Biomedical subjects

M J Reid

Publications and source records attributed to M J Reid.

At least 19 recordsLinked to original sources

PubMed2005

The distance to the Perseus spiral arm in the Milky Way.

We have measured the distance to the massive star-forming region W3OH in the Perseus spiral arm of the Milky Way to be 1.95 +/- 0.04 kiloparsecs (5.86 x10(16) km). This distance was determined by triangulation, with Earth's orbit as one segment of a triangle, using the Very Long Baseline Array. This resolves the long-standing problem that there is a discrepancy of a factor of 2 between different techniques used to determine distances. The reason for the discrepancy is that this portion of the Perseus arm has anomalous motions. The orientation of the anomalous motion agrees with spiral density-wave theory, but the magnitude of the motion is somewhat larger than most models predict.

Journal Article↗

PubMed2002

A star in a 15.2-year orbit around the supermassive black hole at the centre of the Milky Way.

Many galaxies are thought to have supermassive black holes at their centres-more than a million times the mass of the Sun. Measurements of stellar velocities and the discovery of variable X-ray emission have provided strong evidence in favour of such a black hole at the centre of the Milky Way, but have hitherto been unable to rule out conclusively the presence of alternative concentrations of mass. Here we report ten years of high-resolution astrometric imaging that allows us to trace two-thirds of the orbit of the star currently closest to the compact radio source (and massive black-hole candidate) Sagittarius A*. The observations, which include both pericentre and apocentre passages, show that the star is on a bound, highly elliptical keplerian orbit around Sgr A*, with an orbital period of 15.2 years and a pericentre distance of only 17 light hours. The orbit with the best fit to the observations requires a central point mass of (3.7 +/- 1.5) x 10(6) solar masses (M(*)). The data no longer allow for a central mass composed of a dense cluster of dark stellar objects or a ball of massive, degenerate fermions.

Journal Article↗

PubMed2001

Structure--function relationships of rat hepatic tryptophan 2,3-dioxygenase: identification of the putative heme-ligating histidine residues.

The liver cytosolic enzyme tryptophan 2,3-dioxygenase (TDO) catalyzes the oxidation of L-tryptophan to formylkynurenine and controls the physiological flux of tryptophan into both the serotonergic and kynureninic pathways. This hemoprotein enzyme is composed of four noncovalently bound subunits of equivalent mass and contains two heme moieties per molecule. Electron paramagnetic resonance analyses have indicated that a histidyl nitrogen is involved in heme ligation [Henry et al., (1976) J. Biol. Chem. 251, 1578], but the identity of the His residue(s) is unknown. In an attempt to characterize the active site of the enzyme we have substituted each of the 12 His residues in the rat TDO subunit with Ala, to determine their relative importance in heme binding. Sequence alignment of the rat liver protein with that of known or putative TDO sequences from other organisms reveals that four of the His residues are conserved in eukaryotes, two of which are also conserved in prokaryotes. Our findings indicate that replacement of the evolutionarily conserved His 76 and 328 residues resulted in a dramatic reduction of TDO activity, whereas that of the eukaryotically conserved His70 resulted in a significant reduction relative to that of the wild-type enzyme. On the other hand, replacement of the other eukaryotically conserved His273 residue, while affecting the relative expression of the enzyme, had little effect on its specific activity. Size-exclusion analyses revealed that the His76Ala and His328Ala mutants retained little or no heme, suggesting that these may be key residues in ligating the prosthetic heme moieties. Whether these His residues are both provided by the same TDO subunit or a different TDO subunit remains to be determined.

Amino Acid Sequence↗

PubMed2001

Cannabinoid-induced alterations in brain disposition of drugs of abuse.

Marijuana contains a complex mixture of compounds including tetrahydrocannabinol (THC), the major psychoactive constituent, and cannabidiol (CBD), a nonpsychoactive constituent. We have shown previously that CBD pretreatment of mice increases brain levels of THC and have now further characterized this effect and determined whether the brain pharmacokinetics of other drugs are also affected. CBD pretreatment of mice (30-60 min) increased brain levels of THC nearly 3-fold, whereas CBD co-administration did not. Because marijuana is often consumed with other drugs, the influence of cannabinoids on the brain levels of several other drugs of abuse was also determined. CBD pretreatment of mice increased brain levels (2- to 4-fold) of subsequently administered cocaine as well as phencyclidine (PCP). Although CBD pretreatment increased blood and brain levels of cocaine comparably, blood levels of PCP were only modestly elevated (up to 50%). Behavioral tests indicated that the CBD-mediated increases in the brain levels of THC, cocaine, and PCP correlated with increased pharmacological responses. Pretreatment with THC instead of CBD could similarly increase brain levels of cocaine, PCP, and CBD, although with a lower potency than CBD. On the other hand, pretreatment of mice with CBD had no effect on the brain levels of several other drugs of abuse including morphine, methadone, or methylenedioxyphenyl-methamphetamine. These findings demonstrate that cannabinoids can increase the brain concentrations and pharmacological actions of several other drugs of abuse, thereby providing a biochemical basis for the common practice of using marijuana concurrently with such drugs.

Anesthetics, Local↗

PubMed2001

The effects of phencyclidine pretreatment on cocaine-mediated hepatotoxicity in mice.

Cocaine-mediated hepatotoxicity (CMH) requires cocaine (CCN) bioactivation by microsomal monooxygenase enzymes that results in cell death. Proposed mechanisms of toxicity involve reactive metabolites that covalently bind to hepatocellular proteins, depletion of cellular reducing equivalents through redox cycling, and/or the generation of reactive oxygen and nitrogen species that alter lipids and proteins. We have previously shown that phencyclidine (PCP) pretreatment potentiated CMH in CF-1 mice without increasing in vitro N-demethylation or N-hydroxylation of CCN. We have now further characterized PCP-potentiated CMH and determined that it is a dose- and time-dependent process, with PCP doses as low as 2.5 mg/kg for 3 days significantly increasing CMH. Immunohistochemistry and histology of livers from mice pretreated with PCP before CCN administration revealed a marked correlation between the regions of CCN metabolite binding and that of necrosis, whereas there was little binding or necrosis in vehicle-pretreated mice. Although hepatic GSH levels were not altered after repetitive PCP treatment alone, a sustained decrease (at least 6 h) in these levels was observed following CCN administration. Inhibitors of inducible nitric oxide synthase (NOS) abrogated PCP-potentiated CMH, although repetitive PCP treatment alone did not increase nitric oxide synthesis systemically or locally in hepatic tissue nor did lipopolysaccharide induction of NOS (without PCP) directly potentiate CMH. The precise mechanisms of PCP potentiation of CMH and involvement of NOS in CMH remain unclear, however, sustained depletion of GSH levels and increased hepatocellular binding of reactive cocaine metabolites have been demonstrated.

Animals↗

PubMed2001

Parent training in head start: a comparison of program response among African American, Asian American, Caucasian, and Hispanic mothers.

The effectiveness of the Incredible Years Parenting Program was evaluated in a low-income sample of Caucasian, African American, Hispanic, and Asian mothers whose children were enrolled in Head Start. Data from two prior intervention studies [Webster-Stratton (1998) Journal of Consulting and Clinical Psychology, 66(5), 715-730; Webster-Stratton et al. (in press) Journal of Clinical Child Psychology] were combined, yielding a sample of 634 families (370 Caucasian, 120 African American, 73 Asian, 71 Hispanic) across 23 Head Start centers. Centers were matched and assigned randomly to either an experimental condition (8-12 weeks of weekly 2-hr parenting classes), or a control condition (the regular Head Start Program without parenting groups). Families in both conditions were assessed using home observations of parent-child interactions and parent reports of parenting style and discipline strategies and child behavior problems in the fall (baseline) and spring (postintervention) of the children's Head Start year. Families were reassessed 1 year later. Following treatment, intervention mothers were observed to be more positive, less critical, more consistent, and more competent in their parenting than were control mothers. Additionally, children of intervention parents were observed to exhibit fewer behavior problems than were control children. Differences in treatment response across ethnic groups were few, and did not exceed the number expected by chance. Parents from all groups reported high satisfaction levels following the parenting program. Results indicate that the Incredible Years Program is accepted by and effective with diverse populations.

Adult↗

PubMed2001

Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression while downregulating T(H)2 cytokine expression in PBMCs from human patients with ragweed allergy.

BACKGROUND: Recent studies have demonstrated that bacterially derived immunostimulatory sequences (ISSs) of DNA can activate the mammalian innate immune system and promote the development of T(H)1 cells. Promotion of T(H)1 immunity by means of immunotherapy in allergic patients has led to the alleviation of symptoms that result from allergen-specific T(H)2 responses. OBJECTIVE: Our purpose was to investigate whether the T(H)1-enhancing properties of ISSs could be used to alter the T(H)2-dominated immune response of allergic PBMCs in vitro. METHODS: Ragweed protein-linked ISS (PLI) was generated from a specific, highly active 22-base ISS and Amb a 1, the immunodominant allergen in ragweed pollen, to combine the T(H)1-enhancing properties of ISSs with allergen selectivity, and its activity was investigated in PBMC cultures from subjects with ragweed allergy. RESULTS: PLI was markedly successful at reversing the dominant allergen-induced T(H)2 profile while greatly enhancing IFN-gamma production. Delivering ISSs in a linked form proved to be much more effective at modulating the resulting cytokine profile than delivering free ISSs in a mixture with unlinked Amb a 1. PLI also demonstrated cytokine-modulating properties, even when used to stimulate cells that had already been primed for 6 days with Amb a 1. The antigen specificity of the action of PLI was confirmed by the observations that PLI enhances Amb a 1--specific T-cell proliferation. CONCLUSION: These data indicate that delivery of ISSs within an antigen-specific context exhibits potent cytokine-modulating activity and, combined with its reduced allergenicity, makes this molecule a strong candidate for use in improved immunotherapy applications.

Adjuvants, Immunologic↗

PubMed2001

Preventing conduct problems, promoting social competence: a parent and teacher training partnership in head start.

Studied the effectiveness of parent and teacher training as a selective prevention program for 272 Head Start mothers and their 4-year-old children and 61 Head Start teachers. Fourteen Head Start centers (34 classrooms) were randomly assigned to (a) an experimental condition in which parents, teachers, and family service workers participated in the prevention program (Incredible Years) or (b) a control condition consisting of the regular Head Start program. Assessments included teacher and parent reports of child behavior and independent observations at home and at school. Construct scores combining observational and report data were calculated for negative and positive parenting style, parent-teacher bonding, child conduct problems at home and at school, and teacher classroom management style. Following the 12-session weekly program, experimental mothers had significantly lower negative parenting and significantly higher positive parenting scores than control mothers. Parent-teacher bonding was significantly higher for experimental than for control mothers. Experimental children showed significantly fewer conduct problems at school than control children. Children of mothers who attended 6 or more intervention sessions showed significantly fewer conduct problems at home than control children. Children who were the "highest risk" at baseline (high rates of noncompliant and aggressive behavior) showed more clinically significant reductions in these behaviors than high-risk control children. After training, experimental teachers showed significantly better classroom management skills than control teachers. One year later the experimental effects were maintained for parents who attended more than 6 groups. The clinically significant reductions in behavior problems for the highest risk experimental children were also maintained. Implications of this prevention program as a strategy for reducing risk factors leading to delinquency by promoting social competence, school readiness, and reducing conduct problems are discussed.

Child, Preschool↗

PubMed2000

Cross-reactivity among conifer pollens.

BACKGROUND: There are increasing reports of Cupressaceae pollinosis from various geographic areas. Cross-reactivity among a limited number of species within the Cupressaceae family has been suggested. Juniperus ashei (mountain cedar) is the leading cause of respiratory allergy in South Texas. OBJECTIVE: This study examines in vivo and in vitro cross-reactivity among 12 Cupressaceae species, one Taxodiaceae species, one Pinaceae species, and an angiosperm. METHODS: Cross-reactivity among pollen extracts of mountain cedar (MC) and the other 14 trees was investigated by: (1) prick skin testing of each tree pollen extract in ten patients with MC pollinosis. (2) Ouchterlony gel immunodiffusion employing rabbit antisera to MC. (3) IgE immunoblotting using high-titer MC pooled human sera, and immunoblot inhibition after pre-incubation with MC protein. (4) Monoclonal antibody immunoblotting using a murine monoclonal antibody with strong affinity for the gp40 major allergen of MC. RESULTS: Positive skin wheal-and-flare responses occurred to all 12 Cupressaceae and Japanese cedar (the Taxodiaceae), but not to the Pinaceae or the angiosperm. In Ouchterlony gels, lines of identity or partial identity formed between MC and all pollens except the Pinaceae and the angiosperm. Immunoblots demonstrated IgE binding to the 40 to 42 kD protein in each Cupressaceae, and to a parallel band in Japanese cedar at 43 to 46 kD. Immunoblot inhibition by MC pollen was complete for all trees. The monoclonal bound both the 40 to 42 kD protein in 11 of 12 Cupressaceae species and the 46 kD band in Japanese cedar, but bound no protein bands in the Pinaceae or the angiosperm. CONCLUSION: Pollen proteins of the 12 Cupressaceae (including MC) and the Taxodiaceae (Japanese cedar) are extensively cross-reactive. In particular, the MC major allergen, gp40, is cross-reactive with 40 to 42 kD proteins of the other Cupressaceae and with the Japanese cedar major allergen of 46 kD. Component-based immunotherapy may someday allow a standard treatment for both Juniper-allergic and C. japonica-allergic patients.

Animals↗

PubMed1999

A longitudinal study of mothers' overreactive discipline and toddlers' externalizing behavior.

The association between children's externalizing behavior problems and mothers' overreactive discipline was examined in a longitudinally assessed sample of toddlers and their mothers. Path analyses indicated that mothers' overreactive discipline and children's externalizing behaviors were significantly and similarly stable over a 2 1/2-year period. No evidence of a cross-time influence of either variable on the other was observed. Mothers' overreactive discipline at Time 2 had a significant effect on Time 2 externalizing behavior. No significant effects of children's behavior on mothers' discipline were found. Mothers' depressive symptomatology and marital discord predicted initial overreactivity and were related to externalizing problems through their relations to overreactivity. The results support the appropriateness of implementing parenting interventions for externalizing problems before age 2 years.

Adult↗

PubMed1999

Treatment of young children's bedtime refusal and nighttime wakings: a comparison of "standard" and graduated ignoring procedures.

Young children with sleep problems received either "standard" or graduated ignoring treatment. Both brief treatments were superior to a wait-list control condition and resulted in comparable improvements in bedtime and nighttime sleep problems. At bedtime, the treatments did not differ with respect to maternal compliance and stress. For nighttime wakings, mothers in the graduated ignoring group reported higher rates of compliance and less treatment-related stress. Maternal characteristics predicted treatment outcome in the standard ignoring condition. Following treatment, only positive side effects were observed. When compared to the wait-list group, mothers in the standard ignoring group reported less verbose discipline and decreased stress in parenting, while mothers in the graduated ignoring group reported improved parent-child relationships. Treatment gains were maintained over a 2-month follow-up period.

Behavior Therapy↗

PubMed1998

Involvement of cytochrome P450 3A in the metabolism and covalent binding of 14C-monocrotaline in rat liver microsomes.

The metabolism and covalent binding of 14C-monocrotaline in Sprague-Dawley (SD) rat liver microsomes was investigated using the inducers dexamethasone, clotrimazole, pregnenolone-16 alpha-carbonitrile, and phenobarbital. Monocrotaline is a pyrrolizidine alkaloid (PA) that causes a syndrome in rats that is a model for human primary pulmonary hypertension. It has been documented that bioactivation of PAs (dehydrogenation to reactive pyrroles) in the liver by cytochromes P450 is required for their toxicity. Covalent binding of these reactive pyrroles to tissue macromolecules has been hypothesized to correspond to PA toxicosis. We correlated metabolism and total microsomal covalent binding of 14C-monocrotaline with cytochrome P450 3A using the aforementioned inducers, troleandomycin (a cytochrome P450 3A inhibitor), erythromycin N-demethylase assay of cytochrome P450 3A activity, and Western blots employing anti-rat cytochrome P450 3A antibodies. In addition, autoradiography of membranes electroblotted from SDS-PAGE demonstrated the formation of radiolabeled adducts with specific protein(s). The most intensely radiolabeled protein bands have an apparent molecular weight of approximately 52 kDa, which was similar to the molecular weight detected by anti-rat cytochrome P450 3A antibodies in the Western blots. No radiolabeled proteins were detected in microsomes pretreated with troleandomycin.

Animals↗

PubMed1998

Effect of monocrotaline metabolites on glutathione levels in human and bovine pulmonary artery endothelial cells.

After being dehydrogenated by cytochrome P450 enzymes in the liver, monocrotaline's highly-reactive pyrrole metabolite, dehydromonocrotaline, is believed to interact with pulmonary artery endothelial cells to initiate a pulmonary vascular toxicity resembling pulmonary hypertension. Glutathione, an abundant antioxidant in pulmonary artery endothelial cells, has been shown to react with and detoxify the pyrrolic metabolites derived from monocrotaline in the liver. Using high-performance liquid chromatography with electrochemical detection, glutathione levels were measured in a time- and dose-dependent manner in human pulmonary artery endothelial cells following treatment with dehydromonocrotaline, dehydroretronecine and N-ethylmaleimide and bovine pulmonary artery endothelial cells after treatment with dehydromonocrotaline. The bovine cells had 40% less glutathione than the human in the control groups. Bovine pulmonary artery endothelial glutathione levels were depleted 20% more than the human at 15 minutes when treated with 100 microM dehydromonocrotaline. 15 microM N-ethylmaleimide caused an 80% depletion of glutathione compared to a 30% depletion with 15 microM dehydromonocrotaline in human pulmonary artery endothelial cells.

Analysis of Variance↗

PubMed1997

Monocrotaline metabolism and distribution in Fisher 344 and Sprague-Dawley rats.

The metabolism and distribution of 14C-monocrotaline in Fisher 344 (F344) rats was compared with that in Sprague-Dawley (SD) rats. In vitro microsomal preparations, in situ isolated perfused livers and in vivo excretion and distribution studies were used to discern any differences between these two strains. These strains have previously been shown to differ in their susceptibility to monocrotaline-induced pulmonary hypertension. Hepatic phase I metabolism appears to be similar in both strains with N-oxidation and dehydrogenation to the reactive pyrroles as the major pathways. During the liver perfusions, SD rats generated more monocrotalic acid than F344 rats, but the microsome and excretion studies demonstrated no significant differences in the amount of monocrotalic acid. Monocrotalic acid is a stable byproducer of dehydromonocrotaline reacting with cellular nucleophiles and indicates the amount of monocrotaline dehydrogenation when carboxylesterase activity is negligible. These data suggest that the differences in strain susceptibility to pulmonary vascular toxicity is most likely due to differences in their response to the toxic metabolites.

Animals↗

PubMed1994

Effects of maternal distraction and reprimands on toddlers' transgressions and negative affect.

Misbehaviors occur at a high rate during the toddler years, and parents use a variety of methods to control these behaviors. The present investigation compared the effectiveness of two commonly used strategies, distraction and reprimands. Twenty mothers and their 17- to 39-month-old children were observed in a laboratory setting in which mothers used either distraction then reprimands or reprimands followed by distraction in response to their children's transgressions. When reprimands were used as the initial strategy, they were significantly more effective than distraction in controlling children's transgressions. Distraction was effective in maintaining low rates of transgression when preceded by a period of reprimands. However, when reprimands were instituted following a period of distraction, children's rates of negative affect increased significantly. Implications for the etiology and management of child behavior problems are discussed.

Adult↗

PubMed1993

Survey of fatalities from skin testing and immunotherapy 1985-1989.

BACKGROUND: The Committee on Allergen Standardization of the American Academy of Allergy and Immunology (AAAI) began a study of fatalities associated with skin testing and immunotherapy in an effort to identify risk factors and to ascertain whether any additional precautions are required to prevent and treat serious reactions. METHODS: Questionnaire data was obtained from members of the AAAI and the American College of Allergy and Immunology, regarding 17 fatalities associated with immunotherapy for the years 1985 to 1989. In this period, no fatalities were reported with skin testing. The mean age of patients who died was 36.0 years (range: 10 to 77 years), and 69% were female. Of the patients who died, 76% had asthma, and most were reported to have had factors associated with severity (i.e., lability, required steroids, and/or prior hospitalizations). The only patient who had rhinitis alone had cardiovascular disease and was receiving a beta-blocker. High sensitivity by skin test or RAST was reported by 71%, and 36% reported prior systemic reactions. Sixty-five percent of the patients were undergoing build-up therapy. Fatalities involved use of allergen doses between 1:1 million to 1:10 wt/vol. Other factors associated with fatalities were: changing to a new vial of extract, 5; dosing error or inappropriate dose adjustment, 5; allergen season, 5; symptomatic before injection, 4; not waiting after injection, 2; and home injection, 1. Onset of anaphylaxis occurred within 20 minutes in eleven patients, within 20 to 30 minutes in one, and after more than 30 minutes in one. In eleven cases the cause of death was associated with respiratory compromise. These data reinforce the need for special precautions in treating high-risk patients with asthma. The annual fatality rate from administration of allergenic extracts in the United States remains very low: 1 fatality per 2 million doses, but additional educational efforts to further reduce the fatality rate are needed.

Academies and Institutes↗

PubMed1992

HLA-DR4-associated nonresponsiveness to mountain-cedar allergen.

We did human lymphocyte antigen (HLA)-DR and DQ typing on 37 subjects with mountain-cedar (MC) pollinosis as defined by history and a positive skin test. Of these 37 subjects, 31 were subdivided into 18 subjects with a single positive skin test (SPST) and 13 subjects with multiple positive skin tests (MPSTs). We also typed 51 subjects without MC sensitivity or atopy as defined by history and negative skin tests to a battery of aeroallergens. We also typed 116 subjects in whom MC sensitivity had not been determined. Total IgE, Mc-specific immunoglobulin E (sIgE), and MC-sIgE binding bands by immunoblot were also determined on the subjects with SPSTs and MPSTs. No significant differences were found between the subjects with SPSTs and MPSTs for HLA type, total IgE, MC sIgE, or bands bound by MC sIgE by immunoblot. There was a strong negative relationship between HLA-DR4 and subjects with MC pollinosis; chi-square, 14.857; p = 0.0096; and odds ratio, 0.139. These findings suggest that there is no difference in genetic immunoregulation between subjects with SPSTs and MPSTs but that the presence of the DR4 gene product is associated with a decreased risk of an IgE response to MC and protection from MC pollenosis.

Allergens↗

PubMed1992

Complicating features of asthma.

The recognition of factors other than asthma that make asthma worse, are confused with asthma, or occur concurrently with asthma and may or may not interact with asthma is as important as dealing with the asthma itself. In this article I have tried to give an overview of some of these factors: what they are, how they affect patients with asthma, and what to do about them. The recognition of a covert chronic sinusitis, for example, is often key to controlling a person's disease when it appears that everything is being done appropriately. Close attention to these factors will increase the success of treatment of asthma and improve the quality of life of patients.

Adolescent↗