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PubMed1999

Health professionals' perspectives on service delivery in two Northern Ireland communities.

This research builds on the findings of an ethnographic study of health inequalities in two small, rural communities in Northern Ireland. Through further analysis of existing data, this second study aimed to explore health professionals' perspectives on issues of service delivery relevant to government policy on primary care. Anthropological fieldwork was conducted for two consecutive 4-month periods during 1995 and 1996 in one predominantly Catholic and one predominantly Protestant town. To preserve confidentiality, the locations have been given the pseudonyms, respectively, of Ballymacross and Hunterstown. Research tools included fieldwork journals and a fieldwork diary, meetings with key informants, tape-recorded interviews, group discussions, participant observation and use of secondary material such as census data, local newspapers and community health profiles. Interviews with 15 health workers revealed that there was not a coherent approach to achieving health gain, little collaborative enterprise and minimal interaction between the different professional groups. The National Health Service (NHS)-employed primary care professionals, more than local community workers, appeared to be demoralized, exhausted and suspicious of the business-orientated health service. In this respect, the primary care-led NHS appeared not to be working. It is concluded that a shared health agenda should be developed by NHS-employed primary care professionals and local community workers to create a health-inducing environment at community level. This needs to be complemented by the establishment of formal mechanisms for inter-agency working at local, professional and government levels.

Community Participation↗
PubMed2006

Nursing advocacy in an Australian multidisciplinary context: findings on medico-centrism.

As a follow-up to a recent study which highlighted the existence of medical dominance in multi-disciplinary team (MDT) meetings, this paper presents research findings from an Australian study which shows that medico-centrism is a key cause of tension within MDTs. The findings are from a 1-year qualitative study in a regional hospital that explored the ethical decision-making of health professionals within an acute care medical unit. This exploration was conducted through an iterative, phenomenological, qualitative research methodology that consisted of open-ended interviews with a multi-disciplinary representation of health professionals and a sample of consumers for whom they care. The paper situates the notion of nursing advocacy within the context of medico-centrism and examines how the nursing profession interfaces with other disciplines. The findings indicate that the professional framework of nursing includes the language of advocacy, whilst the framework of doctors centres around the medical decision-making process. All professional groups made reference to the MDT as the modus operandi for patient-centred care. All participants noted that time and familiarity with patients and their families is essential for patient-centred care and this could be achieved through MDT collaboration. However, doctors who have scant time to spend with patients saw it as their responsibility to direct the decisions of the MDT and viewed the MDT as adding confusion to the decision-making process. Nurses reported that the limited amount of time spent by doctors in patient consultation translated into the need for advocacy. Professional and clinical confidence and experience are noted as necessary to successfully engage in the process of advocacy. The findings of this article indicate that the adoption of an advocacy role by nurses represents an important means through which MDT operation can be enhanced, medico-centrism limited and patient-centred care improved.

Cross-Sectional Studies↗
PubMed2006

Methylnaltrexone: MNTX.

Methylnaltrexone is a peripheral opioid receptor antagonist undergoing phase III clinical trials for the treatment of opioid-induced constipation in patients with advanced medical illness who are being treated with narcotics for pain. The compound does not cross the blood-brain barrier in humans and reverses the opioid effects without interfering with pain relief. Some opioid-induced adverse events that the drug may potentially target include constipation, nausea/vomiting, cough suppression and urinary retention. Methylnaltrexone was discovered by researchers at the University of Chicago, Chicago, Illinois, USA and is in joint development with Progenics Pharmaceuticals and Wyeth Pharmaceuticals. Progenics is conducting clinical trials with three methylnaltrexone dosage forms: subcutaneous, IV and oral. Progenics plans to complete the clinical development of methylnaltrexone alone, after which potential pharmaceutical or biotechnology partners will be looked at to provide financial support and marketing expertise, particularly outside the US market. In December 2005, Progenics and Wyeth Pharmaceutical (Wyeth) entered into an exclusive, worldwide agreement for the joint development and commercialisation of methylnaltrexone for the treatment of opioid-induced side effects, including constipation and postoperative bowel dysfunction. Under the terms of the licensing agreement, Wyeth has worldwide rights to the compound and Progenics retains the option to co-promote methylnaltrexone in the US. The companies will collaborate on the worldwide development of methylnaltrexone. Under the terms of the agreement, Wyeth has made an up-front payment to Progenics and will also make additional milestone payments. Wyeth will also pay Progenics royalties on worldwide sales, and co-promotion fees within the US. Wyeth is also responsible for all future development and commercialisation costs. Wyeth will develop oral methylnaltrexone worldwide. Progenics will lead the US development of subcutaneous and intravenous methylnaltrexone, while Wyeth will lead development of these parenteral products outside the US.UR Labs licensed methylnaltrexone from the University of Chicago. In October 2001, Progenics in-licensed the methynaltrexone patent portfolio in exchange for rights to future methynaltrexone royalties. In December 2005, Progenics acquired a substantial portion of the royalty and milestone payments in exchange for 686,000 shares of Progenic's common stock and 2.6 million US dollars in cash. In April 2005, Progenics Pharmaceuticals made a public offering of 2 million shares of its common stock, pursuant to an effective shelf registration statement. Progenics intends to use the net proceeds from this offering to fund clinical trials of methylnaltrexone, to fund clinical trials of other product candidates and for other research and development programs. All primary and secondary endpoints were statistically significant in Progenic's second phase III trial of subcutaneous methylnaltrexone (0.15 mg/kg or 0.30 mg/kg). The trial was initiated in January 2004 in 133 patients with opioid-induced constipation at 27 nursing homes and hospices in the US. Enrollment was completed in September 2005 and results announced in February 2006. In March 2005, Progenics announced results from the pivotal phase III trial of subcutaneous methylnaltrexone for the reversal of opioid-induced constipation. This trial involved a total of 150 patients from 16 hospices in the US who had advanced medical illnesses and who were receiving occasional opioids. Progenics has completed a phase IIb dose-ranging study with subcutaneous methylnaltrexone for treatment of narcotic-induced constipation in patients with cancer or AIDS. Positive top-line results from a phase II clinical trial of methylnaltrexone in the management of postoperative bowel dysfunction were reported in January 2005. The endpoints of the study included restoration of bowel function and discharge eligibility. Reversal of urinary retention was a secondary endpoint in this study. Progenics plans to complete a more in-depth analysis of this phase II data and present the finding to the US FDA. Methylnaltrexone (IV) is scheduled to enter phase III clinical studies in this indication in 2006. An NDA is expected to be submitted for the intravenous formulation of methylnaltrexone in late 2007/early 2008. Progenics also plans to initiate a phase II study of methylnaltrexone in women who have undergone hysterectomies. This patient population is also at high risk for ileus. In May 2004, Progenics Pharmaceuticals completed phase I clinical trials using two different oral formulations of methylnaltrexone. Analysis of preliminary data from 61 healthy volunteers who received methylnaltrexone at three dose levels indicated that the drug was well tolerated and exhibited predictable pharmacokinetics. Based on these phase I studies, Progenics selected an oral formulation and dose levels of methylnaltrexone that will be tested in phase II clinical trials for relief of opioid-induced constipation in patients with chronic-pain. The technology licensed from UR Labs, Inc., is the subject of issued US and European patents and several related US and foreign patent applications relating to certain compositions, formulations and uses of methylnaltrexone filed by the University of Chicago. Progenics have continued to expand the patent coverage relating to methylnaltrexone with the filing of new patent applications.

Clinical Trials as Topic↗
PubMedDate not supplied

[A new decision support tool in the campaign against maternal mortality: the Dystocia Risk Score].

At Ziguinchor Regional Hospital (ZRH) in Senegal, 80% of maternal deaths are associated with late referral of dystocia cases. The gynecology and obstetrics team of the ZRH, in collaboration with the teaching staff of the Institute of Health and Development (ISED), tried to find ways to combat maternal mortality and stillbirth, based on double-entry contigency tables and a logical framework. We developed a tool more elaborate than a simple decision tree: the dystocial risk score. This tool has three components: A column provides a list of eight characteristics to check for in the woman: history of cesarean section, limping, less than 150 cm in height, no living child, less than 18 years old, more than 35 years old, other risk factors, no risk factors. A horizontal section provides a checklist of possible outcomes of the pregnancy itself: obstacle praevia, precedence, noncephalic presentation, uterine length of over 35 cm, loss of amniotic fluid over 12 hours or more, other abnormalities, no abnormalities. A rectangular grid indicates the prognosis. This grid consists of three zones: a large blue zone (dangerous), a medium-sized grey zone (doubtful) and a small blue zone (hopeful). A positive DRS is obtained if there is at least one cross in the dangerous zone and/or at least two crosses in the doubtful zone. If these conditions are not fulfilled, the DRS is negative. A positive DRS indicates that the woman should be referred to a center specialized in obstetric emergency care. This tool was validated in a study of 376 pregnant women carried out over a period of six months. It was found to have a sensitivity of 83.6%, a specificity of 90.1%, a positive predictive value of 72.3% and a negative predictive value of 94.1%. The DRS is a simple, easy-to-use decision-making tool. The large-scale use of this tool (by midwives, chief nurses and health workers) would accelerate the identification of pregnant women with a high risk of dystocia. The timely referral of these women to specialized emergency obstetrics centers would increase the efficacy of care and would reduce the levels of maternal mortality and stillbirth.

Decision Support Techniques↗
PubMed2004

An abundant placental transcript containing an IAP-LTR is allelic to mouse pregnancy-specific glycoprotein 23 (Psg23): cloning and genetic analysis.

Several families of endogenous retroviruses (ERVs) are expressed in mammalian placental tissues, and are implicated in aspects of placental development and function. We characterized the structure of abundant ERV-related transcripts in mouse placenta. In addition to the 7 kb full-length type I and 5 kb type I deleted intracisternal A-particle (IAP) transcripts, we identified and cloned an abundant 2 kb transcript encoding a novel member of the pregnancy-specific glycoprotein (Psg) gene family, which contains an IAP long terminal repeat (LTR) in the 3' untranslated region (UTR). The polyadenylation signal for the transcript is provided by the inserted LTR sequence. This sequence is allelic to Psg23 and is therefore denoted as Psg23(LTR). The transcript encodes a protein of 471 amino acids and has a domain organisation similar to previously described Psg proteins. Modelling of the protein N-domain produced a structure in good agreement with an existing crystalline structure for mouse sCEACAM1a. The LTR insertion is widely distributed among inbred mouse strains but is not found in 129/sv, CBA/2, or in wild mice. Cloning of the genomic region downstream of the LTR insertion site from the C57Bl/6J strain indicates that the insertion consists of a solo LTR without additional IAP sequence, and identified the original Psg23 polyadenylation signal sequence downstream of the insertion site. Psg23(LTR) was mapped to proximal chromosome 7 using the European collaborative interspecific mouse backcross (EUCIB) panel, and to yeast artificial chromosome (YAC) E072, which contains other members of the Psg gene family, by polymerase chain reaction (PCR). Northern blot analysis of RNA from adult and fetal mouse tissues and in situ hybridization to mid-gestation mouse embryos indicated that Psg23(LTR) is expressed predominantly in placental spongiotrophoblast. We detected a small, but statistically non-significant, bias in favour of transmission of Psg23(LTR) to the offspring of heterozygous parents. However, a larger study would be required to determine whether this allele is selectively advantageous to the developing embryo.

Alleles↗
PubMed1992

Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help.

In lymphoid follicles, CD4+ T lymphocytes provide contact-dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed Th function. The CD4+ T cell-restricted surface activation protein, 5c8 Ag (T-BAM), has recently been shown to be a component of the contact-dependent helper signal to B cells. To further dissect this process, we utilized a Jurkat T cell lymphoma clone, termed D1.1, that constitutively expresses T-BAM and activates peripheral B cells to express surface CD23 in a contact-dependent mechanism that is inhibited by mAb anti-T-BAM (5c8). Similar to its effect on peripheral B cells, Jurkat D1.1 activates B cells from lymphoid organs, as well as a B cell lymphoma clone, RAMOS 266,4CN 3F10 (RAMOS 266), to up-regulate surface CD23. Interestingly, mAb to the B cell surface molecule, CD40 (mAb G28-5 and B-B20), inhibit D1.1 induced activation of RAMOS 266 and peripheral and lymphoid B cells. In contrast, mAb to CR2 or the adhesion molecules, LFA1, LFA3, or ICAM-1, have little effect. The inhibitory effect of anti-CD40 mAb on B cell activation induced by D1.1 is specific because anti-CD40 potentiates, rather than inhibits, the up-regulation of CD23 on B cells induced by rIL-4. Moreover, cross-linking CD40 molecules by anti-CD40 mAb bound to Fc gamma RII+ (CD32) L cells induces B cell CD23 expression. In vivo, T-BAM-expressing cells are CD4+ T cells that are restricted to lymphoid organs and are localized in the mantle and centrocytic zones of lymphoid follicles and the spleen periarteriolar lymphoid sheath in association with CD40+ B cells. Taken together, these data demonstrate that T-BAM on T cells and CD40 on B cells are involved in contact-dependent T-B help interactions that occur in lymphoid follicles.

Antigens, CD↗
PubMed2005

Challenges and opportunities for medications development in alcoholism: an international perspective on collaborations between academia and industry.

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on September 30, 2004. The organizers and cochairs were Bankole A. Johnson, DSc, MD, PhD, and Karl Mann, MD. The presentations included the following: (1) A Perspective from Academia, by Bankole A. Johnson, DSc, MD, PhD; (2) A Perspective from NIAAA, by Mark L. Willenbring, MD; (3) A Perspective from US Clinical Practice, by Robert M. Swift, MD, PhD; (4) A European Perspective on Medications Development, by Otto M. Lesch, MD, PhD, and (5) A Scandinavian Perspective on Evidence-Based Addiction Treatment, by Mats Berglund, MD.

Academies and Institutes↗
PubMed2001

Smoking in Maywood: the unhealthy southern migrant hypothesis among African Americans.

OBJECTIVES: This paper examines the "unhealthy Southern migrant" hypothesis with regard to cigarette smoking among African Americans. METHODS: Using data collected in 1992 from a sample of 1,518 African Americans in Maywood, Illinois, as part of the International Collaborative Study of Hypertension in Blacks, logistic regression analysis was conducted to examine and compare smoking behavior and sociodemographic characteristics of Southern and Midwestern-born respondents. RESULTS: African Americans born in the South were less likely (OR = .69, CI = 95%, 0.53, 0.90) to be smokers than those born in the Midwest, after controlling for other sociodemographic variables, prior smoking status, and age of arrival to Maywood. CONCLUSIONS: The results do not support the "unhealthy Southern migrant" hypothesis, with regard to cigarette smoking, and indicate the need to identify factors that protect Southern-born African-American migrants from smoking.

Adult↗
PubMed2001

The lateralized linguistic cerebellum: a review and a new hypothesis.

During the past 2 decades the collaboration across disciplines and the methodologic and conceptual advances of contemporary neuroscience have brought about a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Growing insights in the neuroanatomy of the cerebellum and its interconnections, evidence from functional neuroimaging and neurophysiological research, and advancements in clinical and experimental neuropsychology have established the view that the cerebellum participates in a much wider range of functions than conventionally accepted. This increase of insight has brought to the fore that the cerebellum modulates cognitive functioning of at least those parts of the brain to which it is reciprocally connected. This article reviews the recently acknowledged role of the cerebellum in cognition and addresses in more detail experimental and clinical data disclosing the modulatory role of the cerebellum in various non-motor language processes such as lexical retrieval, syntax, and language dynamics. In agreement with the findings indicating a topographical organization of the cerebellar structures involved in language pathology we advance the concept of a "lateralized linguistic cerebellum." In our view crossed cerebral diaschisis processes, reflecting a functional depression of supratentorial language areas due to reduced input via cerebellocortical pathways, might represent the relevant pathomechanism for linguistic deficits associated with cerebellar pathology.

Aphasia↗
PubMed1994

Outcome of schizophrenia: some transcultural observations with particular reference to developing countries.

The present paper provides a description of data based and methodologically sound studies of outcome of schizophrenia from developing and non-Western countries and compares the results. Major studies reviewed include the 2- and 5-year follow-up of the cohort of the International Pilot Study of Schizophrenia, the patients of the World Health Organization Collaborative Study on the Determinants of Outcome of Severe Mental Disorders, a few Indian studies including the study sponsored by the Indian Council of Medical Research and some studies from Colombia and South-East Asia. The studies are compared in terms of the quality of methodology and the rate of attrition. Although the outcome criteria of these studies are not similar, it is obvious that the outcome of schizophrenia in developing countries is generally more favourable. The reasons for this are far from clear. Research concerning the issues pertaining to better outcome of schizophrenia in developing countries in the context of socio-cultural differences in woefully lacking. This is an area that deserves research attention.

Cross-Cultural Comparison↗
PubMed1996

The European Consultation-Liaison Workgroup (ECLW) Collaborative Study. I. General outline.

Previous C-L psychiatric service research is seriously limited by its parochial nature; very few results can be generalized outside of the hospital in which the original study was performed because of differences in the nature of the hospital and the type of C-L service. This article presents the general outline and methodology of a European multicentered C-L service delivery study effected by the European Consultation-Liaison Workgroup for General Hospital Psychiatry and Psychosomatics (ECLW). The study is unique in its kind as it allows the comparison of very different C-L services; for example, some services are run by C-L psychiatrists, others are run by C-L psychosomaticists and the study encompasses a large variety of different settings. As a result, both common factors in C-L service delivery and specific local patterns can be explored. The overall hypothesis tested in this study was that the most developed services would see (as well as more patients) a wider variety of clinical problems than small services. The implication is that the absence of well-developed C-L services in a general hospital may mean that there are patients with unmet mental health needs. In separate articles the training and reliability testing of the new Patient Registration Form (PRF) and the Institutional and Provider characteristics will be described. The former includes the use of ICD-10 in the general hospital setting. This study is a collaborative effort made by 226 consultants from 56 psychiatric C-L services in 11 countries. Each consultant recorded details of 1 year's caseload leading to a thorough description of 14,717 patients collected between 1991 and 1993. The advanced methodology included a multicentered international approach, rigid training for all participating consultants, and the development and testing of new instruments. This will allow us to assess the impact of important structural and process variables on the outcome of C-L service delivery in several European countries. These results will be reported in papers both in the international and national literature of the participating countries.

Adolescent↗
PubMed1997

Murine albino-deletion complex: high-resolution microsatellite map and genetically anchored YAC framework map.

The murine albino-deletion complex developed as part of the Oak Ridge specific-locus test covers 6-11 cM of chromosome 7. This complex has proven to be a valuable resource for localizing traits to a small target region for positional cloning. In this study, we mapped the endpoints of deletions in this complex using all of the available Mit simple-sequence length polymorphism (SSLP) markers. Concurrently, this mapping has determined the map order of nearly all of the SSLP markers, most of which were previously unresolved. The SSLP-based deletion map was confirmed and genetic distances were determined using the European Collaborative Interspecific Backcross panel of nearly a thousand mice. The average SSLP marker resolution is 0.3-0.4 cM, comparable to the cloning capacity of yeast artificial chromosomes (YACs). The SSLP markers were then used to construct a genetically anchored YAC framework map that further confirms the deletion map. We find that the largest deleted region distal to Tyr is about two to three times larger than the largest proximal deletion region, and the original C3H/101 regions flanking the deletions (moved to an St2A cch/cch background) are smaller than anticipated, which we suggest may result from increased recombination rates immediately flanking the deleted regions.

Animals↗
PubMed1995

Effect of non-tuberculous Mycobacteria infection on tuberculin results among primary school children in Kenya.

Few tuberculosis studies carried out in Kenya since 1948 have reported on the variations of the occurrence and geographical distributions of non-tuberculous Mycobacteria infection. They have however not been able to clearly relate infection outcome to the use of tuberculin tests as epidemiologic and clinical tool. The present survey, conducted by Kenya Medical Research Institute in collaboration with the International Union Against Tuberculosis and Lung Diseases between 1986 and 1990 among school children aged 6-13 years in 18 randomly selected districts, investigated the following: the prevalence of sensitivity to tuberculin PPD RT 23 and PPD scrofulaceum RS 95 sensitin; geographic distribution of the reactions from the tests and; the influence of non-tuberculous Mycobacteria on the tuberculin results. The WHO cluster sampling procedures were used to select 30 schools in each of the 18 districts. Each child was tested with an intradermal dose of 2 TU of PPD RT 23 with Tween 80 (PPD RT 23) on the right hand and 2 TU of PPD Scrofulaceum RS 95 sensitin with tween 80 (PPD RS 95) on the left hand. The results were read after 72 hours of testing. A total of 1015 BCG scar negative children was included in the survey. Of these, 981 were tested and read. Over 47% of the children did not react to both antigens while 6.1% and 22.7% reacted to human type tuberculin and environmental sensitin respectively. There was cross reaction between the two tests in 23.8% of the children from low altitude area who had more and larger reaction to the tests than the middle and higher altitude regions of the country.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1998

The evaluation of the health care needs of women with disabilities.

There are 27 million disabled women in the United States. These women face many unique challenges in accessing medical care and frequently report an insensitivity to their specific health care needs. Disabled women also have a wide array of health-related issues, including multiple concurrent medical disorders, psychosocial issues, and socioeconomic concerns. Their overall experience is that of a fragmented health care delivery system that often is inadequate in many important areas such as reproductive health, post-reproductive health, sexuality, etc.In order to address these issues, the departments of neurology and gyn/ob formed a multidisciplinary Women's Health Collaborative Research Group (WHCRG). Its mission is to develop a wellness model of comprehensive women-centered care that meets the special health care requirements of women with chronic disabling conditions. The Women's Health Issues Survey is a 72-item self-report needs assessment that was administered to over 300 women with multiple sclerosis, stroke, and other neurologic disorders. The results of the survey were critical to the planning and implementation of a center for women with disability.Approximately 50% of the women (median age 45 years) were moderately to severely disabled, as measured by the Kurtzke Expanded Disability Status Scale. Over 20% of those surveyed reported a history of uterine fibroids, endometriosis or ovarian cysts, irregular menstrual periods, and deterioration of their neurologic condition (eg, multiple sclerosis) during menstruation. Forty percent were sexually inactive. Seventy percent of the postmenopausal cohort were not taking hormone replacement therapy.The ability to identify and survey a representative sample of disabled women and develop a database linking demographic, physical disability, economic, and health care access information is a key step in implementing a cross-functional approach toward improving the level and scope of health care for disabled women.

Journal Article↗
PubMed2005

Prevention of work related eye injuries: long term assessment of the effectiveness of a multicomponent intervention among metal workers.

BACKGROUND: Systematic assessments of the effectiveness of interventions to prevent work related eye injuries are needed. AIM: To investigate the long term effectiveness of a multicomponent prevention campaign. METHODS: The campaign (conducted in collaboration with the local Employers' Association and Trade Unions) targeted all 237 metal-ware factories in the district of Imola, Italy. Based on preliminary inspections, the main intervention included distribution to all factories of specific educational brochures and broadcasting/publication of television/radio programmes and local newspaper articles containing expert advice on the subject. This was followed by a four year "post-intervention reinforcement" period of unannounced official inspections. Main outcome measures analysed were eye injury rates (versus non-eye injury rates) among metal workers during "pre-intervention" (1988-90), "peri-intervention" (1991-92), "post-intervention reinforcement" (1993-96), "late post-intervention" (1997-2000), and "very late post-intervention" (2001-03) periods with respect to two comparison sectors (construction and wood/ceramics). RESULTS: A Poisson regression in which the eye injury rates were modelled for each sector, period, and interaction, adjusting for non-eye injury rates, was chosen. The periods did not by themselves determine an overall reduction in eye injuries. The period/sector interaction terms were related to significant reductions for the metal sector when crossed with the "post-intervention reinforcement" (IRR = 0.77, 95% CI 0.61 to 0.97; % decline = 23.4), the "late post-intervention" (IRR = 0.63, 95% CI 0.50 to 0.79; % decline = 37.4), and the "very late post-intervention" (IRR = 0.58, 95% CI 0.43 to 0.77; % decline = 42.4) periods, suggesting a sustained reduction in eye injury risk following the main intervention. CONCLUSION: Results suggest that a carefully coordinated, extensive, multicomponent intervention can lead to lasting reductions in the burden of eye injuries.

Accidents, Occupational↗
PubMed1991

Manganese superoxide dismutase from Thermus thermophilus. A structural model refined at 1.8 A resolution.

The structure of Mn(III) superoxide dismutase (Mn(III)SOD) from Thermus thermophilus, a tetramer of chains 203 residues in length, has been refined by restrained least-squares methods. The R-factor [formula: see text] for the 54,056 unique reflections measured between 10.0 and 1.8 A (96% of all possible reflections) is 0.176 for a model comprising the protein dimer and 180 bound solvents, the asymmetric unit of the P4(1)2(1)2 cell. The monomer chain forms two domains as determined by distance plots: the N-terminal domain is dominated by two long antiparallel helices (residues 21 to 45 and 69 to 89) and the C-terminal domain (residues 100 to 203) is an alpha + beta structure including a three-stranded sheet. Features that may be important for the folding and function of this MnSOD include: (1) a cis-proline in a turn preceding the first long helix; (2) a residue inserted at position 30 that distorts the helix near the first Mn ligand; and (3) the locations of glycine and proline residues in the domain connector (residues 92 to 99) and in the vicinity of the short cross connection (residues 150 to 159) that links two strands of the beta-sheet. Domain-domain contacts include salt bridges between arginine residues and acidic side chains, an extensive hydrophobic interface, and at least ten hydrogen-bonded interactions. The tetramer possesses 222 symmetry but is held together by only two types of interfaces. The dimer interface at the non-crystallographic dyad is extensive (1000 A2 buried surface/monomer) and incorporates 17 trapped or structural solvents. The dimer interface at the crystallographic dyad buries fewer residues (750 A2/monomer) and resembles a snap fastener in which a type I turn thrusts into a hydrophobic basket formed by a ring of helices in the opposing chain. Each of the metal sites is fully occupied, with the Mn(III) five-co-ordinate in trigonal bipyramidal geometry. One of the axial ligands is solvent; the four protein ligands are His28, His83, Asp166 and His170. Surrounding the metal-ligand cluster is a shell of predominantly hydrophobic residues from both chains of the asymmetric unit (Phe86A, Trp87A, Trp132A, Trp168A, Tyr183A, Tyr172B, Tyr173B), and both chains collaborate in the formation of a solvent-lined channel that terminates at Tyr36 and His32 near the metal ion and is presumed to be the path by which substrate or other inner-sphere ligands reach the metal.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed2006

In-medium effects on phase space distributions of antikaons measured in proton-nucleus collisions.

Differential production cross sections of K+/- mesons have been measured in p + C and p + Au collisions at 1.6, 2.5, and 3.5 GeV proton beam energy. At beam energies close to the production threshold, the K- multiplicity is strongly enhanced with respect to proton-proton collisions. According to microscopic transport calculations, this enhancement is caused by two effects: the strangeness exchange reaction NY --> K- NN and an attractive in-medium K- N potential at saturation density.

Journal Article↗
PubMed2000

A cultural change in cancer education and training.

Collaborative education and training is the only way forward for the cancer care work force. The Calman-Hine report has become the benchmark on which to build practice since its launch in 1995. A forward looking group--the Cancer Care Alliance of Teesside, South Durham and North Yorkshire Education Group and the University of Teesside--adopted its principles from the Calman-Hine Report and developed some strategic projects to address and achieve them. A needs assessment of cancer education influenced the agenda within the Cancer Care Alliance. The education portfolio that was developed had a multiprofessional focus, incorporating both academic and non-academic study.

Attitude of Health Personnel↗