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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells.

Human T-cell leukemia virus type I (HTLV-I) can infect a variety of human cell types, but only T lymphocytes are efficiently immortalized after HTLV-I infection. This study reports an attempt to infect and to immortalize NK cells with HTLV-I. Co-cultivation of freshly isolated NK cells with a HTLV-I-producing T cell line did not result in NK cell infection. However, NK cells activated with an anti-CD16 mAb and co-cultivated with a HTLV-I-producing T cell line were reproducibly infected by HTLV-I. HTLV-I infection was documented in NK cell lines and clones by the detection of defective integrated provirus by both Southern blot and polymerase chain reaction analysis. Although HTLV-I-infected NK cells produced viral proteins, they did not produce infectious viral particles. HTLV-I-infected NK cells were phenotypically indistinguishable from their uninfected counterparts (CD16+, CD2+, CD56+, CD3-). They also retained the ability to mediate both natural and antibody-dependent cell cytotoxicity. The IL-2-dependent proliferation of HTLV-I-infected NK cells was significantly greater than that of uninfected NK cells. The doubling time of this infected population was reduced from 9 days to 3 days, and the overall survival of the culture in the absence of restimulation was extended from 5 wk to 18 wk. Unlike T lymphocytes, HTLV-I-infected NK cells were not immortal, implying a fundamental difference between these two lymphocyte populations.

Base Sequence↗
PubMed1992

Identification and functional characterization of a TIA-1-related nucleolysin.

We recently reported the molecular cloning of a cytotoxic granule-associated RNA-binding protein designated TIA-1. The ability of recombinant TIA-1 to induce DNA fragmentation in permeabilized cells suggested that this protein is the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. Here we report the characterization of a cDNA encoding a TIA-1-related protein designated TIAR. The deduced amino acid sequence of TIAR reveals it to be a 42-kDa protein possessing three RNA-binding domains and a carboxyl-terminal auxiliary domain. Although the RNA-binding domains of TIA-1 and TIAR share greater than 85% amino acid homology, their carboxyl-terminal auxiliary domains are only 51% homologous. The carboxyl terminus of TIAR contains a lysosome-targeting motif, indicating that TIAR is probably a cytotoxic granule-associated protein. Like TIA-1, purified recombinant TIAR induced DNA fragmentation in permeabilized target cells. Although immunoblotting analysis of post-nuclear supernatants revealed TIA-1 protein to be restricted to CTLs, PCR analysis revealed the expression of TIA-1 and TIAR mRNA transcripts in a wide variety of cell types. Our data suggest that the granules of CTLs contain at least two candidate nucleolysins involved in CTL killing.

Amino Acid Sequence↗
PubMed1992

Chemical synthesis of RNA using fast oligonucleotide deprotection chemistry.

The exocyclic amine protecting groups in oligonucleotide synthesis which require 8-16 hours at 55 degrees C for deprotection in ammonia have been replaced with more labile base protecting groups (dimethylformamidine for adenine and guanine and isobutyryl for cytosine). Using these fast oligonucleotide deprotecting groups which require 2-3 hours at 55 degrees C for complete deprotection, a new set of cyanoethyl phosphoramidite ribonucleoside monomers and supports has been developed. Ribozymes and substrate RNAs which were synthesized with these phosphoramidites were assayed and were found to have full catalytic (biological) activity.

Base Sequence↗
PubMed1992

The effect of endothelin 1 on the retinal microvascular pericyte.

The effect of the highly vasoactive peptide endothelin 1 (ET1) was tested on bovine retinal microvascular pericytes propagated in vitro. Specific binding of 125I-ET1 to retinal pericytes was documented by autoradiography. ET1 caused contraction of pericytes at a concentration of 0.1 nM which was accompanied by increases in inositol phosphates. Exposure of pericytes to 10 nM ET1 resulted in the aggregation and realignment of muscle-specific actins into bundles which were oriented parallel to the long axis of the cell, and ET1 was also mitogenic to pericytes in the presence of low levels of fetal calf serum. These observations suggest that ET1 may play an important role in endothelial cell-pericyte interactions within the microvasculature of the retina and that it may be involved in the autoregulation of retinal blood flow.

Actins↗
PubMed1992

High molecular weight proteins in the nematode C. elegans bind [3H]ryanodine and form a large conductance channel.

Single-channel properties of a polypeptide fraction from the nematode Caenorhabditis elegans highly enriched in binding sites were studied in planar bilayers. [3H]Ryanodine binding sites were purified by sucrose gradient centrifugation of C. elegans microsomes solubilized in CHAPS detergent. The highest [3H]ryanodine binding activity sedimented at approximately 18% sucrose (wt/vol), and was composed of a major polypeptide with a M(r) of 360,000 and a minor polypeptide with a M(r) of 170,000. The ryanodine-binding polypeptide(s) formed a Ca(2+)-permeable channel with a permeability ratio P(divalent)/P(monovalent) = 4 and two conductance states of 215 pS and 78 pS in 0.25 M KCl. Ryanodine locked the channel in the 78 pS state and inhibited transitions between the 215 pS and 78 pS states. These data demonstrated the presence of a ryanodine receptor in C. elegans with functional properties comparable to those described in mammalian muscle.

Animals↗
PubMed1992

Increased rate of tuberculin skin test conversion among workers at a university hospital.

OBJECTIVES: To summarize the results of an investigation of increased rates of tuberculin skin test conversion in employees at a university hospital. DESIGN: The results of annual tuberculin skin tests performed on all 1,845 hospital employees from 1986 to 1991 were reviewed. SETTING: A 450-bed acute tertiary care university hospital. RESULTS: The rate of tuberculin skin test conversion was 0.35% (standard deviation +/- 0.15) from 1986 to 1989 and increased to 1.7% during 1991. Investigation revealed deviations from the Centers for Disease Control (CDC) guidelines for tuberculosis control, which included the failure to consider tuberculosis as a probable cause of community-acquired pneumonia and the failure to initiate isolation precautions when tuberculosis was suspected. CONCLUSIONS: The epidemic appeared to be secondary to delays in diagnosis and isolation of patients with pulmonary tuberculosis. Future control measures should include isolation of all hospital patients admitted with pneumonia until tuberculosis has been excluded.

Centers for Disease Control and Prevention, U.S.↗
PubMed1992

Signaling function of reconstituted CD16: zeta: gamma receptor complex isoforms.

Natural killer cells express an Fc receptor for IgG (CD16) in association with disulfide-linked dimers composed of two homologous subunits: the zeta chain of the T cell antigen receptor complex and the gamma chain of the mast cell/basophil Fc receptor for IgE. The ability of zeta and gamma to transduce CD16-mediated activation signals was compared by reconstituting distinct CD16 receptor isoforms composed of various combinations of zeta- and gamma-containing dimers. Stably transformed non-hematopoietic and hematopoietic cell lines were established that expressed chimeric molecules comprising the extracellular domain of CD16 joined to the transmembrane and intracellular domains of zeta or gamma. Reconstituted CD16 receptor complexes triggered Ca2+ influx, tyrosine phosphorylation, and IL-2 production in stable transformants of the Jurkat T cell line. However, cross-linking of the CD16/gamma chimera induced a specific pattern of tyrosine phosphorylation and was more efficient at signal transduction than a CD16, zeta-zeta complex, suggesting that zeta and gamma cytoplasmic domains may be coupled to distinct tyrosine kinase pathways that differentially regulate CD16-mediated activation signals. By contrast, both CD16/zeta and CD16/gamma chimeric molecules were not functional in stable transformants of the fibroblast Chinese Hamster Ovary cell line, indicating a requirement for downstream signaling components present in hematopoietic cells. Finally, the zeta transmembrane domain appears to preferentially associate with CD16 rather than the CD3:TCR complex, suggesting that a hierarchy of molecular interactions governs NK and T cell differentiation.

Animals↗
PubMed1992

The effect of general practitioners' advice to heavy drinking men.

The objective of the study was to determine the effectiveness of advice from general practitioners to heavy drinking men (consuming 350-1050 grams of alcohol per week) to reduce their alcohol consumption. One hundred and fifty-four men recruited from eight general practices were allocated randomly to treatment and control groups. Men in the treatment group received advice from their own general practitioner. At one year follow-up, when analyzed according to intention to treat, the treatment group had reduced their consumption by an excess of 65 grams of alcohol per week when compared with the control group (p less than 0.05). General practitioners should be recommended to screen for alcohol consumption amongst their patients and to give advice to those found to be at risk because of their drinking.

Adult↗
PubMed1992

Subsurface demineralization in dental enamel and other permeable solids during acid dissolution.

Subsurface demineralization of dental enamel during acid dissolution has been reported many times, but its cause remains obscure. At first, the phenomenon was thought to result from the physical structure of enamel. More recent studies have shown that subsurface demineralization occurs in other permeable solids, indicating that there must be more fundamental factors involved in this curious effect. In order for this phenomenon to be investigated, dissolution experiments were carried out by means of real-time scanning microradiography in various systems, including enamel, or aggregates of hydroxyapatite (calcium, strontium, or barium), or hydroxides (calcium or magnesium). These were chosen to discriminate between effects of structure and composition. It was found that it was not possible for the demineralization observed in these systems to be attributed to a common feature. From this, it is concluded that subsurface demineralization in enamel and other mineralized tissues should not be ascribed to a single cause.

Acetates↗
PubMed1992

Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.

PURPOSE: To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer. PATIENTS AND METHODS: Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2. RESULTS: The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm. CONCLUSION: Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.

Adult↗
PubMed1992

Structure and function of the CD16:zeta:gamma complex expressed on human natural-killer cells.

Natural-killer (NK) cells are large granular lymphocytes involved in host defense against tumor cells and virally-infected cells. In addition to natural cytotoxicity, NK cells can effect antibody-dependent cytotoxicity mediated by CD16 (Fc gamma RIIIA alpha). It has recently been shown that CD16 is associated with disulfide-linked dimers composed of 2 homologous sub-units, zeta and gamma. These transducing molecules are also associated with other multimeric cell-surface receptors such as the T-cell antigen receptor (CD3:TCR) complex (zeta and gamma) and the high-affinity Fc receptor for IgE (Fc epsilon RI) expressed on basophils and mast cells (gamma). These results show that distinct cell-surface receptors utilize common transducing sub-units, and emphasize the homology between the CD16, Fc epsilon RI and CD3:TCR complexes. However within the lymphoid cells, the gamma-gamma homodimer is preferentially expressed in NK cells and cytotoxic T cells, suggesting that specific combinations of these transducing dimers might sub-serve distinct signal-transducing functions, and contribute to lymphocyte heterogeneity.

CD3 Complex↗
PubMed1992

Evidence of cytotoxic T-cell destruction of epidermal cells in human graft-vs-host disease. Immunohistology with monoclonal antibody TIA-1.

A newly described mouse monoclonal IgG1 antibody, TIA-1, binds serine esterase-positive granule membranes of cytotoxic human T cells and is a candidate for an effector molecule involved in T-cell cytolytic mechanisms analogous to those of the perforin system. We performed immunohistologic studies on frozen human skin (n = 5) and lip (n = 21) sections as well as on control frozen sections of tonsils, purified cytolytic T (CD8) cells, and B cells using an indirect immunoperoxidase system. We found a strong association of TIA-1+ cells with CD8+ cells invading the epidermis in lip and skin lesions of graft-vs-host disease in human marrow allograft recipients, as well as a sharp geographic association of TIA+ lymphocytes with CD8+ regions in human tonsil sections. Double staining of CD8 and TIA-1 antigens with fluorescein isothiocyanate and Texas red confirmed that 80% to 90% of the CD8 cells were TIA-1+ in the epidermal infiltrates. Leu-7 activity (natural killer cell) was minimal and found in only three of 17 lip biopsy specimens. These data provide new evidence that direct cytolytic attack by donor T lymphocytes is the mechanism of epithelial target cell killing in human graft-vs-host disease.

Adolescent↗