Biomedical subjects

E Matthews

Publications and source records attributed to E Matthews.

At least 19 recordsLinked to original sources

PubMed2004

Glycosidase activity in the excretory-secretory products of the liver fluke, Fasciola hepatica.

Fasciola hepatica secretes proteolytic enzymes and other molecules that are essential for host penetration and migration. This mixture may include enzymes required for the degradation of supramucosal gels, which defend epithelial surfaces against pathogen entry. These contain hydrated mucins that are heavily glycosylated. Excretory-secretory products (ES) from F. hepatica were examined for a range of glycosidase activities, using synthetic 4-methylumbelliferyl glycosides as substrates. The ES product contained at least 8 different glycosidase activities, the most abundant of which were beta-N-acetylhexosaminidase, beta-galactosidase and beta-glucosidase. Alpha-fucosidase, beta-glucuronidase, alpha-galactosidase, alpha-mannosidase and neuraminidase were also present. Beta-N-acetylhexosaminidase and beta-galactosidase were present in multiple isoforms (at least 4), whereas beta-glucosidase appeared to exist as one isoenzyme with a pI < 3.8. All three enzymes had acidic pH optima (4.5-5.0). Ovine small intestinal mucin was degraded by ES at pH 4.5 or 7.0, with or without active cathepsin L, the major protease found in F. hepatica ES. The ability of F. hepatica ES to degrade mucin in the presence or absence of active cathepsin L suggests that cathepsin L is not essential for mucin degradation. The abundance of beta-galactosidase and beta-hexosaminidase in ES supports a role for these enzymes in mucin degradation.

Animals↗

PubMed2003

To tell or not to tell: barriers and facilitators in family communication about genetic risk.

Communication about genetic risk in families is an important issue for genetic counsellors. The objective of this study was to explore the barriers and facilitators in family communication about genetic risk. Semi-structured interviews were undertaken with patients in the Northeast of Scotland who had attended genetic counselling for risk of hereditary breast and ovarian cancer and Huntington's disease, and with some spouses/partners. The interviews confirmed that the issue of disclosure was a problem for some, and that there were generic communication issues common to both groups. Telling family members about genetic risk was generally seen as a family responsibility and family structures, dynamics and 'rules' influenced disclosure decisions. A sense of responsibility towards younger generations was also important. The level of certainty felt by a person in relation to his or her own risk estimate also influenced what he or she could tell other family members. Communication within a family about genetic risk is a complex issue and is influenced by both pre-existing familial and cultural factors and individuals' responses to risk information. If genetic counsellors understood how these factors operate in individual families they might be able to identify effective strategies to promote considered decisions and prevent unnecessary emotional distress.

Adult↗

PubMed2003

Adolescent and young adult tobacco prevention and cessation: current status and future directions.

OBJECTIVE: To summarise the evidence on adolescent and young adult prevention and cessation, and provide future directions for research. DATA SOURCES: Data were collected from published literature. Searches for adolescent prevention were conducted using PubMed, PsycInfo, and ERIC; and for cessation, PubMed, and two major reviews that span January 1978 to May 2002. PubMed, PsychInfo, and SCCI were searched for young adults from January 1990 to May 2002. STUDY SELECTION: Data included smoking prevention studies published from January 1990 to May 2002 and conducted in the USA; all identified smoking cessation studies for adolescents. Young adult data were limited to initiation and cessation studies. DATA EXTRACTION: Extraction of data was by consensus of the authors. DATA SYNTHESIS: Results of the review are qualitative in nature using a consensus approach of the authors. CONCLUSIONS: School based curricula alone have been generally ineffective in the long term in preventing adolescents from initiating tobacco use but are effective when combined with other approaches such as media and smoke-free policies. Prevention research should consider multiple approaches and the social conditions that influence the development of youth problem behaviours including tobacco use. Because youth smoking cessation has been understudied to date, scientifically rigorous adolescent smoking cessation studies need to be conducted with attention to high risk smokers and less than daily smokers. Tobacco prevention and cessation for young adults needs focused attention. Prevention and cessation programmes need to address other tobacco products in addition to cigarettes.

Adolescent↗

PubMed2001

Preventing accidental falls among older people in long stay units.

A fall prevention programme for older long-stay patients in a 95 bedded District Hospital was undertaken. Data on falls and resulting injuries for the year prior to the intervention were compared with equivalent data after one year (Year 1) and after two years (Year 2) of the intervention. In the pre-intervention year 25% of patients had at least one fall compared with 20.9% and 17.4% in Year 1 and Year 2 respectively. This difference was not statistically significant. However, there were 21% fewer falls in Year 1 and 49.3% fewer in Year 2 than in the pre-intervention year. This difference was significant in Year 2. In both intervention years there was a significant reduction in the incidence of fracture from 20.5% of falls (pre-intervention) to 2.8% in Year 1 and no fractures occurred in Year 2. Significant reductions in soft tissue injuries occurred in Year 2 but not in Year 1, dropping from 38.5% (pre-intervention) to 36.1% and 15.4% respectively. The percentage of patients uninjured after a fall increased from 41% to 61.1% to 84.6%. This intervention reduced falls and their adverse consequences for older people living in the long stay unit. The effect of the intervention escalated in Year 2. The intervention cost IR4,800 pounds. Fall prevention should be part of the routine care of older people in all types of long stay care.

Accidental Falls↗

PubMed2000

Enlargement of the receptive field size to low intensity mechanical stimulation in the rat spinal nerve ligation model of neuropathy.

One characteristic of plasticity after peripheral tissue or nerve damage is receptive field reorganization, and enlargement of receptive field size has been suggested to occur in certain models of neuropathic pain. The aim of the present study was to explore whether enlargement of neuronal receptive fields could contribute to the mechanical allodynia found on the ipsilateral paw in the spinal nerve ligation model of neuropathy. After ligation of L(5)-L(6) spinal nerves, all rats developed behavioral signs of mechanical allodynia, while the sham-operated control group displayed no such changes. The characteristics of the evoked responses of the neurones recorded in the dorsal horn of the rats were similar between the spinal nerve ligation, the sham operated control group, and the nonoperated control group, except for spontaneous activity, which was significantly increased in the spinal nerve ligation group. The mean size of the receptive field on the ipsilateral hindpaw, mapped using low-intensity stimulation with 9-g von Frey hair, was significantly increased in the spinal nerve ligation group, as compared to the sham-operated group. No significant difference was seen with 15- or 75-g von Frey hairs. The distribution of the receptive fields over the plantar surface of the paw was similar between the study groups. The enlargement of receptive field for non-noxious touch could be an indication of central sensitization in this model.

Animals↗

PubMed2000

Down-regulation of TGF-beta1 production restores immunogenicity in prostate cancer cells.

The objective of this study is to determine if a non-immunogenic Dunning's rat prostate cancer cell line, MATLyLu, can become immunogenic by reducing the endogenous production of TGF-beta1. An expression construct containing a DNA sequence in an antisense orientation to TGF-beta1 (TGF-beta1 antisense) was stably transfected into MATLyLu cells. Following transfection, cellular content of TGF-beta1 reduced from 70 to 10 pg per 2x10(4) cells and the rate of in vitro 3H-thymidine incorporation increased 3-5-fold. After subcutaneous injection of tumour cells into syngeneic male hosts (Copenhagen rats), the tumour incidence was 100% (15/15) for the wild type MATLyLu cells and cells transfected with the control construct, but only 43% (9/21, P< or =0.05) for cells transfected with TGF-beta1 antisense. However, when cells were injected into immunodeficient hosts (athymic nude rats), the incidence of tumour development was 100% (10/10) for both the wild type MATLyLu cells and cells transfected with the control construct and 90% (9/10) for cells transfected with TGF-beta1 antisense. These observations support the concept that MATLyLu cells are immunogenic, when the endogenous production of TGF-beta1 is down-regulated.

Animals↗

PubMed2000

Autonomy and the psychiatric patient.

The aim of this paper is to consider possible justifications for the denial of the right to refuse treatment in the case of certain kinds of psychiatric patients. The basis of this right in general is first considered: arguments based on Kantian conceptions of autonomy are rejected as confused, and preference is given to Millian arguments based on the right to make decisions about one's own life, however irrational, as long as they do not harm others. In light of this discussion, it is argued that mentally disordered people cannot be denied this right on grounds of their 'irrationality', which is anyway a vague concept with several meanings. In conclusion, it is argued that there may be a case for such a denial in those sorts of mental disorder which involve a 'disturbance of personal identity'.

Coercion↗

PubMed1998

Climate forcings in the industrial era.

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. One consequence of this partial balance is that the natural forcing due to solar irradiance changes may play a larger role in long-term climate change than inferred from comparison with GHGs alone. Current trends in GHG climate forcings are smaller than in popular "business as usual" or 1% per year CO2 growth scenarios. The summary implication is a paradigm change for long-term climate projections: uncertainties in climate forcings have supplanted global climate sensitivity as the predominant issue.

Climate↗

PubMed1998

Is health care a need?

This paper aims to provide an argument for saying that a publicly funded health care system, available to all free at the point of delivery, is morally superior to a market system, and to provide a framework for deciding questions about which forms of health care should be included in such a public system. The argument presents health care as a 'head', in the sense of something to which human beings are morally entitled as a necessary condition for a life worthy of human dignity. Alternative arguments for similar conclusions, proposed by Daniels and Buchanan, are critically examined and rejected.

Beneficence↗

PubMed1998

Communication about risk: diversity among primary care professionals.

OBJECTIVE: We aimed to identify the important clinical topics and to report current practice of communication about risk in primary care. METHODS: We carried out a qualitative study using six semi-structured focus group discussions with primary care professionals. The subjects were 36 primary care professionals from general practice, practice nurse, district nurse, community psychiatric nurse and health visitor disciplines. RESULTS: All clinical topics were felt to raise issues of effective risk communication. Participants expressed concern about the lack of accessible up-to-date information and the problems of conveying information to patients. They described the circumstances and contexts in which communication varies and is difficult, and identified media and medico-legal influences and professional uncertainty as also contributing to the problems of risk communication. Specific training in risk communication was identified as an important need. CONCLUSIONS: The complexity of risk communication and diversity of influences on it will require wide-ranging interventions in order to address them. Standardized communication may be a difficult goal to attain.

Communication↗

PubMed1998

Communication about risk: the responses of primary care professionals to standardizing the 'language of risk' and communication tools.

OBJECTIVE: We aimed to gauge responses of primary care professionals to standardization of the 'language of risk' and risk communication tools. METHODS: We carried out a qualitative study using six semi-structured focus group discussions. The subjects were 36 primary care professionals from general practice, practice nurse, district nurse, community psychiatric nurse and health visitor disciplines. RESULTS: Between professionals, the standardization of the language of risk was felt to have potential benefit in making professionals consistent in their appreciation of risks and communication with each other. Between professionals and patients, standardized language was thought inappropriate or insufficient because of contextual variation in communication and interpretation of risk information by patients. The use of more-detailed comparisons of risks was felt to be a potentially effective development of risk communication in practice. CONCLUSIONS: A standard language of risk communication was perceived as being potentially helpful for communication between professionals, but many respondents were sceptical about its usefulness in communication with patients.

Communication↗

PubMed1998

Activation of coagulation and angiogenesis in cancer: immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer.

Thrombin-catalyzed, cross-linked fibrin (XLF) formation is a characteristic histopathological finding in many human and experimental tumors and is thought to be of importance in the local host defense response. Although the pathogenesis of tumor-associated fibrin deposition is not entirely clear, several tumor procoagulants have been described as likely primary stimuli for the generation of thrombin (and XLF) in the tumor microenvironment (TME). In a previous study of a variety of human tumors we have shown that tissue factor (TF) is the major procoagulant. However, the relative contribution to fibrin deposition in the TME of tumor cell TF and host cell TF (eg, macrophage-derived) was not established. In addition, recent evidence has implicated TF in the regulation of the synthesis of the pro-angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells. In the current study we used in situ techniques to determine the cellular localization of XLF, TF, VEGF, and an alternative tumor procoagulant, so-called cancer procoagulant (CP), a cysteine protease that activates clotting factor X. In lung cancer we have found XLF localized predominantly to the surface of tumor-associated macrophages, as well as to some endothelial cells and perivascular fibroblasts in the stromal area of the tumors co-distributed with TF at the interface of the tumor and host cells. Cancer pro-coagulant was localized to tumor cells in several cases but not in conjunction with the deposition of XLF. TF and VEGF were co-localized in both lung cancer and breast cancer cells by in situ hybridization and immunohistochemical staining. Furthermore, a strong relationship was found between the synthesis of TF and VEGF levels in human breast cancer cell lines (r2 = 0.84; P < 0.0001). Taken together, these data are consistent with a highly complex interaction between tumor cells, macrophages, and endothelial cells in the TME leading to fibrin formation and tumor angiogenesis.

Blood Coagulation↗

PubMed1997

Changes in regional cerebral blood flow following light treatment for seasonal affective disorder: responders versus nonresponders.

BACKGROUND: Several brain imaging studies of antidepressant pharmacologic treatment utilizing single photon emission computed tomography (SPECT) have reported a normalization of deficits in cerebral blood flow (CBF) associated with recovery; other studies report no change, or a reduction in CBF following successful treatment. There have been no published SPECT studies of seasonal affective disorder (SAD) assessing response to light treatment in relation to changes in regional CBF (rCBF). In this study, we sought to test the hypothesis that increases in rCBF would be observed in SAD patients who responded to light treatment. METHODS: Ten depressed patients with SAD underwent functional brain imaging studies with 99mTc-hexamethylpropyleneamine oxime SPECT before and after light treatment. RESULTS: Relative increases in rCBF were observed in all brain regions compared to cerebellum in treatment responders, whereas nonresponders showed no change or decreases in rCBF relative to cerebellum. Significant differences in mean percentage change in rCBF between responders (n = 5) and nonresponders (n = 5) were detected in frontal and cingulate cortex, and thalamus. CONCLUSIONS: These findings provide preliminary support for the hypothesis that an increase in rCBF is associated with recovery from depression in SAD.

Adult↗

PubMed1997

Economic considerations for device design and development.

The importance of the design and development process is often underestimated in the rush to get products to market. Studies have shown that sensible investment in this process will lead to manageable risk levels, consumer confidence and high levels of return. This article recommends procedures that manufacturers should follow to improve the quality and efficiency of their development endeavours, and thus maximize their product performance and market presence.

Biomedical Engineering↗

PubMed1996

Isolation of InsP4 and InsP6 binding proteins from human platelets: InsP4 promotes Ca2+ efflux from inside-out plasma membrane vesicles containing 104 kDa GAP1IP4BP protein.

A low-density membrane fraction from human platelets contained the plasma membrane marker glycoprotein Ib (GpIb) and selective binding sites for InsP4 and InsP6. It was separated from the bulk of InsP3-receptor-containing membranes, but was heterogeneous, probably also containing surface-connected canalicular system and some lighter elements of the internal dense tubule system. After loading with calcium oxalate and re-centrifugation on Percoll gradients, this mixed fraction was subfractionated into light membranes containing all of the GpIb, high-affinity InsP4 binding sites (KD = 18 nM) and phosphate-stimulated Ca2+ transport activity. InsP4 (EC50 0.6 microM), but not InsP3 or InsP6, released up to 35% of the accumulated Ca2+ from these vesicles, which were shown to be inside-out plasma membrane vesicles by a biotinylation labelling technique and selective removal of right-side-out plasma membrane vesicles with streptavidin-agarose. Most of the InsP4, and all of the InsP6, binding was present in the much denser calcium oxalate-loaded subfractions, which were free of GpIb. InsP6 binding activity was chromatographically purified as a 116 kDa protein (KD for InsP6 = 5.9 nM), with an amino acid content and two internal peptide sequences identical to those of 116 kDa vinculin. A 104 kDa InsP4 binding protein (KD for InsP4 = 12 nM), probably identical to GAP1IP4BP described by Cullen, Hsuan, Truong, Letcher, Jackson, Dawson and Irvine [(1995) Nature (London) 376, 527-530], was also isolated. This InsP4 receptor may mediate Ca2+ influx in platelets that occurs subsequent to receptor-stimulated production of InsP3 and unloading of internal Ca2+ stores.

Binding Sites↗

PubMed1995

Purification and characterization of the human type 1 Ins(1,4,5)P3 receptor from platelets and comparison with receptor subtypes in other normal and transformed blood cells.

We report the first purification of a native human form of the Ins(1,4,5)P3 (InsP3) receptor. This receptor, isolated from platelets, has an apparent molecular mass on SDS/PAGE of 252 kDa and is chromatographed by gel filtration as an oligomer of about 1 x 10(6) kDa. [3H]InsP3 bound to a single class of sites on the purified receptor protein with a Kd of 27 nM and a Bmax. of 2.2 nmol/mg of protein. The platelet InsP3 receptor, like the rodent cerebellar receptors, was identified immunochemically as a type 1 receptor, but unlike its brain counterparts bound poorly to concanavalin A and other lectins and was not significantly phosphorylated by protein kinase A. All cultured megakaryocytic leukaemia cell lines (e.g. Dami, CHRF-288 and Meg-01) and HEL cells were also immunopositive for type 1 receptor, which was substantially increased in some cases by DMSO or phorbol 12-myristate 13-acetate (PMA) which induce further megakaryocytic differentiation. Normal mixed lymphocyte and granulocyte fractions and an enriched T-cell fraction from human blood had measurable InsP3-binding activity, but no detectable type 1 protein. In contrast, Jurkat E6-1 (T-cell lymphoma) cells and the transformed B-cell line RPMI 8392 were immunopositive for type 1 receptor. HL-60 (human promyelocytic leukaemia) cells had no detectable type 1 receptor unless they were stimulated to differentiate along monocyte/macrophage lines by PMA. We conclude that: (1) of the major normal blood cells only platelets contain type 1 InsP3 receptors; (2) some neoplastic transformed blood cell lines also express type 1 receptors, in contrast to their normal counterparts; and (3) increased levels of type 1 InsP3 receptor are induced in some transformed cells under conditions that favour their further terminal differentiation.

Animals↗

PubMed1994

Ca2+ release by inositol 1,4,5-trisphosphate is blocked by the K(+)-channel blockers apamin and tetrapentylammonium ion, and a monoclonal antibody to a 63 kDa membrane protein: reversal of blockade by K+ ionophores nigericin and valinomycin and purification of the 63 kDa antibody-binding protein.

Ins(1,4,5)P3-induced Ca2+ release from platelet membrane vesicles was blocked by apamin, a selective inhibitor of low-conductance Ca(2+)-activated K+ channels, and by tetrapentylammonium ion, and was weakly inhibited by tetraethylammonium ion. Other K(+)-channel blockers, i.e. charybdotoxin, 4-aminopyridine and glybenclamide were ineffective. A monoclonal antibody (mAb 213-21) obtained by immunizing mice with the InsP3-sensitive membrane fraction from platelets also blocked Ca2+ release by InsP3 from membrane vesicles obtained from platelets, cerebellum, aortic smooth muscle, HEL cells and sea-urchin eggs. ATP-dependent Ca2+ uptake and binding of [3H]InsP3 to platelet membranes was unaffected by either K(+)-channel blockers or mAb 213-21. Blockade of Ca2+ release by apamin, tetrapentylammonium and mAb 213-21 was not affected by the Na+/H+ carrier monensin or the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), but could be completely reversed by the K+/H+ ionophore nigericin and partially reversed by the K+ carrier valinomycin. The antibody-binding protein (ABP) solubilized from platelets, cerebellum, and smooth muscle chromatographed identically on gel filtration, anion-exchange and heparin-TSK h.p.l.c. ABP was purified to apparent homogeneity from platelets and aortic smooth muscle as a 63 kDa protein by immunoaffinity chromatography on mAb 213-21-agarose. These results suggest that optimal Ca2+ release by InsP3 from platelet membrane vesicles may require the tandem function of a K+ channel. A counterflow of K+ ions could prevent the build-up of a membrane potential (inside negative) that would tend to oppose Ca2+ release. The 63 kDa protein may function to regulate K+ permeability that is coupled to the Ca2+ efflux via the InsP3 receptor.

Animals↗

PubMed1992

Recollected in tranquillity. A profile of Ernest Matthews. Interview by Colin Davis.

Emeritus Professor Ernest Matthews, living in happy retirement in a delightful, small nineteenth century house in Petersfield, looks about 70 years old, and is in fact 17 years older. He has made many contributions to the advancement of dentistry, and we asked him, as he looked back over the years, how he saw the dental world today compared with 60 years ago when he qualified.

England↗