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Biomedical subjects

P Whitehead

Publications and source records attributed to P Whitehead.

At least 19 recordsLinked to original sources
PubMed2003

Strategic management of non-point source pollution from sewage sludge.

In the UK, the recycling of sewage sludge to land is expected to double by 2006 but the security of this route is threatened by environmental concerns and health scares. Strategic investment is needed to ensure sustainable and secure sludge recycling outlets. At present, the security of this landbank for sludge recycling is determined by legislation relating to nutrient rather than potentially toxic elements (PTEs) applications to land--especially the environmental risk linked to soil phosphorus (P) saturation. We believe that not all land has an equal risk of contributing nutrients derived from applications to land to receiving waters. We are currently investigating whether it is possible to minimise nutrient loss by applying sludge to land outside Critical Source Areas (CSAs) regardless of soil P Index status. Research is underway to develop a predictive and spatially-sensitive, semi-distributed model of critical thresholds for sludge application that goes beyond traditional "end-of-pipe" or "edge-of-field" modelling, to include hydrological flow paths and delivery mechanisms to receiving waters from non-point sources at the catchment scale.

Conservation of Natural Resources↗
PubMed2001

The environmental impact of heavy metals from sewage sludge in ferralsols (São Paulo, Brazil).

The spreading of sewage sludge on acidic ferralsol soil was simulated in a column experiment in order to estimate the potential impact on water and soil quality. Drainage and runoff water were sampled daily over a 2-month experiment and analysed for Fe, Ni, Cu, Pb and DOC. Results show a clear influence of the sludge on the water quality, especially at the start of the experiment, increasing the export of Cu, Ni, Pb and in DOC from the soil, mainly in dissolved form. Nickel was usually the most mobile element in the sludge and in the soil. In the soil, Pb mobility was complex and increased drastically with time compared to the other elements. No significant increase in soil heavy metal content due to the sludge spreading was recorded on this time scale.

Agriculture↗
PubMed1996

20S human proteasomes bind with a specific orientation to lipid monolayers in vitro.

20S Proteasomes are non-lysosomal, high molecular weight proteinases implicated in the degradation of misfolded proteins and several short-lived regulatory proteins. They have a well established role, as the core of the 26S proteasome complex, in the ubiquitin-dependent proteolytic pathway and in antigen processing. While correctly folded proteins are not degraded by the 20S proteasome, unfolding, for example by oxidation, may render them degradable. The 20S proteasome is a 700-kDa cylindrical particle, composed of 14 subunits of molecular masses 20-35 kDa. There is evidence that 20S proteasomes are in close proximity to or associate with the endoplasmic reticulum and nuclear and plasma membranes in vivo. To better understand the lipid association of 20S proteasomes in vitro, we used a lipid monolayer system as a simple model system for biological membranes. The structure and orientation of the monolayer lipid bound 20S proteasomes has been determined by electron microscopy. 20S proteasomes associated in an "end-on' configuration specifically on PI lipid monolayers forming large arrays, with their channels opposite the lipid headgroups. On ER and Golgi lipid films 20S proteasomes were oriented in the same way as on the PI lipid film but were monodisperse. Protein molecules were randomly oriented in the presence of PA, PG, PS, PC and mitochondrial lipid monolayers. We show that 20S proteasomes bind to phospholipids in vitro in a preferred orientation which places the proteasome channel perpendicular to the membrane.

Cell Membrane↗
PubMed1996

The emerging syndrome of envenoming by the New Guinea small-eyed snake Micropechis ikaheka.

The New Guinea small-eyed or ikaheka snake, Micropechis ikaheka, which occurs throughout New Guinea and some adjacent islands, is feared by the indigenes. The first proven human fatality was in the 1950s and this species has since been implicated in many other cases of severe and fatal envenoming. Reliable attribution of envenoming to this species in victims unable to capture or kill the snake recently became possible by the use of enzyme immunoassay. Eleven cases of proven envenoming by M. ikaheka, with two fatalities, were identified in Papua New Guinea and Irian Jaya. Five patients showed no clinical signs of envenoming. The other six patients showed symptoms typical of envenoming by other Australasian elapids: mild local swelling, local lymphadenopathy, neurotoxicity, generalized myalgia, spontaneous systemic bleeding, incoagulable blood and passage of dark urine (haemoglobinuria or myoglobinuria). Two patients developed hypotension and two died of respiratory paralysis 19 and 38 h after being bitten. In vitro studies indicate that the venom is rich in phospholipase A2, is indirectly haemolytic, anticoagulant and inhibits platelets, but is not procoagulant or fibrinolytic. It shows predominantly post-synaptic neurotoxic and myotoxic activity. Anecdotally, Commonwealth Serum Laboratories' (CSL) death adder antivenom has proved ineffective whereas CSL polyvalent antivenom may be beneficial. Anticholinesterase drugs might prove effective in improving neuromuscular transmission and should be tested in patients with neurotoxic envenoming.

Adult↗
PubMed1995

Predicting diabetic control from competence, adherence, adjustment, and psychopathology.

OBJECTIVE: To determine what psychological and behavioral factors were most predictive of diabetic control. METHOD: Seventy-nine youths with diabetes were assessed cross-sectionally, using youths' reports of self-esteem, anxiety, and attitudes about diabetes, and parents' reports of competence and psychopathology (from the Child Behavior Checklist) and diabetic adherence as independent variables. Glycosylated hemoglobin A1c was the dependent variable, reflecting diabetic control. After the effects of several background variables were partialed out, a principal-components analysis grouped the substantive variables into three larger components. RESULTS: Among the background variables, duration of illness and family size significantly predicted diabetic control. Among substantive components, Competence/Adherence (including Total Competence, dietary compliance, and frequency of blood glucose checks) was highly predictive of diabetic control, primarily due to the effect of Total Competence. Adjustment (including self-esteem, anxiety levels, and attitudes about diabetes) and Psychopathology were less predictive. A model was constructed showing the relationships between these predictive components and diabetic control. CONCLUSIONS: In this generally well-adjusted sample, that Total Competence, more than other measures, predicted diabetic control suggests it could be used by clinicians to anticipate diabetic youths at risk.

Adolescent↗
PubMed1995

Morphometric abnormalities in brains of great blue heron hatchlings exposed in the wild to PCDDs.

Great blue heron hatchlings from colonies in the Strait of Georgia, British Columbia, Canada are being monitored for environmental contaminant exposure and effects by the Canadian Wildlife Service. The contaminants of concern are polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), primarily derived from kraft pulp mill effluent. The levels of PCDDs and PCDFs in eggs from the most contaminated colonies peaked in 1988 and 1989 and dropped dramatically through 1990 to 1992. Brains of heron hatchlings (taken as eggs from the wild and hatched in the laboratory) were analyzed for gross morphological abnormalities. Brains from highly contaminated colonies (Crofton, British Columbia and University of British Columbia Endowment Lands) in 1988 exhibited a high frequency of intercerebral asymmetry. The frequency of this abnormality decreased in subsequent years as the levels of TCDD and TCDD-TEQs (toxic equivalence factors) decreased. The asymmetry was significantly correlated with the level of TCDD and TCDD-TEQs in eggs taken from the same nest. Yolk-free body weight negatively correlated and the brain somatic index positively correlated with the TCDD level in such pair-matched eggs. These results indicate that gross brain morphology, and specifically intercerebral asymmetry, may be useful as a biomarker for the developmental neurotoxic effects of PCDDs and related chemicals.

Abnormalities, Drug-Induced↗
PubMed1994

Linear IgA disease: cylindroma demonstrates heterogeneity of the target antigens.

Serum from 58 patients with linear IgA disease was tested by indirect immunofluorescence on the novel substrate cylindroma, which produces an abundance of basement membrane components. The use of split skin and of cylindroma has identified 2 target antigens. The majority of patients have a target antigen associated with epidermal cells and similar in distribution on cylindroma to hemidesmosome proteins. A minority have a dermal antigen with the distribution of collagen VII on cylindroma. These data support the hypothesis that linear IgA disease is a heterogeneous disease with regard to the target antigens.

Adenoma↗
PubMed1994

Analysis of p53 in human cutaneous melanoma cell lines.

Mutations in the p53 tumour suppressor gene have been detected in a variety of human malignancies. Mutations have been found predominantly in conserved regions two to five. Our aim was to analyse p53 at the protein and DNA level in seven melanoma cell lines of cutaneous origin (HMB-2, DX3, LT5.1, MJM, SK23, A375P and A375M), including two parental/metastatic derivatives (A375P and A375M; DX3 and LT5.1). By immunohistochemical staining with three mouse monoclonal antibodies and a rabbit polyclonal serum, it was possible to observe differential nuclear expression of p53. The quantitation of p53 protein levels by ELISA correlated with the nuclear staining pattern. Western blotting showed an intact p53 protein in all cell lines; p53 was polymorphic in three cell lines (MJM, A375P and A375M). DNA sequencing studies showed that all cell lines had wild type p53. These results suggest that p53 is unlikely to play a significant role in the genesis of cutaneous melanoma.

Cell Nucleus↗
PubMed1993

Antibody to an abnormal protein in amyotrophic lateral sclerosis identifies Lewy body-like inclusions in ALS and Lewy bodies in Parkinson's disease.

Ubiquitinated cytoplasmic inclusions are a characteristic feature of the neuronal pathology of neurodegenerative diseases. Immunocytochemical techniques have identified intermediate filaments associated with ubiquitin-immunoreactive inclusions in Alzheimer's disease (AD), Parkinson's disease (PD), and Pick's disease; however, no core protein has been detected in the ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS). The pathogenesis of these inclusions is not known, but the inclusion may result from an accumulation of an abnormal proteins. Here we report a novel protein of 32.5 kDa detected by polyacrylamide gel electrophoresis, in the spinal cord in ALS patients. A polyclonal antibody raised against this protein and used for Western blotting, suggests that the novel protein is related to actin. Immunocytochemical studies using this antibody indicate that the protein is found in Lewy body-like inclusions in anterior horn cells of ALS, and in Lewy bodies in the substantia nigra in PD.

Actins↗
PubMed1993

Monospecific monoclonal antibodies to keratin 1 carboxy terminal (synthetic peptide) and to keratin 10 as markers of epidermal differentiation.

Monospecific antibodies to individual keratin polypeptides can be used to examine the tissue and cellular coexpression of members of keratin pairs. Monospecific monoclonal and polyclonal antibodies have been raised to keratins 1 and 10 using both crude cytoskeletal extracts and synthetic peptides. The tissue distribution of these keratins has been determined against a panel of freshly frozen normal tissues from humans, rodents and pigs. Epidermal expression has been examined in psoriatic plaques, and healing wounds, as examples of epidermal hyperproliferation. Cultured keratinocytes in monolayer (low calcium), stratified (high calcium), and complex cultures, transformed keratinocytes, and tumour cell lines, have been examined for the in vitro expression of these keratins. The sensitivity and precise localization of reactivity with these monospecific antibodies gives a highly accurate picture of individual cell expression. There is confirmation of coexpression of keratins 1 and 10 in epidermal and mucosal sites, and with keratin 16 in hyperproliferative states. These monospecific antibodies provide an important means of examining keratin expression in epidermal tumours and keratinizing disorders, and of seeking keratin mutations in cell lines and in skin diseases.

Adult↗
PubMed1993

The epidemiology of incomplete childhood immunization: an analysis of reported immunization status in outer western Sydney.

We surveyed parents of children enrolled in kindergarten in 1992 in outer western Sydney and the Blue Mountains. Using parents' reports, we determined the prevalence of immunization uptake for children starting school, compared the prevalence of immunization uptake among Catholic, government and independent schools, and identified immunization providers. We also documented parental beliefs about immunization and their influence on immunization status, and identified risk factors for incomplete immunization. Nearly 89% of children were reported to be fully immunized. Immunization status did not vary significantly among the different types of school. General practitioners provided 84% of all immunizations and local councils 11%. Incomplete immunization was associated with more negative beliefs in immunization, with post-secondary education and with families who do not speak English at home. Reminder letters had little effect on immunization status.

Attitude to Health↗
PubMed1991

Identification of the target antigen in chronic bullous disease of childhood and linear IgA disease of adults.

Disease-associated autoantibodies to basement membrane proteins have been used to characterize structural components of the epidermal basement membrane such as bullous pemphigoid (BP) antigen and epidermolysis bullosa acquisita (EBA) antigen (type VII collagen). The autoimmune bullous diseases characterized by IgA autoantibodies to the basement membrane zone (BMZ), i.e. linear IgA disease of adults (LAD) and chronic bullous disease of childhood (CBDC) may have circulating antibodies. Previous studies of tissue distribution and ultrastructural binding have suggested that the LAD and CBDC antigens are similar, if not identical, and differ from the target antigens of the other bullous diseases. We present the molecular characterization of the LAD/CBDC antigens by Western blotting of a large series of antisera. Seven of 33 sera (21%) were positive on immunoblotting and bound to the same antigen which has a molecular weight (MW) of 285 kDa. Using both defined polyclonal antisera to BP and LH 7.2 monoclonal antibody to type VII collagen (carboxy terminal) we have shown that the LAD and CBDC antisera both bind to an identical molecular weight protein which clearly differs from both the BP and EBA (type VII collagen) antigens. Although detectable in dermal tissue extracts like EBA, the MW of 285 kDa is heavier than type VII collagen (250 kDa, in our system, using non-collagenous standards). This study confirms the identity of LAD and CBDC antigens to be the same and to differ from previously described basement membrane proteins.

Adolescent↗
PubMed1991

Detection of a novel basement membrane antigen by GDA-J/F3 anti-human sperm fibrous sheath monoclonal antibody.

Basement membrane zones (BMZ) of human epithelia were stained with GDA-J/F3 monoclonal antibody, which was originally raised against sperm cells. Using indirect immunofluorescence and immunoperoxidase techniques, the antibody reacted with the BMZ of stratified squamous epithelia (skin and its appendages, tongue, lip, oesophagus and cervix). It also stained the BMZ of trachea, nasal ciliated mucosa, some mammary ducts of lactating and resting breast, amnion and ureter but failed to react with that of stomach, ileum, colon, rectum, kidney, liver, fallopian tube, lung or their blood vessels. In testes, the antibody did not react with the BMZ of the seminiferous tubules although the sperm tails were stained. Split-skin immunofluorescence and immunoelectron microscopy localized GDA-J/F3 antigen to the inferior border of the lamina densa of the BMZ. In human foetuses, the epidermally associated antigen was detected at an estimated gestational age of 9 weeks, and in the amnion at 15 weeks. The antibody reacted with tissues from monkey but not from mouse, rat, cow or pig suggesting the late appearance of the antigen during evolution. Although the GDA-J/F3 was difficult to characterize biochemically, its tissue distribution, ontogeny and ultrastructural localization suggests that this antigen may be a type VII collagen-associated protein, whose expression is altered in recessive dystrophic epidermolysis bullosa. This disease could represent abnormalities in type VII collagen structure, assembly, transport or interaction with associated proteins.

Animals↗
PubMed1991

Lichen planus pemphigoides: its relationship to bullous pemphigoid.

Clinical and immunopathological studies of three patients with lichen planus pemphigoides (LPP) were carried out to investigate the relationship between LPP and bullous pemphigoid (BP) and to determine whether the antigen in LPP is the classical BP antigen. LPP is usually considered to be the coexistence of lichen planus with BP. The bullae in LPP were subepidermal and indistinguishable from BP. Indirect immunofluorescence demonstrated antibody binding to the epidermal surface of 1 M NaCl-split skin and mucosae, as in BP. The tissue distribution of the LPP antigen mirrored the distribution of BP in stratified squamous epithelia but was absent from transitional epithelia (pig bladder). Immunoelectron microscopy, both direct (two cases) and indirect (one case), showed binding to the lamina lucida as with BP antigen. Western blotting of epidermal extracts using the patients' sera showed that instead of reacting with the classical bullous pemphigoid antigen (220 kDa in our series), the antisera reacted with a unique band of 200 kDa in addition to the band of 180 kDa found as a minor antigen in bullous pemphigoid, but more commonly in pemphigoid gestationis. The relationship between these antigens awaits molecular characterization. These findings suggest that the target antigen in LPP may be unique.

Adult↗
PubMed1991

Oesophageal webs preceding carcinoma and rupture of the oesophagus in cicatricial pemphigoid.

A case in which oesophageal webs preceded the development of carcinoma and rupture of the oesophagus in a 77-year-old woman with cicatricial pemphigoid is reported. Oesophageal webs in cicatricial pemphigoid have been reported but are rare. Clinical, histological, radiological and post-mortem features are described. Western immunoblotting of serum demonstrated a 180-kDa antigen which comprises one of the antigens reported in cicatricial pemphigoid.

Aged↗
PubMed1991

Factors relating to the development of respiratory symptoms in coffee process workers.

After several cases of occupational asthma had been reported in a coffee processing factory in England, 197 coffee workers representing 80% of the production workforce were studied to determine the factors affecting the development of work related respiratory symptoms of wheeze, cough, and dyspnoea. Two computer administered questionnaires concerning the presence of respiratory symptoms and the occurrence of work related respiratory symptoms were used. Workers underwent skin prick testing to green coffee bean extract (GCB) and 11 common inhalant allergen extracts and bronchial provocation testing with methacholine. The presence of specific immunoglobulin E (IgE) antibodies to GCB and castor bean extract (CAB) were determined by a radioallergosorbent test (RAST). The prevalence of work related respiratory symptoms was 12.7%, bronchial hyperresponsiveness 30%, atopy 54%, positive GCB skin prick test 14.7%, positive GCB RAST 14%, and positive CAB RAST 14.7%. None of the workers was sensitised to fungi present in the factory and the numbers of certain species of fungi, despite being greater than may be found out of doors or in an uncontaminated indoor environment, were fewer than are generally associated with the presence of work related respiratory symptoms among agricultural workers. Storage mites were not isolated. Green coffee bean extract and CAB RAST were significantly correlated using the McNemar test but there was limited allergenic cross reactivity in RAST inhibition studies of the two extracts. The only factors that were significantly and independently associated with work related symptoms were CAB RAST and duration of employment. Bronchial hyperresponsiveness was not independently associated with work related respiratory symptoms. The significant independent associations of bronchial hyperresponsiveness included GCB RAST, duration of employment, and resting forced expiratory volume in one second. Exposure to CAB, a highly potent antigen, may be overriding the effects of other factors such a GCB, atopy, bronchial hyperresponsiveness, and smoking. This study suggests that CAB contamination remains a potential problem in the coffee processing industry and all efforts to eliminate it from the working environment should continue.

Adolescent↗