Search PubMed⌕ Search

Biomedical subjects

A Howard

Publications and source records attributed to A Howard.

At least 91 records · Page 5Linked to original sources
PubMed1988

Site-directed antibodies for probing the structure and biogenesis of phosphatidylinositol glycan-linked membrane proteins: application to placental alkaline phosphatase.

An immunological approach to the study of the structure and biogenesis of the phosphatidylinositol glycan (PI-G) membrane anchor at the carboxyl terminus of human placental alkaline phosphatase (PLAP) is described. Based on the protein sequence predicted from full length PLAP cDNA, two epitopes were chosen in the region of the carboxyl terminus for the production of site-directed antibodies. The exo site represents the last nine residues of preproPLAP, (res. 505-513), which is part of the sequence that is expected to be cleaved from the nascent protein during processing and addition of the PI-G tail. A second site, the endo sequence, was selected close to the expected carboxyl terminus in mature PI-G-tailed PLAP (res. 474-484 of proPLAP). The two peptides were synthesized, polyclonal antibodies to the conjugated peptides were prepared, and the antisera were characterized. Analytical methods for both synthetic peptides and proteins are presented. Preliminary applications to the isolation and characterization of the PI-G-linked carboxyl terminus of mature PLAP and to the characterization of nascent PLAP are described. The application of both carboxyl terminal-directed antibodies, and a third antibody directed to the amino terminus of mature PLAP, in studies employing mutant forms of PLAP and to the PI-G tailing process itself are discussed. The immunological approach used here for PLAP should be applicable generally to the study of other PI-G-tailed proteins.

Alkaline Phosphatase↗
PubMed1988

The gait of pacers. 1: kinematics of the racing stride.

Standardbred pacers have been studied under race conditions to describe the gait of the pacer, and to determine relationships between stage of the race, finish order and selected gait kinematics. Overlap increased with the stage of the race while pacing speed decreased marginally for low order pacers and increased for high order finishers. High order finishing pacers appear to have greater stance and stride lengths than do low order finishers. Pacers could be separated into low order and high order groups on the basis of their movement patterns. High order pacers exhibited greater ranges of limb motion than did low order finishers.

Animals↗
PubMed1988

The gait of pacers. 2: factors influencing pacing speed.

Standardbred pacers were studied at four different nominated speeds and selected gait kinematics were analysed to determine factors which contribute to pacing speed. A deterministic model is proposed in which pacing speed is a function of stride length and stride timing variables. Stance length and suspension time remained relatively constant over the different pacing speeds. Variables which discriminated best between pacing speeds were suspension length and overlap time. At near maximal speed, the pacers increased speeds with increased stride length. This was attributed to an increased suspension length with little difference in suspension times. A 22 per cent increase in pacing speed resulted in a 13 per cent increase in stride length, 26 per cent increase in suspension distance, 8 per cent increase in stride frequency, 35 per cent and 16 per cent increases in advanced placement and completion times and a 23 per cent decrease in the period of overlap.

Animals↗
PubMed1988

Clozapine-induced agranulocytosis: non-cross-reactivity with other psychotropic drugs.

Clozapine, an atypical neuroleptic with unique clinical and preclinical properties, represents a potentially valuable addition to the psychopharmacopeia. Its development and use have been limited by its higher frequency, compared with other pharmacologic treatments, of the potentially fatal side effect of agranulocytosis. This article describes the natural history of five cases of agranulocytosis that occurred in the course of clozapine treatment. The cases were generally uniform as to onset, recovery, and hematologic features. No patient had hematologic reactions to treatment with psychotropic agents before or after clozapine treatment. These findings, along with other work in progress, suggest that clozapine's granulocytoxic effects are produced by a highly specific immune-mediated mechanism.

Adult↗
PubMed1986

Structural studies of Rubisco from tobacco.

An electron density map of ribulose 1,5-bisphosphate carboxylase-oxygenase (Rubisco) from tobacco (Nicotiana tabacum) has been obtained by X-ray crystallography at a nominal resolution of 0.34 nm. Phases were determined by multiple isomorphous replacement with three heavy atom derivatives and then refined by solvent flattening. Rubisco is barrel-shaped, and has (422) symmetry. The fourfold axis runs down an open central channel, concentric with the barrel. The molecule measures 10.5 nm along the fourfold axis, and has a diameter of 13 nm perpendicular to the fourfold axis at the widest point. The diameter of the central channel is 2.8 nm at the centre of the molecule, and 0.6 nm at its narrowest constriction. Portions of the polypeptide backbone of the promoter have been traced and some 127 residues have been assigned to 14 alpha-helices. The amino acid sequences of Rubisco from Rhodospirillum rubrum and from the large subunit of tobacco are sufficiently similar to suggest that the two chains are folded in the same general way.

Models, Molecular↗
PubMed1986

Psychological consequences of majority-minority status: a questionnaire study of two high schools.

A questionnaire survey of high school students investigated the psychological phenomena associated with teenagers' membership in majority and minority groups. In the majority group, the socioeconomic status of parents was consonant with that of the high school; in the minority group, the status was dissonant with that of the school. The psychological impact of attending high schools that were consonant or dissonant with the student's family background was examined. The results are discussed in terms of the students' personal adjustments: views of their parents; and political, social, and personal attitudes and values. Minority teenagers were found to be more oriented to the home (especially to the mother) and to scholastic and future achievement, whereas majority teenagers were more oriented to their school peer group. Gender differences were also examined.

Adaptation, Psychological↗
PubMed1986

Antibodies to peptidoglycan in juvenile onset ankylosing spondylitis and pauciarticular onset juvenile arthritis associated with chronic iridocyclitis.

Using an indirect enzyme linked immunosorbent assay, antibodies of the IgG class to Streptococcus pyogenes group A peptidoglycan-polysaccharide polymers (PG-GSP) were measured in the sera of 37 patients with juvenile onset ankylosing spondylitis (JAS), 22 with pauciarticular onset juvenile arthritis associated with chronic iridocyclitis and 20 healthy children. Mean antibody activity, measured in arbitrary units, was of 184 U in JAS and 250 U in chronic iridocyclitis (p = NS). The results in both groups differed significantly from those found in healthy children (p less than 0.001 and p less than 0.01, respectively). This suggests either a possible role of bacterial cell wall products in the pathogenesis of these disorders or a state of immune reactivity to PG-GSP in these children.

Antibodies↗
PubMed1985

The visualization and characterization of two immunological forms of alpha 2 macroglobulin by immunoelectrophoretic methods.

Two peaks of alpha 2 macroglobulin (alpha 2M) were demonstrated in serum or plasma treated with trypsin using crossed immunoelectro-phoresis (CIEP). Both peaks moved the same distance in the first dimension and separated only when electrophoresed into antibody containing gel. The double peak phenomenon was shown not to be an artefact of the antiserum used and that the sample had to be fresh for both peaks to be visualised. Using the methods of staggered well CIEP and crossed thin layer gel chromatography (CTLGC) both peaks were shown to be of very similar antigenicity and molecular size. The technique of line immunoelectrophoresis (LIEP) demonstrated that the newly described lower peak was the alpha 2M/protease complex. The lowest concentration of alpha 2M/protease complexes that could be detected was 0.03 g/l. The two peaks of alpha 2M do not follow the theory of rocket immunoelectrophoresis (RIEP) and this is discussed.

Chromatography, Thin Layer↗
PubMed1985

Autoantibodies in childhood scleroderma.

The clinical presentation of scleroderma in childhood is even more varied than in adult life. This study of 19 children shows that antinuclear antibodies (ANA) detected on the HEp2 cell substrate are just as common as in the adult disorders. All seven children with diffuse scleroderma or acrosclerosis were ANA positive, as were eight of the 12 with more localised disease. Antinucleolar antibodies were particularly frequent (58% overall), but anticentromere antibody was not observed. Enzyme-linked immunosorbent assays (ELISAs) for antibodies to collagen types I-V, in contrast to adult scleroderma, gave normal results in all childhood cases.

Antibodies, Antinuclear↗
PubMed1985

Dexamethasone suppression tests in patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder and major depressive disorder are associated by several lines of evidence. To explore the possible relationship between the two disorders, the authors administered 1-mg dexamethasone suppression tests to 18 patients with obsessive-compulsive disorder and 51 patients with major depressive disorder. None of the obsessive-compulsive patients were classified as nonsuppressors on the basis of a 4:00 p.m. serum cortisol level, whereas 37% of the depressed patients were nonsuppressors. The mean cortisol levels of the two groups differed significantly. Factors that may influence hypothalamic-pituitary-adrenal function, such as age, depressive symptoms, and severity of illness, are discussed in light of these results.

Adolescent↗
PubMed1985

IgG-anti-IgG antibodies in juvenile chronic arthritis.

IgG antiglobulins were measured in 117 children with seronegative juvenile chronic arthritis (JCA). 100 had active disease, and these had significantly higher levels of IgG antiglobulins (mean 0.45 +/- 0.16 micrograms/ml) than the control group (mean 0.25 +/- 0.16 micrograms/ml (p less than 0.01]. The inactive group of patients had a mean of 0.14 +/- 0.06 micrograms/ml, comparable to a group of cord bloods from normal births (mean 0.14 +/- 0.05 micrograms/ml). In the active patients there was no difference when subdivision was made according to their mode of onset into pauciarticular, polyarticular, or systemic.

Adrenal Cortex Hormones↗
PubMed1985

Can genetic polymorphism of alpha-2-macroglobulin be detected by immunoelectrophoresis? A study using sera, plasma and joint fluids from patients with rheumatoid arthritis and controls.

The technique of immunoelectrophoresis (IEP) was used to examine polymorphism of the endopeptidase inhibitor alpha-2-macroglobulin (alpha 2M) by measuring its electrophoretic mobility. Examination of the variability of the method showed that a large intra- and inter-plate variation occurred (3.3 and 11.6%, respectively). It was also shown that alpha 2M from plasma moves significantly slower than that from serum and that the mobility of alpha 2M from plasma can be increased to that of serum by treatment with trypsin. Upon comparing sera, plasma and synovial fluids from a control group (normal subjects and patients with osteoarthritis) with a group of patients with rheumatoid arthritis, no difference in alpha 2M mobility could be demonstrated. It is concluded that genetic polymorphism of alpha 2M cannot be detected by the technique of IEP.

Arthritis, Rheumatoid↗
PubMed1984

Affinity chromatography of solubilized opioid binding sites using CH-Sepharose modified with a new naltrexone derivative.

An affinity gel containing a newly synthesized derivative of naltrexone, beta-naltrexyl-6-ethylenediamine (NED), was used to purify opioid binding sites by 300-450-fold. Binding sites solubilized from brains of toad, rat and cow using digitonin in the presence of 0.5 M NaCl are retained by the gel and can be eluted with naloxone (1-3 microM) in yields of 20-25%. The biospecificity of the interaction of opioid binding sites with modified beads is supported by the following: 1) unmodified beads do not retain the binding sites, 2) binding sites prebound with an opioid are not retained, 3) dilution of NED gels with unmodified Sepharose progressively reduced efficiency of retention and 4) specific receptor ligands elute binding sites retained on the NED gels.

Animals↗
PubMed1984

Rapid activation of tyrosine hydroxylase in response to nerve growth factor.

Nerve growth factor protein (NGF) was found to rapidly promote the activation of tyrosine hydroxylase in cultured rat PC12 pheochromocytoma cells. PC12 cultures were exposed to NGF for periods of less than 1 h and the soluble contents of homogenates prepared from the cells were assayed for tyrosine hydroxylase activity. Under these conditions, the specific enzymatic activity was increased by 60 +/- 10% (n = 13) in comparison with that in untreated sister cultures. The increase was half maximal by 2-5 min of exposure and at NGF concentrations of about 10 ng/ml (0.36 nM). Antiserum against NGF blocked the effect. Tyrosine hydroxylase activity could also be rapidly increased by NGF in cultures of PC12 cells that had been treated with the factor for several weeks in order to produce a neuron-like phenotype. This was achieved by withdrawing NGF for about 4 h and then readding it for 30 min. The NGF-induced increase of tyrosine hydroxylase activity in PC12 cultures was not affected by inhibition of protein synthesis and therefore appeared to be due to activation of the enzyme. Kinetic experiments revealed that NGF brought about no change in the apparent Km of the enzyme for tyrosine or for cofactor (6- methyltetrahydropteridine ), but that it did significantly increase the apparent maximum specific activity of the enzyme. These observations suggest that NGF (perhaps released by target organs) could promote a rapid and local enhancement of noradrenergic transmission in the sympathetic nervous system.

Adrenal Gland Neoplasms↗
PubMed1983

Safety and efficacy of bupropion in elderly patients: preliminary observations.

The efficacy and safety of bupropion, an atypical antidepressant, were assessed in depressed patients aged 55 and above. Data were analyzed for 38 patients who completed 4 weeks of double-blind treatment with bupropion in maximum doses of 150 or 450 mg/day; imipramine, up to 200 mg/day; or placebo. Preliminary results suggest that bupropion does have antidepressant activity and is well tolerated in this population. A particular advantage is suggested in terms of cardiovascular side effects.

Age Factors↗