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Biomedical subjects

R W Anderson

Publications and source records attributed to R W Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Influenza basic polymerase 2 peptides are recognized by influenza nucleoprotein-specific cytotoxic T lymphocytes.

Cytotoxic T lymphocytes (CTL) play an important role in limiting viral infections and in eradicating virus from host tissues. Recent progress in understanding the processing and presentation of viral antigens to CTL indicates that the CTL antigen receptor recognizes peptides derived from viral proteins that are bound to an antigen binding groove present in class I major histocompatibility complex (MHC) molecules. In understanding CTL anti-viral responses and in creating vaccines designed to elicit CTL responses, it is critical to identify the portions of viral proteins that bind class I molecules and are recognized by T cell receptors. Previous findings have indicated that a significant portion of the CTL response of H-2d mice to influenza virus is specific for one of the viral polymerases (PB2). To identify the region of PB2 naturally processed and presented by influenza virus-infected mouse cells to CTL, 31 PB2 peptides of 9-16 residues in length were chosen and chemically synthesized. Two peptides, PB2, residues 146-159 and 187-195, were found to sensitize histocompatible target cells for recognition by influenza virus-specific CTL. When CTL were generated to individual viral proteins using influenza-vaccinia recombinant viruses, we found, to our surprise, that PB2-specific CTL failed to recognize cells sensitized with PB2 peptides 146-159 and 187-195. Further analysis showed that these PB2 peptides were, in fact, recognized by nucleoprotein (NP)-specific CTL generated by NP-vac virus priming and influenza A virus stimulation, or NP peptide stimulation in vitro of NP-vac or influenza A-primed CTL. These results demonstrate that while screening peptide libraries one cannot assume that positive peptides necessarily identify the viral protein to which the CTL response is directed.

Algorithms↗
PubMed1992

Use of dental instruments for bridging during electric pulp testing.

It has been suggested that dental instruments can be used as bridging instruments to facilitate electric pulp testing of teeth with extensive restorations. This study reports a clinical investigation to evaluate the effectiveness of this procedure. One hundred seventeen vital teeth in 20 volunteers were tested. Ten endodontically treated teeth functioned as controls. Following appropriate isolation and asepsis technique, baseline recordings of the threshold response with the electric pulp tester were taken. With the use of dental explorers and endodontic files to bridge between the probe tip and the tooth surface, recordings were made of the threshold responses. Findings indicate that electrically conductive dental instruments can be reliably used as bridging instruments with the electric pulp tester.

Dental Instruments↗
PubMed1992

Response of pulpal blood flow to intra-arterial infusion of endothelin.

Laser Doppler flowmetry was used to determine the effect of the vasoconstrictor endothelin 1 (ET-1) on the pulpal blood flow of intact dogs' teeth during mandibular arterial infusion. ET-1 produced a profound decrease in pulpal blood flow of a relatively long duration at lower doses than similar infusions of norepinephrine. The decrease in pulpal blood flow in response to ET-1 was partially attenuated by the calcium channel blocker nifedipine. These findings demonstrate the presence of receptors for ET-1 in the microvasculature of the dental pulp and suggests that ET-1 may function in the local control of the pulpal microcirculation.

Animals↗
PubMed1992

Cellular and molecular analysis of plasmodium development in Physarum.

The development of an amoeba into a plasmodium involves extensive changes in cellular organisation and gene expression. The genetic basis of a number of recessive mutations that block plasmodium development has been elucidated. The stage at which development becomes abnormal has been determined for all the mutants, as has the terminal phenotype. In order to investigate the changes in gene expression that accompany plasmodium development, a cDNA library has been made using RNA isolated from cell populations in which development was occurring.

Animals↗
PubMed1992

A developmental mutation (npfL1) resulting in cell death in Physarum polycephalum.

In Physarum, microscopic uninucleate amoebae develop into macroscopic multinucleate plasmodia. In the mutant strain, RA614, plasmodium development is blocked. RA614 carries a recessive mutation (npfL1) in a gene that functions in sexual as well as apogamic development. In npfL+ apogamic development, binucleate cells arise from uninucleate cells by mitosis without cytokinesis at the end of an extended cell cycle. In npfL1 cultures, apogamic development became abnormal at the end of the extended cell cycle. The cells developed a characteristic rounded, vacuolated appearance, nuclear fusion and vigorous cytoplasmic motion occurred, and the cells eventually died. Nuclei were not visible by phase-contrast microscopy in most of the abnormally developing cells, but fluorescence microscopy after DAPI staining revealed intensely staining, condensed nuclei without nucleoli. Studies of tubulin organization during npfL1 development indicated a high frequency of abnormal mitotic spindles and, in some interphase cells, abnormally thick microtubules. Some of these features were observed at low frequency in the parental npfL+ strain and may represent a pathway of cell death, resembling apoptosis, that may be triggered in more than one way. Nuclear fusion occurred during interphase and mitosis in npfL1 cells, and multipolar spindles were also observed. None of these features were observed in npfL+ cells, suggesting that a specific effect of the npfL1 mutation may be an incomplete alteration of nuclear structure from the amoebal to the plasmodial state.

Animals↗
PubMed1992

Harvey A. K. Whitney Lecture. Of perceived value.

Current issues in pharmacy are discussed and recommendations are made to help pharmacy demonstrate its value in health care. There is a need for pharmacy to actively demonstrate and communicate its value in health care. Educational requirements should reflect the values of the profession. In the debate over the entry-level Pharm.D. degree, the profession must not lose sight of the principal goal of elevating the basic competencies of all pharmacists. Graduate-level education will continue to be valuable, but the degrees and programs should be modified to meet current and future needs. Residency training will become increasingly essential. A well-defined corps of pharmacy technicians is needed. The profession should strive to meet the needs of society rather than confining itself to traditional practice definitions. This will involve increased interaction with patients. Also, pharmacy directors must become more creative in allocating existing resources and building arguments for expansion. When patients recognize the value of pharmacy services, they will seek out and demand those services. Pharmacists must get involved in deliberations regarding health-care reform. They have a responsibility to promote preventive medicine and healthy life-styles. They should actively promote the rational use of all medications. Although tremendous progress has been made in advancing the concept of pharmaceutical care, the profession still has work to do in communicating its value to the public.

Awards and Prizes↗
PubMed1992

Medications and temporaries in endodontic treatment.

We have attempted to present in this article an overview of the medications used as intracanal dressings during root canal treatment and the materials used to seal endodontic access preparations. Because all the medications reviewed have an antimicrobial effect (with the exception of steroids), they seemingly would be useful in root canal treatment. However, the potentially harmful side effects of the chemical agents, which include cytotoxicity and antigenicity, may make the treatment worse than the cure. With an improved understanding of the principles of root canal cleaning, strong medications placed into canals may be unnecessary. At best, intracanal dressings should be used only in situations that might benefit from such therapy. Temporary restoration of endodontically treated teeth is an essential part of root canal therapy. Commonly used materials and techniques for their uses have been presented. With proper temporization and timely final restoration, the potential for coronal microleakage will be minimized.

Dental Cements↗
PubMed1991

A vasoactive peptide, endothelin-3, is produced by and specifically binds to primary astrocytes.

Primary rat astrocytes were found by immunohistochemistry to display positive staining for endothelin-3, located predominantly in the perinuclear area. The ability of these cells to produce and release endothelin-3 was confirmed by a combination of reverse-phase HPLC and radioimmunoassay, specific for endothelin-3, which demonstrated immunoreactive peptide in cellular extracts and astrocyte-conditioned medium. In addition, astrocytes were shown to possess a single class of binding sites for endothelin with comparable high affinity for endothelin-1, -2 and -3. These results suggest that astrocytes, by virtue of their ability to produce and secrete endothelin-3, serve as a potential extravascular source of intracerebral vasoregulation capable of influencing regional cerebral blood flow.

Animals↗
PubMed1991

Effect of endodontic procedures on root dentin permeability.

The purpose of this study was to quantitate the sequential effects of endodontic procedures on the permeability of human root dentin in vitro. Forty single-rooted teeth were used. Both the crown and the apical 2 mm of the root were removed. The hydraulic conductance of the root before and after various endodontic procedures was measured using a fluid filtration method. Measurements were also made of dentin thickness, intracanal diameter changes, and changes in intracanal surface area. The results showed that instrumentation by K files alone or in combination with Gates Glidden drills did not alter radicular dentin permeability when the cementum remained intact. After removing the cementum, the creation of a smear layer and smear plugs on the canal surface tended to offset the expected increase in dentin permeability created by increasing the intracanal surface area and decreasing root dentin thickness. EDTA treatment inside the instrumented canal to remove the smear layer did not increase permeability significantly. The use of K files followed by Gates Glidden drills tended to remove more cervical dentin, increased the intracanal surface area, and increased the hydraulic conductance of root dentin more than the use of K files alone.

Dental Cementum↗
PubMed1991

Selective autoregulation of endothelins in primary astrocyte cultures: endothelin receptor-mediated potentiation of endothelin-1 secretion.

Observations that primary rat astrocytes express high-affinity binding sites for endothelins and, in addition, are capable of producing not only endothelin-3 but also endothelin-1 prompted the investigation of a possible relation between endothelin peptides and receptors in these cells. Sarafotoxin S6b, an endothelin receptor agonist, was used as a tool to study endothelin receptor-mediated changes in the secretion of endothelin-1 and -3. The effects of sarafotoxin S6b and endothelin-1 in stimulating inositolphospholipid turnover as well as in inducing AP1 in primary astrocyte cultures were found to be similar. A low cross-reactivity of sarafotoxin S6b with endothelin-1 and -3 in the endothelin radioimmunoassays used here, along with a distinctly different elution position in high-performance liquid chromatography, allowed a clear discrimination between sarafotoxin and endothelins in the culture media. Stimulation of primary rat astrocytes with 10(-7) M sarafotoxin S6b for 1 hour resulted in a substantial increase in endothelin-1 immunoreactivity in the medium. This immunoreactivity reached a peak at 3 hours and showed no further increase after 8 and 24 hours. Treatment of our cultures with phorbol myristate acetate, lipopolysaccharide, tumor necrosis factor alpha, and norepinephrine for 24 hours led to only a moderate elevation of endothelin-1 immunoreactivity. Immunoreactive endothelin-3 was not affected by any of the treatments tested. Thus, our data suggest that endothelins in primary rat astrocytes are subject to selective autoregulation, as demonstrated by the potentiation of endothelin-1 secretion after activation of glial endothelin receptors.

Animals↗
PubMed1991

Pharmacists' knowledge of infusion devices.

Results of a mail survey of pharmacists' knowledge of infusion-device technology are presented. In order to develop recommendations on how to prepare pharmacists to take responsible roles in the use of infusion devices, a survey was mailed to 576 directors of pharmacy in hospitals and home health-care companies, deans of pharmacy schools, and executives of state pharmaceutical associations. A total of 237 responses (41.2%) was received. Directors in both hospital and home health-care settings predicted increases in the use of infusion devices in their respective settings within the coming five years. Practitioners and deans concurred that pharmacy schools are not providing adequate instruction in the use of these devices. All four groups of respondents believed that the competencies most essential in the use of these devices are knowledge of therapeutic applications and the ability to select the most appropriate pump to meet clinical needs. Use of drug-infusion technology will increase in the coming five years, and undergraduate, postgraduate, and inservice pharmacy curricula must prepare pharmacists to use it appropriately.

Home Care Services↗
PubMed1991

Hospital administrators' perceptions of pharmacy directors.

The results of a national survey of hospital administrators' perceptions of pharmacy directors are reported. A questionnaire was mailed to a random sample of 1000 hospital administrators nationwide. The questionnaire asked each administrator to rate the managerial skills of pharmacy directors in general and the pharmacy director at his or her institution on a 5-point scale. The value the administrator placed on clinical pharmacy services was investigated, as was the administrator's knowledge of the education of the pharmacy director and the reporting structure between administrator and pharmacy director. The net response rate was 47.8% (478 usable replies). The hospital administrators believed that pharmacy directors in general need to improve their relationship with the nursing staff, their basic managerial skills, and their communication skills. They believed that the pharmacy director at their own institution excelled at keeping up with progressive pharmacy practice, inventory management, and interacting with the pharmacy and therapeutics committee. The administrators indicated that it is very important for the pharmacy department to be involved in therapeutic drug monitoring and medication counseling and to be progressive in their offerings of services. Hospital administrators had a positive perception of the abilities of pharmacy directors but believed that there is still room for improvement.

Attitude of Health Personnel↗
PubMed1990

Endothelins, peptides with potent vasoactive properties, are produced by human macrophages.

Endothelins are peptides, originally isolated from endothelial cells, with potent vasoactive and mitogenic properties. In this study, we demonstrate that human macrophages synthesize and secrete endothelins. Cultured human macrophages were found by immunocytochemistry to stain positively for endothelin 1 and endothelin 3. Their capability to produce and release these peptides was confirmed by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassays, specific for endothelin 1 and 3, respectively. Immunoreactive peptides were identified both in cellular extracts and in macrophage-conditioned medium. The secretion of endothelin 1, but not of endothelin 3, from macrophages could be stimulated 6-10-fold by lipopolysaccharide or phorbol myristate acetate (PMA). Northern blot analysis of total macrophage RNA using an endothelin 1 cDNA probe revealed induction of endothelin mRNA in PMA-treated macrophages. Furthermore, immunoreactive endothelin 1 and 3 were found in U937 cells, a human promonocytic line, and in freshly isolated human monocytes. In contrast, no immunoreactive endothelin was detected in cell extracts from human neutrophils and lymphocytes. The expression of endothelins in tissue macrophages was demonstrated in paraffin sections of human lung using immunohistochemistry. In conclusion, the finding that human macrophages produce endothelins suggests an important role for these peptides in the microenvironment of tissue macrophages. Macrophage-derived endothelins may have an essential function in blood vessel physiology, and aberrant production may contribute to vessel pathology.

Cells, Cultured↗
PubMed1990

Longitudinal evaluation of the seal of endodontic retrofillings.

The apical seal obtained with various retrofilling materials placed in prepared, extracted human anterior teeth was measured at various time intervals. Materials evaluated were cold-burnished gutta-percha, amalgam, amalgam with a cavity varnish, SuperEBA cement, and a glass ionomer restorative material (Ketac-Silver). Control groups included teeth retrofilled with either gutta-percha without sealer or TERM. The root canals were cleaned and shaped and the root ends were prepared for retrofilling. The materials were placed into the preparations and allowed to set for 24 h. Microleakage was measured at 24 h, 1, 2, and 3 wk, and 1, 2, and 3 months after insertion of the retrofilling using a fluid filtration technique. Multiple range analysis indicated that Ketac-Silver produced a significantly inferior seal when compared with the other materials at all time periods. There was no significant difference among SuperEBA, amalgam, and amalgam with a cavity varnish.

Dental Leakage↗
PubMed1990

Microleakage of temporary endodontic restorations in teeth restored with amalgam.

Microleakage of seven temporary restorative materials was evaluated in endodontic access preparations made in teeth restored with amalgam. Ten teeth were used for each of the seven materials: Cavit, Cavit-G, TERM, zinc phosphate cement, polycarboxylate cement, glass ionomer cement, and IRM. A class I amalgam was placed in the occlusal surface of each experimental tooth and an endodontic access preparation was made entirely within the amalgam. Then the access preparation was restored with one of the temporary restorative materials, and microleakage was evaluated using a fluid filtration technique. The amount of microleakage was quantitated by measuring the fluid flow at 15 min, 1 h, 24 h, 1 wk, and 2 wk after insertion of the temporary restoration. Cavit, Cavit-G, TERM, IRM, and glass ionomer cement all provided excellent seals while zinc phosphate cement and polycarboxylate cement provided less effective seals.

Dental Amalgam↗
PubMed1990

HLA-B37 and HLA-A2.1 molecules bind largely nonoverlapping sets of peptides.

T-cell recognition of peptides that are bound and presented by class I major histocompatibility complex molecules is highly specific. At present it is unclear what role class I peptide binding plays relative to T-cell receptor specificity in determination of immune recognition. A previous study from our group demonstrated that the HLA-A2.1 molecule could bind to 25% of the members of a panel of unrelated synthetic peptides as assessed by a functional peptide competition assay. To determine the peptide-binding specificity of another HLA class I molecule, we have examined the capacity of this panel of peptides to compete for the presentation of influenza virus nucleoprotein peptide NP-(335-350) by HLA-B37 to NP-peptide-specific HLA-B37-restricted cytotoxic T-lymphocyte lines. Forty-two percent of peptides tested were capable of inhibiting NP-(335-350) presentation by HLA-B37. Remarkably, none of these HLA-B37-binding peptides belong to the subset that was previously shown to bind to the HLA-A2.1 molecule. Only the NP-(335-350) peptide was capable of binding to both HLA-A2.1 and HLA-B37. These findings demonstrate that the peptide-binding specificities of HLA-B37 and HLA-A2.1 are largely nonoverlapping and suggest that, from the universe of peptides, individual HLA class I molecules can bind to clearly distinct subsets of these peptides.

Adult↗
PubMed1990

The kinetics of peptide binding to HLA-A2 and the conformation of the peptide-A2 complex can be determined by amino acid side chains on the floor of the peptide binding groove.

The ability of amino acid side chains in the floor of the peptide binding groove of HLA-A2 to affect the presentation of a viral peptide to peptide-specific cytotoxic T lymphocytes (CTL) has been examined. HLA-A2 molecules with naturally occurring single amino acid substitutions of Phe to Tyr at position 9 (HLA-A2.4a, Tyr9) and Tyr to Cys at position 99 (HLA-A2.4b, Cys99) and a site directed mutant with a Val to Leu substitution at position 95 (Leu95) were examined for their ability to present the influenza virus matrix M1 55-73 peptide and several sequence variants of the M1 peptide to a panel of 36 M1 55-73-specific HLA-A2.1-restricted CTL lines. The Leu95 molecule demonstrated enhanced kinetics of M1 peptide presentation and the ability to be sensitized by lower concentrations of the M1 peptide than the A2.1 molecule. The Tyr9 and Cys99 molecules exposed to M1 peptide were not recognized by 33 out of 36 CTL lines. The Tyr9 and Cys99 HLA-A2 molecules could bind the M1 55-73 peptide because at least one CTL line was found that could recognize each of these molecules that were exposed to the M1 peptide. CTL recognition patterns of variant M1 peptides presented by the Tyr9 molecule demonstrated that the amino acid at position 9 can be a critical determinant of the conformation of the peptide-A2 complex, and indicated that a particular peptide can bind in the HLA-A2 peptide binding groove in more than one conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗