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Biomedical subjects

C Reynolds

Publications and source records attributed to C Reynolds.

At least 91 records · Page 5Linked to original sources

Smoking in child family day care homes: policies and practice in New South Wales.

OBJECTIVES: To provide estimates of the numbers of New South Wales children in Family Day Care who may be exposed to environmental tobacco smoke while attending day care; to describe existing smoking policies; and to analyse these policies with the aim of providing guidelines for smoking policy in Family Day Care. SETTING: All 109 Family Day Care schemes in NSW. METHOD: Scheme coordinators were sent a questionnaire regarding the proportion of carers who smoked while caring for children; the nature, enforcement and experience of smoking policies; and barriers to implementation of a no-smoking policy. RESULTS: A mean of 10% of Family Day Care caregivers were reported to smoke while caring for children (range, 0-60%). An estimated 2045 children were potentially exposed to environmental tobacco smoke in the 86 schemes which provided this information. Thirty-five per cent of schemes had formal no-smoking policies. A range of advantages, disadvantages and perceived practical and legal barriers to implementation of a no-smoking policy in Family Day Care were described. Forty-four per cent of schemes with no-smoking policies reported no implementation problems. CONCLUSIONS: There is considerable potential for exposure of children to environmental tobacco smoke in Family Day Care homes. There is legal support for Family Day Care caregivers not to expose children under their care to environmental tobacco smoke. A formal (and enforced) no-smoking policy should exist in every Family Day Care scheme, and a "top-down" directive is most likely to be successful. The issue of other smokers in the caregiver's household needs to be specifically addressed in any such directive.

Child↗

An evaluation of mechanisms by which tolerance to organ-specific antigens is lost using a transgenic mouse model.

Patients with type I diabetes lose immunologic tolerance to beta cell Ag and produce anti-self (beta cell) antibodies. We have examined mechanisms by which this self tolerance is lost using transgenic mice in which islet cells express human CD4. These mice are immunologically tolerant to this human protein; the tolerance appears to be characterized by the presence of self reactive B cells and nonresponsive T cells. Autoantibodies can be induced by immunization with CD4 in CFA; this autoantibody response is accompanied by minor peri-islet inflammation but diabetes is not induced. Tolerance can also be broken by provision of an independent covalently linked T cell epitope. Although this mimic can lead to the appearance of an autoantibody response, the autoimmune response can not be maintained by the endogenous Ag. We have also demonstrated that an inflammatory lesion leading to death of the CD4-containing beta cells may not be sufficient to break tolerance. These results have implications for potential mechanisms relating to the appearance of autoantibodies in patients with type I diabetes.

Animals↗

Importance of genetic effects for monoamine oxidase activity in thrombocytes in twins reared apart and twins reared together.

The relative importance of shared genes, shared environments, and individual specific environmental effects for monoamine oxidase (MAO) activity in thrombocytes was assessed in the Swedish Adoption/Twin Study of Aging. The sample consists of identical twins separated at an early age and reared apart (30 pairs), identical twins reared together (60 pairs), fraternal twins reared apart (66 pairs), and fraternal twins reared together (68 pairs), whose average age was 63.5 years; 49% were female. Consistent with the literature, the heritability of MAO activity was 0.77 and did not differ across cohort (under or over 63 years of age) or gender. Sharing rearing environments or similar experiences later in life does not result in familial similarity for MAO activity.

Adoption↗

A cross-national self-report measure of depressive symptomatology.

The Center for Epidemiological Studies Depression scale (CES-D) was administered in Swedish to two representative samples, one aged 84 to 90 (mean = 87), the second aged 29 to 95 (mean = 61). There were both linear and quadratic differences with age: the oldest individuals were highest on depressive symptoms, but younger adults were higher than middle-aged. Dimensions or subscales identified by previous studies were generally replicated, including a sadness and depressed mood factor, a psychomotor retardation and loss of energy factor, and a well-being factor (on which items are reverse-scored to indicate depression). The findings support cross-national use of the CES-D to assess self-reported symptoms of depression in adults and older adults.

Adult↗

Efficient analysis of nonviable poliovirus capsid mutants.

Nonviable poliovirus capsid mutants were studied by an efficient infection-transfection system. Phenotypically, nonviable poliovirus capsid mutants appear to segregate into three classes: those that form only protomers, those that can form pentamers, and one that can form completed virions.

Capsid↗

Two crystal forms of the lentil lectin diffract to high resolution.

The legume lectins are an important class of polysaccharide-binding proteins with a wide range of biochemical and immunological applications. Two high-resolution crystal forms are obtained for the lentil (Lens culinaris) lectin: a monoclinic P21 and an orthorhombic P212121. The unit cell dimensions for the monoclinic form are a = 58.0 A, b = 56.0 A, c = 82.1 A, beta = 104.4 degrees, while for the orthorhombic form a = 56.4 A, b = 74.6 A, c = 124.9 A. The asymmetric unit contains one dimer in both cases. The crystals diffract to 1.7 A resolution using synchrotron radiation. Preliminary data have been collected to 2.3 A on both crystal forms using a conventional X-ray source.

Crystallography↗

Biometrical analysis of individual growth curves.

Longitudinal data for height (length) between birth and 2 years of age were examined for 690 Dutch Registry twin pairs. A two-stage analysis was performed, where individual growth curves were first fit to available data for each subject using a linear multiple regression procedure and estimated individual growth curve parameters were then subjected to multivariate biometrical analysis. Quadratic polynomial curves were found to adequately represent observed growth patterns for the majority of cases (median R2 = .98). A specific scalar model of sex limitation best characterized individual variation in growth curve parameters. That is, there was significantly greater genetic variation for boys than for girls in both the predicted length and rate of growth at 1 year of age and the amount of deceleration in individual growth curves across age.

Anthropometry↗

Multi-state investigation of the actual disinfection/sterilization of endoscopes in health care facilities.

PURPOSE: The purpose of this investigation was to observe and assess the actual disinfection or sterilization of endoscopes in health care facilities. MATERIALS AND METHODS: A total of 22 hospitals and four ambulatory care centers in three states were studied. Facility protocols were reviewed, interviews conducted with relevant personnel, actual disinfection or sterilization procedures observed, and biologic tests performed to determine and assess disinfection/sterilization procedures. RESULTS: Fundamental errors observed during the course of the investigation included respective failures to time the period of disinfection, to clean all channels, to flush all channels with disinfectant, to fully immerse the endoscope in the disinfectant solution, and to use a disinfectant. At 78% of the facilities, failure to sterilize all biopsy forceps was observed. A total of 23.9% of the bacterial cultures from the internal channels of 71 gastrointestinal endoscopes grew 100,000 colonies or more of bacteria. These cultures were obtained after the completion of all disinfection/sterilization procedures and the device was deemed ready for use in the next patient. CONCLUSIONS: These data indicate that actual disinfection/sterilization procedures for endoscopes are not always optimal, and high-level disinfection of gastrointestinal endoscopes is not always achieved.

Acquired Immunodeficiency Syndrome↗

Folding and processing of the capsid protein precursor P1 is kinetically retarded in neutralization site 3B mutants of poliovirus.

Poliovirus mutants in neutralizing antigenic site 3B were constructed by replacing the glutamic acid residue at amino acid 74 of capsid protein VP2 (VP2074E), using site-specific mutagenesis methods. All viable mutants display small-plaque phenotypes. Characterization of these mutants indicates that capsid assembly is perturbed. Although the defect in capsid assembly reduces the yield of mutant virus particles per cell, the resultant assembled particle is wild-type-like in structure and infectivity. Analyses of capsid assembly intermediates show a transient accumulation of the unprocessed capsid protein precursor, P1, indicating that cleavage of the mutant P1 by the 3CD protease is retarded. The mutant VP0-VP3-VP1 complex generated upon P1 cleavage appears assembly competent, forming pentamer and empty capsid assembly intermediates and infectious virion particles. Although the structure of the infectious mutant virus is virtually identical with that of the wild-type virus, the thermal stability of the mutant virus is dramatically increased over that of the wild-type virus. Thus, mutations at this residue are pleiotropic, altering the kinetics of capsid assembly and generating a virus that is more thermostable and more resistant to neutralization by the site 3B monoclonal antibodies.

Amino Acid Sequence↗

Effects of clozapine and thiothixene on glucose metabolic rate in schizophrenia.

Twelve patients with schizophrenia received positron emission tomography scans with 18F-deoxyglucose before and after 4 to 6 weeks of treatment with clozapine or thiothixene. Both stereotaxic and magnetic resonance image template methods were used to position regions of interest for metabolic rate analysis. Clozapine increased and thiothixene decreased metabolic rates in the basal ganglia; these effects were most marked on the right side. Within the basal ganglia, a superior to inferior gradient in drug effect was found for thiothixene but not clozapine. This gradient resembled in some respects observations on regional differences in D2 receptors in human autoradiography. Baseline metabolic rates also predicted clinical medication response, with right inferior caudate metabolic rates differentiating clozapine and thiothixene responders. Larger sample studies are needed to replicate and extend these initial findings.

Adult↗

The two different receptors for tumor necrosis factor mediate distinct cellular responses.

The individual roles of the murine type 1 and type 2 tumor necrosis factor (TNF) receptors (TNF-R1 and TNF-R2) were investigated utilizing (i) the strong species specificity of TNF-R2 for murine TNF compared to human TNF and (ii) agonistic rabbit polyclonal antibodies directed against the individual TNF receptors. Proliferation of mouse thymocytes and the murine cytotoxic T-cell line CT-6 is stimulated by murine TNF but not by human TNF. Consistent with this observation, polyclonal antibodies directed against TNF-R2 induced proliferation in both of these cell types, whereas polyclonal antibodies directed against TNF-R1 had no effect. In contrast, cytotoxicity in murine LM cells (which are sensitive to murine and human TNF) was induced by antibodies against TNF-R1 but not by antibodies against TNF-R2. Also, the steady-state level of manganous superoxide dismutase mRNA in the murine NIH 3T3 cell line was induced by murine TNF, human TNF, and anti-TNF-R1 but not by anti-TNF-R2. These results suggest that TNF-R2 initiates signals for the proliferation of thymocytes and cytotoxic T cells, whereas TNF-R1 initiates signals for cytotoxicity and the induction of the protective activity, manganous superoxide dismutase. The nonredundant signaling observed for the two TNF receptors cannot be explained simply by the differential expression of the two TNF receptors in the various cell types, because LM cells express on their surface higher levels of TNF-R2 than TNF-R1, and LM cells, NIH 3T3 cells, and thymus cells all express mRNA corresponding to both receptor types. It is therefore likely that the two receptors initiate distinct signaling pathways that result in the induction of different cellular responses.

3T3 Cells↗

Identification of residues in VP2 that contribute to poliovirus neutralization antigenic site 3B.

Amino acid substitutions were placed at residues 74, 243, and 246 in capsid protein VP2 of poliovirus serotype 1, using site-specific mutagenesis methods. The proximity of these residues to those previously identified in neutralization site 3B suggests that these residues may also contribute to neutralization site 3B and potentially be under antibody selective pressure to mutate. However, sequence analyses of independent serotype 1 isolates indicate high sequence conservation at these residues, suggesting selective pressures are present within the virus to maintain sequences within these loop regions. All viable mutants display partial or complete resistance to neutralization by the site 3B neutralizing monoclonal antibodies. Cross-neutralization data with the site-specifically generated viral mutants confirm that these residues do indeed contribute to forming neutralization site 3B and also identify the participation of a new loop region within site 3B. However, many amino acid substitutions generate nonviable virus mutants and even conservative amino acid substitutions produce growth-compromised virus mutants. These data suggest that previous definition of neutralization antigenic sites by isolation of neutralization resistant mutants favors detection of viable mutant viruses with more normal growth characteristics and is inherently biased against detection of neutralization antigenic sites formed by residues critical for other stages of virus replication.

Amino Acid Sequence↗

Glove use by health care workers: results of a tristate investigation.

The Center for Devices and Radiological Health, in collaboration with the state health departments of Iowa, Maryland, and Massachusetts, conducted a multi-state, multi-institutional investigation of glove use by health care workers (HCWs). Twenty-two hospitals and four ambulatory care centers were included in the investigation. All 26 health care facilities were found to have adopted universal precautions policies for glove use by HCWs, per Centers for Disease Control guidelines. Four hundred five observations were made of HCWs performing procedures that may involve contact with patient body fluids, particularly blood. The prevalence of glove use during selected procedures was as follows: arterial blood gas procedures, 92.3%; intravenous line initiation/maintenance, 77.6%; and phlebotomy, 70.6%. Glove use during phlebotomy (p less than 0.001) and intravenous line procedures (p less than 0.05) was significantly lower in the state with a prevalence of the acquired immunodeficiency syndrome (AIDS) below the national average than in the states with a higher AIDS prevalence. The investigation suggests that health care facilities have responded to the Centers for Disease Control and Occupational Safety and Health Administration campaign to adopt universal precaution policies for glove use by HCWs. Actual glove use by HCWs appears to be substantial but not universal. Glove use by HCWs is significantly related to statewide AIDS prevalence.

Acquired Immunodeficiency Syndrome↗

T-lymphocyte requirement for diabetes in RT6-depleted diabetes-resistant BB rats.

Diabetes-prone (DP) BB rats develop spontaneous autoimmune insulin-dependent diabetes mellitus (IDDM). The cell populations involved in the expression of diabetes are not precisely known but probably include natural killer (NK) cells, macrophages, and T lymphocytes. Because the DP rat has few lymphocytes of the CD5+/CD+ phenotype, cytotoxic T lymphocytes (Tc) are not believed to be important in the process. Diabetes-resistant (DR) BB rats that are depleted of RT6+ T lymphocytes also become diabetic and provide an additional model of IDDM. We report that diabetes in DR rats depleted of RT6+ T lymphocytes is prevented by the concomitant depletion of either the CD5+ or the CD8+ population. In contrast, coadministration of anti-asialogangliosideM1 (alpha-ASGM1), an antiserum that principally recognizes NK cells, failed to prevent hyperglycemia in RT6-depleted rats. We propose that the initiation of diabetes in both DP and RT6-depleted DR rats is T-lymphocyte dependent. However, the final common pathway leading to autoimmune beta-cell destruction in IDDM may be different in these models. The RT6-depleted DR rat requires a cell that is sensitive to anti-CD8 (possibly a Tc), whereas the DP rat requires an anti-ASGM1-sensitive cell.

ADP Ribose Transferases↗