Mathematical models of HIV pathogenesis.
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Apoptosis↗
Biomedical subjects
R W Anderson
Publications and source records attributed to R W Anderson.
Electronic balance as quality assurance for cytotoxic drug admixtures.
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Antineoplastic Agents↗
Preventing medication errors in cancer chemotherapy.
Recommendations for preventing medication errors in cancer chemotherapy are made. Before a health care provider is granted privileges to prescribe, dispense, or administer antineoplastic agents, he or she should undergo a tailored educational program and possibly testing or certification. Appropriate reference materials should be developed. Each institution should develop a dose-verification process with as many independent checks as possible. A detailed checklist covering prescribing, transcribing, dispensing, and administration should be used. Oral orders are not acceptable. All doses should be calculated independently by the physician, the pharmacist, and the nurse. Dosage limits should be established and a review process set up for doses that exceed the limits. These limits should be entered into pharmacy computer systems, listed on preprinted order forms, stated on the product packaging, placed in strategic locations in the institution, and communicated to employees. The prescribing vocabulary must be standardized. Acronyms, abbreviations, and brand names must be avoided and steps taken to avoid other sources of confusion in the written orders, such as trailing zeros. Preprinted antineoplastic drug order forms containing checklists can help avoid errors. Manufacturers should be encouraged to avoid or eliminate ambiguities in drug names and dosing information. Patients must be educated about all aspects of their cancer chemotherapy, as patients represent a last line of defense against errors. An interdisciplinary team at each practice site should review every medication error reported. Pharmacists should be involved at all sites where antineoplastic agents are dispensed. Although it may not be possible to eliminate all medication errors in cancer chemotherapy, the risk can be minimized through specific steps. Because of their training and experience, pharmacists should take the lead in this effort.
Antineoplastic Agents↗
Free beta hCG screening of hydropic and non-hydropic Turner syndrome pregnancies.
Fourteen cases of Turner syndrome (45,X), two cases of mosaic Turner syndrome (45,X/47,XXX and 45,X/ 46,XX), and one case of Turner syndrome involving an isochromosome X [46,X,i(X)(q10)] were ascertained by prenatal maternal serum alpha-fetoprotein (MSAFP) and free beta human chorionic gonadotropin (hCG) screening or by ultrasound. Patient-specific risks for Down syndrome were calculated and used as the criteria to determine offering further testing. Eleven of the 17 cases had hydrops and presented with an increased Down syndrome risk based on MSAFP and free beta hCG screening. The median MOM level was 0.98 and 4.04 for MSAFP and free beta hCG, respectively. Three cases had hydrops but screened negative. The two cases of mosaic Turner syndrome were non-hydropic and screened positive. The 46,X,i(X)(q10) case was non-hydropic but had elevated MSAFP and free beta hCG levels. These data suggest that Turner syndrome pregnancies do not appear to screen positive due to hydrops alone, but screening may also be influenced by the inherent genetic imbalance in the fetus and placenta. Because the MSAFP levels in our series were within the normative range in all except one case with an elevated MSAFP, free beta hCG alone was the most effective screening marker for Turner syndrome pregnancies.
Adolescent↗
Prenatal maternal dried blood screening with alpha-fetoprotein and free beta-human chorionic gonadotropin for open neural tube defect and Down syndrome.
OBJECTIVE: Our purpose was to evaluate second-trimester prenatal screening for open neural tube defects and Down syndrome by use of dried blood specimen collection and transport. STUDY DESIGN: A prospective study of 7497 dried blood specimens from patients <35 years old was performed. Specimens were assayed for maternal blood alpha-fetoprotein and free beta-human chorionic gonadotropin. Patient-specific risks for both disorders were calculated and used to determine whether further evaluation was indicated. The study included an evaluation of the median and SD of analyte multiple of the median levels. RESULTS: The initial positive rate for open neural tube defect was 4.4% adjusted to 2.7% after ultrasonographic revision and collection of a second sample. The initial positive rate for Down syndrome was 3.6% adjusted to 2.8% after ultrasonographic revision. All seven cases of open neural tube defect were detected within the increased risk group. Six of 8 (75%) cases of Down syndrome were detected. The median alpha-fetoprotein multiple of the median was 3.5 in open neural tube defect cases and 0.6 in Down syndrome cases. The median free beta-human chorionic gonadotropin multiple of the median was 2.4 in Down syndrome cases. The SD (log e) of alpha- fetoprotein and free beta-human chorionic gonadotropin in 5868 unaffected white patients was 0.4022 and 0.5635, respectively. CONCLUSION: Second-trimester dried blood screening for open neural tube defects and Down syndrome can achieve screening efficiency comparable to serum-based protocols with distinct advantages over the conventional method of blood collection.
Adult↗
Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease.
The purpose of this study was to evaluate long-term survival benefits of bypass surgery and angioplasty versus medical therapy in 9263 patients at Duke University Medical Center between 1984 and 1990 with coronary artery disease confirmed by cardiac catheterization to involve one, two, or three vessels. Clinical data were prospectively entered into an established cardiovascular database, and annual follow-up was 97% complete for a mean interval of 5.3 years and a maximal interval of 10 years. Outcomes were analyzed with the Coronary Artery Surgery Study "method A" to define patient groups treated by medicine (n = 2449), angioplasty (n = 2924), or bypass surgery (n = 3890). Differences among treatment groups in baseline characteristics were adjusted by Cox proportional hazard models. The anatomic severity of coronary artery stenosis best defined survival benefit from bypass surgery and angioplasty versus medical treatment. One or both interventional treatments provided better long-term survival than did medical treatment for all levels of disease severity. All patients with single-vessel disease, except those with at least 95% proximal left anterior descending stenosis, benefited from angioplasty versus bypass. All patients with three-vessel disease and those two-vessel patients with > or = 95% proximal left anterior descending stenosis benefited from bypass surgery versus angioplasty. All other patients with two-vessel disease and those with > or = 95% proximal left anterior descending stenosis only had similar survival with either interventional treatment. The absolute survival benefit was greatest for patients with severe three-vessel disease treated with bypass surgery.
Angioplasty, Balloon, Coronary↗
An assessment of the ability of various materials to seal furcation canals in molar teeth.
Ninety-seven maxillary and mandibular molar teeth were evaluated for the presence of naturally occurring furcation canals using the fluid filtration method. Only one specimen demonstrated a naturally occurring patent furcation canal. An artificial furcation canal was created with a 0.33-mm drill bit in the 96 teeth lacking naturally occurring furcation canals. Fluid filtration measurements were made before and after the artificial canal was made, and these served as the negative and positive controls for each tooth. The 96 teeth were randomly divided into eight equal groups, and the floor of the pulp chambers was sealed using 3 mm of either Tytin or Dispersalloy amalgams, Vitremer, FluoroCore, gutta-percha with sealer, Tytin with Ali-Bond 2 or Amalgambond, or Dispersalloy with Ali-Bond 2. Analysis of measured microleakage at 3 months indicated that Tytin amalgam used alone had significantly more microleakage than all other materials; however, this difference did not exist when bonding agents were used with Tytin. All materials leaked significantly less than the positive controls.
Dental Leakage↗
Root surface temperatures produced during post space preparation.
In vitro root surface temperatures produced during post space preparation were measured. The preparations were made using a GPX bur with rotational speeds of 6,500, 8,000, 9,500, 11,000, and 15,000 rpm. The overall mean temperature increase ranged from 0.66 degree to 4.81 degrees C and was greatest at 8,000 rpm. When speeds > 8,000 rpm were used, temperature increases also resulted, but they were significantly less than that which occurred at 8,000 rpm. Damage to the supporting structures of teeth should not occur when this bur is used, at any of the speeds evaluated, to create a post space.
Analysis of Variance↗
How adaptive antibodies facilitate the evolution of natural antibodies.
It is shown how Ig specificities, randomly generated in conventional B cells, come to be expressed in the genetically-determinate B1 population. Thus the adaptive antibody population facilitates the evolution of the natural antibody repertoire, in accordance with the Baldwin effect in the evolution of instinct. The evolution of these two populations is discussed under both the 'proximal usage' and 'preferential expression' hypotheses of biased Ig gene segment usage. This process is independent of theories of B1 function.
Animals↗
Push-out strength and SEM evaluation of resin composite bonded to internal cervical dentin.
The bond strength of a resin composite used with a dual-cured dentin bonding system to internal cervical bovine dentin was evaluated using a direct or indirect placement technique. Teeth were sectioned transversely to produce 4 mm-thick specimens. The root canals were enlarged to a standardized taper, treated with a dentin bonding system, and filled with a light-cured resin composite using either direct, incremental composite placement or indirect composite placement of a pre-polymerized composite inlay. The debond stress of indirectly placed restorations using a composite inlay was 8.5 (SD +/- 2.7) MPa which was significantly greater (p < 0.0001) than the value of 5.0 (SD +/- 1.9) MPa for composite placed in a conventional, incremental manner. SEM evaluation revealed the indirect placement technique demonstrated increased resin tag density and length as compared to the direct technique. Enhanced retention of resin composite to endodontically prepared dentin treated with a dentin bonding system was obtained by using a composite inlay technique as opposed to direct, incremental buildup of the material.
Acid Etching, Dental↗
Learning and evolution: a quantitative genetics approach.
Recent models of the interactions between learning and evolution show that learning increases the rate at which populations find optima in fixed environments. However, learning ability is only advantageous in variable environments. In this study, quantitative genetics models are used to investigate the effects of individual learning on evolution. Two models of populations of learning individuals are constructed and analyzed. In the first model, the effect of learning is represented as an increase in the variance of selection. Dynamical equations and equilibrium conditions are derived for a population of learning individuals under fixed and variable environmental selection. In the second model, the amount of individual learning effort is regulated by a second gene specifying the duration of a critical learning period. The second model includes a model of the learning process to determine the individual fitness costs and benefits accrued during the learning period. Individuals are then selected for the optimal learning investment. The similarities of the results from these two models suggest that the net effects of learning on evolution are relatively independent of the mechanisms underlying the learning process.
Animals↗
HIV results in the frame. Paradox remains.
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CD4-Positive T-Lymphocytes↗
Antigen processing in vivo and the elicitation of primary CTL responses.
CD8+ T lymphocytes (TCD8+) play an important role in cellular immune responses. TCD8+ recognize MHC class I molecules complexed to peptides of 8 to 10 residues derived largely from cytosolic proteins. Proteins are generally thought to be fragmented in the cytoplasm and delivered to nascent class I molecules in the endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To explore the extent to which TCD8+ induction in vivo is limited by proteolysis or peptide transport into the ER, mice were immunized with recombinant vaccinia viruses containing mini-genes encoding antigenic peptides (bypassing the need for proteolysis), or these peptides with a NH2-terminal ER insertion sequence (bypassing the requirements for both proteolysis and transport). Additionally, mice were immunized with recombinant vaccinia viruses encoding rapidly degraded fragments of proteins. We report that limitations in induction of TCD8+ responses vary among Ags: for some, full length proteins are as immunogenic as other forms tested; for others, maximal responses are induced by peptides or by peptides targeted to the ER. Most importantly, in every circumstance examined, targeting peptides to the ER never diminished, and in some cases greatly enhanced, the TCD8+ immune response and provide an important alternative strategy in the design of live viral or naked DNA vaccines for the treatment of cancer and infectious diseases.
Amino Acid Sequence↗
Antigen-presenting cell lines internalize peptide antigens via fluid-phase endocytosis.
In this report, we present experimental evidence that antigen-presenting cell lines take up peptide antigens in a manner consistent with fluid-phase endocytosis. Using the fluid phase endocytic marker inulin and a mathematical model for fluid phase uptake, we have found a basal uptake rate constant of approximately 0.9-2 microns 3/cell minutes in A20, TA3, and J774 cells. An influenza virus peptide, PB2(303-313), the octapeptide, angiotensin II, an ovalbumin peptide, OVA(323-339), and a guinea pig myelin basic protein peptide, MBP(72-86), have uptake rate constants comparable to inulin, i.e., between 1 and 4 microns3/cell minutes in A20 cells. However, another influenza virus peptide, PB2(146-159), has an uptake rate constant approximately sixfold higher than that found for inulin in A20 cells. We have also determined that the peptide antigens we tested are retained in A20 cells similarly to inulin, with half-times calculated to be from 2 to 13 min as compared to 2 min for inulin. Notably, these results were obtained over short incubation times (up to 20 min) and under conditions that restrict peptide proteolysis and also protein synthesis. We conclude from these studies that peptide antigens enter antigen-presenting cells via fluid-phase endocytosis.
Animals↗
Hans J. Bremermann: a pioneer in mathematical biology.
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Biology↗
On the maternal transmission of immunity: a 'molecular attention' hypothesis.
Maternally-derived antibodies can provide passive protection to their offspring. More subtle phenomena associated with maternal antibodies concern their influence in shaping the immune repertoire and priming the neonatal immune response. These phenomena suggest that maternal antibodies play a role in the education of the neonatal immune system. The educational effects are thought to be mediated by idiotypic interactions among antibodies and B cells in the context of an idiotypic network. This paper proposes that maternal antibodies trigger localized idiotypic network activity that serves to amplify and translate information concerning the molecular shapes of potential antigens. The triggering molecular signals are contained in the binding regions of the antibody molecules. These antibodies form complexes and are taken up by antigen presenting cells or retained by follicular dendritic cells and thereby incorporated into more traditional cellular immune memory mechanisms. This mechanism for maternal transmission of immunity is termed the molecular attention hypothesis and is contrasted to the dynamic memory hypothesis. Experiments are proposed that may help indicate which models are more appropriate and will further our understanding of these intriguing natural phenomena. Finally, analogies are drawn to attention in neural systems.
Animals↗
Modulation of alloreactivity in transplant recipients by phenotypic manipulation of donor endothelium.
Phenotypic manipulation of allograft endothelium to reduce immunogenicity would have a significant impact on transplantation. In this study we have demonstrated that random seeding of a heart allograft with endothelium, of host origin, not only promotes long-term survival, but reduces the requirement for pharmacologic immunosuppression. We propose that this simple technology could easily be extrapolated to the clinical arena where hypothermia and preservation solutions have allowed allografts to remain ex vivo for extended periods.
Animals↗
Evaluation of the seal of various amalgam products used as root-end fillings.
Different formulations of amalgam have physical properties that may make them behave differently in the often-contaminated root end environment. Five different brands of amalgam were evaluated for microleakage of root-end fillings placed in extracted human teeth. These included a zinc-free spherical amalgam, a zinc-free admixture amalgam, two zinc-containing admixture amalgams, and a zinc-containing lathe-cut amalgam. The amalgams were placed either into dry root-end preparations or into preparations contaminated with human blood. The fluid filtration method was used to measure microleakage at 1, 2, 4, 8, 12, and 24 wk after placement. Analysis of variance revealed significant differences in the rates of microleakage at every measurement period. Scheffé's test showed that the zinc-free spherical amalgam had significantly greater leakage than all the other products evaluated. There were no significant differences between any of the other products. Blood contamination did not adversely affect the seal of any amalgam.
Analysis of Variance↗