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Biomedical subjects

R Watt

Publications and source records attributed to R Watt.

At least 19 recordsLinked to original sources
PubMed1999

Photoassembly of the manganese cluster and oxygen evolution from monomeric and dimeric CP47 reaction center photosystem II complexes.

Isolated subcomplexes of photosystem II from spinach (CP47RC), composed of D1, D2, cytochrome b(559), CP47, and a number of hydrophobic small subunits but devoid of CP43 and the extrinsic proteins of the oxygen-evolving complex, were shown to reconstitute the Mn(4)Ca(1)Cl(x) cluster of the water-splitting system and to evolve oxygen. The photoactivation process in CP47RC dimers proceeds by the same two-step mechanism as observed in PSII membranes and exhibits the same stoichiometry for Mn(2+), but with a 10-fold lower affinity for Ca(2+) and an increased susceptibility to photodamage. After the lower Ca(2+) affinity and the 10-fold smaller absorption cross-section for photons in CP47 dimers is taken into account, the intrinsic rate constant for the rate-limiting calcium-dependent dark step is indistinguishable for the two systems. The monomeric form of CP47RC also showed capacity to photoactivate and catalyze water oxidation, but with lower activity than the dimeric form and increased susceptibility to photodamage. After optimization of the various parameters affecting the photoactivation process in dimeric CP47RC subcores, 18% of the complexes were functionally reconstituted and the quantum efficiency for oxygen production by reactivated centers approached 96% of that observed for reconstituted photosystem II-enriched membranes.

Dimerization↗
PubMed1999

An alarming lack of public awareness towards oral cancer.

OBJECTIVE: To determine public awareness and knowledge of oral cancer in Great Britain. DESIGN: The respondents were selected according to a systematic probability sample designed to be representative of all adults in Great Britain (GB). The overall design was similar to previous omnibus surveys carried out by National Opinion Poll (NOP). The survey was carried out in ten regions of GB in September 1995 and was commissioned by the Health Education Authority (HEA). SUBJECTS AND METHODS: A random sample of 1,894 members of the public over the age of 16 years were asked in face-to-face interviews their knowledge relating to cancer, with particular reference to oral cancer, its causes and those at high risk and general attitudes to cancer. RESULTS: Oral cancer was one of the least heard of cancers by the public with only 56% of the participants being aware, whereas 96% had heard of skin cancer, 97% lung cancer and 86% cervical cancer. There was a 76% awareness of the link between smoking and oral cancer but only 19% were aware of its association with alcohol misuse. Whereas 94% agreed that early detection can improve the treatment outcome, a disheartening 43% believed that whether a person developed a cancer or not was a matter of chance and therefore was unavoidable. CONCLUSIONS: This survey highlights a general lack of awareness among the public about mouth cancer and a lack of knowledge about its causation especially the excess risk associated with alcohol. RECOMMENDATIONS: There is a clear need to inform and educate the public in matters relating to the known risk factors associated with oral cancer. A media campaign informing the public about oral cancer is clearly required. The need for the reduction in the incidence of oral cancer should be included in 'Our healthier nation' targets. An overall health promotion strategy to reduce cancers should include oral cancer as a priority. In addition the European Code against Cancer which aims to improve prevention, the early detection of oral cancer and the necessity for fast track referral should be made more widely known. Recognition of oral cancer in local strategies for oral health should be encouraged.

Adolescent↗
PubMed1999

Inequalities in oral health: a review of the evidence and recommendations for action.

Reducing inequalities in health has become one of the main health policy issues in the late 1990s. The Labour Government set up an independent inquiry into inequalities in health under Sir Donald Acheson to make recommendations on approaches to reducing health inequalities. This paper reviews the evidence on inequalities in oral health in Britain. Dramatic improvements in dental health in children and young adults have taken place in the past 30 years. The levels of caries in permanent teeth of children is low. Widening inequalities in oral health however exist between social classes, regions of England, and among certain minority ethnic groups in pre-school children. The main social class and minority ethnic differences in dental caries is in pre-school children. Wide district and regional differences also exist in prevalence of caries in young children. The area differences relate very strongly to deprivation. In adults the differences in decay experience is less unequal than in children but there are marked social class inequalities in edentulousness. Dental caries decreased in all social classes in the United Kingdom. The main causes of the inequalities are differences in patterns of consumption of non milk extrinsic sugars and fluoridated toothpaste. Improvements in oral health that have occurred over the last 30 years have been largely a result of fluoride toothpaste and social, economic and environmental factors. Oral health inequalities will only be reduced through the implementation of effective and appropriate oral health promotion policy. Treatment services will never successfully tackle the underlying cause of oral diseases.

Adult↗
PubMed1997

UBI4, the polyubiquitin gene of Saccharomyces cerevisiae, is a heat shock gene that is also subject to catabolite derepression control.

Carbon and nitrogen regulation of UBI4, the stress-inducible polyubiquitin gene of Saccharomyces cerevisiae, was investigated using a UBI4 promoter-LacZ fusion gene (UBI4-LacZ). Expression of this gene in cells grown on different media indicated that the UBI4 promoter is more active during growth on respiratory than on fermentable carbon sources but is not subject to appreciable control by nitrogen catabolite repression. UBI4-LacZ expression was virtually identical in cells having constitutively high (ras2, sra1-13) or constitutively low (ras2) levels of cyclic AMP-dependent protein kinase activity, indicating that this kinase does not exert a major influence on UBI4 expression. Catabolite derepression control of the UBI4 promoter was confirmed by measurements of UBI4-LacZ expression in hap mutant and wild-type strains before and after transfer from glucose to lactate. Mutagenesis of the perfect consensus for HAP2/3/4 complex binding at position -542 resulted in considerable reduction of UBI4 promoter derepression with respiratory adaptation in HAP wild-type cells and abolished the reduced UBI4-LacZ derepression normally seen when aerobic cultures of the hap1 mutant are transferred from glucose to lactate. This HAP2/3/4 binding site is therefore a major element contributing to catabolite derepression of the UBI4 promoter, although data obtained with hapl mutant cells indicated that HAP1 also contributes to this derepression. The HAP2/3/4 and HAP1 systems are normally found to activate genes for mitochondrial (respiratory) functions. Their involvement in mediating higher activity of the UBI4 promoter during respiratory growth may reflect the contribution of UBI4 expression to tolerance of oxidative stress.

Biopolymers↗
PubMed1994

Polyubiquitin gene expression contributes to oxidative stress resistance in respiratory yeast (Saccharomyces cerevisiae).

UBI4, the polyubiquitin gene of Saccharomyces cerevisiae, is expressed at a low level in vegetative cells, yet induced strongly in response to starvation, cadmium, DNA-damaging agents and heat shock. UBI4 is also expressed at a higher basal level in cells growing by respiration as compared to glucose-repressed cells growing by fermentation. This higher UBI4 expression of respiratory cultures probably helps to counteract the greater oxidative stress of respiratory growth. The effects of inactivating UBI4 on high temperature viability are more marked with respiratory cultures. Also loss of UBI4 leads to a considerably increased rate of killing of respiring cells by hydrogen peroxide, whereas the same gene inactivation has relatively little effect on the peroxide sensitivity of cells in which mitochondrial functions are repressed. This is the first study to reveal that ubiquitin levels in cells can influence their ability to withstand oxidative stress.

Biopolymers↗
PubMed1994

A computational examination of image segmentation and the initial stages of human vision.

A novel approach to the question of image segmentation is considered. Instead of relying on edge-detection mechanisms to encircle the image of an object, it is proposed that the general Gestalt-like properties of images of objects can be used. These manifest themselves as particularly simple properties at relatively coarse spatial scales when the image is filtered with orientation-selective filters. The first part of the paper is concerned with a computational analysis of this proposal. A key issue is the question of how the information in filtered images is extracted. A simple primitive parametric description of zero-bounded blobs is used in this paper. It is shown how such a scheme can support readily the clustering of features with Gestalt-like properties. In the second part of the paper, two general difficulties for vision that are particularly severe for the present scheme are considered. The first of these are the effects of strongly asymmetric illumination. The second are the effects of using a cluttered scene. In each case the nature of the problem is examined and the nature of the computational solution considered.

Contrast Sensitivity↗
PubMed1991

Removal of lymphocytotoxic antibodies by pretransplant immunoadsorption therapy in highly sensitized renal transplant recipients.

A high level of panel-reactive antibodies (PRA) in potential renal transplant recipients is associated with a long waiting time until transplantation and correlates inversely with graft outcome. We report our experience with the employment of immunoadsorption (IA) using a column composed to sepharose-bound staphylococcal protein A (which has a relatively selective affinity for binding IgG compared with other immunoglobulins) to decrease the PRA levels and expedite transplantation in 6 highly sensitized potential renal transplant recipients (1 primary and 5 awaiting second transplants). All patients had PRA levels of greater than or equal to 70% for a duration of 1 year prior to IA. Only patients with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted for the study. IA procedures were performed on alternate days until a twofold decrease in antibody titer had occurred (maximum: 6 procedures). Repeat procedures were initiated if the HLA antibody titer returned to its baseline value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive immunosuppression until transplantation. A total of 44 immunoadsorption procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/- 0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and PRA activity decreased 75 +/- 16% after the primary treatment course. Four patients received cadaveric grafts within 3.7 +/- 1.2 months following the last IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks posttransplant. The remaining graft demonstrated primary nonfunction. All four patients had a past positive crossmatch using pre-IA sera with their respective donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return of the PRA towards baseline levels within a few weeks after IA. We conclude that IA can effectively remove HLA antibodies and expedite graft availability in highly sensitized patients.

Adult↗
PubMed1990

Immunodepletion in xenotransplantation.

Xenograft transplantation is perhaps the most immunologically difficult problem in transplantation today. An overwhelming hyperacute rejection reaction (HAR) occurs within minutes of organ implantation. Preformed antibodies are thought to initiate this process. We used a pig-to-dog renal xenograft transplant model and investigated methods of decreasing the severity of hyperacute rejection. Female pigs weighing 15-20 kg were used as donors. Recipients were mongrel dogs weighing 15-25 kg. Experimental dogs were all given a number of treatments of IgG depletion using an antibody removal system (Dupont-Excorim). This machine immunoadsorbs plasma against a column containing immobilized staphylococcal protein A, which is known to bind the IgG Fc receptor. An 84% reduction in the IgG levels and a 71% reduction in IgM levels was achieved. Postoperative assessment was made of urine output, time to onset of HAR, and histopathological examination of the rejected kidneys. Although cross-matches between donor lymphocytes and recipient sera remained strongly positive in the treated dogs, there was a two- to fourfold reduction in the titers. The time to onset of HAR was prolonged in the experimental group, and the urine output was increased slightly. The histopathologic changes in the experimental group generally showed signs of HAR, but of less intensity than in the nonimmunodepleted control group.

Animals↗
PubMed1989

Induction of c-fos protein by activation of vasopressin receptors in smooth muscle cells.

Stimulation of vasopressin (V1) receptors of rat aortic smooth muscle cells (A-10, ATCC CRL 1476) results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) with the mobilization of intracellular calcium. When A-10 cells are exposed to arginine vasopressin (AVP), there is an increase in the level of c-fos oncoprotein. The extent of induction of c-fos oncoprotein depends on both the time of exposure of the cells to AVP, reaching a maximum at 60 min after which there is a slow decline, and the concentration of AVP used, with an approximate EC50 of 1 nM which corresponds well with the Kd of vasopressin binding to these receptors. This vasopressin-mediated increase in c-fos protein level is inhibited by a V1/V2 antagonist (SKF 101498) suggesting that this is a receptor-mediated event. In addition dDAVP, a V2 selective agonist, is much less effective than AVP in inducing c-fos protein suggesting that AVP mediates its effect via V1 receptors. Desensitization of vasopressin receptors by prolonged exposure to AVP resulted in no additional induction of c-fos protein level in response to second challenge of AVP. In addition to AVP, phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC), also stimulates the accumulation of c-fos protein although to a lesser extent than AVP. The above data suggest that c-fos protein levels in smooth muscle cells are regulated by AVP and the hormonal effect may be mediated through PI turnover and DAG, IP3 and Ca2+ signals.

Animals↗
PubMed1989

Levels of myc protein, as analyzed by flow cytometry, correlate with cell growth potential in malignant B-cell lymphomas.

We have analyzed c-myc protein expression during the cell cycle in malignant B-cell lymphomas by dual flow cytometric detection of a fluoresceinated polyclonal anti-myc antibody and propidium iodide which binds stochiometrically to DNA. The data obtained were correlated to other parameters of cell activation such as histopathological grading, expression of the activation antigen 4F2, light scatter (proportional to cellular volume), DNA synthesis and percentage of S-phase cells. The c-myc protein level was strongly correlated to parameters of DNA synthesis/content. In addition, the oncoprotein level was largely unvarying from the late G1 phase through the rest of the cell cycle in both malignant cells and normal purified B cells stimulated to proliferate in vitro.

B-Lymphocytes↗
PubMed1989

Automated measurements of isolated heart muscle contractions: effects of halothane, calcium, and magnesium on guinea pig left atrial muscle.

An in vitro method for automatically measuring muscle contraction force has been demonstrated in a study of the effects of the inhalation anesthetic halothane followed by calcium chloride or magnesium sulfate on isolated guinea pig left atrial muscle. An automated computer-controlled system was used to collect muscle contraction force waveforms and to analyze contraction waveforms for comparison of variables before and after drug administration. Two concentrations of halothane (0.5 and 1.5%) were administered to the atrial preparation for 30 minutes and followed by calcium chloride or magnesium sulfate. Six variables (latency, time to peak tension, peak tension, maximum rate of change of pressure, force time integral, and relaxation time) were automatically determined from averaged stimulus-response curves. Results were normalized and compared with controls administered only calcium and magnesium and with controls administered no drugs. The automated system greatly simplified data collection and accumulation and statistical analysis of multiple responses. The system made possible averaging and analysis of more data with less variability than is normally obtained with manual systems. The results confirm several known actions of these agents. Halothane prolongs latency (9 and 21% for 0.5 and 1.5% halothane, respectively) and shortens time to peak tension (6 and 17% for 0.5 and 1.5% halothane, respectively) and relaxation time (17 and 39% for 0.5 and 1.5% halothane, respectively). At high halothane concentrations (1.5%) calcium chloride shortens latency (10%) and prolongs time to peak tension (11%); magnesium sulfate prolongs latency (14%) and shortens time to peak tension (10%).

Animals↗
PubMed1988

Stabilization of myc proto-oncogene proteins during Friend murine erythroleukemia cell differentiation.

A rapid and dramatic decrease in c-myc mRNA has been associated with the differentiation of a variety of cell types and may be a critical step in the maturation process. In this study, we have simultaneously measured steady-state c-myc protein and c-myc mRNA levels in differentiating Friend murine erythroleukemia (MEL) cells. Northern blot analysis of poly(A+) RNA indicated a greater than 85% decrease in c-myc transcripts following a brief exposure to the inducing agents, dimethyl sulfoxide or hypoxanthine. The short half-life of the c-myc protein (approximately 30 min) suggests that its level should fall in a similar fashion. Surprisingly, immunoblots of total cell proteins and immunoprecipitations of 35S-labeled protein revealed that c-myc protein levels remain approximately constant. This unexpected finding was accounted for in part by an increase in the c-myc protein half-life to 75-85 min. Immunoprecipitation of [35S]methionine-labeled proteins also demonstrated that the undifferentiated MEL cell synthesizes equal amounts of two c-myc-related proteins, p59 and p61. In contrast, MEL cell populations in the late stages of differentiation express predominantly the higher molecular weight species. This latter observation represents the first report of a temporal shift in the relative abundance of the two c-myc isoforms during cell differentiation.

Animals↗
PubMed1988

Assessment of c-myc expression in individual leukemic cells.

The expression of the proto-oncogene c-myc was studied at the protein level in cells obtained from patients with AML and CML. In florid AML and during the blastic phase of CML the majority of cells contain c-myc protein with the amount of protein differing widely among the cells of individual patients. In contrast, during complete remission in AML and during the chronic phase of CML cells containing c-myc protein are rare. Several studies demonstrated a discordance in the amount of c-myc transcript and the amount of c-myc protein present in cell populations thereby suggesting the presence of translational or post-translational regulation of c-myc expression. Further, the data suggest that high levels of c-myc protein in the leukemic cells of AML patients are associated with a poor response to therapy and that high levels in AML patients in CR or in the peripheral blood of chronic phase CML patients may be indicative of impending acute leukemia.

Gene Expression Regulation↗
PubMed1987

Cyclic AMP-mediated suppression of normal and neoplastic B cell proliferation is associated with regulation of myc and Ha-ras protooncogenes.

Cyclic AMP functions as a negative regulator of cell proliferation in a variety of cell systems. We show here that the proliferation of normal and neoplastic B cells can be inhibited by high intracellular levels of cAMP. Thus forskolin treatment of the neoplastic B precursor cell line Reh induced a rapid increase in the cAMP level, which was followed by an accumulation of cells in the G0/G1 phase of the cell cycle over a period of 2-3 days. Similar inhibition of Reh cell proliferation after 3 days was observed whether forskolin was present continuously or only during the first 5 hr. Both c-myc and c-Ha-ras protein levels were transiently down-regulated at 4 hr of forskolin treatment, suggesting that these protooncogenes play a role in the process leading to cAMP-mediated growth cessation. Northern-blot analysis showed that the steady-state levels of c-myc RNA rapidly declined in all phases of the cell cycle, to return to control levels within a time period of 24 hr. In contrast, the c-Ha-ras mRNA level was steadily maintained. Thus the expression of c-myc and c-Ha-ras protein was regulated at different metabolic levels. The reduced proliferative capacity of the B precursor cell line in the presence of forskolin was not linked to induced differentiation. This was judged from the lack of appearance of three different B cell differentiation markers; cytoplasmic immunoglobulin heavy chain and two antigens recognized by the monoclonal antibodies B1 (CD20) and HH1 (CD37). We also showed that forskolin partially inhibited the proliferation of normal B lymphocytes stimulated by anti-immunoglobulins (anti-mu) and B cell growth factor (BCGF). The burst of c-myc mRNA during activation of normal B cells was also reduced by forskolin.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Regulation of c-myc transcription and protein expression during activation of normal human B cells.

The close link between an actively expressed c-myc gene locus and cellular proliferation has been established in a variety of cell types. By using normal human peripheral blood B cells as a model for in vivo quiescence, we have assessed the expression pattern of the c-myc gene in terms of transcriptional activation and concurrent production of c-myc protein, following induction by antibodies directed against antigens on the cell membrane. Both the 1F5 monoclonal antibody, which reacts with the pan B cell antigen CD20, and the anti-mu could promote transcriptional activation of the c-myc gene roughly corresponding to the increased levels of cytoplasmic c-myc mRNAs. In addition, more than 80% of the B cells could be induced to express c-myc protein by either stimulus. Since treatment only with polyclonal anti-mu renders the B cells competent to proliferate in the presence of BCGF, c-myc protein expression is not per se sufficient for cell cycle progression into S phase.

B-Lymphocytes↗
PubMed1986

Dexamethasone-suppressible hyperaldosteronism. Adrenal transition cell hyperplasia?

Dexamethasone-suppressible hyperaldosteronism is a rare familial syndrome in which hypokalemia, suppression of plasma renin concentration, and elevated aldosterone secretion are corrected by treatment with glucocorticoids. Regulation of adrenocortical function and body electrolytes was studied in two affected brothers. Both were hypertensive (210/128 and 160/106 mm Hg) with hypokalemia (3.3 and 3.5 mM) and low plasma renin concentrations. Aldosterone was elevated intermittently with levels as high as 45 ng/dl (normal range, 4-16 ng/dl). Cortisol concentrations were normal but were correlated with aldosterone levels (r = 0.9 and 0.7). Concentrations of 11-deoxycorticosterone (19 and 21 ng/dl; normal range, 4-16 ng/dl) and 18-hydroxycortisol (1000 and 950 ng/dl; normal range, 34-150 ng/dl) were elevated, and diurnal changes in both were the same as those seen with aldosterone. Infusion of adrenocorticotropic hormone (ACTH) caused exaggerated increases of aldosterone, 11-deoxycorticosterone, and 18-hydroxycortisol; cortisol response was normal. A 4-week trial of dexamethasone normalized blood pressure and caused a natriuresis, a fall in aldosterone, and a rise in plasma renin. Administration of ACTH after dexamethasone treatment again caused exaggerated increases of aldosterone. Aldosterone did not respond to angiotensin II before dexamethasone therapy (r = 0.01), but it showed a normal response after therapy (r = 0.8, p less than 0.01). Neither administration of dopamine (1 microgram/kg/min) nor long-term therapy with bromocriptine (2.5 mg t.i.d. for 4 weeks) affected aldosterone biosynthesis. Thus, loss of dopaminergic inhibition of mineralocorticoid biosynthesis does not account for hyperaldosteronism in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗