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Biomedical subjects

J Christensen

Publications and source records attributed to J Christensen.

At least 73 records · Page 4Linked to original sources
PubMed1999

Two new members of the emerging KDWK family of combinatorial transcription modulators bind as a heterodimer to flexibly spaced PuCGPy half-sites.

Initially recognized as a HeLa factor essential for parvovirus DNA replication, parvovirus initiation factor (PIF) is a site-specific DNA-binding complex consisting of p96 and p79 subunits. We have cloned and sequenced the human cDNAs encoding each subunit and characterized their products expressed from recombinant baculoviruses. The p96 and p79 polypeptides have 40% amino acid identity, focused particularly within a 94-residue region containing the sequence KDWK. This motif, first described for the Drosophila homeobox activator DEAF-1, identifies an emerging group of metazoan transcriptional modulators. During viral replication, PIF critically regulates the viral nickase, but in the host cell it probably modulates transcription, since each subunit is active in promoter activation assays and the complex binds to previously described regulatory elements in the tyrosine aminotransferase and transferrin receptor promoters. Within its recognition site, PIF binds coordinately to two copies of the tetranucleotide PuCGPy, which, remarkably, can be spaced from 1 to 15 nucleotides apart, a novel flexibility that we suggest may be characteristic of the KDWK family. Such tetranucleotides are common in promoter regions, particularly in activating transcription factor/cyclic AMP response element-binding protein (ATF/CREB) and E-box motifs, suggesting that PIF may modulate the transcription of many genes.

Amino Acid Motifs↗
PubMed1999

The role of the pediatric nurse practitioner in the comprehensive management of pediatric oncology patients in the inpatient setting.

The role of the pediatric nurse practitioner (PNP) in the comprehensive management of pediatric oncology patients in the inpatient setting was examined at a large tertiary teaching hospital. This article shows role responsibilities including new diagnosis teaching, procedures, routine chemotherapy, patients' comprehensive medical management, coordination of nursing care across settings, phone triage, and professional development. A PNP's typical day is highlighted to illustrate the innovative merging of traditional ambulatory care roles with that of the PNP as a comprehensive manager of pediatric oncology patients in the inpatient setting. This role provides a more seamless care experience and provides critical links in the delivery of health care to pediatric oncology patients.

Drug Therapy↗
PubMed1998

Multiple change-point analysis applied to the monitoring of Salmonella prevalence in Danish pigs and pork.

In the nation-wide Salmonella Control Program in Denmark, the occurrence of Salmonella enterica in pork, pigs at slaughter and herds is monitored. The objective of the present study was to retrospectively evaluate changes in sero-prevalence of meat juice samples and in the occurrence of Salmonella enterica in pork in 1995 and 1996. Three sets of data were used in this work: (1) serological test results of meat juice samples from pigs at slaughter (approximately 14000 samples per week); (2) bacteriological test results of pork (approximately 550 samples per week); and (3) data on the salmonella level of all Danish herds with an expected kill of over 100 pigs per year. The change-point analysis was applied to detect the change-points that divided the study period into intervals in which the prevalence was constant and to estimate the average prevalences in those intervals. Progress in the Danish Salmonella Control Program was visualised when using the results of the change-point analysis (1995-96) as baseline prevalences and compared with the current year (1997). The change-point analysis provided an indication of a seasonal pattern in salmonella occurrence with lower sero-prevalence in summer than in winter. The sero-prevalence (percent positive meat juice samples) might be a better predictor of prevalence in pork than the proportion of herds with moderate or high sero-prevalence.

Animals↗
PubMed1998

Herd size and sero-prevalence of Salmonella enterica in Danish swine herds: a random-effects model for register data.

The association between herd size and sero-prevalence of Salmonella was assessed in a random-effects model with herd size, county and date of slaughter as fixed effects. A total of 510,915 meat-juice samples from 14,593 herds located in 13 counties in Denmark was included in the study. A random-effects model was developed from separate models for smaller strata of data from herds with approximately equal sizes. The combined model was analysed and the results reported. Herd size was positively associated with the sero-prevalence of Salmonella enterica, but the size of the association was biologically of little importance, because the within-herd and the between-herd variations were relatively large in comparison. The relative magnitudes of the variance components indicated that factors associated with both the herd level and the pig level could be important in the prediction of seroprevalence of S. enterica.

Analysis of Variance↗
PubMed1998

Vaccination with Aleutian mink disease parvovirus (AMDV) capsid proteins enhances disease, while vaccination with the major non-structural AMDV protein causes partial protection from disease.

Vaccination studies were performed with partially purified recombinant AMDV VP1/2 capsids as well as with the major AMDV non-structural protein (NS1). All vaccine constructs induced an antibody response, but did not prevent infection upon challenge with AMDV. The severity of Aleutian disease (AD) was judged by the serum gammaglobulin level, the quantity of peripheral blood CD8 lymphocytes, antibody titers to VP1/2 and NS1 proteins and mink death rates. The VP1/2 vaccine constructs enhanced the disease process with drastic death rates for the vaccinated mink. On the contrary, the NS1 vaccine constructs resulted in milder AD than seen in the non-vaccinated mink.

Aleutian Mink Disease Virus↗
PubMed1998

CD28 co-stimulation stabilizes the expression of the CD40 ligand on T cells.

The ligand for CD40 (CD40L) is a protein which is expressed on CD4 T cells following their activation: CD40-CD40L interactions are absolutely required for the induction of T cell-dependent antibody responses, yet little is known about the mechanisms whereby CD40L+ primary T cells activate naive B cells, since the protein is only transiently expressed and is rapidly down-regulated following T cell-B cell contact. We show here, using a variety of assays, that co-stimulation of primary murine T cells via CD3 and CD28 stabilizes the expression of the CD40L protein. Firstly, T cells stimulated in this manner express higher levels of CD40L when activated in the presence of B cells, compared to CD3-activated T cells. Secondly, the CD40L expressed on CD28-co-stimulated T cells is more resistant to B cell-induced down-regulation. Finally, CD3/CD28-preactivated, rested T cells re-express higher levels of CD40L more rapidly following re-stimulation via CD3 than T cells preactivated via CD3 alone. CD3/CD28-preactivated T cells, but not CD3-activated cells, are competent to induce DNA synthesis in naive B cells, and this requires re-stimulation via CD3 and prolonged ligation of CD40. These data therefore reinforce the concept that naive T cells need to be activated initially by cognate interaction with B7-bearing antigen-presenting cells (such as dendritic cells), before becoming competent helper effector cells capable of driving B cells into proliferation via a CD40-dependent pathway.

Animals↗
PubMed1998

Anticipation in familial cavernous angioma: ascertainment bias or genetic cause.

OBJECTIVES: Anticipation has been linked to unstable trinucleotide repeats in many neurological disorders. We examined the hypothesis of genetic anticipation in familial cavernous angioma (FCA) of the central nervous system. MATERIAL AND METHODS: The mean ASO of affected individuals was compared between successive generations in 55 families. Intergenerational pair-wise comparisons were employed to avoid several ascertainment biases. Regarding severity of disease both type of manifestation and number of cavernous angiomas were compared between generations. RESULTS: The mean ASO decreased significantly both from the first to the second generation (31.6 vs 17.8 years; P = 0.000) and from the second to the third generation (17.8 vs 6.7 years; P = 0.002). The pair-wise comparisons also showed significantly earlier ASO. No clear evidence for anticipation with regard to severity of disease was found. CONCLUSIONS: Molecular genetic studies will determine whether trinucleotide repeats are the underlying mechanism for our observation of anticipation in FCA.

Adolescent↗
PubMed1998

Children sold for transplants: medical and legal aspects. Amnesty International--Danish Working Group for Children.

Over the last few decades there has been a substantially higher percentage of successful organ transplants but also a significant imbalance between the demand for and the supply of organs, creating the basis for a highly profitable black market trade in human organs. Sometimes there are reports that children have been kidnapped, only to reappear later lacking one kidney, or that they simply disappear and are subsequently killed to have all their transplantable organs removed for profit. The European Union feels that there is a need for action and that it has a duty to act in this field, especially for ethical reasons. There is now established close co-operation between the various European transplant organizations. The legal protection of children with regard to organ transplantation is not specifically mentioned in the existing conventions because this issue was not foreseen at the time of their preparation. However, the issue is covered in a broader sense by more general provisions. There are endless rumours surrounding this area. Members of various organizations who travel in the suspected countries say that the trafficking in children who are sold for transplantation is well known, but it is too difficult and very dangerous to catch the people involved. We have to conclude that it has been impossible to prove or disprove the rumours, but they are consistent and we all, especially in the health care professions, have an obligation to be keenly aware of how and where organs are obtained.

Child↗
PubMed1997

Avoparcin used as a growth promoter is associated with the occurrence of vancomycin-resistant Enterococcus faecium on Danish poultry and pig farms.

We determined the association between the use of the glycopeptide antibiotic avoparcin as a growth promoter and the occurrence of Enterococcus faecium (VREF) with high-level resistance to vancomycin (MIC > or = 64 micrograms ml-1) on poultry and pig farms. The investigations were conducted as retrospective cohort studies, where groups of farms exposed or not exposed to avoparcin between September 1994 and April 1995 were compared. In poultry, the association between the use of avoparcin and the occurrence of VREF was confounded by the use of broad-spectrum antibiotics, and the adjusted relative risk was 2.9 (1.4-5.9). In pigs, the association had a similar magnitude with a non-adjusted relative risk of 3.3 (0.9-12.3). The similar findings in the two studies provide evidence in favour of a causal association between the use of avoparcin and the occurrence of VREF on farms, and suggest that food animals constitute a potential reservoir of infection for VREF in humans.

Animals↗
PubMed1997

Evaluation of producer-recorded causes of preweaning mortality in Danish sow herds.

The validity of producer-recorded preweaning mortality causes was evaluated in 31 Danish sow herds. For 1206 piglets producer-recorded preweaning mortality cause was compared with post-mortem diagnosis. The predominant preweaning mortality causes at post-mortem were injury (trauma, lain on, and savaged), miscellaneous (unknown, starvation, illthrift, euthanasia, and low viability), and diarrhoea, with 391, 219, and 119 recordings, respectively. The sensitivity of producer-recorded preweaning mortality causes was generally low, and further analyses showed that the probability of being born alive and the probability of being given 'a producer diagnosis other than unknown' were associated with the herd and that a correct producer-recorded mortality cause relative to the post-mortem diagnosis depended on the mortality cause. Rare mortality causes with primarily internal signs tended to be misclassified. The producers often gave 'a diagnosis other than unknown' to pigs with a weight at death under 0.75 kg and it was often correct. To pigs with a weight at death over 1.75 kg, they rarely gave 'a diagnosis other than unknown', but when they did it was often correct.

Age Factors↗
PubMed1997

Wrapping things up: a qualitative analysis of the closing moments of the medical visit.

The purpose of this preliminary study is to develop an operational definition of the closure phase of the medical visit. A listening group developed a definition of closure by consensus based on audiotaped data from 22 office visits to physicians. The group noted new problems in closure not previously raised. Closure was defined as the final phase of the medical visit in which the doctor and patient shift perspective to the future, finalize plans, and say goodbye. Two distinct organizational frameworks of closure are outlined. Thirty-six percent of closures were interrupted in some way. New problems occurred in 23% of visits, even those with open-ended beginnings and early physician requests for all patient concerns. Doctors' communication involved expression of emotion, patient education, clarification, summary, and parting comments. Patient communication included expression of emotion, information sharing, and parting comments. Doctors' communication skills for closure are proposed. Closure is a distinctive phase of the visit with an organizational framework and specific tasks. The frequency of new problems in closure suggests that physicians may have the potential to improve their effectiveness.

Clinical Competence↗
PubMed1997

Acute and transient psychotic disorder: a 1-year follow-up study.

A study sample consisting of 51 patients suffering from acute and transient psychotic disorder (ATPD) (ICD-10) on initial examination was evaluated at 1-year follow-up. The findings show a diagnostic change in half of the patients (48%), most often to schizophrenia (15%) and affective disorder (28%). From index admission to follow-up, patients with an unchanged diagnosis of ATPD manage fairly well with regard to psychosocial functioning, and no deteriorating development is observed. In the majority of cases no personality disorder (PD) (ICD-10, 54%; DSM-IV, 71%) is apparent, and the ATPD is not related to any specific PD. With regard to diagnostic stability, no significant demographic, social or clinical predictors were found. The findings highlight the need for validation of the concept of ATPD, and point to the fact that brief psychotic episodes with an acute onset may be an early manifestation of severe mental disorder (schizophrenia and affective disorder).

Acute Disease↗
PubMed1997

A novel cellular site-specific DNA-binding protein cooperates with the viral NS1 polypeptide to initiate parvovirus DNA replication.

Replication of linear single-stranded parvovirus DNA proceeds by a rolling-hairpin mechanism which generates long, palindromic, duplex concatamers. Processing to monomer length requires initiation from origins of DNA replication located at the 3' and 5' ends of each embedded monomer, reactions which can be recapitulated in vitro for minute virus of mice (MVM). To determine which cellular proteins were essential for replication from these origins, S100 extracts from 293S cells were fractionated on phosphocellulose. When recombined, these fractions were able to support replication in vitro, dependent on the viral initiator protein NS1, using plasmid forms of the 5' origin or the minimal 3' origin as templates. Fraction P-cell 1 contains two factors, replication protein A (RPA) and proliferating-cell nuclear antigen (PCNA), known to be essential for simian virus 40 replication in vitro. When P-cell 1 was replaced with purified recombinant RPA and PCNA, NS1-mediated MVM replication initiated from the 5' origin but not from the 3' origin. The 3' origin is a 50-bp sequence containing three distinct recognition elements, an NS1 binding site, a site at which NS1 nicks the DNA to generate the priming 3' OH, and a region containing a consensus activated transcription factor (ATF) binding site. To identify the missing factor(s) for 3' origin replication, P-cell 1 was fractionated by further chromatography and active fractions were identified by their ability to complement RPA, PCNA, and P-cell 2 for NS1-mediated, origin-specific replication. Gel shift and UV cross-linking analysis of the replication-competent fractions revealed a novel 110-kDa sequence-specific DNA binding protein which recognized the consensus ATF binding site region of the origin and which we have termed parvovirus initiation factor, or PIF. Binding of PIF appears to activate the endonuclease function of NS1, allowing efficient and specific nicking of the 3' minimal origin under stringent conditions in vitro.

Animals↗
PubMed1997

Parvovirus initiation factor PIF: a novel human DNA-binding factor which coordinately recognizes two ACGT motifs.

A novel human site-specific DNA-binding factor has been partially purified from extracts of HeLa S3 cells. This factor, designated PIF, for parvovirus initiation factor, binds to the minimal origin of DNA replication at the 3' end of the minute virus of mice (MVM) genome and functions as an essential cofactor in the replication initiation process. Here we show that PIF is required for the viral replicator protein NS1 to nick and become covalently attached to a specific site in the origin sequence in a reaction which requires ATP hydrolysis. DNase I and copper ortho-phenanthroline degradation of the PIF-DNA complexes showed that PIF protects a stretch of some 20 nucleotides, covering the entire region in the minimal left-end origin not already known to be occupied by NS1. Methylation and carboxy-ethylation interference analysis identified two ACGT motifs, spaced by five nucleotides, as the sequences responsible for this binding. A series of mutant oligonucleotides was then used as competitive inhibitors in gel mobility shift assays to confirm that PIF recognizes both of these ACGT sequences and to demonstrate that the two motifs comprise a single binding site rather than two separate sites. Competitive inhibition of the origin nicking assay, using the same group of oligonucleotides, confirmed that the same cellular factor is responsible for both mobility shift and nicking activities. UV cross-linking and relative mobility assays suggest that PIF binds DNA as a heterodimer or higher-order multimer with subunits in the 80- to 100-kDa range.

Animals↗