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Biomedical subjects

S Moss

Publications and source records attributed to S Moss.

At least 19 recordsLinked to original sources
PubMed1999

Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells.

The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B protein kinase and triggers mitosis. Although the active p34-cyclin B protein kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated the possibility that other kinases may initially trigger the phosphorylation and activation of p54(cdc25-c). We have examined the effects of the calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II) or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II) results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25-c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is no increase in histone H1 kinase activity. Our data suggest that a calcium-calmodulin-dependent step may be involved in the initial activation of p54(cdc25-c).

Benzylamines↗
PubMed1999

Oxidized LDL can induce macrophage survival, DNA synthesis, and enhanced proliferative response to CSF-1 and GM-CSF.

Modification of low density lipoprotein (LDL), eg, by oxidation, has been proposed as being important for the formation of foam cells and therefore for the development of atherosclerotic plaques. There are a number of reports showing that macrophage-derived foam cells can proliferate in both human and animal lesions, particularly in the early phase of the disease and possibly involving macrophage-colony stimulating factor (M-CSF, or CSF-1). We studied the in vitro effects of oxidized LDL (ox-LDL) on murine bone marrow-derived macrophages (BMMs), a cell population with a high proliferative capacity in vitro in response to CSF-1 and a dependence for survival on the presence of this growth factor. We report here that treatment of BMMs with low doses of ox-LDL, but not with native LDL, led to cell survival, DNA synthesis, and an enhanced response to the proliferative actions of CSF-1 and granulocyte macrophage-CSF (GM-CSF); the effects were dependent on the degree of LDL oxidation. For CSF-1, a synergistic effect was noticeable at suboptimal doses. The effect of ox-LDL occurred even in the absence of endogenous CSF-1 or GM-CSF. Our findings suggest that ox-LDL, and possibly other modified forms of LDL, could maintain macrophage (and foam cell) survival and therefore lengthen their tenure in a plaque; the modified LDL could also cause local macrophage proliferation or "prime" them so that they could proliferate better in response to CSF-1 (and GM-CSF) concentrations that may be present in the atheroma.

Animals↗
PubMed1998

Human monoclonal antibodies specific to hepatitis B virus generated in a human/mouse radiation chimera: the Trimera system.

An approach to develop fully human monoclonal antibodies in a human/mouse radiation chimera, the Trimera system, is described. In this system, functional human lymphocytes are engrafted in normal strains of mice which are rendered immuno-incompetent by lethal total body irradiation followed by radioprotection with severe combined immunodeficient (SCID) mouse bone marrow. Following transplantation, human lymphocytes colonize murine lymphatic organs and secrete human immunoglobulins. We have established this system as a tool to develop fully human monoclonal antibodies, and applied it for the generation of monoclonal antibodies specific for hepatitis B virus surface antigen. A strong memory response to hepatitis B surface antigen was elicited in Trimera engrafted with lymphocytes from human donors positive for antibodies to hepatitis B surface antigen. The human specific antibody fraction in the Trimera was 10(2)-10(3)-fold higher as compared with that found in the donors. Spleens were harvested from Trimera mice showing high specific-antibody titres and cells were fused to a human-mouse heteromyeloma fusion partner. Several stable hybridoma clones were isolated and characterized. These hybridomas produce high-affinity, IgG, anti-hepatitis B surface antigen antibodies demonstrating the potential of the Trimera system for generating fully human monoclonal antibodies. The biological function and the neutralizing activity of these antibodies are currently being tested.

Amino Acid Sequence↗
PubMed1998

Reliability and validity of the PAS-ADD Checklist for detecting psychiatric disorders in adults with intellectual disability.

The PAS-ADD Checklist is a screening instrument specifically designed to help staff recognize mental health problems in the people with intellectual disability for whom they care, and to make informed referral decisions. The instrument consists of a life-events checklist and 29 symptom items scored on a four-point scale. Scores are combined to provide three threshold scores. The crossing of any of these thresholds indicates the need for a fuller assessment. The items are worded in everyday language, making the Checklist suitable for use by individuals who do not have a background in psychopathology. The present paper presents the results of a number of studies evaluating the reliability and validity of the Checklist. Factor analysis of Checklists completed on a community sample of 201 individuals yielded eight factors, of which seven were readily interpretable in diagnostic terms. Internal consistency of the scales was generally acceptable. Inter-rater reliability in respect to individual items gave a fairly low average Kappa of 0.42. However, agreement on case identification, the main purpose of the Checklist, was quite good, with 83% of the decision being in agreement. Validity in relation to clinical opinion was also satisfactory, case detection rising appropriately with the clinically judged severity of disorder. The PAS-ADD Checklist is published and distributed by the Hester Adrian Research Centre, Manchester, England, from where further information and order forms are available on request.

Adolescent↗
PubMed1998

Reliability and validity of the Mini PAS-ADD for assessing psychiatric disorders in adults with intellectual disability.

The Mini PAS-ADD is an assessment schedule for psychiatric disorders in people with an intellectual disability. It is designed to provide a link between the mental health expertise of psychiatrists and psychologists, and the detailed knowledge of individual service users possessed by support staff. In broad terms, the aim of the Mini PAS-ADD is to enable non-psychiatrists accurately to recognize clinically significant psychiatric disorders in the people who they care for, so that they can make informed referral decisions. The instrument comprises 86 psychiatric symptoms and generates a series of subscores on: depression, anxiety and phobias, mania, obsessive-compulsive disorder, psychosis, unspecified disorder (including dementia), and pervasive developmental disorder (autism). The present paper reports the results of a study investigating internal consistency, inter-rater agreement and validity in relation to clinical opinion, using a sample of 68 people with intellectual disability who were in contact with psychiatric services. In terms of the instrument fulfilling its main intended function, i.e. accurate case recognition, the crucial question was whether the support workers, with their lesser knowledge of psychopathology, were also able to correctly identify cases identified by expert clinicians. The validity results in this respect (81% agreement on case recognition) were sufficiently good that it is to be anticipated that the Mini PAS-ADD should have a significant impact on the identification of psychiatric disorders in the community of people with intellectual disability.

Adult↗
PubMed1998

Breast cancer screening programmes in 22 countries: current policies, administration and guidelines. International Breast Cancer Screening Network (IBSN) and the European Network of Pilot Projects for Breast Cancer Screening.

BACKGROUND: Currently there are at least 22 countries worldwide where national, regional or pilot population-based breast cancer screening programmes have been established. A collaborative effort has been undertaken by the International Breast Cancer Screening Network (IBSN), an international voluntary collaborative effort administered from the National Cancer Institute in the US for the purposes of producing international data on the policies, funding and administration, and results of population-based breast cancer screening. METHODS: Two surveys conducted by the IBSN in 1990 and 1995 describe the status of population-based breast cancer screening in countries which had or planned to establish breast cancer screening programmes in their countries. The 1990 survey was sent to ten countries in the IBSN and was completed by nine countries. The 1995 survey was sent to and completed by the 13 countries in the organization at that time and an additional nine countries in the European Network. RESULTS: The programmes vary in how they have been organized and have changed from 1990 to 1995. The most notable change is the increase in the number of countries that have established or plan to establish organized breast cancer screening programmes. A second major change is in guidelines for the lower age limit for mammography screening and the use of the clinical breast examination and breast self-examination as additional detection methods. CONCLUSION: As high quality population-based breast cancer screening programmes are implemented in more countries, they will offer an unprecedented opportunity to assess the level of coverage of the population for initial and repeat screening, evaluation of performance, and, in the longer term, outcome of screening in terms of reduction in the incidence of late-stage disease and in mortality.

Adult↗
PubMed1998

Calculating appropriate target cancer detection rates and expected interval cancer rates for the UK NHS Breast Screening Programme. Interval Cancer Working Group.

OBJECTIVES: To enable better monitoring of interim outcome measures in the NHS Breast Screening Programme by providing revised targets for cancer detection rates, and revised expected interval cancer rates. DESIGN AND SETTING: Expected detection rates of invasive cancers at prevalent screen are calculated, using estimates of the underlying England and Wales incidence rates and age specific prevalence incidence ratios from the Swedish Two County Study. Expected interval cancer rates are also derived from this study, and are used to calculate expected detection rates at rescreening. RESULTS: The expected invasive cancer detection rates at first screen for women aged 50-52 is 3.6 per 1000. The expected rate at rescreening for women aged 53-64 is 4.0 per 1000. Expected interval cancer rates for women screened from 1995/6 onwards are 0.45 per 1000, 0.65 per 1000, and 1.2-1.3 per 1000 for the periods within 0-<12, 12-<24, and 24-<36 months of screening. CONCLUSIONS: The target cancer detection rates and expected interval cancer rates for the NHS Breast Screening Programme have been revised in the light of more recent data. Monitoring of the extent to which the programme is meeting these revised targets will give a more accurate indication of the potential to meet the Health of the Nation target of a 25% reduction in breast cancer mortality by the year 2000.

Breast Neoplasms↗
PubMed1997

Bovine leukemia virus-gp51 antigen expression is associated with CD5 and IgM markers on infected lymphocytes.

Cows that develop a persistent lymphocytosis (PL) as a result of bovine leukemia virus (BLV) infection develop massive proliferation of B-lymphocytes expressing both IgM and CD5 markers. The association of these two markers on peripheral blood mononuclear cells (PBMC) derived from BLV-infected cows and also expressing BLV-gp51 antigen marker on these cells was determined by three-color cytometric analysis. After in vitro cultivation of PBMC in the presence of PHA for 24 h, the mean percentages of marker-reactive cells of five PL+ cows were as follows; 43% +/- 4.5 of the PBMC expressed BLV-gp51 antigen; 90% +/- 1.6 of these cells expressed both IgM and CD5 at the same time, whereas but 7.5% +/- 1.9 expressed only IgM and 2.9% +/- 0.4 expressed only CD5. The PBMC, IgM positive cells accounted for 77.8% +/- 6.8, while both CD5 and BLV-gp51 were detected simultaneously on 52.0% +/- 2.4 of the IgM+ cells, while the CD5 marker and BLV-gp51 antigen were detected independently on 35.0% +/- 1.9 and in 9.0% +/- 3.1, respectively of the IgM+ cells. Of the CD5+ cells (equivalent to 75.5% +/- 9.0 of the PBMC), 54.7% +/- 4.7 expressed simultaneously IgM and BLV-gp51, while BLV-gp51 and IgM were expressed separately by 3.0% +/- 0.5 and 37.8% +/- 3.3, respectively. An association between the B-cell phenotype and BLV tropism might exist. It is also possible that cells bearing both IgM and CD5 markers are the main target cells for BLV infection.

Animals↗
PubMed1997

A single serine residue confers tetrodotoxin insensitivity on the rat sensory-neuron-specific sodium channel SNS.

Sensory neurons express a sodium channel (SNS) that is highly resistant to block by tetrodotoxin (IC50 = 60 microM). SNS is 65% homologous to the cardiac sodium channel, in which a single hydrophilic residue in the SS2 segment is critical for tetrodotoxin resistance. By site-directed mutagenesis, we have substituted phenylalanine for serine at the equivalent position in SNS: this mutated (S356F) SNS channel is functionally similar to wild-type SNS when expressed in Xenopus oocytes, but is potently blocked by tetrodotoxin and saxitoxin with IC50s of 2.8 nM and 8.2 nM, respectively. These data provide clues to the rational design of selective blockers of SNS with potential as analgesic drugs.

Animals↗
PubMed1997

Reliability of the ICD 10 version of the Psychiatric Assessment Schedule for Adults with Developmental Disability (PAS-ADD).

The Psychiatric Assessment Schedule for Adults with Developmental Disability (PAS-ADD) is a semi-structured clinical interview designed for use with respondents who have learning disability. The first version was based on the Present State Examination. The revised version was derived from the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), and makes ICD 10 diagnoses using the SCAN diagnostic program. This current version has a 4-point scale of severity, compared with the 3-point scale of the first version. It also has a new module relating to psychotic disorders. The sample consisted of 40 individuals representing a spectrum of neurotic, depressive and psychotic disorders. Videotapes of 40 PAS-ADD interviews were re-rated by trained interviewers who had not been involved in the original study in which the videotapes were produced. The mean Kappa across all individual item codes was 0.65, ranging from 0.94 to 0.35. The mean Kappa agreement on item groups was 0.66. Correlation between total symptom scores was 0.74. Agreement on index of definition was Kappa 0.70. We concluded that, agreement was generally lower than for the ICD 9 version. This was probably due mainly to the increase in the severity categories from three to four. However, the new items (most of which related to psychosis) were of comparable reliability to other items.

Adult↗
PubMed1997

Validity of the PAS-ADD for detecting psychiatric symptoms in adults with learning disability (mental retardation).

The Psychiatric Assessment Schedule for Adults with Developmental Disability (PAS-ADD) is a semi-structured interview for use with respondents who have learning disability and for key informants. This report investigates the ability of the instrument to detect symptoms that had been found to exist during routine clinical assessment of the patients. Field trials involved 95 referred patients with learning disability and a key informant for each sample member. Clinical opinions of the referring psychiatrists were sought using a symptom checklist. Referrer checklist symptoms and PAS-ADD data were both factor analysed. Validity testing involved (a) computation of correlations between PAS-ADD factors and checklist data and (b) comparison of PAS-ADD and referrers' diagnoses. Results indicated good validity for the PAS-ADD in relation to psychotic symptoms and depressive symptoms. Anxiety symptom identification was not well validated, probably due to small numbers. Expansive mood identified by the referrers was not detected by the PAS-ADD because there is currently no corresponding section in the interview. Where the PAS-ADD produced a diagnosis (in 58 members of the sample), 44 were in agreement with the referrer. Probability of diagnosis by PAS-ADD increased with the number of relevant active symptoms identified by the referrer. The PAS-ADD has been shown in a previous report to have the sensitivity to detect mental disorders not known to psychiatric services. For psychotic and depressive conditions, our results showed that symptom detection was in good agreement with the information provided by the referring psychiatrists on their patients. The PAS-ADD needs a section on hypomania and further investigation of its detection of anxiety disorders.

Adolescent↗
PubMed1997

Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study.

Rapid tranquilization is a routinely practiced method of calming agitated psychotic patients by use of neuroleptics, benzodiazepines, or both in combination. Although several studies have examined the efficacy of the three approaches, none have compared these treatments in a prospective, randomized, double-blind, multicenter trial. Ninety-eight psychotic, agitated, and aggressive patients (73 men and 25 women) were prospectively enrolled during an 18-month period in emergency departments in five university or general hospitals. Patients were randomly assigned to receive intramuscular injections of lorazepam (2 mg), haloperidol (5 mg), or both in combination. Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours, based on clinical need. They were evaluated hourly after the first injection until at least 12 hours after the last. Efficacy was assessed on the Agitated Behavior Scale (ABS), a modified Brief Psychiatric Rating Scale (MBPRS), Clinical Global impressions (CGI) scale, and an Alertness Scale. Effective symptom reduction was achieved in each treatment group with significant (P < .01) mean decreases from baseline at every hourly ABS evaluation. Significant (P < .05) mean differences on the ABS (hour 1) and MBPRS (hours 2 and 3) suggest that tranquilization was most rapid in patients receiving the combination treatment. Study event incidence (side effects) did not differ significantly between treatment groups, although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms. The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation.

Adolescent↗
PubMed1997

Dementia in older people with intellectual disability: symptoms of physical and mental illness, and levels of adaptive behaviour.

Detailed data on health and functional ability of 101 people with intellectual disability over 50 years of age are presented. Using a combination of informant interviewing, observation and measurement of cognitive change over a 3-year period, 12 of these individuals were identified as suffering from dementia. Their data are compared to those of the non-dementia sufferers. The people suffering from dementia had a greater number of chronic physical health problems and chronic disability resulting from physical health problems. Their capacity for self-directed activity was lower. The subjects had a reduced capacity to enjoy things, and were more irritable and more prone to violence. However, the outlook is somewhat different from a strategic perspective. The population of people with intellectual disability shows considerable epidemiological changes across the lifespan because of the effects of differential survival. The interaction of these factors tends to mask the impact of dementia-related skill loss in this population.

Adaptation, Psychological↗
PubMed1997

Mental disorders and problematic behaviours in people with intellectual disability: future directions for research.

In recent years there has been a major growth of interest in the field of mental health and intellectual disability. This article outlines some of the issues that will be important to address in the coming years. The issues discussed include: the interaction of biological and environmental factors in the aetiology of behavioural and psychiatric disorders; diagnosis and classification; epidemiology; dementia; recognition of mental illness in the community; treatment; service provision; and training.

Conduct Disorder↗