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PubMed1975

Individual differences and setting as determinants of acute adverse reactions to psychoactive drugs.

The relationship between setting and individual differences in determining acute adverse reactions to psychoactive drugs was examined using retrospective data from 483 drug users. Five dimensions of setting were identified. Although there were some small setting main effects, these effects failed to reach significance when shared variance with individual difference variables was considered. For acute adverse reactions to LSD, however, there were seven independent interaction effects between setting and individual difference variables. There were two interaction effects of smaller magnitude related to acute adverse reactions to marijuana. The significance of these results for the current controversy over the relative importance of situational vs. personality determinants of behavior was discussed.

Adult↗

PubMed2003

A twin study of anxiety-related behaviours in pre-school children.

BACKGROUND: From middle childhood onwards, substantial evidence points to phenotypic differentiation between anxiety diagnostic categories such as generalised anxiety, separation anxiety, specific phobia, and obsessive-compulsive disorders. However, little is known about the genetics of these categories and especially about the phenotypic and genetic structure of related behaviours in pre-school children. METHODS: We examined the phenotypic differentiation and genetics of mother-reported anxiety-related behaviours in 4,564 four-year-old twin pairs, from a population-based sample. RESULTS: Confirmatory factor analyses provided support for five correlated factors: General Distress, Separation Anxiety, Fears, Obsessive-Compulsive Behaviours, and Shyness/Inhibition. Genetic influences were found on all five factors, but the pattern of influences differed considerably across them, with particularly high heritability estimates for Obsessive-Compulsive Behaviours and Shyness/Inhibition, and substantial shared environmental influence on Separation Anxiety. Multivariate genetic analyses revealed moderate genetic correlations between the five factors. Genetic overlap was particularly pronounced between General Distress and the other anxiety-related behaviours, accounting for about half of their covariance. Genetic variance on Obsessive-Compulsive Behaviours was the least correlated with the other scales. The shared environmental influences correlated highly across the factors, accounting for the greatest proportion of covariation between Separation Anxiety, Fears and Obsessive-Compulsive Behaviours. The non-shared environment influences were largely variable specific. CONCLUSIONS: These data provide evidence for phenotypic and genetic overlap as well as differentiation between aspects of anxiety-related behaviours in young children. We conclude that research with young children will benefit from more specific assessments of anxiety-related behaviours in addition to less differentiated assessments of 'internalising' symptoms.

Anxiety Disorders↗

PubMed1982

The interrelationships between acid phosphatase, aminopeptidase, diamine oxidase, citric acid, beta-glucuronidase, pH and zinc in human prostatic fluid.

Biochemical analysis of 328 human prostatic fluid samples were performed. The urea concentration of 69 samples was similar to that of serum and not indicative of significant contamination with urine. The pH of normal fluids was acidic (mean pH = 6.7). The interrelationships between zinc, citrate, acid phosphatase aminopeptidase, beta-glucuronidase, diamine oxidase and pH were investigated by factor analysis. Two significant factors were extracted, the first accounted for 89% of their common variance and the second for 11%. Zinc, citrate, acid phosphatase and aminopeptidase were positively and pH was negatively related to factor one. Beta-glucuronidase was positively related to factor two and diamine oxidase was largely independent of both factors. It was concluded that variables related to factor one share a common secretory control and mechanism, that some other mechanism operates in the case of beta-glucuronidase and that diamine oxidase may not be a true secretory product of the prostate.

Acid Phosphatase↗

PubMed2002

Visual perception of movement kinematics and the acquisition of "action prototypes".

Recognizing a class of movements as belonging to a "nominal" action category, such as walking, running, or throwing, is a fundamental human ability. Three experiments were undertaken to test the hypothesis that common ("prototypical") features of moving displays could be learned by observation. Participants viewed moving stick-figure displays resembling forearm flexion movements in the sagittal plane. Four displays (presentation displays) were first presented in which one or more movement dimensions were combined with 2 respective cues: direction (up, down), speed (fast, slow), and extent (long, short). Eight test displays were then shown, and the observer indicated whether each test display was like or unlike those previously seen. The results showed that without corrective feedback, a single cue (e.g., up or down) could be correctly recognized, on average, with the proportion correct between .66 and .87. When two cues were manipulated (e.g., up and slow), recognition accuracy remained high, ranging between .72 and .89. Three-cue displays were also easily identified. These results provide the first empirical demonstration of action-prototype learning for categories of human action and show how apparently complex kinematic patterns can be categorized in terms of common features or cues. It was also shown that probability of correct recognition of kinematic properties was reduced when the set of 4 presentation displays were more variable with respect to their shared kinematic property, such as speed or amplitude. Finally, while not conclusive, the results (from 2 of the 3 experiments) did suggest that similarity (or "likeness") with respect to a common kinematic property (or properties) is more easily recognized than dissimilarity.

Biomechanical Phenomena↗

PubMed2001

A survey of the dose of ACE inhibitors prescribed by general physicians for patients with heart failure.

AIM: To describe the pattern of angiotensin converting enzyme (ACE) inhibitor doses prescribed by general physicians for patients with chronic heart failure and to review the current evidence favouring the use of higher doses. DESIGN: A retrospective survey of the medications of 125 patients with chronic heart failure (in both inpatient and outpatient settings) was carried out between December 1999 and February 2000. RESULTS: Altogether 18.4% of patients surveyed were receiving no ACE inhibitor, the majority of these (65%) having a contraindication to such an agent. Of those patients who were prescribed an ACE inhibitor, 65% were receiving a high dose. The majority of patients who were prescribed a low dose of ACE inhibitor had no identifiable contraindication to receiving a higher dose. Of all patients with chronic heart failure studied, 25% were receiving either no ACE inhibitor or only a low dose in the absence of contraindication. CONCLUSION: Since no objectively measurable variable has been shown to share a clear relationship with the outcome benefits of ACE inhibitors, no convenient and reliable assessment exists for determining when an adequate dose has been reached for each patient. There is an abundance of evidence favouring high dose ACE inhibitors in heart failure; evidence for the role of low doses is much less clear. The fact that only half of the patients with chronic heart failure were found to be receiving a high dose of ACE inhibitor is probably testimony to inaccurate perceptions and unreliable assumptions among physicians. It is likely that a change in current prescribing patterns would benefit patients with chronic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Different prion disease phenotypes result from inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain.

BACKGROUND: Given the theoretical proposal that bovine spongiform encephalopathy (BSE) could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c.) inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic. Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990. Control groups comprised five cattle inoculated with sheep brain free from scrapie, five cattle inoculated with saline, and for comparison with BSE, naturally infected cattle and cattle i.c. inoculated with BSE brainstem homogenate from a parallel study. Phenotypic characterisation of the disease forms transmitted to cattle was conducted by morphological, immunohistochemical, biochemical and biological methods. RESULTS: Disease occurred in 16 cattle, nine inoculated with the pre-1975 inoculum and seven inoculated with the post-1990 inoculum, with four cattle still alive at 83 months post challenge (as at June 2006). The different inocula produced predominantly two different disease phenotypes as determined by histopathological, immunohistochemical and Western immunoblotting methods and biological characterisation on transmission to mice, neither of which was identical to BSE. Whilst the disease presentation was uniform in all scrapie-affected cattle of the pre-1975 group, the post-1990 inoculum produced a more variable disease, with two animals sharing immunohistochemical and molecular profile characteristics with animals in the pre-1975 group. CONCLUSION: The study has demonstrated that cattle inoculated with different pooled scrapie sources can develop different prion disease phenotypes, which were not consistent with the phenotype of BSE of cattle and whose isolates did not have the strain typing characteristics of the BSE agent on transmission to mice.

Animals↗

PubMedDate not supplied

Spirituality and life-threatening illness: a phenomenologic study.

PURPOSE/OBJECTIVES: To examine the lived experience of individuals when confronted with a life-threatening disease. RESEARCH APPROACH: Qualitative, phenomenologic using Giorgi's approach. SETTING: Patients' homes in the Midwest. PARTICIPANTS: Five women and two men, aged 44-74 years, who had a variety of diagnoses, including breast cancer, colorectal cancer, prostate cancer, pulmonary fibrosis, and myocardial infarction. METHODOLOGIC APPROACH: Subjects were recruited through flyers posted at support groups and religious establishments and by word of mouth. MAIN RESEARCH VARIABLES: Willingness to volunteer to share their stories. FINDINGS: Participants described how their spirituality provided comfort throughout their journey, strength in facing the life-threatening illness, many blessings despite the hardship of the illness, and trust in a higher power to see them through the journey. All participants described a sense of meaning in their lives throughout their experience. CONCLUSIONS: Spirituality greatly affected patients' journeys through a life-threatening illness and provided a sense of meaning despite the illness. INTERPRETATION: Nurses need to acknowledge patients' spirituality and, in turn, assist patients in meeting their spiritual needs. By understanding the study participants' experiences, nurses can better support their patients, provide time and space for spiritual practices, and honor patients' spiritual journeys.

Adult↗

PubMed1998

Clinical findings among sexually abused children with and without developmental disabilities.

Although children with developmental disabilities have a heightened risk for sexual abuse compared to those without disabilities, little is known about effects of sexual abuse on this population. Some researchers suggest that the effects are similar, and victims appear to share the same range of variability as people without disabilities. Others suggest that the effects may be complicated by limited coping resources and disability-related issues. Documented effects of sexual abuse on individuals with developmental disabilities was discussed. Clinical findings among a group of 43 children with and 43 children without developmental disabilities referred for treatment of child sexual abuse were also presented.

Adaptation, Psychological↗

PubMed2002

Enrofloxacin resistance in Escherichia coli isolated from dogs with urinary tract infections.

OBJECTIVE: To assess the strain heterogeneity of enrofloxacin-resistant Escherichia coli associated with urinary tract infections in dogs at a veterinary medical teaching hospital (VMTH). In addition, strains from other veterinary hospitals in California were compared with the VMTH strains to assess the geographic distribution of specific enrofloxacin-resistant E. coli isolates. DESIGN: Bacteriologic study. SAMPLE POPULATION: 56 isolates of E. coli from urine samples (43 isolates from dogs at the VMTH, 13 isolates from dogs from other veterinary clinics in California). PROCEDURES: Pulsed field gel electrophoresis was performed on 56 isolates of E. coli from urine samples from 56 dogs. All 56 isolates were tested for susceptibility to amoxicillin, chloramphenicol, enrofloxacin, tetracycline, trimethoprim-sulphamethoxazole, cephalexin, and ampicillin. Enrofloxacin usage data from 1994 to 1998 were obtained from the VMTH pharmacy. RESULTS: Several strains of enrofloxacin-resistant E. coli were collected from urine samples from the VMTH, and strains identical to those from the VMTH were collected from other veterinary clinics in California. For the isolates that did share similar DNA banding patterns, variable antibiotic resistance profiles were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The increased occurrence of enrofloxacin-resistant E. coli from urine samples from dogs at the VMTH was not likely attributable to a single enrofloxacin-resistant clone but may be attributed to a collective increase in enrofloxacin resistance among uropathogenic E. coli in dogs in general.

Animals↗

PubMed1996

Clinical research in a hospital--from the lone rider to teamwork.

Clinical research of high international standard is very demanding and requires clinical data of high quality, software, hardware and competence in research design and statistical treatment of data. Most busy clinicians have little time allocated for clinical research and this increases the need for a potent infrastructure. This paper describes how the Norwegian Radium Hospital, a specialized cancer hospital, has reorganized the clinical research process. This includes a new department, the Clinical Research Office, which serves the formal framework, a central Diagnosis Registry, clinical databases and multicentre studies. The department assists about 120 users, mainly clinicians. Installation of a network software package with over 10 programs has strongly provided an internal standardization, reduced the costs and saved clinicians a great deal of time. The hospital is building up about 40 diagnosis-specific clinical databases with up to 200 variables registered. These databases are shared by the treatment group and seem to be important tools for quality assurance. We conclude that the clinical research process benefits from a firm infrastructure facilitating teamwork through extensive use of modern information technology. We are now ready for the next phase, which is to work for a better external technical framework for cooperation with other institutions throughout the world.

Cancer Care Facilities↗

PubMed2002

Representing nested semantic information in a linear string of text using XML.

XML has been widely adopted as an important data interchange language. The structure of XML enables sharing of data elements with variable degrees of nesting as long as the elements are grouped in a strict tree-like fashion. This requirement potentially restricts the usefulness of XML for marking up written text, which often includes features that do not properly nest within other features. We encountered this problem while marking up medical text with structured semantic information from a Natural Language Processor. Traditional approaches to this problem separate the structured information from the actual text mark up. This paper introduces an alternative solution, which tightly integrates the semantic structure with the text. The resulting XML markup preserves the linearity of the medical texts and can therefore be easily expanded with additional types of information.

Programming Languages↗

PubMed1986

Immune response to the pre-S(1) region of the hepatitis B surface antigen (HBsAg): a pre-S(1)-specific T cell response can bypass nonresponsiveness to the pre-S(2) and S regions of HBsAg.

Hepatitis B surface antigen (HBsAg) particles are composed of a major polypeptide, p25, and additional polypeptides of higher m.w., namely p33 and p39, are variably present. All three polypeptides share the 226 amino acid residues of the S region: p33 consists of the p25 sequence plus an NH2-terminal 55 residues (pre-S(2], and p39 consists of the p33 sequence plus an NH2-terminal 108-119 residues (pre-S(1). In previous studies we demonstrated the influence of two Ir genes on the humoral and cellular immune responses to the S region and identified nonresponder phenotypes (H-2f,s). Subsequent studies showed that the immune response to the pre-S(2) region was regulated by H-2-linked genes independently of the S region response, such that immunization of S region nonresponder, pre-(S2) region responder mice (H-2s) with HBsAg/p33 circumvented nonresponse to the S region. In the present study, we have extended this analysis to the pre-S(1) region of HBsAg, with the following results: 1) and pre-S(1) region is immunogenic at the T and B cell levels; 2) anti-pre-S(1) specific antibody production is regulated by H-2-linked genes and can be independent of anti-S and anti-pre-S(2) antibody production; 3) immunization of H-2f strains with HBsAg/p39 particles containing the pre-S(1) region can bypass nonresponsiveness to the S and pre-S(2) regions in terms of antibody production; 4) two synthetic peptides, p32-53 and p94-117, define murine and human antibody binding sites on the pre-S(1) region, and p1-21 and p12-32 define additional human antibody binding sites; 5) pre-S(1)-specific T cells can be elicited in S and pre-S(2) region nonresponder mice (H-2f) and provide functional T cell help for S-pre-S(2)-, and pre-S(1)-specific antibody production; and 6) a T cell recognition site in the pre-S(1) region, p12-32 was identified. These results are relevant to HBV vaccine development, and possibly to viral clearance mechanisms, since the higher m.w. polypeptides are preferentially expressed on intact virions.

Acute Disease↗

PubMed1988

[Structural organization of the genome of paramyxoviruses].

The review summarizes the recent papers on the studies of primary structure of genome of a number of paramyxoviruses from the three genera of a family. The cited data demonstrate that despite the common principles of the genetic material arrangement shared by paramyxoviruses, they are variable in the genome, the primary structure of intragenic region, as well as the strategy of coding for some proteins. The data on the arrangement of the genetic material is discussed as useful as a criterion for classification of single stranded viruses with unsegmented genome.

Genes, Viral↗

PubMed1987

Regulation of metabolite fluxes and concentrations in living cells and organisms.

A quantitative framework for the analysis of metabolic control depends on the recognition of input and output fluxes occurring in steady-state systems in which the concentrations of intermediates are constant--the fluxes and concentrations peculiar to a given steady state are determined by the catalytic components of the system. Control of the variables is a global function shared among the components in a complex pattern, for reasons which are evident when the detailed properties of such systems are analysed. Such properties include circuit design and a host of factors affecting the sensitivity of catalytic components to substrates and effectors.

Cell Membrane Permeability↗

PubMed1975

Distribution and association of heavy and light chain variable region subgroups among human IgA immunoglobulins.

A series of randomly selected human IgA myeloma proteins were examined for the presence of the VHIII subgroup as defined by the possession of an unblocked amino terminal amino acid and characteristic linked residues along the heavy chain. Blocked heavy chains were classified as VHB proteins. The data showed that 20 of 30 such random alpha chains (67%) were classifiable as members of the VHIII subgroup. Similarly, 75% of heavy chains isolated from pools of normal serum IgA contained a VHIII variable region. The pattern stands in marked contrast to the situation in human IgG proteins where approximately 20% of heavy chains from both pools and myeloma proteins are VHIII. There was thus a clear divergence of the pattern of variable region: constant region association between these two classes of immunoglobulin. Some more limited data were obtainable for the light chains of the IgA myeloma proteins. Certain predilections for light chain subgroup:heavy chain subgroup (VHIII or VHB) associations were discernable, but more data are required for definite conclusions. Overall, this study suggests that although the pool of available variable region sequences is indeed shared among human IgA and IgG proteins, the partitioning is not exactly equivalent between the two immunoglobulin classes. The pattern is particularly apparent at present for the VHIII subgroup which comprises approximately 70% of human alpha chains and only about 20% of human gamma chains.

Amino Acid Sequence↗

PubMed1998

B cell responses to a peptide epitope. V. Kinetic regulation of repertoire discrimination and antibody optimization for epitope.

The influence of imposing various conformational constraints on immune responses to a model epitope within a synthetic peptide immunogen was examined in mice. Although overall immunogenicity was affected, the model epitope (sequence DPAF) remained the predominant recognition site regardless of the conformation in which it was presented. A comparison of anti-DPAF mAbs obtained in response to two analogue peptides, PS1CT3 and CysCT3, in which the DPAF segment was either unconstrained or held within a cyclic loop, respectively, revealed a significant homology in the paratope composition. At one level a subset of anti-PS1CT3 and anti-CysCT3 mAbs was found to share a common heavy chain variable region. In addition, nucleotide sequence homology comparisons of both heavy and light chain variable regions identified the presence of anti-PS1CT3 and anti-CysCT3 mAbs that collectively appeared to derive from a common progenitor, but with nonidentical somatic mutations. Interestingly, however, no bias toward homologous Ag could be discerned on measurement of relative affinities of the mAbs for the two peptides. In contrast, mAb binding on-rates clearly discriminated between peptides representing the homologous vs the heterologous confomer of the DPAF epitope. Thus, it would appear that the kinetics of Ag recognition dominate over equilibrium binding criteria both in epitope-driven repertoire selection and Ab maturation in a humoral response.

Amino Acid Sequence↗

PubMed1996

Urinary stone proteins: an update.

The discovery of an organic component in kidney stones dates back to 1684. More than 150 years elapsed before the incrustation of this organic component, which is now called the matrix, was proposed as the mechanism of stone formation. The composition of the matrix remained largely unknown until the development of electron microscopy and the advances in biochemistry combined in the 1950's to usher in the modern era of renal stone matrix investigation. Composed mainly of selectively incorporated proteins generally characterized by high glutamic and aspartic acid content and the frequent occurrence of gamma-carboxyglutamic acid, the matrix displays a variable and complex composition and shares a few proteins in many stones. The embryonic stone may first appear in the renal tubules where it can acquire the blood and cell membrane proteins recently found by analysis of stone protein extracts. The combination of supersaturation, an appropriate environment, the availability of calcium binding proteins which may be abnormal, and the incorporation of proteins extracted from leukocytes and cell wall membranes may induce stone formation.

Amino Acid Sequence↗

PubMed2003

Nonparametric longitudinal allele-sharing model.

Basically no methods are available for the analysis of quantitative traits in longitudinal genetic epidemiological studies. We introduce a nonparametric factorial design for longitudinal data on independent sib pairs, modelling the phenotypic quadratic differences as the dependent variable. Factors are the number of alleles shared identically by descent (IBD) and the age categories at which the dependent variable is measured, allowing for dependence due to age. To identify a linked marker a rank statistic tests the influence of IBD group on phenotypic quadratic differences. No assumptions are made on normality or variances of the dependent variable. We apply our method to 71 sib pairs from the Framingham Heart Study data provided at the Genetic Analysis Workshop 13. For all 15 available markers on chromosome 17 we analyzed the influence on systolic blood pressure. In addition, different selection strategies to sample from the whole data are discussed.

Adult↗