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Biomedical subjects

L Ryder

Publications and source records attributed to L Ryder.

At least 19 recordsLinked to original sources
PubMed2003

T-cell receptor excisional circles, telomere length, proliferation and apoptosis in peripheral blood mononuclear cells of human immunodeficiency virus-infected individuals after 18 months of treatment induced viral suppression.

This study evaluated the effect of highly active antiretroviral therapy (HAART)-induced viral suppression on T-cell receptor excisional circles (TRECs), telomere length, proliferative responses and spontaneous as well as phytohaemagglutinin (PHA)-stimulated lymphocyte apoptosis in 27 human immunodeficiency virus (HIV)-infected individuals followed for 18 months during HAART. Our results show that HAART significantly increased the level of TRECs in CD4+ cells (P = 0.003) after 18 months of almost continuously suppressed HIV-RNA levels. Lymphocyte proliferative responses and apoptosis levels in patients were significantly lower and significantly higher, respectively, compared with healthy controls. The proliferative response and apoptosis levels did not change during follow up. Changes in telomere length were observed in CD4+ and in CD8+ T cells. The study demonstrated that HAART induces normal TREC levels in the CD4+ T-cell pool. However, the other perturbed functions in T cells indicate that immune reconstitution is incomplete and may need longer viral suppression.

Adult↗
PubMed2000

Using prospective outcomes data to improve morbidity and mortality conferences.

Background:Though a traditional part of most training programs, surgical morbidity and mortality (M&M) conferences are not optimal for teaching residents how to understand and improve patient outcomes. They tend to focus on unusual rather than common problems and review complications as singular phenomena, rather than recurrent events related to specific processes of care. For these reasons, we began incorporating data from our general surgery outcomes registry into our M&M conference.Developed for both clinical research and quality improvement purposes, the outcomes registry contains prospective information about all patients undergoing general surgery procedures in the operating room (approximately 2000 per year). All adverse events occurring within 30 days of surgery are categorized, using explicit criteria, by clinical nurse coordinators. Individual complications are then collapsed into four severity grades (from a previously validated grading system), from I (not life-threatening, low complexity therapy; eg, superficial wound infection) to IV (death).Application To M&M Conferences:Before each conference the data manager supplies the responsible senior resident with information about caseloads and adverse events for the preceding month. At the conference, individual cases are presented in the context of the department's broader experience with that procedure (eg, rates of wound complications after bowel surgery over the last 2 years). In reviewing trends in complication rates over time, we also explore potential relationships between practice changes and outcomes. When appropriate, local performance is compared to external "benchmarks" using data from published studies.Incorporating prospective outcome data into the M&M conference is both feasible and practical. In addition to its educational value for both resident and attending physicians, we believe this approach creates many opportunities for improving the quality of our surgical practice.

Journal Article↗
PubMed2000

Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate.

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996 - 1999). The mean age of the patients was 41.7 years (range 19 - 80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-epsilon 4/epsilon 4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-epsilon 4/epsilon 4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-epsilon 4/epsilon 4 homozygotes have an increased risk of developing MS. MS patients with the APOE-epsilon 4/epsilon 4 allele may also have an increased rate of disease progression. Multiple Sclerosis (2000) 6 226 - 230

Adult↗
PubMed1997

Population studies of the human V kappa A18 gene polymorphism in Caucasians, blacks and Eskimos. New functional alleles and evidence for evolutionary selection of a more restricted antibody repertoire.

Immunoglobulin gene polymorphisms are interesting because they reflect differences in the available antibody repertoire which may affect the susceptibility to specific infections. Until recently, the human V kappa gene, A18, was known as a nonfunctional gene only. In this study, we cloned and sequenced four apparently functional alleles and determined the gene frequencies in three well-defined populations: Danish Caucasians, eastern Greenland Eskimos and Mozambican blacks. The A18b allele that was recently described in Native American Navajos by Atkinson et al. was found in all three populations with gene frequencies of 8%, 45% and 23% in Caucasians, Eskimos and blacks, respectively. Conversely, the frequencies of the nonfunctional A18a allele were 92%, 55% and 57%. Further, three new A18 alleles, c, d, and e were found exclusively in blacks, among whom they had an total frequency of 19%. These data indicate that both the A18a and A18b alleles originated before the diversification of Africans and non-Africans 90,000 years ago, whereas the A18c, A18d and A18e alleles may have a more recent origin. The functionality of the A18b allele was documented by the demonstration of properly rearranged and somatically hypermutated A18b messenger RNA present in the blood lymphocytes of individuals carrying this allele. The expression clearly exceeded that of a known functional V gene, A2, indicating that functional A18 alleles contribute significantly to the available antibody repertoire. In this context, it is surprising that the functional A18b allele apparently has been negatively selected in the Caucasian population, among whom 85% completely lack a functional gene.

Alleles↗
PubMed1996

Decreased number of CD73 (ecto-5'-nucleotidase) molecules on lymphocytes from patients with primary immunoglobulin deficiencies. Correlation between number of CD73 molecules and T-lymphocyte function in vitro.

CD73 is a bifunctional glycosyl phosphatidylinositol anchored leucocyte differentiation antigen which has specific ecto-5'-nucleotidase (ecto-5'-NT) activity and is an accessory T-lymphocyte activation molecule. The aim of the present study was to investigate the CD73 expression on blood mononuclear cells (BMC) from a group of patients with primary immunoglobulin deficiency (IGD). This group of patients had both significantly decreased levels of ecto-5'-NT on BMC (P = 0.002) and decreased numbers of CD73 molecules per CD73+ lymphocyte (P = 0.01). Five of the 10 patients had a decreased percentage of CD73+ lymphocytes. Among B-lymphocytes the patients had normal percentages of CD73+ cells but four of the 10 patients had numbers of CD73 molecules per CD73+ B-lymphocyte below the normal range. Among CD4-lymphocytes three out of 10 patients had percentages of CD73+ below the normal range and four out of 10 patients had decreased percentages of CD73+ CD8-lymphocytes. Significant correlations were found between in vitro proliferative responses to mitogens and the number of CD73 molecules per CD73+ lymphocyte (rs = 0.60, P < 0.01) and per CD73+ CD8-lymphocyte (rs = 0.64, P < 0.02). In addition, a positive correlation was found between ability to proliferate and level of ecto-5'-NT on BMC (rs = 0.53, P < 0.05). Furthermore the ability of BMC to synthesize ecto-5'-NT was studied. During 2 days culture ecto-5'-NT activity increased markedly on BMC from both patients and healthy donors. The level of activity on BMC from all patients attained levels higher than on freshly isolated BMC from healthy donors. This shows that the decreased levels of ecto-5'-NT found on freshly isolated BMC from patients with IGD is due to defective regulation of the enzyme activity in vivo.

5'-Nucleotidase↗
PubMed1996

Recombination-dependent growth in exonuclease-depleted recBC sbcBC strains of Escherichia coli K-12.

Analysis of the aroLM-sbcCD interval of the Escherichia coli K-12 chromosome revealed a new gene (rdgC) encoding a function required for growth in recombination-deficient recBC sbcBC strains. Deletion of rdgC does not reduce viability, conjugational recombination, or DNA repair in rec+, recA, recB, recF, or recJ mutants. However, it makes the growth of recBC sbcBC strains reliant on the RecA, RecF, and RuvC proteins and, to a large extent, on RuvAB. The recBC sbcBC delta rdgC ruvAB construct forms colonies, but cell viability is reduced to < 5%. A recBC sbcBC delta rdgC derivative carrying the temperature-sensitive recA200 allele grows at 32 degrees but not 42 degrees. Multicopy rdgC+ plasmids reduce the growth rate of recBC sbcBC strains, while multicopy sbcC+ plasmids that reactivate SbcCD nuclease cannot be maintained without RdgC protein. The data presented are interpreted to suggest that exonuclease-depleted recBC sbcBC strains have difficulty removing the displaced arm of a collapsed replication fork and that this problem is compounded in the absence of RdgC. Recombination then becomes necessary to repair the fork and allow chromosome duplication to be completed. The possibility that RdgC is an exonuclease is discussed.

Amino Acid Sequence↗
PubMed1994

A mutation in helicase motif III of E. coli RecG protein abolishes branch migration of Holliday junctions.

The RecG protein of Escherichia coli catalyses branch migration of Holliday junctions made by RecA and dissociates synthetic X junctions into duplex products in reactions that require hydrolysis of ATP. To investigate the mode of action of this enzyme a chromosomal mutation that inactivates recG (recG162) was cloned and sequenced. The recG162 mutation is a G:C to A:T transition, which produces an Ala428 to Val substitution in the protein. This change affects a motif (motif III) in the protein that is highly conserved in DNA and RNA helicases. RecG162 protein was purified and shown to retain the ability to bind synthetic X and Y junctions. However, it does not dissociate these junctions and fails to catalyse branch migration of Holliday junction intermediates purified from a RecA strand exchange reaction. RecG162 retains a DNA-dependent ATPase activity, but this is much reduced relative to the wild-type protein, especially with single-stranded DNA as a co-factor. These results suggest that branch migration by RecG is related to a junction-targeted DNA helicase activity.

Adenosine Triphosphatases↗
PubMed1994

Mutation of recF, recJ, recO, recQ, or recR improves Hfr recombination in resolvase-deficient ruv recG strains of Escherichia coli.

The formation of recombinants in Hfr crosses was studied in Escherichia coli strains carrying combinations of genes known to affect recombination and DNA repair. Mutations in ruv and recG eliminate activities that have been shown to process Holliday junction intermediates by nuclease cleavage and/or branch migration. Strains carrying null mutations in both ruv and recG produce few recombinants in Hfr crosses and are extremely sensitive to UV light. The introduction of additional mutations in recF, recJ, recO, recQ, or recR is shown to increase the yield of recombinants by 6- to 20-fold via a mechanism that depends on recBC. The products of these genes have been linked with the initiation of recombination. We propose that mutation of recF, recJ, recO, recQ, or recR redirects recombination to events initiated by the RecBCD enzyme. The strains constructed were also tested for sensitivity to UV light. Addition of recF, recJ, recN, recO, recQ, or recR mutations had no effect on the survival of ruv recG strains. The implications of these findings are discussed in relation to molecular models for recombination and DNA repair that invoke different roles for the branch migration activities of the RuvAB and RecG proteins.

Crosses, Genetic↗
PubMed1993

Reverse branch migration of Holliday junctions by RecG protein: a new mechanism for resolution of intermediates in recombination and DNA repair.

The RecG protein of E. coli is a junction-specific DNA helicase involved in recombination and DNA repair. The function of the protein was investigated using an in vitro recombination reaction catalyzed by RecA. We show that RecG counters RecA-driven strand exchange by catalyzing branch migration of the Holliday junction in the reverse direction. This activity represents a new mechanism for resolving recombination intermediates that is independent of junction cleavage. We discuss how reverse branch migration can facilitate DNA repair, promote recombination in conjugational crosses, and confine the distribution of Chi-stimulated cross-overs. We suggest that the RecG mechanism for resolution of junctions is universal and provides a simple system that allows gene conversion without associated crossing over.

Adenosine Triphosphatases↗
PubMed1991

[Immunomodulating effect of LongoVital in patients with recurrent aphthous stomatitis. 2].

LongoVital (LV) (DK. reg. no. 5178/75) is a herbal-based tablet enriched with recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4 (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31 otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during six months' daily LV intake in a double-blind, randomised, crossover 1-year study. Fourteen had had LV during the first six months (GrA) and 17 LV during the latter six months (GrB). OKT4+ percentages increased significantly during the LV period in both groups (p less than 0.05). OKT8+ percentages increased in both groups, however, only significantly in GrA (P less than 0.05). It is concluded that LV acts as an immunostimulator in patients with RAU and that the increase in T-lymphocyte subsets may account for the previously reported benefit of LV in RAU prevention.

Adult↗
PubMed1991

Comparison of CATEGO-derived ICD-8 and DSM-III classifications using the composite international diagnostic interview in severely ill subjects.

Two classifications, DSM-III and CATEGO4-derived ICD-8, included in the CIDI, are compared in 63 in-patients and out-patients with a broad range of psychiatric illness. Agreement for main diagnosis between these classifications was statistically significant for two time frames, the present state and lifetime. However, while diagnostic assignment by CATEGO4 remained fairly constant between time frames, there was a marked shift in DSM-III-assigned diagnosis, with cases changing from anxiety state diagnosis (present state) to affective disorder (lifetime). Thirty-nine subjects were assigned a DSM-III diagnosis of affective disorder for lifetime illness compared with 21 assigned to this diagnostic group by CATEGO4.

Adolescent↗
PubMed1990

Immunomodulation by LongoVital in patients with recurrent aphthous ulceration.

LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4 (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31 otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during 6 months' daily LV intake in a double-blind, randomized, crossover 1-year study. Fourteen had had LV during the first 6 months (GrA) and 17 LV during the latter 6 months (GrB). OKT4+ percentages increased significantly during the LV period in both groups (P less than 0.05). OKT8+ percentages increased in both groups, however, only significantly in GrA (P less than 0.05). It is concluded that LV acts as an immunostimulator in patients with RAU and that the increase in T-lymphocyte subsets may account for the previously reported benefit of LV in RAU prevention.

Adult↗
PubMed1989

IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes.

The restriction enzymes MspI and BglII identify two different two-allele restriction fragment length polymorphisms (RFLP) in the human IL-6 genes of healthy Danes. Co-dominant segregation was demonstrated for both marker-systems and the test for Hardy-Weinberg equilibrium showed no significant deviation from expectations. There is a strong correlation between the two marker systems. The two IL-6 RFLP's were studied in Danish patients with rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, and systemic lupus erythematosus. The frequencies of the MspI and BglII marker phenotypes did not differ between healthy controls and the three disease groups. No extra or missing DNA fragments were observed in the disease groups when compared with controls.

Arthritis, Juvenile↗