PubMed Health⌕ Search

Biomedical subjects

Ross Brown

Publications and source records attributed to Ross Brown.

6 recordsLinked to original sources
PubMed2004

B7+ T cells in myeloma: an acquired marker of prior chronic antigen presentation.

Murine T cells do not endogenously upregulate CD80 expression but rather acquire CD80 from antigen presenting cells (APC) during CD28 ligation. Murine CD80+ memory T cells undergo apoptosis in the presence of high levels of antigen while naive CD80+ T cells are capable of acting as APC and T cell:T cell ligation induces anergy and unresponsiveness to antigen rechallenge. Reversing T cell unresponsiveness may be a key factor in the development of immunotherapy strategies for patients with myeloma. We have determined that B7+ T cells (CD80+ or CD86+) are common in patients with myeloma (n = 45), can be either CD4 or CD8, tend to be associated with stable disease and are polyclonal memory T cells (CD45RO). CD80 mRNA expression was present in CD80+ monocytes but not in CD3+ cells with a similar level of CD80 antigen expression. CD80 and CD86 antigen expression was upregulated on B cells but not T cells during incubation with trimeric human CD40 ligand (huCD40LT) + IL-2. Although there was a gradual loss of expression during in vitro culture, CD80+ T cells could be purified for further study. We conclude that B7 expression is common on T cells of patients with myeloma but that this is acquired rather than endogenously produced. B7+ CD45RO+ T cells constitute a population of memory T cells chronically exposed to antigen and warrant further study.

Animals↗
PubMed2004

Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta in patients with myeloma.

The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44(+)) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor beta(1) (TGFbeta(1)) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGFbeta(1). As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon-gamma neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123-) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon-gamma to future immunotherapy trials involving these patients should be considered.

B7-1 Antigen↗
PubMed2003

Rapid diagnosis of an ulnar fracture with portable hand-held ultrasound.

Orthopedic fractures are a common injury in operational activities, which are injuries that often occur in isolated or hostile environments. Clinical ultrasound devices have become more user-friendly and lighter, allowing them to be easily transported with forward medical teams. The bone-soft tissue interface has a very large acoustic impedance with a high reflectance that can be used to visualize breaks in contour including fractures. Herein reported is a case of an ulnar fracture that was quickly visualized in the early phase of a multisystem trauma resuscitation with a hand-held ultrasound device. The implications for operational medicine are discussed.

Accidents, Traffic↗
PubMed2002

The hand-held FAST: experience with hand-held trauma sonography in a level-I urban trauma center.

AIMS: To describe the effectiveness of a portable hand-held ultrasound machine when used by clinicians in the early evaluation and resuscitation of trauma victims. METHODS: The study was a prospective evaluation in a level-I urban trauma center. The focussed assessment with sonography for trauma is a specifically defined examination for free fluid known as the focused assessment with sonography for trauma (FAST) exam. Seventy-one patients had a hand-held FAST (HHFAST) examination performed with a Sonosite 180, 2.4 kg ultrasound machine. Sixty-seven examinations were immediately repeated with a Toshiba SSH 140A portable floor-based machine. This repeat scan (formal FAST or FFAST) was used as a comparison standard between the devices for study purposes. Four patients had a HHFAST only, all with positive result, two being taken for immediate laparotomy, and two having a follow-up computed tomographic (CT) scan. Patient follow-up from other imaging studies, operative intervention, and clinical outcomes were also compared to the performance of each device. RESULTS: There were 58 victims of blunt, and 13 of penetrating abdominal trauma. One examination was indeterminate using both machines. The apparent HHFAST performance yielded; sensitivity, specificity, positive predictive value, negative predictable value, and accuracy (S, S, PPV, NPV, A) of 83, 100, 100, 98, 98%. Upon review, a CT scan finding and benign clinical course found the HHFAST diagnosis to be correct rather than the FFAST in one case. Considering the ultimate clinical course of the patients, yielded a (S, S, PPV, NPV, A) of 78, 100, 100, 97, and 97% for the HHFAST and 75, 98, 86, 97, and 96% for the FFAST. Statistically, there was no significant difference in the actual performance of the HHFAST compared to the FFAST in this clinical setting. DISCUSSION: Hand-held portable sonography can simplify early and accurate performance of FAST exams in victims of abdominal trauma.

Abdominal Injuries↗
PubMed2002

The biology and cytogenetics of multiple myeloma.

Despite the advances in our knowledge of myeloma cell biology, our understanding of myeloma pathogenesis is still incomplete. In this review, we present a summary of the cellular and molecular aspects of B-cell development and immunoglobulin (lg) gene rearrangement which have been important in defining the characteristics of the myeloma plasma cell (MPC). The PMC has undergone variable gene recombination, somatic hypermutation and isotype switching, and is therefore at a postgerminal center stage of development. The finding of preswitch clonal cells and isotype variants have raised interesting questions about the cell of origin of myeloma, for which no conclusive data is as yet available. However much information has been obtained about the chromosomal and genetic aberrations in myeloma, including monosomy 13, Ig heavy chain (IgH) switch region translocations, numerical abnormalities and a multitude of heterogeneous changes. A variety of techniques have been developed to overcome the insensitivity of conventional karyotyping, utilizing molecular cytogenetic strategies ranging from the delineation of precise loci by fluorescent in situ hybridization, a more "global" assessment of the genome by multicolor spectral karyotyping, to the quantitation of chromosomal material of specific origin by comparative genomic hybridization. Whether the abnormalities detected represent oncogenic insults, are involved in disease progression or are simply "by-products" of genetic instability is still unclear. For IgH translocations, the role of candidate genes such as Cyclin D1 and FGFR3 has been studied extensively by quantitating their expression and assessment of their oncogenicity (e.g. for FGFR3) in animal models. The significance of other aberrations such as c-myc, ras and p53 has also been investigated. With the advent of oligonucleotide microarrays, the expression of thousands of genes can be efficiently examined. So far, this approach seems promising in defining subgroups of different disease behavior, and may highlight specific genes and molecular mechanisms which are important in myeloma pathogenesis.

Animals↗