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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 721 records · Page 40Linked to original sources
PubMed1991

Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-beta 1 therapy.

Platelet-derived growth factor (PDGF-BB homodimer) and transforming growth factor-beta 1 (TGF-beta 1) are potent wound-healing hormones that accelerate incisional repair. To identify more precisely and quantitatively the stage(s) of wound healing influenced by growth-factor therapy, we investigated the three sequential tissue repair processes--inflammatory cell influx, intracellular procollagen type I (PC-I) synthesis, and collagen cross-linking--in recombinant growth factor--treated wounds. Using newly developed automated, quantitative image-analysis techniques, we observed that PDGF-BB markedly augmented the directed migration of macrophages into wounds during the first week after wounding and triggered and earlier and more sustained influx of PC-I--containing fibroblasts into the wound when compared with results in TGF-beta 1-treated or control wounds (p = 0.015 at day 2; p = 0.007 at day 21). In contrast, automated image analysis revealed TGF-beta 1-treated wound fibroblasts had a nearly twofold increase in intracellular levels of PC-I protein when compared with PDGF-BB-treated or control wound fibroblasts (p = 0.004 at day 4). However, the influence of TGF-beta 1 was transient, and the longer duration of PDGF-BB activity suggested a later influence, perhaps on the collagen remodeling phase, which is ultimately required for increased wound strength. To address this possibility, collagen cross-linking in growth factor-treated wounds was inhibited by beta-aminoproprionitrile (BAPN) treatment, and wound breaking strength was analyzed. Both PDGF-BB and TGF-beta 1 continued to enhance repair in BAPN-treated rats, indicating that they do not function primarily at the level of collagen cross-linking. Thus, PDGF-BB appears to enhance the inflammatory phase of wound healing to indirectly trigger PC-I synthesis, whereas TGF-beta 1 quantitatively enhances PC-I synthesis directly, accounting for their differing duration of activities within healing wounds.

Aminopropionitrile↗
PubMed1990

Monoclonal antibodies distinguishing alpha and beta forms of calcitonin gene-related peptide.

A panel of 18 monoclonal antibodies was raised to the human calcitonin gene related peptide (CGRP). Of these mabs, seven were specific for alpha CGRP and five for beta CGRP, while the remainder reacted with both alpha and beta CGRP. Nine different epitopes on CGRP were defined with these mabs. In addition, the mabs were tested in various combinations to develop a series of two site assays specific for alpha or for beta CGRP as well as assays able to detect both.

Amino Acid Sequence↗
PubMed1990

Malignant melanoma in the foot of a horse.

A 24-year-old horse had a malignant melanoma of the right forefoot. Because surgical excision of the melanoma was incomplete, as determined by histologic examination of the excised tissue margins, the tumor margins were injected with a matrix therapeutic implant containing cis-diamminedichloroplatinum, epinephrine, and purified bovine collagen matrix. The foot healed and the horse remained clinically free of disease for 26 months before recurrence of malignant melanoma. Surgical exploration of the digit revealed extensive involvement of the foot, and the horse was euthanatized.

Animals↗
PubMed1990

Differential expression of interleukin 1 alpha by Thy-1+ and Thy-1- lung fibroblast subpopulations: enhancement of interleukin 1 alpha production by tumor necrosis factor-alpha.

The purpose of this investigation was to determine whether subpopulations of murine lung fibroblasts produced interleukin 1 (IL 1). We previously identified two major populations of pulmonary fibroblasts based on the presence or absence of Thy-1. Thy-1+ and Thy-1- subsets synthesize fibronectin and type I and III collagen, but only the Thy-1- population displays class II major histocompatibility complex antigens after stimulation with interferon-gamma and presents antigen to T helper clones. Interestingly, in the current study we determined that only Thy-1- fibroblast lines and clones synthesized IL 1. Although constitutive production was low, tumor necrosis factor -alpha (TNF-alpha) stimulated 5-20-fold increases in IL 1 production in Thy-1- fibroblasts. The Thy-1+ fibroblasts did not produce IL 1 even after TNF-alpha treatment. Northern blot analysis of TNF-alpha treated cells revealed that in the Thy-1- subset increased mRNA levels for IL 1 alpha were detected, while IL 1 beta mRNA was not detected. Furthermore, IL 1 activity from TNF-alpha-treated Thy-1- fibroblast membranes and supernatants was completely neutralized by IL 1 alpha-specific antibodies. These observations support the hypothesis that the antigen-presenting Thy-1- subset is important for promoting the inflammation associated with pulmonary fibrosis. In addition, the existence of functional subsets of lung fibroblasts is further substantiated by differential expression of IL 1.

Animals↗
PubMed1990

Immunological studies before and during interferon therapy in chronic HBV infection: identification of factors predicting response.

Lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis B virus infection. To assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, CD4/CD8 ratio, natural killer cell activity, IgM anti-HBc antibody levels and concanavalin A-induced lymphocyte proliferative response in 30 patients before treatment. In addition, to investigate the mechanisms of action of interferon in promoting hepatitis B virus clearance, we serially measured the CD4/CD8 ratios, natural killer activity and lymphocyte proliferative response at wk 4, 8 and 12 of treatment. A beneficial response to therapy was defined as the sustained clearance of HBeAg and serum hepatitis B virus DNA within 1 yr of commencing therapy. Elevated IgM anti-HBc levels were associated with a beneficial response to therapy, but there was no correlation observed between response and pretreatment CD4/CD8 ratio, natural killer activity or lymphocyte proliferative response. Six of seven human leukocyte antigen DR3-positive patients responded. No measurable changes in the immunological parameters studied were observed in the nonresponder group, whereas a significant rise in CD4/CD8 ratio, associated with a fall in peripheral CD8 number and a decline in measurable NK activity, was seen in the responder group. These changes were maximal at the time of hepatitis B virus DNA clearance, which was associated with a transient increase in hepatic inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗