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PubMed2002

Neither axotomy nor target-tissue inflammation changes the NOS- or VIP-synthesis rate in distal bowel-projecting neurons of the porcine inferior mesenteric ganglion (IMG).

The present study was aimed at disclosing axotomy- and inflammation-induced changes in the chemical coding of retrogradely labelled distal bowel-projecting neurons in the porcine IMG. Particular attention was paid to the changes in the expression pattern of vasoactive intestinal polypeptide and nitric oxide synthase (as a marker of nitric oxide) in affected cells, as these substances are thought to play a crucial role in the regeneration of injured sympathetic neurons. However, while both pathological processes failed to induce an increase in the number of sympathetic bowel-projecting neurons exhibiting vasoactive intestinal polypeptide or nitric oxide synthase, axotomy, but not target-tissue inflammation, led to the upregulation in the expression pattern of galanin, pituitary adenylate cyclase-activating peptide and/or Leu5-enkephalin in the affected perikarya. On the other hand, axotomy resulted in a diminished density of vasoactive intestinal polypeptide-immunoreactive intraganglionic nerve fibres, whilst target-tissue inflammation evoked a distinct increase in the number of visible vasoactive intestinal polypeptide-immunoreactive terminals, especially in those regions where bowel-projecting neurons were located. Thus, the data obtained in the present study run counter to the results of the injury-related responses observed in neurons of the sympathetic chain ganglia, suggesting the existence of either species- or target tissue-dependent differences in the injury-induced responses of the affected sympathetic neurons.

Animals↗
PubMed1991

Mutation of the p53 gene in human acute myelogenous leukemia.

Heterogeneity of p53 protein expression is seen in blast cells of patients with acute myelogenous leukemia (AML). p53 protein is detected in the blasts of certain AML patients but not in others. We have identified p53 protein variants with abnormal mobility on gel electrophoresis and/or prolonged half-life (t 1/2). We have sequenced the p53 coding sequence from primary blast cells of five AML patients and from the AML cell line (OCIM2). In OCIM2, a point mutation in codon 274 was identified that changes a valine residue to aspartic acid. A wild type p53 allele was not detected in these cells. Two point mutations (codon 135, cysteine to serine; codon 246, methionine to valine) were identified in cDNA from blasts of one AML patient. Both mutations were present in blast colonies grown from single blast progenitor cells, indicating that individual leukemia cells had sustained mutation of both p53 alleles. The cDNAs sequenced from blast samples of four other patients, including one with prolonged p53 protein t 1/2 and one with no detectable p53 protein, were fully wild type. Thus, the heterogeneity of p53 expression cannot be explained in all cases by genetic change in the p53 coding sequence. The prolonged t 1/2 of p53 protein seen in some AML blasts may therefore reflect changes not inherent to p53. A model is proposed in which mutational inactivation of p53, although not required for the evolution of neoplasia, would confer a selective advantage, favoring clonal outgrowth during disease progression.

Base Sequence↗
PubMed1999

Participation in change: self-reflection of staff in a psychiatric admission unit.

This paper reports on a comprehensive nursing research and development project carried out in the psychiatric admission unit of The Mental Hospital, Keropudas, Finland. The purpose of the project was to plan, implement and evaluate the functioning of the ward in order to orient it more towards patient-centered practices. This study was an action research project, the methodological foundations of which were based on the action theory and dialectics. This article reports on the staff's written essays based on self-reflection concerning the orientation of action towards change. The essays were analyzed using the method of continuous comparison. This analysis yielded a conceptual outline of how the orientation of action towards change manifested itself in the internal regulation of the ward staff. The main category of data to result from selective coding was participation in change. Participation was enthusiastic, hesitant or withdrawn.

Attitude of Health Personnel↗
PubMed1991

Evidence that a novel tetracycline resistance gene found on two Bacteroides transposons encodes an NADP-requiring oxidoreductase.

Two transposons, Tn4351 and Tn4400, which were originally isolated from the obligate anaerobe Bacteroides fragilis, carry a tetracycline resistance (Tcr) gene that confers resistance only on aerobically grown Escherichia coli. This aerobic Tcr gene, designated tetX, has been shown previously to act by chemically modifying tetracycline in a reaction that appears to require oxygen. We have now obtained the DNA sequence of tetX and 0.6 kb of its upstream region from Tn4400. Analysis of the DNA sequence of tetX revealed that this gene encoded a 43.7-kDa protein. The deduced amino acid sequence of the amino terminus of the protein had homology with a number of enzymes, all of which had in common a requirement for NAD(P). In an earlier study, we had observed that disrupted cells, unlike intact cells, could not carry out the alteration of tetracycline. We have now shown that if NADPH (1 mM) is added to the disrupted cell preparation, alteration of tetracycline occurs. Thus, TetX appears to be an NADP-requiring oxidoreductase. Tn4400 conferred a fivefold-lower level of tetracycline resistance than Tn4351. This finding appears to be due to a lower level of expression of the tetX on Tn4400, because the activity of a tetX-lacZ fusion from Tn4400 was 10-fold lower than that of the same fusion from Tn4351. A comparison of the sequence of the tetX region on Tn4351 with that on Tn4400 showed that the only difference between the upstream regions of the two transposons was a 4-base change 350 bp upstream of the start of the tetX coding region. The 4-base change difference creates a good consensus -35 region on Tn4351 that is not present on Tn4400 and could be creating an extra promoter.

Amino Acid Sequence↗
PubMed1995

Do out-of-office laboratory tests affect diagnoses in general practice?

OBJECTIVE: To find out whether the GP diagnosis changed by out-of-office laboratory test results and whether his diagnosis became more certain. DESIGN: Descriptive study. SETTING: Dutch survey of morbidity and interventions in general practice: stratified random sample of 161 GPs with a total list of 335,000 patients. SUBJECTS: 2,081 episodes of illness with at least one consultation with clinical chemistry, haematology, or serology tests and at least one follow-up consultation. MAIN OUTCOME MEASUREMENTS: Change in ICPC component or chapter between the consultation in which a laboratory test was ordered and the follow up contact; change in exact ICPC code in cases with important diseases (infectious diseases, haematological disorders, endocrine abnormalities, auto-immune processes and malignancies (n = 330)); change in certainty of a diagnosis and change in somatic/psychosocial orientation. RESULTS: After laboratory tests done in the first consultation the ICPC component changed in 46% of the diagnoses. Of the diagnoses made in first consultations without laboratory tests 41% changed in the follow up consultation. The diagnosis after laboratory tests was the same as before in 51% of the consultations with important diseases. Certainty about a diagnosis increased significantly after laboratory tests (p < 0.001). An abnormal laboratory result did not affect the clinical certainty of the general practitioner or the percentage of altered diagnoses. CONCLUSION: The usefulness of tests should be assessed not only in terms of the number of diagnoses changed or of the percentage of abnormal results, but also in terms of the changed certainty concerning a diagnosis.

Clinical Laboratory Techniques↗
PubMed2003

[Genetic diversity of human Parvovirus B19 VP1 unique region].

OBJECTIVE: Human Parvovirus B19 (HPV B19) is a small (23 nm), non-enveloped DNA virus found in 1974. It has been proved that HPV B19 is associated with a variety of childhood diseases, such as erythema infectious, transient aplastic crisis, aplastic anemia, idiopathic thrombocytopenic purpura and arthropathy, etc. There have been no any effective vaccines to prevent HPV B19 infection so far. The HPV B19 genome is composed of 5.6 kb single strand DNA. This genome encodes a nonstructural protein NS1, two structural proteins VP1 and VP2. Most neutralizing linear epitopes of HPV B19 cluster in the VP1 unique and VP1-VP2 junction regions. Only proteins encoded by genes of the VP1 unique and VP1-VP2 junction regions can stimulate bodies to produce protective antibodies. Aim of the present study was to get the VP1 unique region gene of HPV B19 and to analyze the genetic diversity so as to further study its function and application. METHODS: The VP1 unique region gene of HPV B19 was amplified from the serum of a child with idiopathic thrombocytopenic purpura by PCR. The purified PCR product was cloned into pGEM-T easy vector and transfected into the host strain E. coli (DH5 alpha). Positive clones were chosen and then the target gene was sequenced. RESULTS: The target gene sequence of HPV B19 VP1 unique region was amplified and cloned successfully. It had 705 nucleotides. Compared with the relevant sequences published in Genbank, the sequencing results were revealed with two nucleotides changes in the HPV B19 VP1 unique region, but their coding amino acid were not changed. CONCLUSION: It is suggested that genetic diversity exists in the VP1 unique region of HPV B19. Construction of the recombinant plasmid of HPV B19 VP1 unique region gene might benefit to further study.

Capsid Proteins↗
PubMedDate not supplied

Assuring accountability for the poor: patient advocates.

The three patient advocate groups that existed in this particular state hospital and differing structures, functions and degrees of effectiveness. However, all three seemed necessary to assure that the serving institution and its professionals would become accountable for the success or failure of their methods and performance. Two of the groups (relatives group and legal aid group) seemed to be functioning effectively within certain limits which each thought to be appropriate in advocating patient causes. Thus, they were providing the countervailing force that is a necessary component of accountability when the persons to be served are a powerless group. The consumer group being the powerless group was not effective in advocating its own cause. It would have been very beneficial to this group had they succeeded. There is a therapeutic effect of having control over one's own life that fosters independence and decreases withdrawal and feelings of alienation from the social order. Certainly these are the goals of the mental health professionals for their patients. In order to realize these goals certain changes would have to be made in the mental health code would have to be changed to include formalized grievance procedures and the desirability of consumer groups would have to be formally established. If this were so, consumers of mental health services might be more effective in advocating their own causes and would be more able to hold the serving institution accountable

Consumer Organizations↗
PubMed1982

[Age-dependent changes in connective tissue].

Alterations of the various connective tissues with aging are investigated by combined morphological and biochemical methods. The aging of connective tissues depends on aging of informational- and structural-macromolecules. Aging-dependent alterations of proteoglycans/GAG and collagen can be caused by changes in genetic information or in the cellular information-coded synthesis, but also by changes in the controls of the various metabolic processes of connective tissue cells. The activities of enzymes involved in the anabolism and the catabolism of proteoglycans/GAG and collagen show reductions with aging, but do not show age-specific variations. The aging of connective tissues is rather a dynamic process (with measurable metabolic parameters of the various connective tissue cells and their products) than a passive or so-called degenerative connective tissue process. The bradytrophy concept of connective tissue cannot be accepted any longer, because connective tissue cells partly have metabolic rates at the same level as parenchymal cells. Furthermore, parenchymal cells can synthesize and degrade mesenchymal structural macromolecules. Connective tissue aging is demonstrated on 3 organ groups: 1. on typical mesenchymal organs: aorta, cartilage and skin, 2. on organs, which are mainly composed by connective tissue: heart and lung, 3. on connective tissues of parenchymal organs: liver and kidney. These various organs exhibit some common basic processes but also differences in connective tissue aging, which are due to the different composition of proteoglycans/GAG and collagen types, and on structure and function. The aging of connective tissues is of special importance for the aging of organs. Besides alterations of cells and GAG, the very important aging fibrosis in several mesenchymal and parenchymal organs is demonstrated and discussed. The connective tissue aging of organs is one of the reasons why the frequency of diseases increases with aging and diseases are grafted more strongly on aging cells, tissues, organs and organisms.

Aging↗
PubMed1977

Structural convergence during protein evolution.

Several recent protein crystallographic structure determinations have demonstrated the existence of considerable tertiary structural similarity among proteins otherwise having little similarity in either amino acid sequence or biological function. In order to assess the possibility that such proteins may have arisen through processes of divergent evolution from a common ancestor, a graphical presentation is given which correlates the pattern of allowed single base substitutions defined by the genetic code with the associated changes in the structural properties of the encoded amino acids. The results show that while a large degree of structural conservation is evident due to codon synonomy, there is, in general, little tendency for the code to be structurally conservative in the majority of the cases where codon single-base changes result in amino acid substitutions. The possible consequences of this pattern of potential amino acid substitutions are discussed in relation to protein evolutionary processes.

Amino Acids↗
PubMed1992

Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses.

A comparison of the sequence of the dengue-2 16681 virus with that of the candidate vaccine strain (16681-PDK53) derived from it identified 53 of the 10,723 nucleotides which differed between the strains. Nucleotide changes occurred in genes coding for all virion and nonvirion proteins, and in the 5' and 3' untranslated regions. Twenty-seven of the nucleotide changes resulted in amino acid alterations. The greatest amino acid sequence differences in the virion proteins occurred in prM (2.20%; 2/91 amino acids) followed by the M protein (1.33%; 1/75 amino acids), the C protein (0.88%; 1/114 amino acid), and the E protein (0.61%; 3/495 amino acids). Differences in the amino acid sequence of nonvirion proteins ranged from 1.51% (6/398 amino acids) in NS4 to 0.33% (3/900 amino acids) in NS5. The encoded protein sequences of 16681-PDK53 were also compared with the published sequences of other flaviviruses to obtain a detailed classification of 17 flaviviruses using the neighbor-joining tree method. The analyses of the sequence data produced dendrograms which supported the traditional groupings based on serological evidence, and they suggested that the flaviviruses have evolved by divergent mutational change and there was no evidence of genetic recombination between members of the group. Comparisons of the sequences of the flavivirus polymerase and helicase-like proteins (NS5 and NS3, respectively) with those from other viruses yielded a classification of the flaviviruses indicating that the primary division of the flaviviruses was between those transmitted by mosquitoes and those transmitted by ticks.

Amino Acid Sequence↗
PubMed1995

Change in rape narratives during exposure therapy for posttraumatic stress disorder.

This paper presents a coding system developed to explore changes in narratives of rape during therapy for posttraumatic stress disorder (PTSD) involving repeated reliving and recounting of the trauma. Relationships between narrative categories hypothesized to be affected by the treatment and treatment outcome were also examined. As hypothesized, narrative length increased from pre- to post-treatment, percentage of actions and dialogue decreased and percentage of thoughts and feelings increased, particularly thoughts reflecting attempts to organize the trauma memory. Also as expected, increase in organized thoughts was correlated negatively with depression. While indices of fragmentation did not significantly decrease during therapy, the hypothesized correlation between decrease in fragmentation and reduction in trauma-related symptoms was detected.

Adolescent↗
PubMed1992

Confidentiality in the age of AIDS.

Confidentiality is a fundamental rule of medicine and has been specifically defined in many codes of medical ethics. A changing clinical environment both because of diseases such as AIDS, which were not anticipated when these clinical codes were created, and because of the changing relationship between the physician, the patient, and the payor for the physician's care creates dilemmas concerning the rule of confidentiality.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Variation of levels of mRNA coding for antenna and reaction center polypeptides in Rhodopseudomonas capsulata in response to changes in oxygen concentration.

The effect of oxygen tension on the transcription of genes coding for the photosynthetic apparatus of Rhodopseudomonas capsulata was determined by the Southern hybridization technique. Restriction endonuclease digests of the R-prime plasmid pRPS404 and a subcloned fragment thereof served as DNA probes for genetically defined regions. The results showed that transcripts corresponding to the genes for certain pigment-binding polypeptides increase in amount by about 40-fold after a drop in oxygen tension. Transcripts hybridizing to genes involved in bacteriochlorophyll biosynthesis increase to a much lesser extent, and several genes involved in carotenoid biosynthesis are not affected by pO2.

Bacterial Proteins↗
PubMed2003

Urbanization and the incidence of abnormalities of squamous and glandular epithelium of the cervix.

BACKGROUND: The large data bases of the Dutch cervical screening program can be exploited to establish the relation between urbanization and the incidence of abnormalities of the squamous and glandular epithelium, including mild or greater changes of the squamous and glandular epithelium of the cervix. METHODS: Six cytology laboratories in the context of the Dutch cervical screening program screened over 190,000 cervical smears. Urbanization (place of residence) data were derived from postal codes. All smears were coded with the Dutch national coding system, the Dutch national classification system KOPAC, in which squamous abnormalities are coded S4-S9, and glandular cell changes are coded G4-G9. From the scores per 1000 screened women, the relative risk (RR) of living in a large city compared with living in rural areas was calculated. To investigate a trend in incidence in relation to urbanization, the Schaafsma method was used. RESULTS: Of the smears with positive cytology, mild squamous dysplasia (S4) had the highest incidence per 1000 screened women (4.32), and the lowest incidence was found for adenocarcinoma (in situ; G7/G9; RR, 0.07). The RR for urban women ranged from 1.73 for moderate squamous dysplasia (S5) to 7.55 for adenocarcinoma (in situ; G7/G9). For smears with positive cytology for both squamous and glandular abnormalities, the Schaafsma method indicated a significant positive trend. CONCLUSIONS: The incidence of squamous and glandular abnormalities are maximal in women who live in a large city, which, in The Netherlands, is where there also is a population at high risk for human papillomavirus and bacterial vaginosis.

Adenocarcinoma↗
PubMed1997

Distributed Learning, Recognition, and Prediction by ART and ARTMAP Neural Networks.

A class of adaptive resonance theory (ART) models for learning, recognition, and prediction with arbitrarily distributed code representations is introduced. Distributed ART neural networks combine the stable fast learning capabilities of winner-take-all ART systems with the noise tolerance and code compression capabilities of multilayer perceptrons. With a winner-take-all code, the unsupervised model dART reduces to fuzzy ART and the supervised model dARTMAP reduces to fuzzy ARTMAP. With a distributed code, these networks automatically apportion learned changes according to the degree of activation of each coding node, which permits fast as well as slow learning without catastrophic forgetting. Distributed ART models replace the traditional neural network path weight with a dynamic weight equal to the rectified difference between coding node activation and an adaptive threshold. Thresholds increase monotonically during learning according to a principle of atrophy due to disuse. However, monotonic change at the synaptic level manifests itself as bidirectional change at the dynamic level, where the result of adaptation resembles long-term potentiation (LTP) for single-pulse or low frequency test inputs but can resemble long-term depression (LTD) for higher frequency test inputs. This paradoxical behavior is traced to dual computational properties of phasic and tonic coding signal components. A parallel distributed match-reset-search process also helps stabilize memory. Without the match-reset-search system, dART becomes a type of distributed competitive learning network.

Journal Article↗
PubMed1986

[The coding of roentgen diagnostic findings of studies based on morphologic structural changes. A computer assisted archive system for scientific purposes].

For the last three years our Institute has been using a system based on a microcomputer for archiving scientifically interesting findings. This computer processes data obtained via computed tomography, sonography and angiography. Besides the coding of examination findings the system also enables compilation of efficiency statistics data. The system can be extended with comparatively little effort for processing MR data as well. Coding is not effected, as in most of the generally used systems, according to diagnosis, but according to the pathological change that can be detected via x-ray film. This prevents erroneous coding due to erroneous evaluation of the finding in question. The examinations can be stored immediately without waiting for verification. Search for defined findings is effected via screen where a search profile is set up interactively. Due to the hierarchic structure of code allocation it is possible to call for more or less detailed findings from the stored data.

Angiography↗
PubMed1991

An approach to a synopsis of EEG parameters, morphology of brain convolutions and mental activities.

A method for the projection of EEG data on the brain surface is proposed. The EEG data are obtained during the performance of mental tasks and represented as probability maps of power and coherence changes with respect to the averaged EEG at rest. The morphological data are obtained from 3D reconstructions of the brain by means of serial slices provided by an MRI scanner. Before scanning the positions of the EEG electrodes were marked by dummy electrodes of plexiglass filled with a contrast medium. Changes of power are color-coded and entered at the respective electrode positions, changes of coherence between the respective positions. The applicability of this procedure in the fields of psychology, psychiatry and neurology is discussed.

Adult↗
PubMed2005

Functions and distribution of NQO1 in human bone marrow: potential clues to benzene toxicity.

NADPH:quinone oxidoreductase 1 (NQO1) may perform multiple functions within the cell. It is known to detoxify benzene-derived quinones and generate antioxidant forms of ubiquinone and Vitamin E. Recently suggested roles for NQO1 which may have relevance for mechanisms underlying benzene toxicity include modulation of cellular redox balance, direct scavenging of superoxide, stabilization of p53 and stabilization of microtubules. The NQO1*2 polymorphism is a single nucleotide polymorphism, a C to T change at position 609 of the NQO1 cDNA coding for a proline to serine change at position 187 of the amino acid structure of the protein. The mutant NQO1*2 protein is rapidly degraded by the ubiquitin proteasomal system resulting in a lack of NQO1 protein in individuals carrying the NQO1*2/*2 genotype. The NQO1*2 polymorphism predisposes to benzene toxicity and to various forms of leukemias. NQO1-knockout animals demonstrate myeloid hyperplasia and increased benzene-induced hematotoxicity. NQO1 is not present in freshly isolated human bone marrow hematopoietic cells but can be induced by benzene metabolites. Increases in NQO1 were not observed in NQO1*2/*2 hematopoietic cells, presumably because of the instability of the NQO1*2 protein, suggesting that cells with this genotype would not benefit from any protective effects of NQO1. NQO1 is present in human bone marrow stroma and particularly in endothelial cells. Studies of the functions and distribution of NQO1 in human bone marrow may provide clues to mechanisms underlying benzene toxicity.

Animals↗