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Biomedical subjects

G Anderson

Publications and source records attributed to G Anderson.

At least 181 records · Page 10Linked to original sources
PubMed1994

Positive selection by purified MHC class II+ thymic epithelial cells in vitro: costimulatory signals mediated by B7 are not involved.

We have investigated the possibility that the costimulatory signals required for activation of mature T cells also play a role in providing differentiation signals for positive selection during T-cell development. We show that purified MHC Class II+ thymic epithelial cells are able to support positive selection in vitro but lack both the functional capacity to deliver costimulatory signals and expression of the costimulatory ligand B7. Our results suggest that the additional signals provided by costimulatory ligands are not required for TCR-mediated positive selection, although other ancillary signals provided by thymic epithelial cells may be involved.

Animals↗
PubMed1994

The pivotal role of the academic health center.

Academic health centers (AHCs) now play major roles in the development, adoption, and evaluation of medical technologies; the provision of advice to other entities involved in medical innovation; and the education of current and future practitioners. However, recent and potential health care reform initiatives could make it increasingly difficult for AHCs to continue to play their historical roles in medical innovation. Policymakers are examining specific options that would explicitly cover the cost of some of these services but could take away some of the autonomy AHCs have enjoyed and could change the role of AHCs in technological innovation.

Academic Medical Centers↗
PubMed1994

Application of the Inverness Blood Grouping System for semiautomated ABO and D testing of patients' samples.

We evaluated the performance of the Inverness Blood Grouping System (IBG Systems, Inc., Laytonsville, MD) for the ABO and D red cell grouping of patients' samples. The IBG System is a semiautomated microplate device for blood grouping and antibody detection We tested 2,051 samples using the IBG System and by manual grouping techniques. In no instance did the IBG System give a final ABO interpretation different from the final manual technique. For three samples, the JBG System's ABO interpretation was different from the manual interpretation. An error in interpretation by the technologist performing the manual testing was responsible for the discrepancies. The IBG System identified one sample as D-positive that was grouped as D-negative by manual testing. The patient's sample had been previously grouped manually as a weak D. Au other D results were in agreement. The IBG System provided ABO interpretatinns without technologist's intervention on 1,765 (86.1%) of the samples. In 153 (7.5%) of the samples, a single, equivocal reaction required visual inspection, but no repeat testing was necessary. In 133 (6.5%) of the samples, either repeat testing or reliance on only the manual results was required for final ABO group interpretation. The IBG System is a reliable and efficient alternative to manual techniques for ABO and D grouping of patients' samples.

Journal Article↗
PubMed1994

A numerical study of rapid heating for high temperature radio frequency hyperthermia.

Hyperthermia is a promising adjuvant cancer treatment modality. However, unresolved engineering problems with the production and regulation of temperature distributions within tissues in vivo have frustrated repeated efforts to implement clinical hyperthermia protocols. A major technical problem with hyperthermia production in vivo is the cooling effect caused by circulating blood in larger vessels. Larger blood vessels, when located in heated tumors, can prevent achievement of sufficiently high temperatures, resulting in loss of therapeutic effect. One possible way of circumventing this problem is the delivery of a critical heat dose during a short-term, high-temperature treatment episode to minimize cooling from blood flow. We investigated the concept of such rapid, high-temperature heating of tissue in a two-dimensional finite element numerical model. The model demonstrates the feasibility of interstitial radiofrequency delivery of a therapeutic heat dose, equivalent to 30 min at 43 degrees C, to a 1 cm3 tumor during a 60-s period. The model assumes circulation of cooling fluid through hollow electrodes. A post processor has been designed to display a 3-D image of the temperature distribution, electric field, and thermal dose delivered to a unit volume within the heated tissue.

Blood Circulation↗
PubMed1994

Effect of human IgG antiphospholipid antibodies on an in vivo thrombosis model in mice.

High levels of IgG antiphospholipid antibodies (aPL) have been associated with clinical thrombosis. It is uncertain however whether these antibodies play a direct role in thrombosis or are merely epiphenomena. To investigate whether antiphospholipid antibodies might play a role in thrombosis, we utilized a novel mouse model in which the dynamics of in vivo thrombosis can be studied. CD1 mice (26-30 g) were passively immunized with 25 mg of human IgG from a patient with the Antiphospholipid Syndrome (IgG-APS) (n = 17), IgG from normal pooled sera (IgG-NHS) (n = 9), or saline solution (n = 12), followed by 40 mg of the same preparations at 48 h. At 72 h, levels of human aPL antibodies, detected using the anticardiolipin ELISA test (aCL ELISA test), in mice immunized with IgG-APS, were 50-100 GPL units. Each animal was anesthetized, femoral vein minimally mobilized and subjected to a standardized "pinch" injury to induce thrombosis. The vessel was transilluminated using acrylic optical fibers connected to a light source, and clot formation and dissolution were visualized by a standard surgical microscope equipped with a video camera, video recorder, and computer assisted analysis system. Results showed that average clot size was significantly larger in mice immunized with IgG-APS compared to those treated with saline (p < 0.037). In addition, the thrombus persisted longer in a significantly higher number of mice immunized with IgG-APS (10/17) compared to mice immunized with IgG-NHS (1/9) or saline (2/12) (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Developmental regulation of bcl-2 expression in the thymus.

An important factor in shaping the T-cell receptor (TcR) repertoire during thymocyte development is the susceptibility of double-positive (CD4+ CD8+) thymocytes to induction of apoptosis (negative selection) when the TcR is engaged by 'self'-antigens. Recent evidence has suggested that this susceptibility to apoptosis may be influenced by the expression of bcl-2, a proto-oncogene known to increase the resistance to apoptosis in various cell systems. Using a semi-quantitative polymerase chain reaction (PCR) technique in conjunction with staged embryonic material and purified thymocyte subpopulations we have investigated patterns of bcl-2 expression during normal T-cell development. Our results show that while bcl-2 alpha gene expression is readily detectable in immature CD3-CD4-CD8- thymocytes and in mature single-positive TcRhi cells, it is drastically reduced in TcR negative double-positive (CD3- CD4+ CD8+) cortical thymocytes of intermediate maturity. Careful mapping of bcl-2 alpha re-expression in relation to the onset of TcR expression within the population of embryonic thymocytes indicates that bcl-2 alpha is up-regulated as soon as TcR molecules are expressed on the surface of CD4+ CD8+ thymocytes. Therefore, thymocytes susceptible to apoptosis on TcR ligation express bcl-2 alpha mRNA suggesting that changing levels of bcl-2 expression are unlikely to be the only determinant regulating susceptibility to apoptosis in the thymus. The possible implications of these changes in bcl-2 expression regarding other facets of thymocyte development will be discussed.

Animals↗
PubMed1993

The prescription of methadone for opiate dependence in Australia, 1985-1991.

OBJECTIVE: To describe the rates and patterns of prescription of methadone for opiate dependence in Australia from 1985 to 1991. DESIGN: Data on the numbers of Australians prescribed methadone in States and Territories were used to calculate prevalence rates of prescription of methadone. RESULTS: In 1985, Queensland had the highest rate of prescription of methadone. After the establishment of the National Campaign Against Drug Abuse, rates increased in most jurisdictions. Assessment procedures and prescribing practices, such as private prescription of methadone, appear to have markedly affected rates of prescription in some States. CONCLUSION: Large differences in rates of methadone prescription have occurred in Australian States and Territories. There are inadequate data to explain how rates of prescription are related to the prevalence of opiate use. Investigations of prevalence of injecting opiate use, demand for treatment and clinic practices are needed to explain these patterns fully.

Adolescent↗
PubMed1993

Microvascular effects of complement blockade with soluble recombinant CR1 on ischemia/reperfusion injury of skeletal muscle.

Reperfusion of ischemic tissue is associated with tissue injury greater than that resulting from ischemia alone. C activation has been hypothesized to mediate the so-called ischemia/reperfusion injury through both membrane attack and C5a-dependent recruitment of neutrophils to sites of C3 fixation on the endothelium via C3 receptors. Adherence of neutrophils is preconditional to expression of their deleterious effects, which are central to the pathophysiology of ischemia/reperfusion injury. This study was designed to evaluate the effect of inhibition of C activation on ischemia/reperfusion injury using a soluble and truncated recombinant human CR1 (sCR1) molecule, a "tail-less" form of the membrane C3b/C4b receptor (CD35) that functions as a regulator of C activation. Capillary perfusion and leukocyte adherence to venular endothelium were measured after reperfusion in a mouse cremaster muscle model that allowed microscopic video observation of microcirculatory changes. Infusion i.v. with sCR1 before a 4-h period of ischemia and during a 3-h subsequent period of reperfusion prevented the increase in leukocyte adherence to venular endothelium seen in controls, and enhanced the number of reperfusing capillaries by 55%. Trypan blue staining showed an increase in muscle cell viability from 11 to 50% in mice receiving sCR1 as compared to controls. Tests of blood samples from mice infused with sCR1 demonstrated nearly complete inhibition of the mouse alternative pathway of C activation, but no detectable loss of the mouse classical pathway of C activation. It was concluded that C activation in this model of skeletal muscle injury is likely to be due to the alternative pathway, and that inhibition of C activation during reperfusion inhibits leukocyte adherence to blood vessel walls and protects the capillary microcirculation.

Animals↗
PubMed1993

MHC class II-positive epithelium and mesenchyme cells are both required for T-cell development in the thymus.

T lymphocytes are produced in the thymus from precursors originating in the haemopoietic tissues. On entering the thymus, they undergo a programme of proliferation, T-cell receptor (TCR) gene rearrangement, differentiation and repertoire selection. Although the thymus provides a unique environment for these events, the role of the thymic stroma in regulating specific developmental stages is not well understood. We therefore devised an in vitro system to study the role of individual thymic stromal components in T-cell development. We report here that the development of TCR-CD4-CD8-T-cell precursors into TCR+ cells expressing CD4 and/or CD8 requires the presence of both major histocompatibility complex class II+ epithelial cells and fetal mesenchyme. The requirement for mesenchymal support can be mapped to the initial stages of intrathymic development because the later stages of maturation, from double-positive CD4+CD8+ thymocytes into single-positive CD4+ or CD8+ cells, can be supported by epithelial cells alone. We also show that the requirement for mesenchymal cells can be met by cells of the fibroblast line 3T3 (but not by supernatants from these cells). To our knowledge, these findings provide the first direct evidence that mesenchymal as well as epithelial cells are involved in T-cell development, and suggest that their involvement is stage-specific and likely to be dependent on short-range or contact-mediated interactions.

3T3 Cells↗
PubMed1993

Analysis of cytokine gene expression in subpopulations of freshly isolated thymocytes and thymic stromal cells using semiquantitative polymerase chain reaction.

Using a semi-quantitative polymerase chain reaction (PCR) technique we have examined the expression of a panel of cytokines during thymus development, localizing the expression to individual components of the thymic stroma and thymocytes at different maturational stages. The expression of interleukin (IL)-7, stem cell factor (SCF), IL-1 alpha and granulocyte-monocyte-colony-stimulating factor (GM-CSF) mRNA was mapped to individual stromal cell types, while the expression of IL-1 alpha and GM-CSF, along with interferon (IFN)-gamma and IL-4 was detected in the lymphoid compartment of fetal day (Fd) 14 thymus. The expression of lymphoid-specific cytokines genes was selectively down-regulated in thymocytes undergoing maturation. CD3-/lo4+8+ cells, representing an intermediate stage of thymocyte maturation, were devoid of cytokine gene expression. Their CD3+ progeny, on the other hand, expressed IFN-gamma mRNA, supporting the notion that positive selection of cells for further maturation induces the reexpression of some cytokine genes. The cytokine profiles of the various stromal components differed. Purified major histocompatibility complex class II+ cortical epithelial cells strongly expressed IL-7 and SCF, but only limited expression of IL-1 alpha and GM-CSF could be detected. Fetal mesenchyme, on the other hand, expressed SCF, IL-1 alpha and GM-CSF but not IL-7. The importance of these cytokine profiles in relation to T cell development is discussed.

Animals↗
PubMed1993

Couplings of character and of chirality in the origin of the genetic system.

Data from the literature and new data presented here suggest that the genetic system (coding and protein synthesis) is based on relationships of character and structure between amino acids and nucleic acids. Character relationships seem to be anticodonic and structurally the greatest preferences are seen between the heteropair, L-amino acids and D-ribose nucleic acids. However, living systems using the other heteropair must have been equally likely. Homopairing (L-L and D-D) in living systems seems unlikely. Awareness of the heterocoupling of steric forms narrows somewhat the problem of understanding the origin of chirality.

Adenosine↗
PubMed1993

Neuroendocrine and behavioral effects of the selective kappa agonist spiradoline in Tourette's syndrome: a pilot study.

To evaluate the role of opioids in Tourette's syndrome (TS), we performed a dose-response study of the behavioral and neuroendocrine effects of the selective kappa agonist spiradoline mesylate (U-62066E) in five TS patients and five normal control subjects, aged 20 to 47. The intramuscularly administered doses of spiradoline were 0.0, 0.8, 1.6, and 3.2 micrograms/kg. Baseline and postdrug tic frequencies were determined from "blind" videotape tic counts and bedside clinician ratings. In comparison with placebo, the lowest dose of spiradoline was associated with significant decreases in cumulative postdrug counts of total tics and phonic tics, as well as in clinician ratings of postdrug motor tic frequencies. By contrast, there was a trend for tic frequencies to increase following the intermediate dose (1.6 micrograms/kg) of spiradoline. As a group, the TS subjects also secreted significantly more growth hormone following the 1.6 micrograms/kg dose of spiradoline than did the normal control subjects. These preliminary findings provide additional evidence for the involvement of opioids in TS and suggest (1) that opioids may exert dual modulatory effects on the expression of tic symptoms and (2) that some TS patients may be characterized by increased sensitivity of kappa receptors regulating growth hormone secretion.

Adult↗