Biomedical subjects

W Olson

Publications and source records attributed to W Olson.

At least 19 recordsLinked to original sources

PubMed2001

gp100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+T cells.

CD4+ T cells modulate the magnitude and durability of CTL responses in vivo, and may serve as effector cells in the tumour microenvironment. In order to identify the tumour epitopes recognized by tumour-reactive human CD4+ T cells, we combined the use of an HLA-DR4/peptide binding algorithm with an IFN-gamma ELISPOT assay. Two known and three novel CD4+ T cell epitopes derived from the gp 100/pmel17 and tyrosinase melanocyte-associated antigens were confirmed or identified. Of major interest, we determined that freshly-isolated PBMC frequencies of Th1-type CD4+ T recognizing these peptides are frequently elevated in HLA-DR4+ melanoma patients (but not normal donors) that are currently disease-free as a result of therapeutic intervention. Epitope-specific CD4+ T cells from normal DR4+ donors could be induced, however, after in vitro stimulation with autologous dendritic cell pulsed with antigens (peptides or antigen-positive melanoma lysates) or infected with recombinant vaccinia virus encoding the relevant antigen. Peptide-reactive CD4+ T cells also recognized HLA-DR4+ melanoma cell lines that constitutively express the relevant antigen. Based on these data, these epitopes may serve as potent vaccine components to promote clinically-relevant Th1-type CD4+ T cell effector function in situ.

Adult↗

PubMed2001

Functional similarity between electrograms recorded from an implantable cardioverter defibrillator emulator and the surface electrocardiogram.

Clinical use of stored electrogram (EGM) configurations currently used in ICDs is limited. The hypothesis that EGMs recorded from electrodes on the ICD surface may improve diagnostic capabilities of the device was tested in the present study. The Buttons on Active Can Emulator (BACE), an ICD-sized device containing four button electrodes, was temporarily placed into a subcutaneous or submuscular left pectoral pocket in 16 patients during ICD implantation. Simultaneous recordings were obtained from the ECG lead II, bipolar EGMs using BACE electrodes, and a bipolar atrial EGM during sinus rhythm (SR), ventricular pacing (VP) at cycle lengths of 500 and 400 ms, and VT. Visible P waves were present in all patients during SR (n = 15), in 5 (33%) of 15 patients during VP, and none of the patients during VT (n = 4) using BACE EGMs and lead II. P and QRS amplitudes and the P:QRS ratio during SR in BACE EGMs were significantly lower than those in lead II. BACE EGMs showed prominent changes in QRS morphology and duration during VP and VT compared to SR, and the magnitude of QRS prolongation during VP was similar to that in lead II. Measurements of PR, QRS, and QT duration during SR showed good agreement between BACE EGMs and lead II. In conclusion, EGMs recorded from electrodes embedded on the ICD housing may potentially improve visual discrimination between supraventricular and ventricular arrhythmias. They also may be useful as a surrogate of the ECG for analysis and monitoring of different components of P-QRS-T complex.

Defibrillators, Implantable↗

PubMed2000

Mature dendritic cells pulsed with freeze-thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4(+) and CD8(+) T lymphocyte responses.

Immunotherapy trials targeting the induction of tumor-reactive T-cell responses in cancer patients appear to hold significant promise. Because nonmutated lineage-specific antigens and mutated idiotypic antigens may be coexpressed by tumor cells, the use of autologous tumor material to promote the broadest range of antitumor T-cell specificities has significant clinical potential in cancer vaccination trials. As a model for vaccination in the cancer setting, we chose to analyze the promotion of T-cell responses against Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line (B-LCL)-derived antigens in vitro. A series of bulk antigenic formats (freeze-thaw lysate, trifluoroacetic acid lysate, extracted membranes, affinity-purified MHC class I- and class II-presented peptides, acid-eluted peptides) prepared from EBV B-LCLs were tested for their ability to stimulate EBV B-LCL-reactive CD4(+) and CD8(+) T lymphocytes in vitro when pulsed onto autologous dendritic cells (DCs). DC presentation of freeze-thaw lysate material derived from (either autologous or allogeneic) EBV B-LCLs with an Mr of 10 kd or larger stimulated optimal anti-EBV B-LCL responsiveness from freshly isolated CD4(+) and CD8(+) peripheral blood T cells. These in vivo "memory" T-cell responses were observed only in EBV-seropositive donors. CD4(+) T-cell responses to lysate-pulsed DCs were Th1 type (ie, strong interferon-gamma and weak interleukin-5 responses). While CD8(+) T-cell responses were also observed in interferon-gamma Elispot assays and in cytotoxicity assays, these responses were of low frequency unless the DC stimulators were induced to "mature" after being fed with tumor lysates. Optimal-length, naturally processed, and MHC class I- or class II-presented tumor peptides were comparatively poorly immunogenic in this model system. (Blood. 2000;96:1857-1864)

Antigens, Neoplasm↗

PubMed2000

Triphasic norgestimate-ethinyl estradiol for treating dysfunctional uterine bleeding.

OBJECTIVE: To compare the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol (E2) and placebo in the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding (DUB). METHODS: In this multicenter, randomized, double-masked study, 201 women (15-50 years of age) with DUB received triphasic norgestimate-ethinyl E2 or placebo, for three consecutive 28-day treatment cycles. Efficacy was determined by evaluating investigator and subject assessments of DUB resolution, abnormal uterine bleeding patterns during an 84-day reference period, and change from baseline in subjects' quality of life. The sample size was based on the assumption that the proportions of subjects exhibiting treatment success (percentage of subjects with investigator and subject overall assessments of DUB resolution of "improved") were 65% for the active group and 40% for the placebo group (alpha = 0.05, 1 - beta = 0.80). RESULTS: More than 80% of subjects receiving triphasic norgestimate-ethinyl E2 had improvements in their abnormal bleeding patterns as assessed by investigators, and the subjects themselves compared with fewer than 50% of subjects in the placebo treatment group (P <.001). Abnormal bleeding patterns were reported by significantly fewer subjects receiving triphasic norgestimate-ethinyl E2 than in the placebo treatment group (P <. 001). Change from baseline in physical functioning (eg, self-care, walking, lifting, exercising) was significantly more improved in the triphasic norgestimate-ethinyl E2 group than in the placebo group. CONCLUSION: The triphasic combination of norgestimate and ethinyl E2 is an effective treatment for metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding.

Adolescent↗

PubMed2000

Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120.

It is well established that the gp120 V3 loop of T-cell-line-adapted human immunodeficiency virus type 1 (HIV-1) binds both cell-associated and soluble polyanions. Virus infectivity is increased by interactions between HIV-1 and heparan sulfate proteoglycans on some cell types, and soluble polyanions such as heparin and dextran sulfate neutralize HIV-1 in vitro. However, the analysis of gp120-polyanion interactions has been limited to T-cell-line-adapted, CXCR4-using virus and virus-derived gp120, and the polyanion binding ability of gp120 regions other than the V3 loop has not been addressed. Here we demonstrate by monoclonal-antibody inhibition, labeled heparin binding, and surface plasmon resonance studies that a second site, most probably corresponding to the newly defined, highly conserved coreceptor binding region on gp120, forms part of the polyanion binding surface. Consistent with the binding of polyanions to the coreceptor binding surface, dextran sulfate interfered with the gp120-CXCR4 association while having no detectable effect on the gp120-CD4 interaction. The interaction between polyanions and X4 or R5X4 gp120 was readily detectable, whereas weak or undetectable binding was observed with R5 gp120. Analysis of mutated forms of X4 gp120 demonstrated that the V3 loop is the major determinant for polyanion binding whereas other regions, including the V1/V2 loop structure and the NH(2) and COOH termini, exert a more subtle influence. A molecular model of the electrostatic potential of the conserved coreceptor binding region confirmed that it is basic but that the overall charge on this surface is dominated by the V3 loop. These results demonstrate a selective interaction of gp120 with polyanions and suggest that the conserved coreceptor binding surface may present a novel and conserved target for therapeutic intervention.

Antibodies, Monoclonal↗

PubMed1999

Use of placebo controls in an oral contraceptive trial: methodological issues and adverse event incidence.

Two multicenter, double-blind, placebo-controlled studies were conducted to evaluate the effectiveness of triphasic norgestimate/ethinyl estradiol (Ortho Tri-Cyclen) for the treatment of acne vulgaris. To our knowledge, these studies were the first double-blind, placebo-controlled trials to evaluate the efficacy of an oral contraceptive (OC) in the treatment of acne; in fact, they are probably the first placebo-controlled trials ever completed using modern OC. This article examines the conduct and feasibility of these studies including discussions on study planning enrollment, maintenance of the blind, continuation rates, and pregnancy prevention. Subjects were between the ages of 15 and 49 years, with moderate acne vulgaris, no contraindications to oral contraceptive use, and were willing to use a nonsteroidal method of birth control during the 6 months of the trial. More than 500 participants were enrolled in 1 year. Discontinuation rates between groups were similar. To explore the reasons for the similar and low discontinuation rates, OC-related side effects were evaluated in comparison to placebo. This analysis revealed that the OC exhibited a side effect profile that was similar, in many cases, to that of placebo. Although pregnancies occurred in the placebo arm, the incidence was consistent with expected failure rates for users of nonsteroidal methods in the general population.

Acne Vulgaris↗

PubMed1999

Slowing the titration rate of tramadol HCl reduces the incidence of discontinuation due to nausea and/or vomiting: a double-blind randomized trial.

BACKGROUND: Ultram [tramadol hydrochloride (HCl)] is a centrally acting analgesic that is widely prescribed for the treatment of moderate to moderately severe chronic pain. Although tramadol is generally well tolerated, some patients discontinue use early in the course of treatment because of nausea and vomiting. OBJECTIVE: To investigate the effect of three initial titration rates of tramadol HCl on the incidence of discontinuation due to nausea and/or vomiting in patients who previously did not tolerate tramadol HCl. METHOD: A multicentre, outpatient, randomized double-blind study was conducted, comprised of two phases: a 14-day open-label run-in phase and a 28-day double-blind phase. In the run-in phase the dose of tramadol was titrated over 4 days to the target of 200 mg/day. Patients who discontinued tramadol HCl due to nausea and/or vomiting in the open-label phase were eligible to enter the 28-day double-blind phase after a 10-day wash-out. Patients were randomized to one of three groups using a 10-, 16- or a 13-day titration schedule in order to achieve a target dosage of either 200 mg/day (10- and 16-day titration groups) or 150 mg/day (13-day titration group). The number of discontinuations due to nausea and/or vomiting in each group were compared. RESULTS: Significantly fewer patients (22%) discontinued because of nausea and/or vomiting in the 13- and 16-day titration groups compared to the 10-day group (P=0.008 and P=0.006, respectively). The time to discontinuation was also significantly delayed in the 13- and 16-day groups compared to the 10-day group (P=0.006 and P=0.007, respectively). The outcome of the 13-day titration to 150 mg/day was essentially the same as that of the 16-day titration to 200 mg/day, suggesting that this is a true rate effect rather than being dose related. CONCLUSION: This study demonstrated that a slower titration rate of tramadol HCl improves tolerability in patients who previously discontinued therapy due to nausea and/or vomiting. This study also demonstrates that the rate of titration of tramadol HCl rather than the target dose is the major determinant of tolerability.

Adult↗

PubMed1999

Dendritic cells transduced with an adenovirus vector encoding Epstein-Barr virus latent membrane protein 2B: a new modality for vaccination.

Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignancies, particularly in immunocompromised hosts. As a strategy for stimulating immunity against EBV for the treatment of EBV-associated tumors, we have genetically engineered dendritic cells (DC) to express EBV antigens, such as latent membrane protein 2B (LMP2B), using recombinant adenovirus vectors. CD8(+) T lymphocytes from HLA-A2.1(+), EBV-seropositive healthy donors were cultured with autologous DC infected with recombinant adenovirus vector AdEGFP, encoding an enhanced green fluorescent protein (EGFP), or AdLMP2B at a multiplicity of infection of 250. After 48 h, >95% of the DC were positive for EGFP expression as assessed by fluorescence-activated cell sorting analysis, indicating efficient gene transfer. AdLMP2-transduced DC were used to stimulate CD8(+) T cells. Responder CD8(+) T cells were tested for gamma interferon (IFN-gamma) release by enzyme-linked spot (ELISPOT) assay and cytotoxic activity. Prior to in vitro stimulation, the frequencies of T-cells directed against two HLA-A2-presented LMP2 peptides (LMP2 329-337 and LMP2 426-434) were very low as assessed by IFN-gamma spot formation (T-cell frequency, <0.003%). IFN-gamma ELISPOT assays performed at day 14 showed a significant (2-log) increase of the day 0 frequency of T cells reactive against the LMP2 329-337 peptide, from 0.003 to 0.3 (P < 0.001). Moreover, specific cytolytic activity was observed against the autologous EBV B-lymphoblastoid cell lines after 21 days of stimulation of T-cell responders with AdLMP2-transduced DC (P < 0.01). In summary, autologous mature DC genetically modified with an adenovirus encoding EBV antigens stimulate the generation of EBV-specific CD8(+) effector T cells in vitro, supporting the potential application of EBV-based adenovirus vector vaccination for the immunotherapy of the EBV-associated malignancies.

Adenoviruses, Human↗

PubMed1998

The tolerability of a triphasic norgestimate/EE-containing OC: results from a double-blind, placebo-controlled trial.

Objective: To compare adverse event data collected during administration of a triphasic norgestimate ethinyl estradiol (EE) containing oral contraceptive (OC) [ORTHO TRI-CYCLEN(R)] or placebo.Methods: Four-hundred fifty-two females between the ages of 15 and 49 years were enrolled in two multicenter, double-blind, randomized, placebo-controlled studies. These studies were conducted to evaluate the effectiveness of triphasic norgestimate/EE in the treatment of acne vulgaris (Redmond G, Olson W, Lippman J, et al. Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized placebo-controlled trial. Obstet Gynecol 1997;89:X-X; Lucky A, Henderson T, Olson W, et al. The effectiveness of norgestimate and ethinyl estradiol in treating acne vulgaris. J Am Acad Dermatol, in press). Participants returned to the study centers monthly for evaluation. At each visit, interviews were conducted to elicit and record the occurrence of adverse events. Reports were derived by nondirected questioning.Results: The table below describes the number and percentage of subjects reporting the event during the 6-month period. Note that, over the range of percentages observed, the differences detectable with a power of 0.80 range from approximately 4% to 12%.Conclusion: Excellent tolerability for the triphasic norgestimate/EE OC is demonstrated by a low rate of side effects that did not differ in a statistically significant manner from placebo.

Journal Article↗

PubMed1996

Rapid detection of bovine herpesvirus 1 in the semen of infected bulls by a nested polymerase chain reaction assay.

A nested polymerase chain reaction (PCR) assay was developed for the detection of bovine herpesvirus 1 (BHV-1) in bovine semen and compared with the virus isolation method. When extended semen, commonly used in the bovine artificial insemination industry, was inoculated with BHV-1, the PCR assay detected BHV-1 DNA in semen inoculated at 0.25-2.5 TCID50 per 0.5 mL. In contrast, the lower limit of detection for virus isolation was 250 TCID50 of BHV-1 inoculated in 0.5 mL of extended semen. These methods were also used to detect BHV-1 in the semen of four bulls which were experimentally infected with BHV-1. All infected bulls demonstrated balanitis at 3 d post-inoculation (DPI) and severe balanoposthitis at 4 DPI. BHV-1 was detected in raw semen by virus isolation and PCR at 2 DPI, before balanitis was evident. For virus isolation, the last day that BHV-1 was detected during primary infection was 7 DPI for two bulls and 9 and 11 DPI for the other two bulls. In contrast, PCR detected BHV-1 in the bulls' semen until 14 or 18 DPI. For individual animals, PCR detected BHV-1 during primary infection for at least 1-10 d longer than virus isolation. Reactivation of BHV-1 from latency without the presence of visible lesions was promoted twice by two series of 5 d dexamethasone injections. For the first series of dexamethasone treatments, a positive virus isolation result was obtained on the 5th d of treatment for only one bull. In contrast, two bulls demonstrated evidence of viral reactivation on this day by PCR. All bulls shed BHV-1 in semen on d 4 after dexamethasone treatment, as evidenced by positive virus isolation and PCR results. One bull was still PCR positive 13 d later. For the second series of dexamethasone treatments, a small amount of virus was isolated from semen collected on d 3 or 4 after treatment for two bulls but not from the other two bulls. In contrast, semen samples from all bulls were PCR positive for either or both of these 2 d. In total, from 80 semen samples, 45 were PCR positive and 26 were virus isolation positive. Thus, the PCR assay detected BHV-1 shedding in bulls earlier, more often, and for a longer duration, than did the virus isolation method.

Animals↗

PubMed1996