Biomedical subjects

Jeffrey Newman

Publications and source records attributed to Jeffrey Newman.

4 recordsLinked to original sources

PubMed2005

Receptor editing in peripheral B cell tolerance.

Receptor editing or secondary Ig gene rearrangement occurs in immature, autoreactive B cells to maintain self-tolerance. Here we show that nonspontaneously autoimmune mice immunized with a peptide mimetope of DNA develop peptide- and DNA-reactive antibodies. Antigen-specific B cells display a follicular B cell phenotype. As these cells move into the memory compartment, many express RAG protein and acquire expression of both kappa and lambda light chains. Thus, this study provides evidence for receptor editing occurring in a mature, antigen-activated B cell population. Because the receptor editing observed here occurred in an autoreactive response to antigen, it may function to maintain peripheral tolerance.

Animals↗

PubMed2004

Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Do-not-resuscitate (DNR) orders are commonly used after severe stroke. We hypothesized that there is significant variability in how these orders are applied after intracerebral hemorrhage and that this influences outcome. METHODS: From a database of all admissions to nonfederal hospitals in California, discharge abstracts were obtained for all patients with a primary diagnosis of intracerebral hemorrhage who were admitted through the emergency department during 1999 and 2000. Characteristics included whether DNR orders were written within the first 24 hours of hospitalization. Case-mix-adjusted hospital DNR use was calculated for each hospital by comparing the actual number of DNR cases with the number predicted from a multivariable model. Outcome (in-hospital death) was evaluated in a separate multivariable model adjusted for individual and hospital characteristics. RESULTS: A total of 8233 patients were treated in 234 hospitals. The percentage of patients with DNR orders varied from 0% to 70% across hospitals. Being treated in a hospital that used DNR orders 10% more often than another hospital with a similar case mix increased a patient's odds of dying during hospitalization by 13% (P<0.001). Patients treated in the quartile of hospitals with the highest adjusted DNR use were more likely to die, and this was not just because of individual patient DNR status. CONCLUSIONS: In-hospital mortality after intracerebral hemorrhage is significantly influenced by the rate at which treating hospitals use DNR orders, even after adjusting for case mix. This is not due solely to individual patient DNR status, but rather some other aspect of overall care.

Cerebral Hemorrhage↗

PubMed2003

Identification of an antigen-specific B cell population.

The difficulty in characterizing antigen-specific B cells that arise in the native B cell repertoire has been a formidable obstacle to understanding both protective and pathogenic antibody responses. We have developed a tetramer-based technique for identifying antigen-specific B cells. Biotin-labeled antigen is made tetrameric by interaction with streptavidin. The enhanced avidity of this antigenic compound for the B cell membrane permits the visualization, characterization and isolation of antigen-specific B cells.

Animals↗

PubMed2002

The effect of anti-CD40 ligand antibody on B cells in human systemic lupus erythematosus.

OBJECTIVE: To determine the immunologic effects of anti-CD40 ligand (anti-CD40L) therapy in 5 patients with systemic lupus erythematosus nephritis who participated in an open-label study of a humanized anti-CD40L monoclonal antibody. METHODS: Serum and peripheral blood mononuclear cells were obtained before, during, and after treatment, and the frequency of Ig and anti-DNA antibody-secreting B cells was analyzed by enzyme-linked immunospot assay and by analysis of Epstein-Barr virus (EBV)-transformed B cell lines. To determine the effect of treatment on somatic mutation of Ig genes, reverse transcriptase-polymerase chain reaction was performed on messenger RNA from 4 patients, using primers specific for the DP-47 heavy chain gene and for IgG. Finally, B cell phenotype was investigated using flow cytometry. RESULTS: Even a brief period of treatment with anti-CD40L markedly reduced the frequency of IgG and IgG anti-DNA antibody-producing B cells, and these changes persisted for several months after cessation of treatment. To confirm these findings, EBV-transformed B cell lines were screened from each of 3 patients, and a 10-fold decrease in anti-DNA antibody-secreting cell lines was found after treatment in all 3 patients. Few differences in mutation patterns were observed before and after treatment; however, the frequency of germline-encoded DP-47 sequences was significantly increased before treatment and normalized following treatment. Flow cytometric analysis of B cells revealed expansion of a CD27-/IgD- B cell subset in some of the patients, which did not change with treatment. CONCLUSION: These are the first mechanistic studies of the effect of anti-CD40L therapy in human autoimmune disease. The results suggest that further studies of CD40L blockade are warranted.

Adult↗