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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1996

ras oncoproteins in human plasma from lung cancer patients and healthy controls.

In order to explore the significance of ras oncoproteins in plasma in the carcinogenic process, we have examined samples from 40 Polish human lung cancer patients prior to treatment. They were compared with 35 healthy donors and have been screened using a direct analysis of the plasma. Proteins were separated by gel electrophoresis, transferred to a nitrocellulose membrane by Western blotting and detected by chemiluminescence, using monoclonal ras antibody as the primary antibody. Elevated increases in ras oncoproteins were determined where an increase was considered to be greater than 2 standard deviations above the mean negative control values. The results showed that in 45% of cancer patients ras oncoprotein levels were statistically significantly increased (P < 0.001, pooled two-sample t-test untransformed, and non-parametric Mann-Whitney test) in the plasma by comparison with 6% in the controls. This would suggest that an increase in ras oncoproteins in plasma could be a possible prognostic marker or biomarker for lung cancer.

Adult↗
PubMed1996

Detection of CYP1A1 mRNA levels and CYP1A1 Msp polymorphisms as possible biomarkers of exposure and susceptibility in smokers and non-smokers.

It is important to determine sensitive biomarkers for both exposure and susceptibility since differences in individual susceptibility to potentially hazardous chemicals may represent a major variable in the assessment of risk. Induction of cytochrome P450IA1 (CYP1A1) may be a measure of environmental exposure to aromatic hydrocarbons in cigarette smoke. This study investigated the use of reverse transcriptase-polymerase chain reaction (RT-PCR) to detect constitutive levels of CYP1A1 mRNA in the peripheral lymphocytes of a population of smokers and non-smokers as a potential marker of exposure. In addition, the presence of an Msp 1 restriction fragment length polymorphism was analyzed using a simple PCR method as a biomarker for susceptibility. DNA and RNA were isolated from the peripheral lymphocytes of 20 smokers and a matched group of non-smokers. RT-PCR was used to detect the endogenous levels of CYP1A1 mRNA with glyceraldehyde-3-phosphate dehydrogenase as a control gene. The 3'-region of CYP1A1 gene was amplified by PCR and underwent restriction digestion with Msp 1 to detect the polymorphism. The endogenous CYP1A1 expression as detected by RT-PCR was very low and variable and there was a slight but not significant increase in the smokers by comparison with non-smokers. Thirty-two of the volunteers were homozygous for the normal allele while 8 were heterozygous for the uncommon Msp 1 allele and none was homozygous for the polymorphism. The allele frequency (0.1) was found to be in Hardy-Weinberg equilibrium. Since only a slight increase was seen in endogenous CYP1A1 mRNA levels in the peripheral lymphocytes of smokers by comparison with non-smokers, the effect may have been diluted by variation in sensitivity to dose, a threshold of exposure effect, or the return of mRNA to baseline between exposures. The wide variation in mRNA levels may reflect the influence and exposure of different environmental factors. The sensitivity of PCR-based methods suggests that they may have an important role in future overall biomonitoring of exposure and susceptibility to environmental chemicals.

Biomarkers↗
PubMed1996

An investigation of some Turkish herbal medicines in Salmonella typhimurium and in the COMET assay in human lymphocytes.

Medicinal plants play a major role in the life of Turkish people and of late medicinal plant usage has increased in many countries. Green plants in general contain mutagenic and carcinogenic substances, but there is little information about the biological activities of herbal medicine. In the present study, therefore, various Turkish medicinal herbs were investigated for their genotoxic potential in the Salmonella typhimurium microsomal activation assay and the alkaline single cell gel electrophoresis (COMET) assay. Extracts from these medicinal herbs and some fractions of these extracts were examined. The species investigated were Arctium minus, Ecballium elatterium, Momordica charantia, Plantago major, Urtica dioica, Viscum album, Salvia triloba, Euphorbia rigida, Stachys lavandulifolia, Acteoside, Abies nordmannia. They are used for various immune disorders and are applied either topically or taken orally as a herbal tea. Of the 19 samples of the extracts and fractions investigated, none produced a positive response in strains TA98 and TA100 with or without metabolic activation, but all produced an increase above negative control values in the COMET assay. Some extracts were investigated further and produced dose-related increases. In the case of Urtica and Euphorbia species, where two fractions from these plants were examined, one fraction produced a greater response than the other. It is suggested that the lesser response of the fractions might be due to less DNA strand-breaking agents in the fractions or they may have antigenotoxic properties. The breaks that are detected in the COMET assay could be alkali-labile AP-sites and intermediates in base- or nucleotide-excision repair and are difficult to interpret in terms of hazard for man. Further studies with additional genotoxicity assays would be required to make such a prediction.

DNA Damage↗
PubMed1996

Polyclonal lymphoid tumor of the choroid plexus presenting as an intraventricular mass in a young gorilla.

An unusual lymphoid lesion with reactive germinal centers, occurring in the choroid plexus of a young gorilla, is reported. It presented as a large mass in the lateral ventricle with hydrocephalus and neurological symptoms. A work-up did not reveal any underlying cause for this lesion. No similar lesion of the choroid plexus has been reported in either human or veterinary literature. Histological work-up, including flow cytometry, gene rearrangement studies and T and B cell markers, favored the lesion being a non-neoplastic lymphoid proliferation of unknown etiology. The prognosis is unknown, although, following complete removal, the animal is well and free of tumor at the time of this report.

Animals↗
PubMed1996

A study of the toxic hazard that might be associated with the consumption of green potato tops.

Eating green potatoes has reportedly led to poisoning attributed to potato glycoalkaloids (PGA), primarily alpha-solanine and alpha-chaconine. Concentrations of PGA increase during the greening of potatoes but are reportedly much higher in potato tops (leaves). As it is known that members of the UK Bangladeshi community consume potato tops, a study of the toxic hazard that may be associated with the consumption of green potato tops has been carried out. PGA in seven potato varieties were determined by HPLC. Tubers protected from light contained 0.05-0.65 mg/100 g alpha-solanine and 0.3-0.63 mg/100 g alpha-chaconine. Concentrations in leaf samples ranged from 0.64 to 22.6 mg alpha-solanine/100 g and 0.06 to 55.7 mg alpha-chaconine/100 g. Aqueous leaf extracts were cytotoxic to Chinese hamster ovary cells and lysed human, rat and hamster blood cells with no difference in sensitivity among species. Oral administration of potato tops to rats, mice and Syrian hamsters had no adverse effects at the highest practicable dose. A mixture of alpha-solanine and alpha-chaconine (1:1, w/w) given orally at doses of up to 50 mg/kg body weight to hamsters had no effect, but a single ip injection of 25 mg/kg body weight or greater was lethal, with bleeding in the gut. High concentrations of cytotoxic PGA were found in some potato tops, but their effect in laboratory animals was minimal. It is concluded that the consumption of moderate quantities of potato tops (2-5 g/kg body weight/day) is unlikely to represent an acute health hazard to humans.

Animals↗
PubMed1996

Crystallization of a designed peptide from a molten globule ensemble.

BACKGROUND: The design of amino acid sequences that adopt a desired three-dimensional fold has been of keen interest over the past decade. However, the design of proteins that adopt unique conformations is still a considerable problem. Until very recently, all of the designed proteins that have been extensively characterized possess the hallmarks of the molten globular state. Molten globular intermediates have been observed in both equilibrium and kinetic protein folding/stability studies, and understanding the forces that determine compact non-native states is critical for a comprehensive understanding of proteins. This paper describes the solution and early solid state characterization of peptides that form molten globular ensembles. RESULTS & CONCLUSIONS: Crystals diffracting to 3.5 A resolution have been grown of a 16-residue peptide (alpha 1A) designed to form a tetramer of alpha-helices. In addition, a closely related peptide, alpha 1, has previously been shown to yield crystals that diffract to 1.2 A resolution. The solution properties of these two peptides were examined to determine whether their well defined crystalline conformations were retained in solution. On the basis of an examination of their NMR spectra, sedimentation equilibria, thermal unfolding, and ANS binding, it is concluded that the peptides form alpha-helical aggregates with properties similar to those of the molten globule state. Thus, for these peptides, the process of crystallization bears many similarities to models of protein folding. Upon dissolution, the peptides rapidly assume compact molten globular states similar to the molten globule like intermediates that are formed at short times after refolding is initiated. Following a rate-determining nucleation step, the peptides crystallize into a single or a small number of conformations in a process that mimics the formation of native structure in proteins.

Amino Acid Sequence↗
PubMed1996

Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families.

The hereditary breast cancer gene BRCA2 was recently cloned and is believed to account for almost half of site-specific breast cancer families and the majority of male breast cancer families. We screened 49 site-specific breast cancer families for mutations in the BRCA2 gene using single strand conformation analysis (SSCA) followed by direct sequencing. We found mutations in eight families, including all four families with male breast cancer. The eight mutations were small deletions with the exception of a single nonsense mutation, an all were predicted to interrupt the BRCA2 coding sequence and to lead to a truncated protein product. Other factors which predicted the presence of a BRCA2 mutation included a case of breast cancer diagnosed at age 35 or below (P = 0.01) and a family history of pancreatic cancer (P = 0.03). Two mutations were seen twice, including a 8535delAG, which was detected in two French Canadian families. Our results suggest the possibility that the proportion of site-specific breast cancer families attributable to BRCA2 may be overestimated.

Adult↗
PubMed1996

Idiopathic myelofibrosis in children.

Childhood myelofibrosis (Mf) is rare with variable outcome reported in the literature. We present clinical and investigate details of three children who presented with idiopathic Mf in early childhood. Two of these children were identical twins and have been haematologically stable over the past 7 years since their diagnosis. The third patient underwent an allogeneic bone marrow transplant (BMT) procedure as her clinical status was deteriorating. She remains engrafted at 13 months post BMT. None of the children had hepatosplenomegaly although extramedullary haemopoiesis was demonstrated on 52Fe studies in two patients. Circulating progenitors in these patients were increased in the face of reduced marrow precursors. The aetiology of childhood Mf is unclear and its natural history seems different from the adult disease. Allogeneic BMT can be an option for definitive treatment.

Adolescent↗
PubMed1996

Assessment of environmental and occupational exposures to butadiene as a model for risk estimation of petrochemical emissions.

1,3-Butadiene (BD) is an important industrial chemical and environmental contaminant, e.g. in urban air, traffic exhausts and tobacco smoke. It has been shown to be genotoxic in vitro and in vivo and carcinogenic in rodents, mice being more sensitive than rats. The present study confirmed this species difference. Using micronuclei in erythrocytes or bone marrow as a marker, mice responded at an effective level of 50 p.p.m., while the highest ineffective level in rats was 500 p.p.m. (inhalation of BD for 5 days). A dose-dependent increase in N-terminal valine haemoglobin adducts was seen in both rats and mice, but the adduct levels in the latter species were on average five times higher. For the first time, specific N6-alkyldeoxyadenosine adducts were identified in lung and liver DNA of rats exposed to BD by inhalation. No significant difference in DNA adduct level was seen in lung tissue of rats and mice at similar exposure levels. Occupational exposure levels to BD in the European Process industry are variable, but generally < 1 p.p.m. Haemoglobin adduct levels were seen to be increased among the worker groups with higher potential exposure to BD (process work, bomb voiding and repair duties) as compared with adduct levels in less exposed workers in maintenance and the laboratory or control personnel. However, the N-terminal valine haemoglobin adducts measured in the workers were one to two orders of magnitude lower than extrapolated for the same exposure dose in mice. In the same workers no exposure-related effects were seen in the cytogenetic parametres studied, i.e. chromosomal aberrations, sister chromatid exchanges or micronuclei in peripheral blood lymphocytes, or in the Ras oncoprotein levels of plasma samples. The studies so far conducted suggest that human exposure at the levels seen in the present day process industry can be documented at the biological dose level using haemoglobin adduct measurement, but not at the biological effect level using cytogenetic biomarkers. In order to quantitate the human genotoxic risk of BD exposure more work needs to be done on the role of other active BD metabolites than 1,2-epoxy-3-butene and on the genetic polymorphisms controlling the variability of individual responses.

Air Pollutants↗
PubMed1996

A comparison of pulmonary and femoral artery thermodilution cardiac indices in paediatric intensive care patients.

We have assessed the agreement between pulmonary artery and femoral artery (COLD) thermodilution measurements of the cardiac index (Cl) in a group of paediatric intensive care patients. The COLD method gave consistently higher cardiac index values than the pulmonary artery catheter (PAC); however, the difference was small, with a mean value of 0.19 l/min-1 m-2 or 4.4% of the mean cardiac index. This difference is not clinically important and suggests that, under these circumstances, the COLD system provides an acceptable alternative to the pulmonary artery catheter for measurement of the cardiac index at the bedside.

Cardiac Output↗
PubMed1996

An in vitro and an in vivo unscheduled DNA synthesis assay with a zinc oxide/hexachloroethane (Zn/HCE) smoke.

1. Since Zn/HCE smoke has been shown previously to be weakly positive in the Ames test, and negative in the bone marrow micronucleus assay, other assays including a second in vivo assay examining unscheduled DNA synthesis (UDS) in rat hepatocytes has been carried out, as recommended by the UK Department of Health guidelines. 2. Zn/HCE smoke was assessed for its ability to induce DNA repair in an UDS assay both in vitro in cultured rat hepatocytes and in rat hepatocytes after in vivo treatment by inhalation. 3. For the in vitro investigation, two studies were carried out assessing media exposed to Zn/HCE smoke using at least seven concentrations up to a toxic level. At the highest concentration of Zn/HCE smoke, where some viable cells were seen, an increase in UDS was observed in both experiments. However this was not statistically significant, was only seen at a level where toxicity was observed and was therefore considered not to be biologically significant. 4. In the in vivo investigation, one study was carried out in three separate parts, assessing two doses of Zn/HCE smoke characterised by their zinc content as approximately 20 and 56 micrograms l-1 air. A dose-related increase in UDS was observed which was not statistically significant. The positive control behaved as anticipated, showing a highly statistically significant response. 5. It was concluded that Zn/HCE smoke did not induce unscheduled DNA repair in the in vitro or in vivo UDS assays under the conditions used in the studies. The overall lack of genotoxic effect of this smoke in this and previous studies in this laboratory would not suggest a major health hazard.

2-Acetylaminofluorene↗
PubMed1996

Biological monitoring of workers exposed to emissions from petroleum plants.

This paper presents some of the results from the Commission of the European Communities collaborative research program (contract number EV5V-CT92-0221), whose aim is to investigate the relationship between exposure to petroleum emissions, benzene, and induction of genetic damage in human cells. Twenty-four workers from petroleum plants in Poland and 35 unexposed controls were examined for cytogenetic effects and ras oncoprotein levels and their relationship to confounding factors (e.g., smoking habit, sex family cancer history, and seasonal influence). Preliminary data of chromosome aberrations (CA) and sister chromatid exchanges (SCE) showed differences among sampling subgroups. In this present study, the levels of ras p21 proteins were determined and further analyses of CA, SCE, high frequency cells (HFC), and proliferative rate index (PRI) have been undertaken. Results show that the exposed group has statistically significant increases in CA, and percent of aberrant cells. There were no differences between exposed and unexposed groups in SCE, HFC, PRI, or the levels of ras p21 proteins. Smoking was found to statistically significantly affect levels of CA, percent of aberrant cells, SCE, HFC, and ras proteins. Sister chromatid exchanges were also statistically significantly sex dependent (7.5 breaks/cells for females and 6.8 breaks/cell for males). There were no statistically significant differences for CA, percent aberrant cells, SCE, HFC, or ras p21 protein levels in subgroups characterized according to cancer cases reported in the immediate family. A seasonal variability was shown with statistically significant increases in various biomarkers in the winter. Unexposed groups also showed increases due to smoking and season. The nonsmoking group individuals also showed statistically significant increases in cytogenetic damage with exposure.

Adult↗
PubMed1996

Social support, social networks and coronary artery disease rehabilitation: a review.

OBJECTIVE: To provide information to the medical community about the importance of social support and networks through examination and definition of social support and network variables, and by reviewing the evidence found in the literature showing a relationship among social support, social networks, coronary artery disease (CAD) and rehabilitation. DATA SOURCES: Psyclit and Sociofile were searched for September 1979 through December 1994. STUDY SELECTION: All publications covering social support, social networks and rehabilitation from CAD as well as large mortality studies. Fifty-one articles were reviewed. DATA EXTRACTION: Original articles were summarized. DATA SYNTHESIS: Individuals who benefit from social support are less likely to become disease-stricken and live longer than those with less support. Social support and networks may have a substantial influence on the speed and quality of recovery following myocardial infarction (MI). CONCLUSIONS: A review of the literature indicates that social support plays an important role in recovery from and adaptation to chronic disease such as CAD and is of equal importance to the primary and secondary prevention of MI. Future research should pay special attention to what types of functional support are of most importance to recovery from MI and bypass surgery, thus allowing for the development of rehabilitation programs and interventions that will emphasize functions that are most needed. Interventions may involve the patient's natural support group to enhance the potential support providers' awareness of the patient's support needs. Social support may be especially important for maintaining compliance with rehabilitation programs for patients with CAD.

Adult↗
PubMed1996

Community health workers' response to violence against women.

This paper reports on a qualitative study of community health workers from a predominantly rural based region in Queensland. The purpose of this study was to determine the community health worker barriers to identification, assessment and intervention on the issue of violence against women. The qualitative research method comprised five structured focus group interviews with 28 community health workers using open-ended questions to explore their perceptions. Analysis of the focus group data revealed that community health workers expressed reluctance to become involved in cases of violence against women. The reasons they provided are grouped under three main themes: barriers to identification; barriers to assessment; and barriers to intervention. Training programs offered to rural community health workers need to be aware of the barriers to identifying, assessing and intervening in cases of violence against women that are highlighted by this study. Further studies are needed to assess the wider relevance of these findings to other groups of community health workers in rural and non-rural settings.

Attitude of Health Personnel↗
PubMed1995

Infant with mos45,x/46,XY/47,XYY/48,XYYY: genetic and clinical findings.

We describe an infant with mos45,X/46,XY/47,XYY/48,XYYY who presented with ambiguous genitalia. Her phenotype was also remarkable for minor ear and eye anomalies and coarctation of the aorta with bicuspid aortic valve. Laparoscopy revealed bilateral Fallopian tubes and a left infantile testis with epididymis. Chromosomal analyses of blood, skin, aorta, right Fallopian tube, and left gonadal tissue showed mos45,X/46,XY/47,XYY/48,XYYY. The 46,XY cell line was identified with routine trypsin-Giemsa banding only in cultured cells from an aortic biopsy. Fluorescence in-situ hybridization (FISH) was utilized to identify the presence of 46,XY cells in other tissues. The clinical manifestations of this patient are discussed and compared with those of similar cases of Y chromosome aneuploidy. To our knowledge, this is the first report of a patient with this unusual karyotype.

Aneuploidy↗