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Biomedical subjects

D Holloway

Publications and source records attributed to D Holloway.

15 recordsLinked to original sources
PubMed2002

Skin irritation thresholds in hairdressers: implications for the development of hand dermatitis.

BACKGROUND: Individuals vary in their ability to react to irritants. OBJECTIVES: To observe the development of clinical hand dermatitis and sensitization prospectively in trainee hairdressers and to compare this with their irritant threshold to sodium lauryl sulphate (SLS). METHODS: Subjects were patch tested to a limited series of occupational importance and their irritant threshold to SLS was determined; patch testing was repeated 6 months later and subjects were assessed for hand dermatitis. RESULTS: The development of hand dermatitis was associated with a lower irritant threshold. A similar association was not found for sensitization. CONCLUSIONS: The development of clinical dermatitis in prospectively followed subjects with greater irritant reactivity has not previously been identified. The association of greater irritant reactivity with a proinflammatory cytokine polymorphism may partly explain this. Further development of the irritant threshold test could contribute to the identification of non-atopic subjects at risk of occupational skin disease.

Adolescent↗
PubMed2001

Managing a complex river catchment: a case study on the River Almond.

The River Almond catchment in the east central belt rates amongst Scotland's most polluted rivers. This paper describes how shifting forms of economic development in the catchment since the 1860s have affected river quality. A legacy of effects from past land uses has combined with the impacts associated with current land uses to present a substantial and complex management challenge. It is argued that there have been, and still are, scientific, legislative and socio-economic constraints on the abilities of managers to respond promptly to changing patterns of impacts on the river system. This response lag has tended to increase the costs of subsequent remediation, and has consequently supported a downward pressure on the quality standards that are considered 'realistic' by river managers. Conversely, advances in science, the expansion of regulatory powers and resources, and an increase in public interest in the environment has helped to clarify the extent of the management problems in the catchment, and allowed major advances in some areas of pollution management. In an attempt to overcome some of the remaining weaknesses of river management, river managers and interest groups have started to form inter-sectoral and multidisciplinary partnerships. The success of these new groupings is highly contingent, not so much on the competence of their scientific advice, but on the priority given to water protection by the land-use decision-makers involved, and the resources they are prepared to commit to funding rehabilitation.

Agriculture↗
PubMed2001

The effect of a single dose of osteoprotegerin in postmenopausal women.

Osteoprotegerin (OPG), a tumor necrosis factor (TNF) receptor family member, is a critical regulator of bone resorption. It is an important inhibitor of the terminal differentiation and activation of osteoclasts. This randomized, double-blind, placebo-controlled, sequential dose escalation study was conducted in postmenopausal women to determine the effect of a single subcutaneous (s.c.) dose of OPG on bone resorption as indicated by the biochemical markers, urinary N-telopeptide (NTX) and deoxypyridinoline (DPD), which are stable collagen degradation products. NTX levels decreased within 12 h after OPG administration. At the highest dose administered (3.0 mg/kg), a mean percent decrease in NTX of approximately 80% was observed 4 days after dosing. Six weeks after dosing a mean decrease of 14% in NTX was observed. The levels of bone-specific alkaline phosphatase (BSAP), a marker of bone formation, did not change for approximately 3 weeks after dosing. Thereafter, a modest decrease, reaching approximately 30% at 6 weeks, was observed in the 3.0-mg/kg dose group. The rapid decrease from baseline in NTX and delayed decrease in BSAP indicated that OPG acted primarily on osteoclasts to decrease bone resorption. OPG injections are well tolerated. This study, for the first time, indicates that a single s.c. injection of OPG is effective in rapidly and profoundly reducing bone turnover for a sustained period and that OPG therefore may be effective in treatment of bone diseases characterized by increased bone resorption such as osteoporosis.

Double-Blind Method↗
PubMed2000

Association of TNFA gene polymorphism at position -308 with susceptibility to irritant contact dermatitis.

Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) alpha-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for the TNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis.

Adolescent↗
PubMed2000

Irritant thresholds in subjects with colophony allergy.

The factors which determine individual susceptibility to the development of allergic contact dermatitis (ACD) are not well defined. Since it is known that the presence of skin irritation is well-documented as a promoter of sensitization, the sensitivity to irritation of subjects with ACD has been compared with a normal control group. Whilst 78% of those with a positive patch test reaction to the contact allergen colophony (colophonium) responded to a concentration of no higher than 2.5% sodium lauryl sulfate (SLS), only 44% of the matched control group reacted at this level of SLS. Thus, the results are consistent with the hypothesis that individuals with enhanced susceptibility to skin irritation are also more liable to develop allergic skin reactivity.

Adolescent↗
PubMed2000

The frequency of fragrance allergy in a patch-test population over a 17-year period.

Fragrances are widely encountered in our daily environment and are known to be a common cause of allergic contact dermatitis. We have reviewed our patch test data from 1980 to 1996 to establish whether the pattern of fragrance allergy has changed with time. During this period, 25,545 patients (10,450 male, 15,005 female) were patch tested with the European standard series. The mean annual frequency of positive reactions to the fragrance mix was 8.5% in females (range 6.1-10.9) and 6.7% in males (range 5.1-12.9). Females were 1.3 times more likely to be allergic to fragrance (P < 0.001, 95% confidence interval, CI 1.17-1.41). Males with fragrance allergy were older than females by 5.6 years (mean age 48.2 vs. 42.6 years; P < 0.001, 95% CI 3.9-7.3). The incidence of a concomitant positive patch test to balsam of Peru in fragrance-sensitive patients showed wide variation, suggesting that it is not a reliable marker of fragrance allergy. There was a positive correlation between the isomers isoeugenol and eugenol. Oak moss remained the most common overall allergen throughout the study, positive in 38.3% of females and 35.6% of males who were tested to the constituents of the fragrance mix. During the period of the study the incidence of positive tests to oak moss increased by 5% yearly (P = 0.001, 95% CI 2.2-8.7). The frequency of allergic reactions to eugenol and geraniol remained relatively constant. Isoeugenol and alpha-amyl cinnamic aldehyde sensitivity increased and hydroxycitronellal showed a slow decline. There was a striking reduction in the frequency of sensitivity to cinnamic aldehyde (by 18% yearly; P < 0.001, 95% CI 14.3-21.0) and cinnamic alcohol (by 9% yearly; P < 0.001, 95% CI 5.2-12.9); these are now uncommon fragrance allergens. These data show temporal trends which may reflect the frequency of population exposure to individual fragrances.

Acrolein↗
PubMed1994

A unique central cholinergic deficit in the spontaneously hypertensive rat: physostigmine reveals a bradycardia associated with sensory stimulation.

Using a sensory stimulation (startle) paradigm in normotensive and hypertensive rats, we evaluated the contribution of central cholinergic mechanisms to the pathology of hypertension. In normotensive Wistar-Kyoto (WKY) rats, transient airpuff stimuli elicit a complex startle reaction consisting of several behavioral and autonomic components. These include jumping (motor response), an increase in blood pressure (pressor response), an early-trial decrease in heart rate (bradycardia) and a later-trial increase in heart rate (tachycardia). Intracerebroventricular (i.c.v.) administration of cholinergic compounds to WKY rats primarily altered the bradycardia component. Thus, depletion of brain acetylcholine with hemicholinium-3 (5 micrograms/kg i.c.v.) abolished bradycardia responses without significantly affecting the motor response, tachycardia or pretest cardiovascular base-line parameters. Furthermore, enhancement of brain acetylcholine with acetylcholinesterase inhibition (physostigmine, 50 micrograms/kg i.c.v.) enhanced bradycardia in WKY rats. The nonspecific muscarinic antagonist scopolamine and the M1 muscarinic receptor antagonist pirenzepine, but neither the M2 muscarinic antagonist methoctramine nor the nicotinic antagonist hexamethonium, attenuated bradycardia. We conclude that a central M1 muscarinic receptor participates in the control of startle-associated bradycardia in the WKY rat. The spontaneously hypertensive rat does not normally exhibit startle-associated bradycardia. Because i.c.v. physostigmine revealed early-trial bradycardia in this strain, we conclude that a selective central cholinergic deficit contributes to a suppression of startle-associated bradycardia in the spontaneously hypertensive rats.

Animals↗
PubMed1993

Pharmacological characterization of WAY-121,520: a potent anti-inflammatory indomethacin-based inhibitor of 5-lipoxygenase (5-LO)/phospholipase A2 (PLA2).

WAY-121,520 inhibited human synovial fluid PLA2 (HSF-PLA2) (IC50 = 4 microM) using arachidonic acid-labeled E. coli as substrate. Further biochemical characterization of WAY-121,520 demonstrated potent inhibition of 5-lipoxygenase (5-LO) activity in the murine macrophage (LTC4, IC50 = 4 nM) and rat PMN (LTB4, IC50 = 10 nM) and an ability to antagonize LTD4 binding to isolated guinea-pig trachea (pKB = 6.0). In vivo anti-inflammatory activity was noted in murine TPA-induced (ED50 = 91 micrograms/ear) and arachidonic acid-induced (66% inhibition at 400 micrograms/ear) ear edema and in leukotriene-dependent antigen-induced bronchoconstriction in the guinea pig (73% inhibition at 50 mg/kg, p.o.). WAY-121,520 represents a novel series of indomethacin-based inhibitors of PLA2 with anti-inflammatory activity resulting from a combination of biochemical activities (inhibition of 5-LO and PLA2 and LTD4 antagonism). This agent may provide added therapeutic efficacy over more selective inhibitors.

Animals↗
PubMed1991

Changes in cell gene expression in human leukemic cells persistently infected with vaccinia virus.

Persistent viral infections in vitro are useful systems to study the coevolution of virus and cell populations. Persistent infection of mouse Friend erythroleukemic cells (FEL) with vaccinia virus results in profound changes of the virus as well as of the cells. To investigate phenotypic changes of other cell types, we have established a persistent infection with vaccinia virus in a human leukemic cell line (K562). This cell line can be induced to differentiate along the erythroid pathway synthesizing embryonic and fetal globins, thus providing a system in which specific genes can be stimulated. After serial passage, the persistently infected cells (K562vac) became spontaneously differentiated, as shown by the increase in the number of cells producing hemoglobin (benzidine positive cells), and resistant to superinfection. These phenotypic changes of the cells were not accompanied by changes in the viral population. Hybridization of cellular RNA with cloned embryonic and fetal globin genes indicated that uninduced K562 cells do not express these genes, whereas cells induced by hemin or butyrate express G gamma (fetal globin) epsilon and zeta (embryonic globins) genes. By contrast vaccinia infected cells spontaneously express the G gamma gene. These results demonstrate that persistent infection with vaccinia virus elicited phenotypic changes in the infected cell population; in this case the constitutive expression of fetal hemoglobin.

Cell Line↗
PubMed1987

Detection of influenza viruses through selective adsorption and detection of the M-protein antigen.

A model system has been developed which permits rapid detection of influenza viruses through targeting of the M (membrane or matrix)-protein; a type-specific antigen, in an enzyme-linked immunosorbent assay system. This technique exploits the hydrophobic properties of M-protein; the M-protein is selectively and rapidly adsorbed to polystyrene surfaces even in the presence of a 5000-fold excess of bovine serum albumin. Hyperimmune antiserum prepared to purified M-protein is used as the detecting reagent. All type A influenza viruses could be detected by this technique, type B influenza viruses reacted to a slight extent and Sendai virus (parainfluenza virus, type 1) did not react. Virus could be detected to levels as low as 3 ng. Purification of M-protein and preparation of hyperimmune sera from other related virus groups, such as type B influenza viruses, paramyxoviruses and rhabdoviruses should permit detection of these agents by a similar technique.

Adsorption↗
PubMed1987

Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease.

We conducted a six-month, randomized, double-blind trial of lecithin therapy in early-onset Alzheimer's disease. We hypothesized that such therapy would retard the progression of the clinical and neuropsychological manifestations of this illness. Of the 73 referred patients, 37 met strict requirements for diagnosis and compliance. The 21 placebo and 16 lecithin-treated patients (mean age 63 years) had a comparable degree of severity of dementia (mean Clinical Dementia Rating 1.6). Lecithin therapy produced an increase in mean plasma choline levels from a baseline of 15.9 to 28.8 nmol/ml. Patients were evaluated by the physician using clinical assessments (CDR, Lawton ADL and other rating scales) and by the neuropsychologist who determined the outcome of therapy on a battery of tests (Mini Mental State Examination, Wepman Aphasia Screen, Verbal Fluency Test, Verbal Selective Reminding Test and Spatial Memory Test). Only 6 (37.5%) of the 16 lecithin-treated patients were considered by the neurologist to be clinically stable or improved as compared to 12 (57.1%) of the 21 patients given placebo (difference -19.6%, 95% confidence limits of -51% to 12%). The neuropsychologic scores showed no differences in the stability of the dementing process over time between the lecithin-treated (50.0%) and placebo (47.6%) groups. On the basis of these clinical and neuropsychological findings, it appears that lecithin alone has no important therapeutic effect in early-onset Alzheimer's disease.

Alzheimer Disease↗
PubMed1986

A laboratory study of cyromazine on Aedes aegypti and Culex quinquefasciatus and its activity on selected predators of mosquito larvae.

In a laboratory study, the insect growth regulator, cyromazine, exerted a high level of biological activity on Aedes aegypti and Culex quinquefasciatus treated in the 4th larval instar. At 1.5 and 1.0 ppm this IGR produced 97 and 99% inhibition of emergence in adult Ae. aegypti, respectively. In Cx. quinquefasciatus, there was 99% inhibition at 1 ppm and complete inhibition at 1.5 ppm. The overall pupal mortality was higher than larval or adult stages of both species. This material induced different types of morphogenetic abnormalities in pupae and adults of the 2 species similar to those induced by other IGRs. However, most abnormalities were observed in the pupal stage. Adverse effects were not detected on the 4 mosquito predator species during the acute or posttreatment tests.

Aedes↗
PubMed1983

Insulin is a physiological inhibitor of urinary zinc excretion in anesthetized dogs.

Renal clearance experiments were performed on anesthetized dogs to determine the role of insulin in regulation of urinary zinc excretion. Intravenous infusion of somatostatin (2 micrograms/min) increased zinc excretion by approximately 100%, in association with 67% decreases in the plasma concentrations of both insulin and glucagon. Infusion of insulin (30 mU X kg-1 X min-1) along with the somatostatin maintained plasma insulin constant and completely eliminated the somatostatin-induced hyperzincuria; indeed, a small decrease in zinc excretion invariably occurred. Infusion of insulin alone (60 mU X kg-1 X min-1) decreased zinc excretion in five of six dogs. Plasma zinc concentration fell progressively, but to the same extent, throughout the experiment in all protocols. None of the hormonal infusions altered glomerular filtration rate, plasma concentrations of sodium, calcium, or magnesium or urinary excretion of these cations. We conclude that insulin, at physiological plasma concentrations, exerts an inhibitory effect on urinary zinc excretion.

Animals↗