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Biomedical subjects

D Moore

Publications and source records attributed to D Moore.

At least 109 records · Page 6Linked to original sources
PubMed1998

Epididymal sperm aneuploidies in three strains of rats detected by multicolor fluorescence in situ hybridization.

A multicolor fluorescence in situ hybridization (FISH) method was developed to detect aneuploidy and diploidy in epididymal sperm of rats using DNA probes specific for chromosomes 4 and Y. Fourteen healthy young-adult rats from three strains were evaluated: inbred Fisher 344/N/ehs, outbred Sprague-Dawley, and outbred WU Wistar/CPB. The hybridization efficiency of the FISH procedure was > 99.9%, the sex-ratio in sperm was approximately 1 as expected, and there was no significant variation among two independent scorers. No significant variations were detected within or among strains in the frequencies of sperm disomy for chromosome 4 (1-6.5 per 10,000 cell per animal) or the Y chromosome (0-2.5 per 10,000 cells per animal). There was a trend toward increased variation among Wistar rats. The frequencies of sperm-carrying hyper- and hypohaploidy for chromosome 4 were similar, suggesting a symmetrical mechanism of chromosome gain and loss during meiosis. The frequencies of Y-Y-4-4 sperm, which represent genomic meiosis II errors, did not differ significantly across strains (0.1-0.7 per 10,000 cells per strain). This FISH method for detecting aneuploidy in rat epididymal sperm provides a promising interspecies biomarker of male germ cell aneuploidy and introduces the rat as an animal model for investigating the heritable risk to offspring associated with paternal genotype, physiology, and exposure to environmental mutagens. There appear to be no significant differences among young healthy rats, mice, and men in the baseline frequencies of sperm with Y chromosomal disomy, the only chromosome for which data currently exists for all three species.

Aneuploidy↗
PubMed1998

Prevalence and risk factors of illicit drug use by people with disabilities.

The authors examined patterns and risk factors of illicit drug use among people with disabilities by use of a random sample of 1,876 persons actively involved in vocational rehabilitation services in three Midwestern states. Compared with regional drug use data from the general population, respondents with disabilities reported higher rates of illicit drug use for nearly every drug category. Factors significantly associated with illicit drug use included level of disability acceptance, best friends' drug use, attitude of disability entitlement, self-esteem, and risk-taking. These findings provide additional insight into illicit drug use among people with disabilities. The authors discuss implications from these findings for rehabilitation and disability policy.

Adaptation, Psychological↗
PubMed1998

A randomized double-blind study of the effect of distant healing in a population with advanced AIDS. Report of a small scale study.

Various forms of distant healing (DH), including prayer and "psychic healing," are widely practiced, but insufficient formal research has been done to indicate whether such efforts actually affect health. We report on a double-blind randomized trial of DH in 40 patients with advanced AIDS. Subjects were pair-matched for age, CD4+ count, and number of AIDS-defining illnesses and randomly selected to either 10 weeks of DH treatment or a control group. DH treatment was performed by self-identified healers representing many different healing and spiritual traditions. Healers were located throughout the United States during the study, and subjects and healers never met. Subjects were assessed by psychometric testing and blood draw at enrollment and followed for 6 months. At 6 months, a blind medical chart review found that treatment subjects acquired significantly fewer new AIDS-defining illnesses (0.1 versus 0.6 per patient, P = 0.04), had lower illness severity (severity score 0.8 versus 2.65, P = 0.03), and required significantly fewer doctor visits (9.2 versus 13.0, P = 0.01), fewer hospitalizations (0.15 versus 0.6, P = 0.04), and fewer days of hospitalization (0.5 versus 3.4, P = 0.04). Treated subjects also showed significantly improved mood compared with controls (Profile of Mood States score -26 versus 14, P = 0.02). There were no significant differences in CD4+ counts. These data support the possibility of a DH effect in AIDS and suggest the value of further research.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Molecular cytogenetic analysis of cytokeratin 20-labeled cells in primary tumors and bone marrow aspirates from colorectal carcinoma patients.

BACKGROUND: Low frequency epithelial cells in bone marrow from colorectal carcinoma patients are associated with an increased risk of recurrence and decreased survival. Current immunohistochemical approaches to detect epithelial cells in bone marrow aspirates rely on antibodies against cytokeratin 18 (CK18). The predictive value of CK18-based detection strategies is limited by false-positives that occur in approximately 30% of cases. Cross-reactivity of anti-CK18 antibodies with nontumor cells may contribute to the false-positive rate. Cytokeratin 20 (CK20) shows more restricted expression than CK18 and labels cells in colorectal tumors. METHODS: Immunofluorescence assays were used to quantify CK20-labeled cells in bone marrow aspirates and tumors from 18 Dukes stage C and D colorectal carcinoma patients to determine whether CK20 is useful in detecting micrometastases. Fluorescent in situ hybridization was used to determine whether CK-labeled subpopulations carried genomic aberrations associated with colorectal carcinoma. RESULTS: CK20-labeled cells occurred at frequencies approximately 5 x 10(-5) in control bone marrow aspirates from patients without colorectal carcinomas. Approximately 10(-4) CK20-labeled cells were present in 4 of 11 bone marrow aspirates (45%) from patients with Dukes stage D colon carcinoma. The mean frequency (5 x 10(-5) of CK20-labeled cells in Dukes stage C and D rectal carcinoma patients was statistically similar to control values. CONCLUSIONS. A subset of CK20-labeled cells in primary tumors and hepatic metastases are aneusomic. CK20-labeled cells in bone marrow aspirates are cytogenetically normal. These data demonstrate that CK20 cells in solid tumors may be cytogenetically aberrant, but suggest caution in the use of CK20 to detect micrometastases in bone marrow aspirates.

Adult↗
PubMed1997

Molecular cytogenetic abnormalities in multiple myeloma and plasma cell leukemia measured using comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to identify recurrent regions of DNA sequence loss and gain in 21 multiple myeloma (MM) and plasma cell leukemia (PCL) primary tumor specimens and cell lines. Multiple regions of non-random sequence loss and gain were observed in 8/8 primary advanced stage tumors and 13/13 cell lines. Identification of sequence copy number changes was facilitated by statistical analyses that reduce subjectivity associated with identification of copy number changes and by requiring that sequence changes are visible using both red- and green-labeled tumor DNA. Loss of sequence on 13q and 14q and gain of sequence on 1q and chromosome 7 occurred in 50-60% of the population. In general, cell lines carry more and larger regions of sequence gain and loss than primary tumors. Regions of sequence copy number change that recur among MM cell lines and primary tumors include, in order of prevalence, enh(1q12qter), dim(13), enh(7), enh(3q22q29), enh(11q13.3qter), dim(14q11.2q31), enh(8q21qter), enh(3p25pter), dim(17p11.2p13), and dim(6q22.1q23). Population distributions of genome-wide changes in primary tumors reveal "hot-spots" of sequence loss from 13q12.1-q21, 13q32-q34, 14q11.2-q13, and 14q23-q31. Genomic changes detected using CGH are consistent with those identified using banding analyses, although recurrent involvement of additional regions of the genome are also evident. A higher prevalence of genomic changes is visible using CGH compared to banding. Identification of recurrent regions of sequence gain and loss provides opportunities to identify regions of the genome that may be involved in the malignant phenotype and/or disease progression.

DNA, Neoplasm↗
PubMed1997

Validation of the Metacomprehension Scale

Evidence for the factorial, convergent and discriminant, and criterion-related validity of the Metacomprehension Scale (MCS) was examined in a sample of 237 young adults. The instrument was factorially heterogeneous but exhibited homogeneity within each of the seven subscales. Evidence for the convergent and discriminant validity of the MCS was examined by correlating the subscales from the MCS with subscales from metacognitive questionnaires measuring similar constructs from related domains. In general, correlations within constructs were larger than correlations between constructs, providing preliminary evidence of the convergent and discriminant validity of the MCS. The criterion-related validity of the MCS relative to other metacognitive measures was examined by using the metacognitive measures and the MCS to predict comprehension performance. The MCS predicted performance better than the other measures of metacognition and accounted for variance in performance not accounted for by the other measures. These results show promise for the value of self-assessments of metacomprehension. Copyright 1997Academic Press

Journal Article↗
PubMed1997

Alpha 2C-adrenoceptors mediate contractile responses to noradrenaline in the human saphenous vein.

We have investigated the subtype of alpha 2-adrenoceptor mediating isometric contractions of human saphenous vein in comparison with alpha 2-adrenoceptor ligand binding sites. Postjunctional alpha 2-adrenoceptors in the human saphenous vein were investigated in terms of the ability of alpha 2-adrenoceptor antagonists to shift the contractile potency of noradrenaline. The following antagonists were employed (potencies, pKB, in human saphenous vein in parentheses): chlorpromazine (6.98 +/- 0.24), BDF 8933 (7.60 +/- 0.06), prazosin (6.62 +/- 0.15), ARC 239 (7.19 +/- 0.15), yohimbine (7.23 +/- 0.09), HV 723 (7.52 +/- 0.14), WB 4101 (7.90 +/- 0.06), SKF 104078 (6.55 +/- 0.08), BRL 44408 (5.72 +/- 0.21). Antagonist potency at postjunctional alpha 2-adrenoceptors was correlated with antagonist affinity at alpha 2-adrenoceptor ligand binding sites in membranes of human platelet (alpha 2A), rat kidney (alpha 2B) and Sf9 cells expressing human recombinant receptors (alpha 2C), labelled with [3H]yohimbine. The correlation with the postjunctional alpha 2-adrenoceptor mediating contraction of the human saphenous vein was best for the human recombinant alpha 2C-adrenoceptor ligand binding site (r = 0.92, n = 8, P < 0.001), as compared to correlations with the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.62, n = 8, n.s.) and with the alpha 2A-adrenoceptor ligand binding site of human platelet (r = 0.23, n = 8, n.s.). It is concluded that the functional postjunctional alpha 2-adrenoceptor mediating contractions of the human saphenous vein closely resembles the human recombinant alpha 2C-adrenoceptor ligand binding site.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Sexually abused children in a national survey of parents: methodological issues.

In a national survey of 1,000 parents, which primarily concerned disciplinary practices and violence toward their children, two questions were asked about whether the children had been sexually abused. This was to assess the feasibility of epidemiological research on contemporaneous sexual abuse using parental interviews rather than the usual adult retrospective approach. From these questions, rates of sexual abuse for children currently 0-17 were estimated at 1.9% in the last year and 5.7% ever. The cases making up these rates included a nearly equal number of boys and girls and no female victims between the ages of 9 and 12, a distribution different from those generally obtained by other epidemiological methods, but due possibly in this case to normal sampling variation. Cases were more likely to be disclosed for children whose parents had themselves been sexually abused, who were from lower income households, or who were living with only one biologic parent. Although some of the findings suggest caution in generalizing about child sexual abuse from survey samples of parents, the method is worthy of exploration if only to gain better epidemiologic data about parent knowledge, reaction, reporting, and coping strategies.

Adolescent↗
PubMed1997

Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm.

Each year more than 20,000 children and young persons of reproductive age are exposed to known mutagens in the form of chemo- and/or radiotherapy for cancer in the States. As more of these treatments are effective there is growing concern that genetic defects are introduced in the germ cells of these young patients. It is well documented for male rodents that treatment with chemo- and radio-therapeutic agents before mating can cause genetic damage in the germ line, and the magnitude of heritable effects depends on the spermatogenic cell stage treated. Similar germinal effects are suspected to occur in humans but remain unproven. Hodgkin's disease (HD) is an example of a malignancy which is typically diagnosed during a patient's reproductive years. In our study we observed eight male HD patients who were treated with NOVP (Novanthrone, Oncovin, Vinblastine, Prednisone) chemotherapy. We evaluated sperm aneuploidy using multi-colour fluorescence in situ hybridization (FISH), and found approximately 5-fold increases in sperm with disomies, diploidies and complex genotypes involving chromosome X, Y and 8. Increases in sex chromosome aneuploidies arose from segregation errors at meiosis I as well as meiosis II. The aneuploidy effects were transient, however, declining to pretreatment levels within approximately 100 days after the end of the therapy. When compared with normal men, some HD patients showed higher proportions of certain sperm aneuploidy types even before their first therapy.

Adult↗
PubMed1997

Structure of the collagen-binding domain from a Staphylococcus aureus adhesin.

The crystal structure of the recombinant 19,000 M(r) binding domain from the Staphylococcus aureus collagen adhesin has been determined at 2 A resolution. The domain fold is a jelly-roll, composed of two antiparallel beta-sheets and two short alpha-helices. Triple-helical collagen model probes were used in a systematic docking search to identify the collagen-binding site. A groove on beta-sheet I exhibited the best surface complementarity to the collagen probes. This site partially overlaps with the peptide sequence previously shown to be critical for collagen binding. Recombinant proteins containing single amino acid mutations designed to disrupt the surface of the putative binding site exhibited significantly lower affinities for collagen. Here we present a structural perspective for the mode of collagen binding by a bacterial surface protein.

Adhesins, Bacterial↗
PubMed1997

Cytogenetically aberrant cells are present in the CD34+CD33-38-19- marrow compartment in children with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL), the most common cancer in childhood, is characterized by clonal proliferation of transformed lymphoblasts that comprise the majority of marrow and/or blood specimens. Although the leukemic cells typically express antigens associated with lymphoid maturation or activation (ie CD19, CD38, etc), it has been suggested that ALL blasts may evolve from a more primitive precursor. Increased understanding of the phenotypic and molecular heterogeneity of cells in ALL may provide clues to leukemogenesis and/ or impact prognostication or treatment. We utilized a phenotype/genotype approach to measure the prevalence and frequency of cytogenetically aberrant cells in a phenotypically defined primitive compartment (CD34+33-19-38-; CD34+Lin-). Bone marrow cells were flow cytometrically sorted into CD34-Lin+, CD34+Lin+ and CD34+Lin- subpopulations. Fluorescence in situ hybridization (FISH) was used to quantify the frequency of cells with aneusomies in the sorted populations. Approximately 26% (5/19) of ALL cases at diagnosis contain cytogenetically aberrant CD34+Lin- cells. The frequency of cytogenetically aberrant cells in the CD34+Lin- compartment is independent of FAB, WBC and blast counts. These data indicate that cytogenetically aberrant cells may reside in a phenotypically defined primitive subpopulation and suggest that ALL blasts in some patients may evolve from a precursor compartment.

ADP-ribosyl Cyclase↗
PubMed1997

Raised affinity for extracellular sodium of the sodium-lithium countertransporter is associated with a family history of hypertension and uraemia in patients with renal disease.

1. Increased affinity for sodium (Km) at an external site of the sodium-lithium countertransporter and altered membrane microviscosity in the surface regions of the lipid bilayer identifies a group of essential hypertensive patients with a genetic predisposition to hypertension. The present study investigated the kinetic properties of the sodium-lithium countertransporter and membrane microviscosity in patients with hypertension, renal disease and impaired renal function. 2. Sixty patients with renal disease (28 chronic renal failure, 30 hypertensive, 23 family history of hypertension) were investigated. Standard erythrocyte sodium-lithium countertransport activity, sodium affinity constant (Km), maximum reaction velocity (Vmax) and membrane microviscosity were measured. 3. Patients with renal disease and a family history of hypertension had significantly lower Km (P < 0.05) values and raised membrane microviscosity measured by 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy (P < 0.05) compared with patients without a family history of hypertension. 4. Uraemic subjects had low K(m) values compared with patients with renal disease and normal renal function (P < 0.05). However, there was no significant difference in membrane microviscosity between uraemic and non-uraemic subjects. 5. In patients with a family history of hypertension, sodium-lithium countertransport activity and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy are important markers of cellular changes in essential hypertension, independent of renal disease. Uraemia, independently of hypertension, produces an alteration in the function of the sodium-lithium countertransporter which has previously been associated with a genetic predisposition to hypertension and cardiovascular disease.

Antiporters↗
PubMed1997

Thrombopoietin measurement in thrombocytosis: dysregulation and lack of feedback inhibition in essential thrombocythaemia.

Essential thrombocythaemia (ET), a myeloproliferative disorder (MPD) manifested by excessive platelet production, lacks a specific diagnostic test to facilitate differentiation from other thrombocytoses. We studied thrombopoietin (TPO) levels in 41 patients with thrombocytosis: 25 ET patients, eight with other MPD, and eight with reactive thrombocytosis. Mean age and platelet counts for these groups were comparable. TPO levels for 96 healthy individuals provided a reference range for normal. The majority of ET patients (19/25 or 76%) had normal TPO levels. No patient with ET had a TPO level below 75 pg/ml, compared with 57% of healthy donors and 8/16 (50%) patients with other thrombocytoses (P<0.05). TPO levels in ET are not appropriately down-regulated, as occurs with cytokines relevant to other MPD. In thrombocytosis, a TPO level <75 pg/ml indicates that ET is unlikely.

Adolescent↗
PubMed1997

Evaluation of an intercostal myoneurovascular transposition as a lower esophageal neosphincter.

Previous work has shown promising results for an intercostal myoneurovascular transposition in the prevention of gastroesophageal reflux following esophagectomy. A first study evaluated the intercostal transposition procedure and compared it with the Nissen fundoplication using a rabbit model of gastroesophageal reflux. Group A underwent partial cardiomyectomy to produce gastroesophageal reflux. Group B underwent cardiomyectomy, and intercostal transposition around the gastric cardia. Group C underwent Nissen fundoplication and cardiomyectomy. All animals had preoperative and 1-week and 4-week postoperative intraesophageal manometry and pH studies. At the 4-week interval, macroscopic and microscopic esophageal histopathology was assessed. The mean change in values from preoperative to 4 weeks postoperative were compared. Group B showed significantly lower reflux time (P < 0.001) and grade of esophagitis (P < 0.005), and significantly greater average lower esophageal sphincter basal pressure (P < 0.001) and abdominal length of sphincter (P < 0.01) when compared with Group A. There was no statistical significance between the results of Group B and Group C. A second study assessed whether reflux was prevented by an anatomical structure, or a muscle flap acting in a physiological manner. At autopsy, the ten rabbits from Group B underwent removal of the intercostal wrap, and the right 11th intercostal muscle as a control. There was a significant difference in the quantity of viable muscle tissue between muscle flaps and controls (P < 0.001), the muscle flaps having generally little viable muscle left 4 weeks after surgery. A further experiment to evaluate this result found that loss of muscle tissue was due to excessive stretch and not due to damage of the intercostal neurovascular bundle during mobilization. Two groups of animals underwent electromyographic studies. The first group underwent recordings of all intercostal muscles. The second group underwent intercostal transposition around the gastric cardia, and insertion of recording electrodes into the muscle flap. The electromyographic activity of the muscle flap was recorded at 0, 2, and 4 weeks after surgery. The second group demonstrated activity in the muscle flaps simultaneous with diaphragmatic contractions. This activity, although much reduced, was still present 4 weeks after surgery. These studies showed that the intercostal transposition and Nissen fundoplication procedures are equally effective in preventing experimental gastroesophageal reflux. The antireflux properties of the intercostal transposition were possibly the result of anatomical buttressing of the gastroesophageal junction, and not due to a fully viable contracting muscle flap.

Animals↗
PubMed1997

Evaluation of a project to enhance knowledge of hereditary diseases and management.

During 1992 and 1993, in a designated suburban area of Perth, Western Australia, information on hereditary disease was provided for health professionals and the general community. This information was in the form of posters, pamphlets, postal flyers and return letter cards, a static display, newspaper articles, advertisements and radio broadcasts, and professional seminars. The aim of this project was to evaluate the effectiveness of combined strategies to convey practical information about hereditary disease to the community and health professionals. Multiple measures of response evaluation were used, which included structured questionnaire surveys of health professionals and members of the community before and after the project. In the community surveys, respondents who were female, married, middle aged, and parents, and had a higher level of education or were born in Australia, New Zealand, or the United Kingdom were generally better informed about hereditary diseases. This intervention resulted in only meagre changes in community knowledge about hereditary disease, even though promotional materials were shown to be appropriate. General Practitioners (GPs) and Child Health Nurses (CHNs) were supportive of clinical genetic services and recognised a need for continuation of education in this field. There is a rapidly increasing need for community and health professional comprehension of the applications of the new genetic technology. This project indicates that routine educational and health promotion strategies will not be enough to achieve desired levels of knowledge and attitude change.

Adult↗
PubMed1997

Coordinated cell elongation alone drives tropic bending in stems of the mushroom fruit body of Coprinus cinereus.

During tropic bending in the stem of the mushroom fruit body of Coprinus cinereus the majority of extension occurred in the upper 20-30% of the stem. By attaching inert markers to the stem, it was shown that the outer flank of the bend initially has a faster rate of extension, although the inner flank matches this growth rate later in the response. Thus bending results from differential enhancement of growth rate rather than sustained differences. Large voids, up to 85 micrometers in diameter, observed in tropically bent stems showed no significant difference in number between inner and outer flanks but are implicated in bending because of their absence from unbent stems. Such voids may prevent the propagation of cracks through the stem tissue during bending. Creases at the external and lumen surfaces were also peculiar to bent stems and could represent constrictions caused by localized accumulation of stresses. Cell morphometric analysis of transverse sections of both flanks of the bend revealed no significant differences in hyphal diameter, distribution, or populations of cell types, but cells of the outer flank were four to five times longer than those of the inner. Thus, tropic bending requires only an increase in length of pre-existing inflated hyphae in the outer flank tissue.

Cell Size↗