Biomedical subjects

A Beavis

Publications and source records attributed to A Beavis.

9 recordsLinked to original sources

PubMed2000

Complementation of Myc-dependent cell proliferation by cDNA expression library screening.

The targeted knockout of the c-myc gene from rat fibroblasts leads to a stable defect in cell proliferation. We used complex cDNA libraries expressed from retroviral vectors and an efficient sorting procedure to rapidly select for cDNAs that can restore the growth rate of c-myc deficient cells. All of the biologically active cDNAs contained either c-myc or N-myc, suggesting that no other cellular genes can effectively bypass the requirement for c-myc in fibroblast proliferation. This approach provides a powerful screening method for cell cycle changes in genetically defined systems.

Animals↗

PubMed2000

In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers.

The CD1 family of major histocompatibility complex (MHC)-like molecules specializes in presenting lipid and glycolipid antigens to alpha/beta T lymphocytes, but little is known about the size of the CD1-restricted T cell population or the frequency of T lymphocytes specific for a given glycolipid antigen. Here, we report the generation and use of mouse CD1d1-glycolipid tetramers to visualize CD1d-restricted T cells. In contrast with previous BIAcore-based estimates of very short half-lives for CD1d-glycolipid complexes, we found that the dissociation rate of several different CD1d-glycolipid complexes was very slow. Fluorescent tetramers of mouse CD1d1 complexed with alpha-galactosylceramide (alphaGalCer), the antigen recognized by mouse Valpha14-Jalpha281/Vbeta8 and human Valpha24-JalphaQ/Vbeta11 natural killer T (NKT) cell T cell receptors (TCRs), allowed us for the first time to accurately describe, based on TCR specificity, the entire population of NKT cells in vivo and to identify a previously unrecognized population of NK1.1-negative "NKT" cells, which expressed a different pattern of integrins. In contrast, natural killer (NK) cells failed to bind the tetramers either empty or loaded with alphaGalCer, suggesting the absence of a CD1d-specific, antigen-nonspecific NK receptor. Mouse CD1d1-alphaGalCer tetramers also stained human NKT cells, indicating that they will be useful for probing a range of mouse and human conditions such as insulin-dependent diabetes mellitus, tumor rejection, and infectious diseases where NKT cells play an important role.

Animals↗

PubMed2000

Implementation of enhanced dynamic wedge in the focus rtp system.

The FOCUS RTP system implementation of Varian's enhanced dynamic wedge (EDW) is presented. Calculations of both dose distributions and wedge factors (WFs) are based on segmented treatment tables (STTs). Calculating dose requires a "transmission matrix" derived from an STT to model the modified fluence from the source. The dose calculation is then performed using either the Clarkson or convolution/superposition algorithms. An initial "primary dose/monitor unit (MU) fraction" WF estimate at the weight point of symmetric and asymmetric fields is calculated from the STT as the ratio of MU delivered on the axis of the weight point divided by total MU delivered for the treatment field. In our approach, we go beyond this initial estimate with a "scatter dose" correction. This requires measured 60 degrees WFs for 5 fields. Scatter corrections derived from measured WFs are interpolated for other wedge angles and field sizes in much the same way as arbitrary wedge angle STTs are derived from a "golden STT" using the "ratio of tangents" formalism. Dose comparisons with measured distributions show good agreement to within 3% or 3 mm for 6-MV beams and all EDW angles. Agreement with measurements to within 1% is obtained for WFs in all symmetric and asymmetric fields for 6- and 10-MV beams. For large wedge angles and field sizes, this represents a significant improvement over the 3% to 4% errors often observed using the MU fraction model alone.

Humans↗

PubMed1999

Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells.

alpha-Galactosylceramide (alpha-GalCer) is a glycolipid with potent antitumor properties that binds to CD1d molecules and activates mouse Valpha14 and human Valpha24 NKT cells. Surprisingly, we found that, as early as 90 min after alpha-GalCer injection in vivo, NK cells also displayed considerable signs of activation, including IFN-gamma production and CD69 induction. NK activation was not observed in RAG- or CD1-deficient mice, and it was decreased by pretreatment with anti-IFN-gamma Abs, suggesting that, despite its rapid induction, it was a secondary event that depended on IFN-gamma release by NKT cells. At later time points, B cells and CD8 T cells also began to express CD69. These findings identify a high-speed communication network between the innate and adaptive immune systems in vivo that is initiated upon NKT cell activation. They also suggest that the antitumor effects of alpha-GalCer result from the sequential recruitment of distinct innate and adaptive effector lymphocytes.

Animals↗

PubMed1999

The molecular characterization of the fetal stem cell marker AA4.

We have identified and characterized the stem cell antigen AA4. This molecule is a type I transmembrane protein whose overall structure suggests a role in cell adhesion. During fetal ontogeny (days 9-14 of development), AA4 is expressed in three major cell types: vascular endothelial cells, aorta-associated hematopoietic clusters, and primitive fetal liver hematopoietic progenitors. In the adult, AA4 is abundant in lung, heart, and whole bone marrow. In the adult hematopoietic compartment, aa4 transcripts are present in bone marrow CD34(-/lo) Lin- Sca-1+ c-Kit+ and CD34hi Lin- Sca-1+ c-Kit+ stem and progenitor cell subsets. Our observations suggest that AA4 plays a role in cell-cell interactions during hematopoietic and vascular development.

3T3 Cells↗

PubMed1997

The inhibitory effects of topically active glucocorticoids on IL-4, IL-5, and interferon-gamma production by cultured primary CD4+ T cells.

This study was conducted to directly compare the in vitro efficacy and potency of several glucocorticoids in inhibiting T-cell cytokine production. The glucocorticoids tested were fluticasone propionate, budesonide, triamcinolone acetonide, and beclomethasone dipropionate, which are currently inhaled therapies for the treatment of allergic airway disease. Also used were betamethasone phosphate and the newly developed mometasone furorate. With a novel cell culture system, purified peripheral blood CD4+ T cells from normal donors were stimulated with immobilized anti-CD3 and soluble anti-CD28 monoclonal antibodies to induce high levels of IL-4, IL-5, and interferon-gamma. By cell sorting, it was found that the IL-5 produced originated from memory cells, whereas both memory and naive cells produced interferon-gamma. Mometasone and fluticasone inhibited IL-5 and IL-4 similarly (mometasone IL-5 inhibitory concentration of 50% = 0.27 +/- 0.1 nmol/L and IL-4 = 0.19 +/- 0.08 nmol/L). For both cytokines, the results indicate that mometasone and fluticasone were more potent than beclomethasone, triamcinolone, budesonide, and betamethasone. Of clinical importance is the finding that all steroids demonstrated less efficacy versus interferon-gamma than IL-4 and IL-5. Glucocorticoid reduction of Th2 cytokines with lesser effects on interferon-gamma would serve to reverse the exaggerated Th2 response that contributes to pathophysiology observed in allergic disease. Therefore the use of topically active glucocorticoids with low systemic bioactivity for the treatment of allergic inflammation may be particularly effective in modulating the cytokine activity that is an important component of the allergic response.

CD4-Positive T-Lymphocytes↗

PubMed1991

An analysis of normal back shape measured by ISIS scanning.

Two hundred seventy-one school children aged 10-16 years and 72 normal adults aged 21-59 years were scanned by ISIS. Subjects with any evidence of scoliosis were excluded from the study. Characteristic ISIS parameters of back shape showed no statistically significant differences related to age or sex for the children. Back shape in both men and women was not significantly different from that of the children, except for kyphosis angles which were greater.

Adolescent↗

PubMed1989

Cervical orthoses.

A biomechanical study is presented to compare the effectiveness of three types of off-the-shelf cervical orthoses and one custom-fit collar in restricting cervical spine motion. A group of 10 normal subjects was studied. The measurements of flexion and extension, lateral side flexion and axial rotation were recorded using various measurement techniques. Interface pressures at the chin and occiput were also measured, along with the warming effect of the collars. The results indicated that all the collars restricted neck movements, for example, the Plastazote collar by 50% of flexion and extension, and that there was no significant difference between off-the-shelf Plastazote and custom-fit collars in restricting movement. Significantly high interface pressures were recorded at the chin, with the subjects wearing the hard and Plastazote orthoses. The warming effect of the soft collar was equal to that of a wool scarf. The study was aimed at improving prescription and although the subjective observations were not validated, the subjects concluded that the custom-fit collars were more comfortable; an important point with such a high rejection rate.

Adult↗

PubMed1988

Hydroxyl-radical-induced iron-catalysed degradation of 2-deoxyribose. Quantitative determination of malondialdehyde.

The degradation of 2-deoxyribose to thiobarbituric acid-reactive material was investigated with two hydroxyl-radical-generating systems: (i) a defined gamma-radiolysis method and (ii) incubation with FeSO4 in phosphate buffer. In each case the thiobarbituric acid-reactive material can be accounted for by malondialdehyde, as measured by an h.p.l.c. method for free malondialdehyde. In the radiolysis system there is a large post-irradiation increase in free malondialdehyde if iron ions are added to the samples. It is proposed that this is due to iron ions catalysing the formation of hydroxyl radicals from radiolytically generated H2O2 as well as stimulating the breakdown of an intermediate deoxyribose degradation product. A mechanism for the formation of malondialdehyde during deoxyribose degradation is proposed.

Catalase↗