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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 289 records · Page 16Linked to original sources
PubMed1995

Comparison of initial laparoscopic cholecystectomy at a community hospital versus a teaching hospital.

OBJECTIVE: To compare the initiation of laparoscopic cholecystectomy at a community hospital versus a tertiary-care teaching hospital. DESIGN: Retrospective chart review. SETTINGS: A general community hospital in Prince George, BC, and a tertiary-care teaching hospital in Vancouver. PATIENTS: One hundred and eighty-two patients in the community hospital and 318 patients in the tertiary-care centre. INTERVENTION: Laparoscopic cholecystectomy for symptomatic gallbladder disease. MAIN OUTCOME MEASURES: Preparation of surgeons for the new technique, complication rates, operating time, conversion rates to open cholecystectomy and duration of hospitalization. RESULTS: All community surgeons took didactic and laboratory courses in preparation for the new procedure and assisted each other for their first 10 cases, but surgeons at the teaching hospital had more varied preparation that included additional extensive laboratory work and preceptorships with surgeons experienced with the procedure. The rates of major complications of laparoscopic cholecystectomy were 6.5% at the community hospital compared with 5% at the tertiary-care centre. The rates of minor complications were 5.5% at community hospital and 5.3% at the tertiary-care centre. The rates of conversion to open cholecystectomy were 6.6% for the community hospital versus 4.7% for teaching hospital. The mean (and standard deviation) operating time was shorter at the community hospital than at the teaching hospital: 72.3 (30) minutes versus 106 (32) minutes (p < 0.0001). The mean (SD) length of stay was 2.5 (1.8) days at the community hospital and 3.4 (1.9) days at the teaching hospital. CONCLUSIONS: The introduction of laparoscopic cholecystectomy during a 2-year period was achieved safely at both hospitals. The complication rates were similar. The length of stay and operating times were shorter in the community hospital.

Adult↗
PubMed1995

Localization of human immunodeficiency virus 1 RNA in thymic tissues from asymptomatic drug addicts.

Thymic tissue was collected from 11 human immunodeficiency virus 1 (HIV-1)-seropositive drug users who died suddenly of drug intoxication or trauma. None of the 11 individuals had symptoms related to HIV-1 infection or were known to be seropositive for HIV-1 before death. Secondary B-cell follicles were present in every thymus, and Warthin-Finckeldey giant cells were noted in three cases. These follicles were enlarged or fragmented and appeared similar to those in lymph nodes excised from the same individuals. Localization of viral RNA by in situ hybridization demonstrated abundant virus in a follicular center cell distribution within hyperplastic follicles and in scattered medullary lymphocytes. In nine thymus glands from seronegative drug addicts and five thymus glands from seronegative trauma victims who were not drug addicts, secondary follicles were absent and no hybridization signal was present. Other than the presence of germinal centers associated with HIV-1 RNA, there were no histologic differences among the thymus glands of seropositive drug addicts, seronegative drug addicts, and seronegative controls without a history of drug abuse. We conclude that the thymus gland in early stages of infection with HIV-1 is characterized by induction of secondary B-cell follicular hyperplasia in medullary tissues, the germinal centers of which contain abundant viral RNA.

Adult↗
PubMed1995

Ethnicity and psychopharmacology. Bridging the gap.

Taken together, the literature reviewed clearly indicates that the disposition and effect of a large number of psychotropic agents are influenced substantially by ethnicity and culture. Recent advances in the realm of pharmacokinetics, pharmacogenetics, and pharmacodynamics have led to a greater understanding of some of the mechanisms responsible for such differences. In comparison, much less currently is known regarding how various psychosocial factors impinge on drug responses in different cultural settings. Progress in research in this area is important for clinical reasons, as psychiatric clinicians will increasingly be confronted with patients with divergent ethnic and cultural backgrounds. In addition, knowledge derived from such research will contribute significantly to a better understanding of how the effects of psychotropic agents are mediated, and also should be valuable for the drug development industry that will have to take into account the increasingly diversifying domestic and international markets.

Antidepressive Agents, Tricyclic↗
PubMed1995

Crystallization of a designed peptide from a molten globule ensemble.

Backgound. The design of amino acid sequences that adopt a desired three-dimensional fold has been of keen interest over the past decade. However, the design of proteins that adopt unique conformations is still a considerable problem. Until very recently, all of the designed proteins that have been extensively characterized possess the hallmarks of the molten globular state. Molten globular intermediates have been observed in both equilibrium and kinetic protein folding/stability studies, and understanding the forces that determine compact non-native states is critical for a comprehensive understanding of proteins. This paper describes the solution and early solid state characterization of peptides that form molten globular ensembles. Results. Crystals diffracting to 3.5&angst; resolution have been grown of a 16-residue peptide (alpha1A) designed to form a tetramer of alpha-helices. In addition, a closely related peptide, alpha1, has previously been shown to yield crystals that diffract to 1.2&angst; resolution. The solution properties of these two peptides were examined to determine whether their well defined crystalline conformations were retained in solution. On the basis of an examination of their NMR spectra, sedimentation equilibria, thermal unfolding, and ANS binding, it is concluded that the peptides form alpha-helical aggregates with properties similar to those of the molten globule state. Thus, for these peptides, the process of crystallization bears many similarities to models of protein folding. Upon dissolution, the peptides rapidly assume compact molten globular states similar to the molten globule like intermediates that are formed at short times after refolding is initiated. Following a rate-determining nucleation step, the peptides crystallize into a single or a small number of conformations in a process that mimics the formation of native structure in proteins.

Journal Article↗
PubMed1994

Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor.

Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56bright subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK cells could be inhibited by both antibodies. CD56dim NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK-enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function.

Antigens, CD↗
PubMed1994

Dominant lethal effects after inhalation exposure to 1,3-butadiene.

Two independent dominant lethal experiments were performed using different protocols with respect to strains of mice, inhalation exposure duration of 1,3-butadiene, and mating regimen. The short communication summarizes the results of the experiments and compares the induced dominant lethality according to the formula published by Ehling in 1978. Despite the differences in methodology the results are in close agreement. The sum of the dominant lethal effects observed during the first three mating weeks after 1 week of butadiene exposure in one experiment (23.1%) is surprisingly similar to the dominant lethal effect observed during 1 week of mating after 10 weeks of butadiene exposure (28.1%) in the other experiment. The results of the two independent experiments strengthen the conclusion that butadiene is a germ cell mutagen. Furthermore, the results indicate that the effect observed after 10 weeks of exposure is representative of the last three treatment weeks, i.e. treated spermatozoa and spermatids.

Administration, Inhalation↗
PubMed1994

Probing the structure of bacteriophage phi 29 prohead RNA with specific mutations.

Bacteriophage phi 29 of Bacillus subtilis packages its double-stranded DNA genome into a preformed prohead in an ATP-dependent reaction. A 174-residue phi 29-encoded RNA molecule (pRNA) is a structural component of the prohead and is essential for DNA packaging. The secondary and tertiary structures of the prohead binding site on pRNA have been probed using a series of specific mutant pRNAs and by measuring binding to RNA-free proheads and in vitro packaging of the DNA-gene product 3 (DNA.gp3) complex. A pseudoknot in pRNA inferred from phylogenetic studies was confirmed with specific mutations, and this pseudoknot was necessary for DNA.gp3 packaging activity. pRNA was truncated progressively from the 5' and 3' ends to isolate the prohead binding site, and three truncated pRNAs of 79, 71, and 62 residues retained prohead binding activity but could not reconstitute proheads for DNA.gp3 packaging. Mutation resulting in changes of the D hairpin loop and its connecting residues within the prohead binding site of pRNA and DNA packaging studies demonstrated that some alteration of secondary structure in this helix was permissible. The analyses provided further confirmation of a discrete prohead binding domain in pRNA and further delineated specific structural requirements for DNA.gp3 packaging activity which may not be required for prohead binding.

Bacillus Phages↗
PubMed1994

Crystallization studies of the human immunodeficiency virus (HIV-1) Tat protein and its trans-activation response element (TAR) RNA.

Small single crystals are reported of a complex between a small peptide fragment of the HIV-1 Tat protein and a fragment of the RNA to which it binds. Tat is responsible for enhancing the level of expression of the human immunodeficiency virus type 1 (HIV-1) and is a logical target for AIDS therapy. Tat may function to increase the level of transcription initiation or to prevent premature termination of transcripts. In vitro, Tat binds through its basic domain (two Lys and six Arg in nine residues) to a three-nucleotide bulge of a stem-loop RNA structure called TAR. Complex formation between Tat and TAR is necessary for Tat activity. Peptides which contain the basic region of Tat also bind to TAR RNA. We have carried out crystallization experiments on a 27-nucleotide fragment of TAR RNA and on complexes between two Tat peptides and TAR.

Journal Article↗
PubMed1994

Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15.

We have recently cloned a novel cytokine, IL-15, with shared bioactivities but no sequence homology with IL-2. We found high affinity IL-15 binding to many cell types, including cells of non-lymphoid origin. Analysis of IL-15 interaction with subunits of the IL-2 receptor (IL-2R) revealed that the alpha subunit was not involved in IL-15 binding. We demonstrated directly in cells transfected with IL-2R subunits that both the beta and gamma chains are required for IL-15 binding and signaling. Hence, IL-15, like IL-2, IL-4 and IL-7, utilizes the common IL-2R gamma subunit found to be defective in X-linked severe combined immunodeficiency in humans. IL-15 is the only cytokine other than IL-2 that has also been shown to share the beta signaling subunit of IL-2R. The differential ability of some cells to bind and respond to IL-2 and IL-15 implies the existence of an additional IL-15-specific component.

Animals↗
PubMed1994

Management of women with mild and moderate cervical dyskaryosis.

OBJECTIVE: To compare the outcomes in women with mild and moderate dyskaryosis after increasing periods of surveillance and thereby to define a rational protocol for managing such women. DESIGN: Prospective study with randomisation of women to one of four treatment groups, each with a different period of surveillance; one group in which the women were given immediate treatment and three other groups in which the women were under surveillance for six, 12, and 24 months. SETTING: A dedicated colposcopy clinic in Aberdeen, Scotland. SUBJECTS: 902 women who presented with a mildly or moderately dyskaryotic smear for the first time. INTERVENTIONS: Cytological and colposcopic examinations at intervals of six months until the allocated period of surveillance was completed, at which time biopsy was performed. Women with severe dyskaryosis were withdrawn from surveillance and a biopsy was performed. MAIN OUTCOME MEASURES: The histological findings after punch biopsy or large loop excision of the transformation zone, and the trends in cytological appearances of serial cervical smears. RESULTS: 793 women completed the study. In all, 769 women had an adequate final smear, of which 197 were normal cytologically, 328 were still mildly or moderately dyskaryotic, and 244 were severely dyskaryotic. Seventeen of the 67 (25%) women with one repeat smear showing non-dyskaryosis had cervical intraepithelial neoplasia grade III compared with only one of the 31 (3%) women with no dyskaryosis in four repeat cervical smears (P < 0.0001). None of the women had invasive cancer. Of 158 women whose index smear showed mild dyskaryosis and who were allocated to the group under surveillance for two years, only 40 had not defaulted or still had dyskaryotic smears by the end of the two years. CONCLUSION: Cytological surveillance, although safe, is not an efficient strategy for managing women with mildly abnormal smears. Women with any degree of dyskaryosis in a smear should be referred for colposcopy.

Adult↗
PubMed1994

The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay.

The effects of antioxidants and various other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes have been investigated using the COMET assay. Hydrogen peroxide (H2O2) and bleomycin (BLM) have produced clear dose-related responses. In 38 independent experiments, there was consistency between the two donors used in the study for the negative and positive control data. The endogenous antioxidant catalase abolished effects with H2O2, but only slightly affected the response with BLM. Superoxide dismutase did not alter the response with H2O2 and only slightly affected BLM. The exogenous antioxidant vitamin C produced a clear dose-related response on its own. In combination with H2O2, there were small protective effects at low doses and exacerbating effects at high doses, but these were within the inter-experimental variability range. Vitamin E (trolox) produced no effects with either H2O2 or BLM, or on its own. Silymarin protected against the effect due to H2O2. Other modifying agents such as apo-transferrin and deferoxamine mesylate produced a clear dose-related protection of effects due to BLM. This protection was less due to H2O2. In the presence of ferrous chloride, the effect due to BLM was exacerbated. In a small sample of 6 smokers and 6 non-smokers, responses from smokers approached borderline significance (P = 0.054) by comparison with non-smokers. These observations would suggest that the COMET assay is a useful tool for examining issues related to oxidative stress in human lymphocytes.

Adult↗
PubMed1994

Identification of bacteriophage phi 29 prohead RNA domains necessary for in vitro DNA-gp3 packaging.

Functional domains of the bacteriophage phi 29 prohead RNA (pRNA) that are essential for in vitro packaging of DNA-gp3 into the prohead were mapped using pRNA mutants. Oligonucleotide-directed mutant pRNAs were produced that contained deletions and sequence alterations but were predicted to retain the overall secondary structure of wild-type pRNA. Mutant pRNAs were compared to wild-type pRNA for prohead binding in a competition assay and for DNA packaging in the defined in vitro system. The prohead binding site was previously localized to residues 22-84 on the 120-residue domain I of pRNA by ribonuclease footprinting (Reid, R. J. D., Bodley, J. W., and Anderson, D. (1994) J. Biol. Chem. 269, 5157-5162). Mutations of pRNA within the prohead binding site resulted in substantial loss of prohead binding capacity, while mutations outside of the footprint had moderate effects on prohead binding. DNA-gp3 packaging activity was correlated with pRNA binding activity for mutations within the footprint. This mutational analysis showed that both sequence and secondary structure of residues 40-91 of pRNA were crucial for prohead binding and that elements of the A helix formed from residues 1-28 and 117-92 were needed for DNA packaging functions other than prohead binding.

Bacillus Phages↗
PubMed1994

Characterization of the prohead-pRNA interaction of bacteriophage phi 29.

The small prohead RNA (pRNA) of the Bacillus subtilis bacteriophage phi 29 is essential for ATP-dependent packaging of viral DNA. The 174-, 124-, and 120-residue forms of pRNA produced in vitro using T7 RNA polymerase were equivalent in prohead binding and DNA packaging activity to pRNAs produced in phi 29-infected cells. pRNA binding to proheads, characterized by the use of Northern hybridization and filter binding assays, was specific, rapid, and irreversible in the presence of 10 mM Mg2+. Proheads produced in phage-infected cells carried 5.8 +/- 2.7 copies of pRNA, and proheads assembled in Escherichia coli in the absence of pRNA bound 6.0 +/- 3.5 copies of pRNA. Footprints of proheads on pRNA generated with the ribonucleases A, T1, and V1 showed that nucleotides 22-84, 5' to 3', were protected from ribonuclease attack. Enhanced cleavage at nucleotides 37-40 with ribonuclease V1 suggested a conformational change of pRNA upon prohead binding.

Bacillus Phages↗
PubMed1994

Mild growth retardation and developmental delay, microcephaly, and a distinctive facial appearance.

We describe a brother and sister from one family and a girl from a second, unrelated family; they have a syndrome of pre- and post-natal growth deficiency, developmental delay, a friendly personality, microcephaly, and a distinctive facial appearance marked by thick eyebrows, full cheeks, and a short nose with the columella inserted below the nasal alae. We think this is a new syndrome probably inherited as an autosomal recessive trait.

Abnormalities, Multiple↗
PubMed1994

A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin.

BACKGROUND: The management of heparin therapy in patients who have a subtherapeutic activated partial thromboplastin time (APTT) despite high doses of heparin is problematic because the risk of heparin-associated bleeding increases with dose. Results of experimental studies in animals indicate that when the APTT response to heparin is blunted by infusion of procoagulants, dose escalation can be avoided without compromising efficacy, by monitoring treatment with a heparin assay. METHODS: A randomized, controlled trial was conducted in which patients with acute deep vein thrombosis, pulmonary embolism, or axillary vein thrombosis who required 35,000 U or more of intravenous heparin by continuous infusion during the previous 24 hours were allocated to have their heparin therapy monitored either by anti-factor Xa levels (targeted range, 0.35 to 0.67 U/mL) or by the APTT (targeted range, 60 to 85 seconds). Both ranges were equivalent to a heparin level of 0.2 to 0.4 U/mL by protamine titration. RESULTS: Three (4.6%) of 65 patients in the anti-factor Xa group experienced recurrent venous thromboembolism compared with four (6.1%) of 66 patients in the APTT group (difference, 1.5%; confidence interval, -6.7% to 8.4%) (P = .7). There were four bleeding events (6.1%) in the APTT group compared with one (1.5%) in the anti-factor Xa group (difference, 4.6%; confidence interval, -3.3% to 7.5%) (P = .4). During the period of heparin therapy before warfarin treatment was begun, the patients in the APTT group required a statistically significantly greater amount of heparin compared with the patients in the anti-factor Xa group. The daily mean APTT was subtherapeutic in patients in the anti-factor Xa group, and it was within the therapeutic range in the APTT group. The daily mean anti-factor Xa levels for both groups were within the therapeutic range. CONCLUSION: The heparin assay is a safe and effective method for monitoring heparin treatment in patients with acute venous thromboembolism whose APTT remains subtherapeutic despite large daily doses of heparin. In such patients, dosage escalation can be avoided if the heparin level is therapeutic.

Acute Disease↗
PubMed1994

A comparison of combat's effects on PTSD scores in veterans with high and low moral development.

This study was designed to explore the effects of moral development on the relationship between combat intensity and severity of posttraumatic stress disorder. The effect of combat intensity on PTSD Interview total scores and several individual stress disorder symptom ratings was substantial in a Low Moral Development sample, but negligible in a High Moral Development group. These data suggest that moral development may blunt the effect of combat severity on PTSD. These effects were strongest on items that describe reexperiencing of the trauma and exaggerated arousal. Possible interpretations of the results and several caveats were discussed.

Adult↗