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Biomedical subjects

M Anderson

Publications and source records attributed to M Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Genome-wide mapping with biallelic markers in Arabidopsis thaliana.

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.

Arabidopsis↗
PubMed1999

Waiting for harm: deliberate self-harm and suicide in young people--a review of the literature.

Mental health professionals, particularly nurses, practicing in child and adolescent psychiatry are key players in the continued development of expertise, awareness and understanding of deliberate self-harm (DSH) and suicide in young people. Enhancing this knowledge and the associated skills will contribute to effective, therapeutic relationships with individuals and their families. The purpose of this paper is to review the current literature surrounding the issue of deliberate self-harm and suicide in young people. The paper will address national and international studies selected from a variety of child and adolescent and general psychiatric literature. The research presented highlights important issues to be addressed in practice. In particular, the evidence supports the influence of mental illness in DSH and suicide, particularly depression and substance abuse. However, a clearly important factor is an individual's experience of family and social life. The literature is considered in the light of relevant governmental policy documents relating to DSH and suicide. The future role of the mental health nurse in child and adolescent psychiatry in the United Kingdom (UK) is discussed in the contexts of family work and assessment.

Adolescent↗
PubMed1999

Human tracheobronchial deposition and effect of a cholinergic aerosol inhaled by extremely slow inhalations.

Ten subjects inhaled the same amounts of cholinergic aerosol of a mass median diameter (MMD) of 7.7 microns in a normal provocation test and in a test with extremely slow inhalations (ESI). This new technique using ESI and large droplets/particles gives a high degree of deposition in small ciliated airways which cannot be obtained by using small particles. The purpose was to compare measured effects with calculated doses of the aerosol in large and small ciliated airways. The effect on large airways was measured by airway resistance (R(aw)), and the effect on small airways was measured by the phase III slope of single breath nitrogen test (N2-delta). Mouth and throat deposition was calculated from human experimental data, and deposition of the cholinergic aerosol into large and small airways was calculated, using a computerized lung model. The study showed that the extremely slow inhalation caused a larger effect on R(aw) and tendency to a larger effect on N2-delta compared to the effect in the normal provocation. Deposited dose in the large airways, in percent of inhaled dose, was calculated to be 25-33% for normal inhalation and 20-24% for ESI. Calculated deposited dose in the small airways (bronchioles; generations 12-16) was 1.8-3.4% for normal inhalation and 18-25% for ESI. For large airways a stronger effect was induced by ESI, perhaps by the more uniform distribution of particles within each generation, compared to normal inhalations when particles deposit near the bifurcations. Concerning the small airways, N2-delta did not differ significantly between normal and ESI provocations, indicating that they did not react much on cholinergic exposure. We believe that our approach using ESI for small airway deposition of a nebulized aerosol can be of value for estimating the effects of various substances on large and small airways.

Administration, Inhalation↗
PubMed1999

Select 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors vary in their ability to reduce egg yolk cholesterol levels in laying hens through alteration of hepatic cholesterol biosynthesis and plasma VLDL composition.

The inability to markedly attenuate cholesterol levels in chicken eggs has led to speculation that cholesterol is essential for yolk formation and that egg production would cease when yolk cholesterol deposition was inadequate for embryonic survival. However, this critical level hypothesis remains unproven. Here, we determine the relative responsiveness of laying hens to three select inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthesis. A control diet, either alone or supplemented with one of two dietary levels (0.03 or 0.06%) of atorvastatin, lovastatin, or simvastatin, was fed to White Leghorn hens for 5 wk. Liver cholesterol concentrations (mg/g tissue) were decreased (P </= 0.05) by each HMGR inhibitor; however, total liver cholesterol (mg) did not differ among treatments. Microsomal hepatic HMGR activities were increased one- to twofold in all HMGR inhibitor-treated groups, while HMGR mRNA levels were unaffected. Diameters of plasma VLDL particles, the main cholesterol-carrying yolk precursor macromolecules, were reduced (P </= 0.05) only in hens fed 0.06% atorvastatin, and the particles contained 38% less total cholesterol (P </= 0.05) than controls. Plasma total cholesterol concentrations were lowered (P </= 0.05) by both doses of atorvastatin (-56, -63%) and simvastatin (-36,-45%). Egg cholesterol contents were maximally reduced by 46% (P </= 0.05), 7% (P > 0.05), and 22% (P </= 0.05) in hens fed the 0.06% level of atorvastatin, lovastatin, and simvastatin, respectively, while overall egg production [-19% (P </= 0.05), +4% (P > 0.05), and -3% (P > 0.05)], was much less affected. We concluded that cholesterol per se may not be an obligatory component for yolk formation in chickens and, as such, may be amenable to further pharmacological manipulation

Animals↗
PubMed1999

Fixation, polyethylene wear, and pelvic osteolysis in primary total hip replacement.

A multicenter retrospective review was performed analyzing 1081 primary total hip replacements in 944 patients using the Harris Galante-I cementless acetabular component with screw fixation. All patients were followed up for a minimum of 5 years with a mean followup of 81 months. Linear polyethylene wear averaged 0.11 mm/year (range, 0-0.86 mm/year). Pelvic osteolysis was seen in 25 patients (2.3%). Migration of the acetabular component was seen in four hips. A subgroup of patients was reanalyzed at a minimum followup of 10 years. The mean linear polyethylene wear rate remained 0.11 mm/year. In this group, only one socket had migrated. There was an association between wear rate and age. On average, younger patients had higher wear rates. The risk for having pelvic osteolysis develop and the need for revision surgery also was age-related. Twenty-two percent of hip replacements (15 hips) in patients younger than 50 years of age at the time of their index operation had pelvic osteolysis develop. In contrast, for patients older than 50 years of age at the time of surgery only 7.8% (eight hips) had osteolysis of the pelvis develop. For patients older than 70 years of age at the time of primary total hip replacement, none had pelvic osteolysis develop.

Adolescent↗
PubMed1999

Human T-cell leukemia virus type 2 Rex protein increases stability and promotes nuclear to cytoplasmic transport of gag/pol and env RNAs.

The human T-cell leukemia virus (HTLV) Rex protein is essential for efficient expression of the viral structural and enzymatic gene products. In this study, we assessed the role of the HTLV-2 rex gene in viral RNA expression and Gag protein production. Following transfection of human JM4 T cells with wild-type and rex mutant full-length proviral constructs, PCR was used for semiquantitative analysis of specific viral RNA transcripts. In the presence of Rex, the total amount of steady-state viral RNA was increased fourfold. Rex significantly up-regulated the level of incompletely spliced RNAs by increasing RNA stability and was associated with a twofold down-regulation of the completely spliced tax/rex RNA. PCR analysis of subcellular RNA fractions, isolated from transfected cells, indicated that the level of gag/pol and env cytoplasmic RNAs were increased 7- to 9-fold in the presence of Rex, whereas Gag protein production was increased 130-fold. These data indicate that HTLV-2 Rex increases the stability and promotes nucleus-to-cytoplasm transport of the incompletely spliced viral RNAs, ultimately resulting in increased structural protein production. Moreover, this model system provides a sensitive approach to further characterize HTLV gene expression from full-length proviral clones following transfection of human T cells.

B-Lymphocytes↗
PubMed1999

Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma.

AIM: To examine the value of immunohistochemistry in defining a keratin profile to aid cervical histopathological diagnosis. METHODS: Immunohistochemical localisation of keratins 17, 10, and 19 was studied in 268 cervical biopsies from 216 women including normal epithelia (with and without human papilloma virus), low and high grade cervical intraepithelial neoplasia, and invasive carcinoma. The percentage of positive immunostaining was scored using a Kontron MOP videoplan image analyser. RESULTS: All major categories of cervical epithelia expressed these keratins to varying degrees. The median percentage of immunostaining for keratin 10 was 40% in normal tissue compared with just 1% in invasive carcinoma (p < 0.0001). The medians for keratin 17 were 0% in the normal group and 80% in carcinomas (p < 0.0001). By contrast, there was no significant difference in staining for keratin 19. Using a combination of the keratin 10 and 17 percentages, it was possible to separate the carcinomas from the benign conditions with a sensitivity of 100% and a specificity of 93%. Further analyses within the groups revealed more extensive staining for keratins 10 and 19 in reserve cell hyperplasia, immature squamous metaplasia, and congenital transformation zone. CONCLUSIONS: The morphological variety within the cervix is reflected, in part, by distinct keratin patterns. There are striking differences in the patterns of keratins 10 and 17 between infiltrating squamous carcinoma and normal cervical epithelia.

Biomarkers, Tumor↗
PubMed1999

Prevalence and associations of MRI-demonstrated brain infarcts in elderly subjects with a history of transient ischemic attack. The Cardiovascular Health Study.

BACKGROUND AND PURPOSE: MRI is more sensitive than CT, but the significance of brain abnormalities seen on MR images obtained in older subjects with transient ischemic attack (TIA) is not clear. We studied the prevalence and risk factors associated with MRI-demonstrated infarcts in elderly subjects with a history of TIA. METHODS: Participants of the Cardiovascular Health Study, aged 65 years or more and without prior stroke, were studied with brain MRI (n=3456). The prevalence of brain infarcts (>/=3 mm) on MRI was determined in subjects with and without TIA. The cardiovascular risk factors and clinical and subclinical cardiovascular disease associated with MRI infarcts were studied in subjects with TIA. RESULTS: Subjects with TIA (n=100) had a higher prevalence of MRI infarcts than subjects without TIA (46% versus 28%; P<0.001). The unadjusted odds ratio for having MRI infarcts in subjects with TIA was 2.20 (95% CI, 1.47 to 3.30) and remained significantly elevated after adjustments for risk factors and cerebrovascular disease (odds ratio, 1.86; 95% CI, 1.23 to 2.83). In subjects with TIA, diastolic blood pressure (P=0.01) and internal carotid artery intima-media thickness (P=0.01) were the only factors predictive of the presence of MRI infarcts by stepwise logistic regression analysis. CONCLUSIONS: MRI infarcts are imaging manifestations of clinically important cerebrovascular disease in subjects with a history of TIA, given their increased prevalence and positive association with increased diastolic blood pressure and internal carotid artery intima-media thickness.

Aged↗
PubMed1999

Tecatas: an ethnotheoretical look at Mexican American female injecting drug users.

Ethnotheory is suggested as a way to study the roles Mexican American female injecting drug users play. It is suggested that ethnotheory extends present theoretical models used to explain and modify female IDUs' behavior; provide insights on female IDUs' roles useful for the development of effective intervention strategies; and suggests a type of ethnographic data collection that uncovers the subject's view of reality. Three detailed ethnographic excerpts from Mexican American female IDUs illustrate how female IDUs manage the array of roles they play and how information gained through ethnotheory is useful in the design of culturally relevant interventions.

Adult↗
PubMed1999

Observations on the effects of low frequency electromagnetic fields on cellular transcription in Drosophila larvae reared in field-free conditions.

Drosophila larvae reared inside a micro-metal box with an internal field strength 0.004 microT, were treated with a magnetic field of 50 Hz, 8 microT. for 20 min. Control experienced 0.004 microT. Cellular transcript levels were assessed using slot blots and quantified using a Phosphorimager. Blots were hybridised using probes against HSP 70a, Histone 1.9, and Copia. The low frequency EMFs very significantly decreased transcript levels, indicating that experimental responses may be influenced by previous exposure or lack of previous exposure.

Analysis of Variance↗
PubMed1999

Expression of transforming growth factor beta type II receptors in head and neck squamous cell carcinoma.

Transforming growth factor (TGF)-beta is a potent regulator of growth and differentiation in normal squamous epithelium. TGF-beta exerts its antiproliferative effect via the TGF-beta type II receptor (TbetaR-II). A decrease in TbetaR-II expression is believed to be responsible, in part, for the resistance of squamous cell carcinoma (SqCC) to the anti-proliferative effects of TGF-beta. In the present study, we used immunohistochemistry and in situ hybridization to analyze the expression of TbetaR-II along the successive oncogenic stages of head and neck squamous neoplasia, from normal epithelium to dysplasia to carcinoma. Quantitation of TbetaR-II expression in 38 SqCCs was assessed on a visual scale ranging from negative (absence of staining) to 3+ (strong staining). Normal squamous epithelium and squamous epithelium in the vicinity of the tumors showed homogenous receptor expression with moderate intensity. Dysplastic epithelium and carcinoma in situ showed a mild decrease in receptor expression intensity. Well-differentiated to moderately differentiated carcinomas showed heterogeneous expression of variable intensity, and poorly differentiated carcinomas were completely devoid of TbetaR-II. In every tumor, the superficial component showed more intense receptor expression than the invasive component. These results indicate that TbetaR-II expression inversely correlates with disease aggressiveness and suggest that aberrant TbetaR-II expression is a contributing factor to the pathogenesis of SqCC.

Activin Receptors, Type I↗
PubMed1999

Behavior based safety. A different way of looking at an old problem.

1. The occupational and environmental health nurse role in behavioral safety initiatives can very to include: serving as a leader, change agent, collaborator with safety professionals, consultant, team participant, educator, coach, and supporter to employees and management. 2. Behavior based safety and health initiatives add to existing knowledge and techniques for improving the health and safety of workers. 3. Behavior based safety relies on employee involvement and places a strong emphasis on observation, measurement, feedback, positive reinforcement, and evaluation. It focuses on identification of system improvements and prevention.

Accidents, Occupational↗
PubMed1998

Interaction between paired-pulse facilitation and long-term potentiation in the projection from hippocampal area CA1 to the subiculum.

Studies of the interaction between long-term potentiation (LTP) and paired-pulse facilitation (PPF) may throw light on the role of presynaptic factors in LTP. We examine here, for the first time, the nature of PPF in the CA1-subiculum projection. PPF peaks at a 50 ms interstimulus interval (ISI) and is evident at ISIs from 10 to 500 ms. There is no PPF effect at a 1000 ms ISI. PPF decreases in magnitude post-LTP induction across the middle range of ISI values tested (30, 50 and 100 ms). There is a positive correlation between initial PPF values and LTP; this correlation increases as the ISI increases. Initial values and the change in PPF post-LTP are also negatively correlated.

Animals↗
PubMed1998

The CHO XRCC1 mutant, EM9, deficient in DNA ligase III activity, exhibits hypersensitivity to camptothecin independent of DNA replication.

We have analyzed the X-ray-sensitive CHO mutant cell line EM9 for sensitivity to the topoisomerase I inhibitor comptothecin. These cells exhibit defective repair of single strand DNA breaks. Recently, EM9 were complemented the DNA ligase III interactive protein, XRCC1. Defective XRCC1 apparently accounts for the low DNA ligase III activity that may explain the single-strand break repair deficiency of EM9 cells. Here, we demonstrate cytotoxic hypersensitivity of EM9 cells following a brief camptothecin treatment. Both the S-phase and non-S-phase populations of EM9 exhibited camptothecin sensitivity relative to the parent cell line AA8. In AA8 cells, only the 55% of the population corresponding to the S-phase subpopulation were sensitive to camptothecin, while the remainder of the population were totally resistant to doses as high as 10 microM. The role of DNA replication in the camptothecin sensitivity was studied using the DNA polymerase inhibitor aphidicolin in co-treatment with camptothecin. Aphidicolin treatment fully protected AA8 cells from camptothecin cytotoxicity. In EM9 cells, aphidicolin protected the S-phase fraction to some degree but all the cells remained sensitive to camptothecin cytotoxicity. These results suggest that EM9 cells are sensitized to camptothecin by a mechanism that is independent of DNA replication and may be a consequence of the XRCC1 mutation or the associated deficiency in DNA ligase III activity. Mechanistic models for the replication-independent cytotoxicity of camptothecin in EM9 cells are discussed.

Animals↗
PubMed1998

The projection from hippocampal area CA1 to the subiculum sustains long-term potentiation.

Long-term potentiation (LTP) is a popular model of the synaptic plasticity which may be engaged by the biological processes underlying learning and memory. Most available studies of LTP have concentrated on the analysis of LTP occurring in 'early' components of the hippocampal circuit (for example, dentate gyrus and area CA1). We examine here, for the first time, LTP as it occurs in the massive, unidirectional projection from CA1 to the subiculum in vivo. We show that this projection sustains high-frequency stimulus-induced LTP (10 trains of 20 stimuli at 200 Hz; intertrain interval 2 s; LTP 181 +/- 9% at 30 min post-LTP induction). In addition, input-output (I/O) curves show a leftward shift for all stimulation values.

Animals↗