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Biomedical subjects

R W Anderson

Publications and source records attributed to R W Anderson.

At least 91 records · Page 5Linked to original sources

Update on safe handling of hazardous drugs: the advice of experts.

Questions related to the handling of hazardous drug products were discussed by a panel of pharmacy practitioners. The panel addressed the following issues: pharmacists' responsibilities for instructing patients, nurses, and physicians on safe handling of hazardous drug products; safe transport of hazardous drug products outside the hospital; disposal of hazardous drug products, items contaminated by these products, and body wastes of patients receiving these drugs; appropriate operation, venting, cleaning, decontamination, and recertification of biological safety cabinets (BSCs); the protective clothing and technique that should be used by workers in BSCs; monitoring the health of workers who handle hazardous drug products; pharmacy's potential liability for nonconformance to published guidelines; whether and how pharmacies that prepare few doses of hazardous drug products should comply with stringent guidelines geared to institutions that handle many doses of these products; and precautions for handling hazardous drug products for oral administration, caustic products, and vesicants. Safe limits for time and amount of exposure to hazardous drugs are unknown, but ASHP's revised Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs and current guidelines from the federal Occupational Health and Safety Administration provide guidance on precautions that should be observed.

Drug-Related Side Effects and Adverse Reactions↗

The HIV cytopathic effect: potential target for therapy?

HIV kills activated infected CD4+ T cells after a burst of replication and the release of large numbers of virions. From a review of the literature on HIV regulatory genes and from preliminary mathematical models of HIV dynamics at four levels (host population epidemiology, the immune system, gene regulation within infected cells, and selection of mutants) we have arrived at the theory that in the etiology of HIV the HIV cytopathic effect may actively be caused by a viral regulatory gene product. The most likely candidate is the rev regulatory protein. Rev and the analogous rex protein from HTLV-I (human T cell leukemia virus) both have two active sites with similar function: one site locates the protein in the nucleus/nucleolus, and the other site interacts with viral mRNAs, facilitating their export from the nucleus to the cytoplasm. Rev seems to have a third functional site near the 3' end. We conjecture that this site may be responsible for the cytopathic effect. We think that rev acts on cellular genes that normally induce senescence and cell death during development, or T-cell maturation, or on terminal differentiation. We propose that mathematical and computer models of the immune system could be used to explore whether suppression of the cytopathic action of the rev protein could be of therapeutic benefit in restoring the ability of the immune system to clear HIV or at least to extend latency. We also suggest how immune deficiency disease might be created as laboratory artifact in animal populations.

CD4 Antigens↗

Mathematical models of HIV infection. I. Threshold conditions for transmission and host survival.

This is the second in a series of papers modeling human immunodeficiency virus (HIV) infections at four levels: transmission, interaction with the immune system, gene regulation, and selection of mutants. In the previous paper (1) we described and presented a theory of the HIV cytopathic effect based upon the models (and a review of the literature). In this article we give mathematical equations of threshold conditions that connect infectivity, length of host survival, and frequency of acts conducive to transmission. The formula is derived not only for homogeneous populations but also for populations of an arbitrary number of subgroups with varying frequencies of risk behavior, varying rates of infection and latency periods, and varying frequencies of interaction with other groups.

Cytopathogenic Effect, Viral↗

Specificity of peptide binding by the HLA-A2.1 molecule.

The HLA-A2 molecule contains a putative peptide binding site that is bounded by two alpha-helices and a beta-pleated sheet floor. Previous studies have demonstrated that the influenza virus matrix peptide M1 55-73 can sensitize target cells for lysis by HLA-A2.1-restricted virus-immune CTL and can induce CTL that can lyse virus-infected target cells. To assess the specificity of peptide binding by the HLA-A2.1 molecule, we examined the ability of seven variant M1 peptides to be recognized by a panel of M1 55-73 peptide-specific HLA-A2.1-restricted CTL lines. The results demonstrate that five out of the seven variant M1 55-73 peptides could be recognized by A2.1-restricted M1 55-73 peptide-specific CTL lines. The two variant peptides that were not recognized by any CTL could bind to HLA-A2.1 as indicated by their ability to compete for presentation of the M1 55-73 peptide. In addition, 5 of a panel of 24 unrelated peptides tested could also compete for M1 55-73 presentation by HLA-A2.1. One peptide derived from the sequence of a rotavirus protein could sensitize HLA-A2.1+ targets for lysis by M1 55-73 peptide-specific CTL. We conclude from these studies that: 1) the HLA-A2.1 molecule can bind a broad spectrum of peptides; 2) T cells selected for the ability to recognize one peptide plus a class I molecule can actually recognize an unrelated peptide presented by that same class I molecule; and 3) a stretch of three adjacent hydrophobic amino acids may be an important common feature of peptides that can bind to HLA-A2.1.

Amino Acid Sequence↗

Localization of an immunorecessive epitope on SV40 T antigen by H-2Db-restricted cytotoxic T-lymphocyte clones and a synthetic peptide.

SV40 tumor (T) antigen possesses four distinct antigenic determinants, sites I, II, III, and IV, recognized by SV40-specific H-2b-restricted cytotoxic T-lymphocytes (CTL) clones. SV40-transformed C57BL/6 (B6) mouse kidney cells, designated K-3, 1, 4, K-1, 4, and K-4, 1, have been isolated by immunological selection with SV40 T antigen site-specific CTL clones in vitro. The cells have lost the expression of all four antigenic sites and cannot be lysed by the CTL clones specific for antigenic sites I, II, III, and IV. To search for additional SV40-specific antigenic sites on SV40 T antigen, B6 mice were immunized with K-3,1,4 cells and stimulated spleen cells with K-3,1,4 cells in vitro. Repeated stimulation of the spleen cell culture with gamma-irradiated K-3,1,4 cells in the presence of IL-2 was necessary to generate CTL activity against K-3,1,4 cells. A new group of H-2Db-restricted CTL clones designated as Y-5 was isolated which were cytotoxic to K-3,1,4 cells. The antigenic site recognized by CTL clone Y-5, site V, was localized in the carboxy terminal half of the SV40 T antigen. By the use of a synthetic peptide corresponding to SV40 T antigen in the carboxy region, the antigenic site V was localized between amino acids 489 and 503.

Amino Acid Sequence↗

A dye penetration study of retrofilling materials.

The apical sealing ability of amalgam, cold-burnished gutta-percha, amalgam with cavity varnish, and SuperEBA cement was evaluated in extracted human teeth. For each experimental group, the roots of 20 single-rooted teeth were sectioned from their crowns. Canals were cleaned, shaped, and obturated with vertically condensed warmed gutta-percha and Kerr Pulp Canal Sealer. Following apical preparation and placement of test materials, root ends were placed in 1% methylene blue dye for 2 wk, after which the roots were sectioned longitudinally, and linear measurements of dye penetration were recorded. Results demonstrated statistically less linear dye penetration in the test group sealed with amalgam and cavity varnish. Statistical differences were not detected among the other test groups.

Dental Amalgam↗

A microleakage study of temporary restorative materials used in endodontics.

The purpose of this study was to quantitatively evaluate the sealing properties of various temporary restorative materials used in standard endodontic access preparations by using a newly introduced fluid filtration method. The materials tested were Cavit, Cavit-G, TERM, glass ionomer cement, zinc phosphate cement, polycarboxylate cement, and IRM. Extracted human incisor, canine, and premolar teeth were used, and each tooth served as its own control by testing for microleakage prior to access preparation. Following access preparation, cotton pellets were placed in the pulp chamber so that the space remaining for the restoration was 4 mm. Immediately after placement of the restoration, the teeth were immersed in Ringer's solution and incubated at 37 degrees C. Microleakage was measured after various time intervals. The results indicated that Cavit, Cavit-G, TERM, and glass ionomer cement provided leakproof seals during the 8-wk testing period, while leakage was observed in 4 of the 10 teeth restored with zinc phosphate cement. IRM and polycarboxylate cement were the least effective of the materials tested for preventing microleakage.

Calcium Sulfate↗

Microleakage of temporary restorations in complex endodontic access preparations.

The microleakage allowed by three temporary restorative materials used for the sealing of teeth with both endodontic access and multisurface cavity preparations was measured and evaluated. Extracted human incisor, canine, and premolar teeth with extensive carious involvement were prepared and restored with either Cavit, IRM, or TERM. Microleakage was measured by a fluid filtration technique at various time intervals and after thermal stress. The results indicated that the TERM restorations provided excellent seals and were statistically superior to Cavit and IRM for restoring complex endodontic access preparations. The IRM restorations demonstrated significantly greater microleakage after thermal stress, while the Cavit restorations were deemed clinically unacceptable because of extensive cracks, expansion, and extrusion from the tooth preparations. These defects were not observed with the IRM and TERM restorations.

Calcium Sulfate↗

A comparison of Flex-R files and K-type files for enlargement of severely curved molar root canals.

A double exposure radiographic technique is introduced and used to evaluate the magnitude of apical canal transportation that occurs during preparation procedures. The balanced force technique and a step-back method for cleaning and shaping root canals were evaluated in mesiobuccal root canals from 80 extracted human molar teeth with curvatures ranging from 30 to 73 degrees. Pre- and posttreatment file positions were examined from clinical and proximal radiographic views by computer digitization. Statistical analysis indicated significantly less apical transportation with the use of the balanced force technique when compared with a step-back technique in canals exhibiting both more and less than 45 degrees of curvature.

Dental Pulp Cavity↗

H-2K molecules have two different C-termini, one of which is K-region specific.

Amino acid sequences encoded by exon 8 of the H-2K and H-2D/L genes appear to be locus specific. The majority of H-2Kb molecules contain 10 amino acids that are derived from exon 8. In contrast, the H-2Db, -Dd and -Ld molecules contain only one amino acid which is encoded by exon 8, even though the genetic information exists to encode 10 amino acids analogous to those encoded by the majority of H-2Kb transcripts. We have produced a rabbit anti-peptide serum reactive with the exon 8 encoded sequence of H-2Kb (alpha K-C) that specifically immunoprecipitates a molecule of 45 K mol. wt from spleen cell lysates of b, d, p, q and k haplotype mice. Further analysis by Western blots indicated that virtually all mouse strains express a 45 K protein reactive with alpha K-C. In sequential immunoprecipitations of spleen cell lysates from b, q, p and d haplotype mice using alpha K-C followed by H-2K or H-2D private specificity alloantisera, the anti-peptide serum removed nearly all of the molecules reactive with the anti-H-2K alloantisera (except in the k haplotype) and none of the molecules reactive with the anti-H-2D serum. In addition, no D-region molecules possessing a long C-terminal sequence were detected with an antiserum directed against a representative D-region long C-terminal peptide. We conclude that even though the genetic information for an extended exon 8 exists in K, D and L locus genes, apparently only K-region molecules are expressed with such a C-terminus. Furthermore, in most haplotypes the great majority of H-2K molecules are produced using long exon 8; however, H-2Kk is produced mostly from short exon 8. The absence or presence of key adenosine residues is predicted to be responsible for the variability in class I exon 8 splicing.

Animals↗

Contribution of atrioventricular synchrony to left ventricular systolic function in a closed-chest canine model of complete heart block: implications for single-chamber rate-variable cardiac pacing.

This study assessed the impact of atrioventricular (AV) synchrony on characteristics of left ventricular (LV) systolic function during ventricular pacing over a wide heart rate range in a conscious closed-chest canine model of complete AV block. Ten healthy adult dogs underwent thoracotomy during which complete AV block was created by formaldehyde injection, and paired ultrasonic sonomicrometers were positioned on the LV anterior-posterior minor axis. Following recovery from surgery, peak and end-diastolic LV transmural pressure, maximum dP/dt, stroke work, end-diastolic minor axis dimension, and maximum velocity of shortening, were quantitated at heart rates of 80, 100, 120, 140, and 160 beats per minute (bpm) during both ventricular pacing alone and AV sequential pacing with increasing AV intervals (0, 50, 100, 150, 200, 250, and 300 ms). Over the heart rate range tested, parameters of LV systolic function did not differ significantly during ventricular pacing with or without AV synchrony. For example, during ventricular pacing alone maximum LV dP/dt varied from 2110 +/- 70 mmHg/s to 2463 +/- 567 mmHg/s, a range essentially identical to that observed in the presence of AV synchrony. On the other hand, although the impact on LV performance of varying AV interval from 0 to 300 ms was small, differences tended to become more pronounced at higher pacing rates. At 80 bpm, neither stroke work nor maximum LV dP/dt were affected by change in AV interval, while at heart rates greater than or equal to 120 bpm both stroke work and LV dP/dt tended to maximize at AV intervals of 50 and 100 ms and thereafter declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fine mapping two distinct antigenic sites on simian virus 40 (SV40) T antigen reactive with SV40-specific cytotoxic T-cell clones by using SV40 deletion mutants.

The existence of two distinct antigenic sites at the surface of simian virus 40 (SV40)-transformed H-2b cells has been previously demonstrated (A. E. Campbell, L. F. Foley, and S. S. Tevethia, J. Immunol. 130:490-492, 1983) by using two independently isolated SV40-specific cytotoxic T-lymphocyte (CTL) clones, K11 and K19. We identified amino acids in the amino-terminal half of SV40 T antigen that are essential for the recognition of antigenic sites by these CTL clones by using H-2b cells transformed by mutants that produce T antigen truncated from the amino-terminal or carboxy-terminal end or carrying overlapping internal deletions in the amino-terminal regions of SV40 T antigen. The results show that CTL clone K11 failed to recognize and lyse target cells missing SV40 T-antigen amino acids 189 to 211, whereas CTL clone K19 lysed these cells. The cell lines missing SV40 T-antigen amino acids 220 to 223 and 220 to 228 were not lysed by CTL clone K19 but were susceptible to lysis by CTL clone K11. Two other cell lines missing amino acids 189 to 223 and 189 to 228 of SV40 T antigen were not lysed by either of the CTL clones but were lysed by SV40-specific bulk-culture CTL if sufficient amounts of relevant restriction elements were expressed at the cell surface. The SV40 T-antigen amino acids critical for the recognition of an antigenic site by CTL clone K11 were identified to be 193 to 211; 220 to 223 were identified as critical for recognition by CTL clone K19. The deletion of these amino acids from the T antigen resulted in the loss of antigenic sites specific for CTL clones K11 and K19.

Amino Acid Sequence↗

A DNA sequence conferring high postmeiotic segregation frequency to heterozygous deletions in Saccharomyces cerevisiae is related to sequences associated with eucaryotic recombination hotspots.

The meiotic behavior of two graded series of deletion mutations in the ADE8 gene in Saccharomyces cerevisiae was analyzed to investigate the molecular basis of meiotic recombination. Postmeiotic segregation (PMS) was observed for a subset of the deletion heterozygosities, including deletions of 38 to 93 base pairs. There was no clear relationship between deletion length and PMS frequency. A common sequence characterized the novel joint region in the alleles which displayed PMS. This sequence is related to repeated sequences recently identified in association with recombination hotspots in the human and mouse genomes. We propose that these particular deletion heterozygosities escape heteroduplex DNA repair because of fortuitous homology to a binding site for a protein.

Alleles↗

Polymorphism and uniparental inheritance of mitochondrial DNA in Physarum polycephalum.

Restriction endonuclease analysis was done on mitochondrial DNA (mtDNA) from 19 plasmodial strains of Physarum polycephalum. The extent of mtDNA variation among these strains was high in comparison with other organisms, and provides a useful source of cytoplasmic genetic markers. The strains were classified into seven groups according to their mtDNA types. Although plasmodia of P. polycephalum are diploid, formed by fusion of amoebal isogametes, each of the 19 plasmodia possessed mtDNA of only a single type. The transmission pattern of mtDNA during plasmodium formation was studied by mating pairs of amoebal strains that contained mtDNA of different types. Transmission was uniparental; the plasmodia that were formed carried mtDNA with the restriction pattern of only one of the two parental types. Since diploid zygotes develop into plasmodia by repeated mitotic cycles in the absence of cell division, it is clear that this uniparental transmission of mtDNA does not depend upon random partitioning either of mitochondria or of mtDNA molecules during cell division.

DNA Restriction Enzymes↗

Liposuction. History, techniques, and complications.

Liposuction is a very safe and predictable means of contouring the body's adiposities. It is an effective surgical method for aesthetic sculpturing with minimal complications. Complications are rare and most commonly include waviness or irregularities of the skin from poor patient selection. We have had in the last 1200 patients one case of a hematoma that was attributed to preoperative ingestion of aspirin. No seromas have occurred in this group of patients. The procedure is relatively pain free, and propoxyphene is usually adequate for pain control. The results have been rewarding for both the surgeon and the patient. Liposuction surgery has arrived as a well-accepted, reliable, and safe procedure for treating unwanted adiposities and contouring the face, neck, and body.

Adipose Tissue↗