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P Anderson

Publications and source records attributed to P Anderson.

At least 307 records · Page 17Linked to original sources
PubMed1991

Expression and tyrosine phosphorylation of the T cell receptor zeta-subunit in human thymocytes.

Recent evidence suggests that the zeta-subunit of the TCR complex plays a critical role in transducing signals initiated by the Ag receptor heterodimer. Because thymic maturation involves specific interactions between the TCR complex and thymic stromal cells, the zeta-subunit has been postulated to also play a role in this process. To assess the potential for zeta to contribute to thymocyte maturation, we have used an anti-zeta mAb (TIA-2) to quantitate its expression in mature (CD3bright) and immature (CD3dim and CD3-) populations of human thymocytes. Using both flow cytometric and immunoblotting analysis, we found that the relative expression of TCR-zeta varied directly with the surface expression of CD3. Importantly, TCR-zeta was detected in the majority of CD3- thymocytes, indicating that its expression precedes the surface appearance of CD3:TCR. In thymocytes, TCR-zeta was found to be constitutively phosphorylated on tyrosine residues. The relative expression of phospho-zeta varied directly with the maturational stage of the thymocyte, with the mature (CD3bright), single positive cells accounting for most of the phospho-zeta found in the human thymus. The expression of phospho-zeta could be significantly increased by activating thymocytes with mAb reactive with either CD3 or CD2. These results suggest that TCR-zeta is functionally linked to the major thymocyte activation receptors.

Cell Differentiation↗
PubMed1991

Tyrosine phosphorylation of the Fc gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing.

NK cells are large granular lymphocytes capable of killing certain tumor cells and virally infected cells in a non-MHC-restricted manner. NK cells can also effect an antibody dependent cytotoxicity that is triggered by CD16, an FcR for IgG. In NK cells, CD16 is expressed in association with zeta, a signal transducing subunit of the TCR complex. Here we show that, just as T cell activation via the TCR complex results in tyrosine phosphorylation of zeta TCR, NK cell activation via CD16 results in tyrosine phosphorylation of zeta NK. Whereas antibody-dependent cytotoxicity also results in tyrosine phosphorylation of zeta, natural cytotoxicity does not. Our results indicate that zeta functions as a transducing element for antibody dependent, but not antibody independent killing by NK cells. Consequently, NK cells are likely to express at least two distinct receptor complexes capable of triggering cytolytic effector function.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1991

CD2 is functionally linked to the zeta-natural killer receptor complex.

Natural killer (NK) cells express two distinct surface receptors capable of triggering cytolytic effector function. The first is CD16, an immunoglobulin Fc receptor that allows NK cells to mediate antibody-dependent killing (ADCC). NK cells express CD16 in association with zeta, a signal-transducing subunit that is also a component of the T cell receptor complex. Activation of NK cells via CD16 results in tyrosine phosphorylation of zeta. The second NK cell triggering receptor is CD2, a 50-55-kDa cell surface molecule that is also expressed on T cells. Here we show that NK cell activation induced by mAb reactive with CD2 (either anti-T11.1 alone or with anti-T11.2 in combination) also results in the tyrosine phosphorylation of zeta. Our results indicate that CD2 is functionally linked to the CD16-zeta complex and suggest that the zeta subunit plays a central role in the signal transduction pathways utilized by NK cells.

Antibodies, Monoclonal↗
PubMed1991

Biochemical identification of a direct physical interaction between the CD4:p56lck and Ti(TcR)/CD3 complexes.

The CD4 and CD8 antigens function in synergy with the TcR/CD3 complex in the generation of intracellular signals leading to T cell proliferation. The association of the protein-tyrosine kinase p56lck with CD4 and CD8 provides a potential mechanism in the generation of intracellular signals. Several studies have shown that CD4 can co-modulate with TcR/CD3 suggesting that these receptor complexes may associated on the surface of the T cell. Nevertheless, it has proven difficult to formally demonstrate a direct physical interaction between the CD4 and TcR/CD3 complexes using biochemical techniques. In this study, we have used the sensitivity of the in vitro kinase assay to show a direct physical linkage between the CD4:p56lck complex and various CD3 subunits. Immunoprecipitation of CD4 from cell lysates derived from the T lymphoblastoid line HPB-ALL results in the co-purification of p56lck with an additional polypeptide at 20 kDa. Re-precipitation analysis and isoelectric focusing demonstrated that this band corresponds to the CD3 epsilon chain. An alternative approach which involves the labeling of microsomal membranes with [gamma-32P]ATP revealed the presence of CD3 epsilon and zeta chains in anti-CD4 immunoprecipitates. By contrast, we were unable to demonstrate the association of the CD4:p56lck and TcR/CD3 complex in resting peripheral blood lymphocytes. These data indicate that the CD4:p56lck and TcR/CD3 complexes have the ability to form stable complexes on the surface of certain T cell lines.

Animals↗
PubMed1991

A correlation between nuclear supercoiling and the response of patients with bladder cancer to radiotherapy.

Single cell tumour suspensions were prepared from biopsy and urine samples from 28 patients with muscle invasive transitional cell carcinoma of the bladder. Nuclear extracts (nucleoids) containing intact chromatin were isolated from these cells and the condensation of DNA supercoils measured by the light scattered from individual nucleoids within a flow cytometer. Exposure of these nucleoids to 10 micrograms ml-1 ethidium bromide produced 78.9% increase in light scatter compared to those treated with 50 micrograms ml-1. This finding is consistent with the known effect of ethidium bromide on DNA supercoiling and confirms that the light scatter signal is responding to changes at this level of DNA organisation. Cell samples were also exposed to 12 Gy of gamma radiation and the effect on nucleoid light scatter recorded. Of the patients studied prior to radiotherapy, those with persistent disease 3 months after treatment generated an increase in nucleoid light scatter of + 9.35 +/- 4.8% after 12 Gy irradiation, of these, 2/14 produced nucleoids that relaxed by more than 10% compared to controls. Those patients with no evidence of disease after radiotherapy gave an increase in nucleoid light scatter after in vitro irradiation of + 19.3 +/- 4.5% of which 10/14 (71%) relaxed by more than 10%. It is proposed that the increased relaxation within the supercoiled DNA from patients whose tumours were undetectable 3 months after therapy, is related to the inherent radiosensitivity of these tumour cells. Such a difference in nucleoid response within tumour cells from patients that responded to radiation may arise due to a decreased affinity of DNA loops for the nuclear matrix. This structural change, at a site associated with the initiation of DNA synthesis, may affect the ability of cells to continue successful cell division after radiation damage.

Biopsy↗
PubMed1991

Randomized controlled trial of general practitioner intervention in women with excessive alcohol consumption.

Seventy two women drinking 21 units (210g) or more of alcohol per week were recruited from an opportunistic screening programme in eight English general practices. The women were randomized into control and treatment groups. Women in the treatment group received ten minutes advice from their general practitioner to reduce alcohol consumption. At one year follow-up, when analyzed by intention to treat, women in the treatment group had reduced their alcohol consumption from an average of 35-24 units per week. Similar reductions were found in the control group (from 37-27 units per week). The lack of evidence for a treatment effect may be explained by contamination of the control group by informal interventions.

Journal Article↗
PubMed1991

Host metabolites that phenotypically increase the resistance of Haemophilus influenzae type b to clearance mechanisms.

Unidentified low-molecular-weight factor(s) in serum or nasopharyngeal secretions were known to phenotypically increase the resistance of Haemophilus influenzae type b (Hib) to bactericidal and opsonic antibodies, and resistance was attributed to two hypothetical mechanisms. Serum components generating resistance were studied. Mechanism 1, present in some Hib strains and their capsule-deficient mutants and accompanied by apparent increases in lipopolysaccharide content, was reproduced with a mixture of glucose, lactate, urea, and bicarbonate. Mechanism 2, present only in capsulated Hib and accompanied by increased capsulation, was reported with a mixture of Ca++ and lactate. Hib incubated with these compounds in buffer or grown in serum filtrate was resistant, but Hib grown in conventional media containing the metabolites in serum filtrate was resistant, but Hib grown in conventional media containing the metabolites was not. The resistant phenotype, which resembles Hib in vivo, may depend on nutrient balance as well as the specific factors. Lactate apparently is an important energy source for Hib.

Bicarbonates↗
PubMed1991

Interleukin-6 response to deliberate colonization of the human urinary tract with gram-negative bacteria.

Intravesical inoculation of patients with Escherichia coli provided an opportunity to examine the interleukin-6 (IL-6) response to a gram-negative bacterial urinary tract infection in humans. All patients secreted IL-6 as a result of infection. Urinary IL-6 was not continuously secreted but appeared as a series of similar peaks during the first 48 h after infection. There was no significant difference in the ability to trigger IL-6 secretion between isogenic adhering or nonadhering strains, but a threshold concentration of 10(5) bacteria per ml of urine was necessary to fully stimulate IL-6 secretion. There was no detectable increase in IL-6 levels in the serum of the colonized individuals, suggesting mainly local IL-6 production. These results demonstrate that IL-6 is a part of the human mucosal response to gram-negative urinary tract infections.

Adult↗
PubMed1991

Scanning and contact microradiographic study of the effect of degree of saturation on the rate of enamel demineralization.

The effect of degree of saturation with respect to hydroxyapatite (DSHA) on enamel section demineralization was studied by contact and scanning microradiography (CMR and SMR). Two aspects were studied: (1) the effect of different values of DSHA at constant pH, and (2) the effect of constant DSHA with variable pH. In the pH range (2.5-4.5) and time scale (0-120 h) studied, the DSHA was more important in determining the rate of enamel lesion progression than was the pH.

Adult↗
PubMed1991

Family-centered nursing in the postanesthesia care unit: the evaluation of practice.

The philosophy of nursing care at the Medical Center Hospital of Vermont (MCHV) is family-centered. In the summer of 1989, an open family visitation policy was implemented. The goals of allowing family members into the PACU were to (1) enhance communication between staff and family members, and (2) evaluate whether patients and family members perceived the open visitation policy as beneficial. The specific focus of phase I of the study is the evaluation of the patients and their families who participated in the experience with the PACU staff. A questionnaire was developed to assess several dimensions of the experience. To date, 46 complete sets of patients and families have responded to the questionnaire. Results show that 89% of the patients and 96% of the families involved felt that the open visitation policy was beneficial. Data were also collected from the PACU nurses who participated and two thirds stated a perceived benefit to patients and family members. Phase II of the study will include implementing a PACU booklet and video preoperatively to prepare patients and family for the perioperative experience. Questionnaires will then be redistributed and responses of the prepared study group will be compared with the phase I control group. The objective of phase II will be to determine the impact of improved environmental awareness of the patient and family on their perception of the PACU visitation.

Adolescent↗
PubMed1991

Phenotypic abnormalities in CD8+ T lymphocyte subsets in patients with rheumatoid arthritis.

We analyzed the cell surface phenotype of CD8+ cells in both peripheral blood and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Utilizing the monoclonal antibodies anti-CD45RA, anti-CD29 and anti-S6F1-, one can define both suppressor effector (CD45RA+CD29-S6F1-) and killer effector (CD45RA-CD29+S6F1+) cells within the CD8 population. In patients with OA, normal proportions of CD8+CD45RA+, CD8+CD29+ and CD8+S6F1+ cells were found in both peripheral blood and SF. The peripheral blood of patients with RA, in contrast, showed a decreased percentage of CD8+CD45RA+ cells (13.4 +/- 2.6) (p less than 0.05), but a normal percentage of CD8+CD29+ and CD8+S6F1+ cells. In the SF of patients with RA, we observed a more dramatic decrease in CD8+CD45RA+ suppressor effector cells (6.4 +/- 5.0) (p less than 0.001), a significant increase in killer effector cells as measured by both CD8 + CD29+ (35.5 +/- 9.9) (p less than 0.001) and CD8 + S6F1+ cells (28.2 +/- 11.4) (p less than 0.01). These changes may contribute to the immunologic abnormalities previously noted in this disease and may provide some insight into the pathophysiologic mechanisms of RA.

Adult↗
PubMed1990

Differential regulation of Ca2+ mobilization in human thymocytes by coaggregation of surface molecules.

Variations in intracellular Ca2+ levels in developing thymocytes are likely to play a major role in both the activation-associated differentiation of thymocytes and in the selection or clonal deletion of cells. Here we examine the role of CD4, CD8, CD2, and CD45 in the regulation of intracellular Ca2+ levels in mature and immature thymocytes. Mature and immature thymocytes, distinguished on the basis of their CD5 expression, were analyzed simultaneously for their ability to mobilize Ca2+ after coaggregation of their CD3/TCR with other thymic surface Ag. Flow cytometric analysis by using Indo-1 showed that coaggregation of CD4, CD8, and CD2 with CD3/TCR clearly enhances a minimal signal delivered via CD3/TCR on immature thymocytes. Coaggregation with class I MHC had no discernible effect. The responsiveness of immature thymocytes correlated strictly with CD3 surface expression, such that loss of responsiveness occurred with reduced CD3 cell-surface density. However, even thymocytes with very low CD3 expression were able to respond to triggering via CD3 under optimal conditions, indicating that the CD3 signal-transducing mechanism is functional on early thymic cells. Intracellular increases in Ca2+ concentrations induced via CD3, could effectively be inhibited by cross-linking of CD45 and CD3 on immature thymocytes. Although triggering via CD2 alone induced a strong Ca2+ flux, prolonged incubation with activating anti-CD2 antibodies made thymocytes refractory to subsequent triggering. Refractoriness was associated with partial loss of surface CD3 and CD3 zeta. Our results indicate that thymic surface Ag are differentially involved in the regulation of intracellular Ca2+ levels in immature as well as mature thymocytes.

Antigens, CD↗
PubMed1990

[Distribution of serum total cholesterol in a population with varying risks of cardiovascular disease].

By means of search in the literature and subsequent meta-analysis, the authors have described the serum total cholesterol values in three different risk groups for cardiovascular disease. High total serum cholesterol levels were associated with increased risk for cardiovascular disease. In addition, it was found that serum total cholesterol increases with age in all groups. A distinct sex difference was observed in the majority of investigations: in the age groups under 25 years and over 50 years, women have higher serum total cholesterol values than men while, in the age group 25-50 years, men have higher values than women. In addition, administration of hormones produces higher serum total cholesterol levels in young women but lower serum total levels among older women. In Danish investigations of serum total cholesterol, the level of serum total cholesterol corresponds to the serum total cholesterol levels in high and middle risk groups for cardiovascular disease.

Adolescent↗
PubMed1990

A monoclonal antibody reactive with a 15-kDa cytoplasmic granule-associated protein defines a subpopulation of CD8+ T lymphocytes.

We have recently described a novel method for the production and characterization of mAb reactive with T cell-restricted intracellular antigens. From a panel of antibodies that react specifically with permeabilized T lymphocytes but not with permeabilized B lymphocytes or native T cells, we have selected one, designated TIA-1, that reacts with 20 to 36% of digitonin permeabilized peripheral blood T lymphocytes. Flow cytometric analysis of purified CD4+ and CD8+ subsets showed TIA-1 to recognize a subpopulation of 49 to 64% of CD8+ lymphocytes. Little or no reactivity with CD4+ resting T lymphocytes was observed. TIA-1 did not react with any of a panel of T cell lines, B cell lines, or monocytoid cell lines. TIA-1 reacted strongly with NK cell clones and CD8+ cytolytic T cell clones, and less strongly with CD4+-activated T cell clones, suggesting a preferential expression in cells possessing cytolytic potential. Cell fractionation experiments showed TIA-1 to be membrane associated. Furthermore, Percoll gradient fractionation of a cytolytic T cell clone (T4T8C1) showed the majority of TIA-1 to be contained in a low density membrane fraction that also contained serine protease activity. Immunoelectron microscopy showed TIA-1 to decorate the membranes of electron lucent and electron dense cytoplasmic granules in this same cytolytic T cell clone. Biochemical analysis showed TIA-1 to be a 15-kDa protein in unstimulated T cells. Upon activation with Con A or anti-CD3 antibodies. TIA-1 was induced to form disulfide linked dimers, trimers, and tetramers of the basic 15-kDa unit. Taken together, our data suggest that TIA-1 is a cytolytic granule associated protein that may define a subpopulation of resting CD8+ T lymphocytes possessing cytolytic potential.

Antibodies, Monoclonal↗