact guidance on microfabricated substrata: the response of teleost fin mesenchyme cells to repeating topographical patterns.

The mesenchymal tissue component of the teleost pectoral fin bud has been explanted onto microfabricated quartz discs containing patterns of regular grooves of dimensions similar to those encountered by contact-guided cells in the intact fin system. Computer-aided analysis of cell migration on five separate patterns, from 1.8 to 7.4 microns repeat spacing, revealed that migration was predominantly aligned parallel to the long axis of the grooves, with individual cells becoming highly polarized, and the highest index of alignment (3.7) produced on the widest repeat spacings. When these cells are cultured on planar quartz, which is both chemically and physically isotropic, they flatten and adopt a morphology similar to that shown by cultured fibroblastic cell types on flat surfaces, suggesting that fin mesenchymal cells are not intrinsically predisposed to adopt an arborized morphology, like that observed in the intact fin bud. These results clearly demonstrate a directional migration in response to substratum topography, from a cell type known to be contact guided in vivo, and in the complete absence of adhesive heterogeneities.

Animals↗
PubMed1988

Antitussive properties of inhaled bronchodilators on induced cough.

We have studied the antitussive effects of two anticholinergic agents, oxitropium bromide (200 micrograms) and ipratropium bromide (80 micrograms), and a combined beta-agonist and anticholinergic preparation containing fenoterol hydrobromide (200 micrograms) and ipratropium bromide (80 micrograms), in 16 normal and ten asthmatic volunteers in a double-blind, randomized, placebo-controlled crossover trial. Cough was induced by inhalation of ultrasonically nebulized distilled water and hypotonic saline solution. All treatments significantly reduced the cough response to inhaled distilled water aerosol when compared with placebo (p less than 0.001). There was no difference between oxitropium bromide and ipratropium bromide (p greater than 0.05), but the combination preparation displayed a greater antitussive effect than either oxitropium bromide (p less than 0.05) or ipratropium bromide (p less than 0.025). Cough frequencies in response to hypotonic 0.18 and 0.32 percent saline aerosol were lower than those obtained with distilled water (p less than 0.005) for all treatments. Asthmatic patients coughed less frequently than normal volunteers in response to all solutions when placebo was given (p less than 0.05), but there is no evidence to suggest that the response to treatment was different in the two groups. Our results suggest that inhaled anticholinergic bronchodilators alone or in combination with beta 2-adrenergic agonists might be effective in the treatment of pathologic cough.

Administration, Inhalation↗
PubMed1988

Modification by pertussis toxin of the responses of bovine anterior pituitary cells to acetylcholine and dopamine: effects on hormone secretion and 86Rb efflux.

Acetylcholine is known to stimulate the secretion of growth hormone and prolactin and the efflux of 86Rb from bovine anterior pituitary cells: dopamine prevents the stimulation of 86Rb efflux and of prolactin but not growth hormone secretion. The sensitivity of these responses to pertussis toxin has been determined. Treatment of bovine anterior pituitary cells in primary culture with pertussis toxin (18 h, 100 ng/ml) did not modify the stimulation of prolactin secretion by acetylcholine, but prevented its inhibition by dopamine. In lactotrophs, dopamine but not acetylcholine receptors are therefore coupled to secretion through a pertussis toxin substrate. The stimulation of 86Rb efflux by acetylcholine was also unaffected by pertussis toxin and, again, its inhibition by dopamine was prevented. Treatment of the cells with pertussis toxin enhanced the secretion of growth hormone in response to acetylcholine. Nitrendepine (1 mumol/l) prevented the cholinergic stimulation of growth hormone but not prolactin secretion from these cells. Acetylcholine increased the cytoplasmic calcium concentration and this rise was enhanced by treatment of the cells with pertussis toxin. Nitrendepine partially inhibited the rise in calcium caused by acetylcholine, and prevented the enhancement of the rise following pertussis toxin treatment. Cholinergic stimulation of growth hormone therefore depends on calcium entry through nitrendepine-sensitive channels, whereas stimulation of prolactin secretion does not, and in somatotrophs a pertussis toxin substrate may limit calcium entry through these channels. These different sensitivities of somatotrophs and lactotrophs to pertussis toxin and nitrendepine may reflect differences in the properties of the predominant calcium currents in the two cell types.

Acetylcholine↗
PubMed1988

Cyclosporin A and anti-glomerular basement membrane antibody glomerulonephritis in rats.

In a telescoped model of antiglomerular basement membrane (GBM) antibody induced nephritis, Lewis strain rats were injected in the footpad with rabbit IgG on day 0 and then given a single intravenous injection of rabbit anti-rat GBM antibody on day 5. Proteinuria developed within 24 h and renal histology 7 days later showed a focal or diffuse proliferative glomerulonephritis. In this study rats treated as above were given Cyclosporin A (CyA) 20 mg/kg daily by intraperitoneal injection from day 0 or from day 5. Rats given CyA plus anti-GBM antibody developed extensive glomerular infiltration with polymorphs and glomerular thrombosis, lesions not seen with unmodified anti-GBM nephritis or in rats who received CyA alone. The mechanism by which CyA given prior to or at the onset of immunological insult in this model worsens glomerular injury is unclear.

Animals↗
PubMed1987

Comparison of the stimulation of glycosaminoglycan synthesis in cultures of mononuclear cells from blood and of fibroblastic cells.

A small molecular weight factor, derived from bovine bone ('matrigenin'), stimulated glycosaminoglycan and proteoglycan synthesis of cultured human fibroblastic cells but not of mononuclear cells from human blood. However, proteoglycan synthesis and secretion by the mononuclear cells was stimulated by the addition of concanavalin A. The proteoglycan from the concanavalin-A-stimulated mononuclear cells was of smaller molecular weight than the proteoglycan from the 'matrigenin'-stimulated fibroblastic cells. The major increase in proteoglycan synthesis and secretion occurred much later during the culture period for concanavalin-A-stimulated mononuclear cells than for 'matrigenin'-stimulated fibroblastic cells.

Cells, Cultured↗