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Biomedical subjects

R Taber

Publications and source records attributed to R Taber.

17 recordsLinked to original sources

A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation.

Forty patients with multiple myeloma scheduled to receive melphalan 200 mg/m(2) followed by autologous stem cell transplantation were randomly assigned to receive oral cryotherapy or room temperature normal saline rinses 30 min before and for 6 h after high-dose therapy. Patients were evaluated for the development of mucositis using the National Cancer Institute grading system as well as evaluation of secondary measures such as days of total parenteral nutrition (TPN), narcotic use, hospitalization, weight loss and resumption of oral caloric intake for 28 days after transplant. Patients self-scored their pain, swallowing, drinking, eating, sleeping and taste alterations for 28 days. The primary end point of this trial was the incidence of grades 3-4 mucositis. Compared to the normal saline group, patients using cryotherapy experienced less grade 3-4 mucositis, 14 vs 74%, P=0.0005. Patients receiving cryotherapy also had statistically lower uses of narcotics and TPN, although there were no differences in length of hospitalization or weight loss. Patient-reported pain was significantly lower and activities were significantly better in the cryotherapy group.

Adult↗

Dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodeficiency virus identified by surface plasmon resonance.

BACKGROUND: Increasing evidence suggests that an effective AIDS vaccine will need to elicit broadly neutralizing antibody responses. However, the mechanisms of antibody-mediated neutralization have not been defined. Previous studies from our lab have identified significant differences in the rates of antibody binding to trimeric SIV envelope proteins that correlate with neutralization sensitivity. Importantly, these results demonstrate differences in monoclonal antibody (MAb) binding to neutralization-sensitive and neutralization-resistant envelope proteins, suggesting that one mechanism for virus neutralization may be related to the stability of antibody binding. To date, little has been done to evaluate the binding properties of polyclonal serum antibodies elicited by SIV infection or vaccination. METHODS: In the current study, we translate these findings with MAbs to study antibody binding properties of polyclonal serum antibody responses generated in rhesus macaques infected with attenuated SIV. Quantitative and qualitative binding properties of well-characterized longitudinal serum samples to trimeric, recombinant SIV gp140 envelope proteins were analyzed using surface plasmon resonance (SPR) technology (Biacore). RESULTS: Results from these studies identified two antibody populations in most of the samples analyzed; one antibody population exhibited fast association/dissociation rates (unstable) while the other population demonstrated slower association/dissociation rates (stable). Over time, the percentage of the total binding response of each antibody population evolved, demonstrating a dynamic evolution of the antibody response that was consistent with the maturation of antibody responses defined using our standard panel of serological assays. However, the current studies provided a higher resolution analysis of polyclonal antibody binding properties, particularly with respect to the early time-points post-infection (PI), that is not possible with standard serological assays. More importantly, the increased stability of the antibody population with time PI corresponded with potent neutralization of homologous SIV in vitro. CONCLUSIONS: These results suggest that the stability of the antibody-envelope interaction may be an important mechanism of serum antibody virus neutralization. In addition, measurements of the 'apparent' rates of association and dissociation may offer unique numerical descriptors to characterize the level of antibody maturation achieved by candidate vaccine strategies capable of eliciting broadly neutralizing antibody responses.

Amino Acid Sequence↗

T-cell presentation of antigen requires cell-to-cell contact for proliferation and anergy induction. Differential MHC requirements for superantigen and autoantigen.

MHC class II+ human T-cell clones are able to simultaneously present and respond to peptide Ag and superantigen resulting in both proliferation and subsequent anergy. A major question remains as to whether a single T cell can present to itself or whether T-T cell interactions are required. We have employed a novel technique for inhibiting cell-to-cell contact that encapsulates individual T cells in agarose gel microdrops. Myelin basic protein-reactive individual CD4+ T-cell clones entrapped within these microdrops neither proliferated nor became anergized to either peptide Ag or Staphylococcal enterotoxin B (SEB), suggesting that cell-to-cell contact was required for T-cell presentation of Ag leading to proliferation and anergy. PMA treatment induced T-cell migration out of gel microdrops, restoring cell-to-cell contact and resulting in proliferation and anergy after T-cell coculture with peptide or superantigen. However, analysis of [Ca+2]i release revealed differences in T-cell responses to SEB versus peptide Ag. The addition of SEB, but not peptide Ag, induced a calcium flux in solitary T cells. Additionally, alpha HLA-DR mAb blocked peptide but not SEB-induced proliferation and anergy induction. Thus, SEB generated an early signal in solitary T cells that may not be a result of self stimulation via MHC class II. However, subsequent cell-to-cell contact was required for proliferation and anergy induction by SEB. These results indicate that peptide Ag requires a MHC class II-dependent cell-to-cell interaction for calcium flux, proliferation, and anergy induction, whereas SEB requires a MHC class II independent cell-to-cell interaction for proliferation and anergy induction after a TCR-generated calcium flux.

Antigen-Presenting Cells↗

Liposomes as vehicles for cellular incorporation of biologically active macromolecules.

Lipid vesicles (liposomes) have recently been shown to be a useful vehicle for the delivery of a variety of compounds to cultured cells. Using large unilamellar vesicles composed of phosphatidylserine [LUV(PS)] we were able to encapsulate poliovirus and purified poliovirus ribonucleic acid (RNA) and show that it can be delivered efficiently to cells in an infectious form. LUV-entrapped poliovirus RNA produced infectious titers 100-fold higher than comparable RNA preparations delivered to cells by other techniques. We have made a quantitative analysis of the uptake and infectivity of the vesicle-encapsulated RNA by using various ratios of RNA copies per vesicle and by determining the percentage uptake of labelled lipid and RNA by HeLa cells.

Cells, Cultured↗

The introduction of poliovirus RNA into cells via lipid vesicles (liposomes).

Large unilamellar vesicles (LUV) composed of phosphatidylserine are capable of encapsulating poliovirus ribonucleic acid (RNA) and delivering it efficiently to cells in an infectious form. The biological activity of vesicle-entrapped poliovirus RNA was 1-2 x 10(4) plaque forming units/nanogram (pfu/ng) and appeared to be enhanced by ribonuclease treatment of the vesicle preparations (infectivity = 1-2 x 10(5) pfu/ng). Vesicle-mediated RNA infection produced equivalent titers in primate and nonprimate cells. Moreover, the data strongly suggest that the ratio of molecules per infectious unit is close to one when the RNA is properly delivered to the cell. A comparative study of LUV and multilamellar vesicles (MLV) indicates that LUV deliver their contents to the cell cytoplasm much more efficiently than MLV. LUV-entrapped poliovirus RNA produced infectious titer 10-100 fold higher than comparable RNA preparations delivered to cells by other techniques.

Animals↗

Biological properties of poliovirus encapsulated in lipid vesicles: antibody resistance and infectivity in virus-resistant cells.

We present evidence that poliovirus can be encapsulated in synthetic large phospholipid vesicles. The virus associated with the vesicles is found to be (i) resistant to antiserum against poliovirus and (ii) infectious for cells that are normally resistant to virus infection because of a membrane restriction. Our interpretation of these results is that the virus is entrapped in the interior aqueous space of the vesicles and that this vesicle-associated virus is introduced directly into the cytoplasm of the cells via fusion of the vesicles with the cellular plasma membrane, bypassing the surface receptor-mediated restriction.

Antibodies, Viral↗

Initial performance of the Stanford Medical pion generator.

A novel, cylindrical geometry, superconducting pion channel has been constructed at Stanford. It can simultaneously deliver up to 60 radially converging pion beams of the same mean momentum but with individually variable momentum spread (0.0-4.3%). Virtually no tuning of the pion beam is required Preliminary tests have demonstrated many of the performance characteristics which facilitate the treatment of selected human tumors.

Cold Temperature↗

The selection of virus-resistant Chinese hamster ovary cells.

We have selected Chinese hamster ovary (CHO) cells resistant to infection by encephalomycarditis (EMC) virus. Thus far, we have obtained five lines resistant to EMC, all of which manifest different phenotypes. Three of the five are not persistently infected with virus, while two lines produce infectious virus and grow in its presence. The nonpersistently infected lines exhibit different resistance profiles to the other viruses we have tested, and they are stable in nonselective growth conditions. Their resistance appears to be due to a genetic alteration in the cell.

Cell Division↗

Persistent reovirus infection of CHO cells resulting in virus resistance.

We obtained a persistently infected line of Chinese hamster ovary cells by selection for resistance to reovirus infection. The cells were persistently infected by a population of viruses that were (i) cytopathic for parental chinese hamster ovary cells and (ii) similar to wild-type reovirus in molecular characteristics. The growth rate, plating efficiency, and morphology of the cells were altered. A large majority of the cells in the population were infected. There was no detectable interferon present in the medium. The cells were relatively resistant to a wide range of viruses.

Animals↗

Etonitazine-induced rigidity and its antagonism by centrally acting muscle relaxants.

Some narcotic drugs have been reported to produce increases in muscle tone in rats. In our laboratory we have found that etonitazine produces a 'lead-pipe' rigidity of the trunk and limb musculature. The reported studies were conducted to characterize etonitazine-induced rigidity more fully, to compare the degree of rigidity with that produced by morphine, codeine and methadone, and to assess the sensitivity of this rigidity to centrally acting muscle relaxants. Of the 4 narcotics tested, etonitazine was far more potent than methadone or morphine for producing rigidity; codeine did not produce peak rigidity comparable to the other 3 narcotics. Etonitazine-induced rigidity occurs at a supraspinal level since the effect was prevented by spinal transsection. Etonitazine-induced rigidity was prevented by the narcotic antagonists cyclazocine, pentazocine and naloxone but not by the serotonin depletor, p-chlorophenylalanine. Etonitazine-induced rigidity was antagonized by centrally acting muscle relaxants, including diazepam, methocarbamol, carisoprodol and zoxazolamine; in agreement with their relative clinical muscle relaxant potencies, diazepam is the most potent antagonist of etonitazine-induced rigidity.

Analgesics, Opioid↗

Effect of pactamycin on synthesis of poliovirus proteins: a method for genetic mapping.

We have studied the effect of the drug pactamycin on protein synthesis in poliovirus-infected HeLa cells. At a concentration which primarily inhibits initiation of protein synthesis, the spectrum of poliovirus proteins synthesized is markedly changed. The amount of NCVP 1, the capsid precursor, is greatly reduced relative to NCVP 2 and the amount of NCVP X is slightly reduced. Since it is believed that there is only one major site for the initiation of protein synthesis on the poliovirus genome, we interpret this differential effect on the poliovirus proteins to be an indication of their relative distance from the initiation site. On this basis, we propose a gene order for the poliovirus genome (5' --> 3') of NCVP 1, NCVP X, NCVP 2.

Antibiotics, Antineoplastic↗