Biomedical subjects

Anne E Bishop

Publications and source records attributed to Anne E Bishop.

5 recordsLinked to original sources

PubMed2002

Interstitial vascularity in fibrosing alveolitis.

The aim of this study was to evaluate interstitial vascularity in cryptogenic fibrosing alveolitis (CFA) and in fibrosing alveolitis associated with systemic sclerosis (FASSc). Open lung biopsies from eight patients with CFA, nine patients with FASSc, and normal lung from 12 patients undergoing surgery for lung cancer were studied. Markers for endothelial cells (CD34) and cell proliferation (proliferating cell nuclear antigen) were localized by sequential immunohistochemistry and quantified using computer-assisted analysis. Vascular distribution was evaluated at increasing distances (up to 160 microm) from the airspaces. Vessel density was markedly reduced in both FASSc (3.9%) and in CFA (4.5%) compared with control samples (20.4%, p < 0.0001). The percentage of tissue occupied by vessels decreased with increasing distance from alveoli in control samples but not in CFA or FASSc samples. Endothelial cell proliferation indices were increased in FASSc but not in CFA, compared with control samples (p = 0.006). In conclusion, there is net vascular ablation and redistribution of blood vessels in areas of interstitial thickening in both CFA and FASSc, which may contribute to gas exchange impairment.

Adult↗

PubMed2002

Nitric oxide in the development of obliterative bronchiolitis in a heterotopic pig model.

BACKGROUND: Inflammation, epithelial cell injury, and development of fibrosis and airway obliteration are the major histological features of posttransplant obliterative bronchiolitis (OB). The expression of inducible nitric oxide synthase (iNOS) in the damaged epithelium, accompanied by peroxynitrite, suggests that endogenous nitric oxide (NO) mediates the epithelial destruction preceding obliteration. To elucidate the role of NO in this cascade, heterotopic bronchial allografts were studied in pigs. METHODS: Allografts or autografts were harvested serially 3-90 days after transplantation and processed for histology and immunocytochemistry for iNOS, nitrotyrosine, a marker of peroxynitrite formation, and superoxide dismutase (SOD). RESULTS: During initial ischemic damage to the epithelium, iNOS, nitrotyrosine, and SOD were found to be strongly expressed in the epithelium of all implants as well as later, after partial recovery, parallel to onset of epithelial destruction and subsequent airway obliteration in allografts. The levels of expression of iNOS in fibroblasts during the early phase of obliteration paralleled the onset of fibrosis. Constant expression of iNOS and SOD, but not nitrotyrosine, occurred in autografts and allografts with blocked alloimmune response. CONCLUSIONS: These findings suggest that an excessive amount of NO promotes posttransplant obliterative bronchiolitis by destroying airway epithelium and stimulating fibroblast activity. SOD may provide protection by binding reactive molecules and preventing peroxynitrite formation.

Animals↗

PubMed2002

iNOS gene upregulation is associated with the early proliferative response of human lung fibroblasts to cytokine stimulation.

Increased release of oxidants has been implicated in the pathogenesis of pulmonary fibrosis. Previous work in the rat showed that formation of the early fibrotic lesion is associated with increased expression of inducible nitric oxide synthase (iNOS) in pulmonary fibroblasts. The aim of this study was to test the hypothesis that NO is involved in the activation of pulmonary fibroblasts. The effects of endogenous and exogenous NO on proliferation of human pulmonary fibroblasts were investigated by administration of cytomix or SNAP, respectively. At low concentrations, both treatments increased cell numbers, an effect attenuated by iNOS inhibitor or NO scavenger. Induction of iNOS was confirmed by measurement of nitrate/nitrite production and by immunodetection. Quantitative RT-PCR showed an increase in iNOS mRNA as early as 3 h after stimulation. These results support the hypothesis and show that upregulation of the iNOS gene is an early event in the proliferative response of human lung fibroblasts to inflammatory stimuli.

Blotting, Western↗

PubMed2002

Embryonic stem cells.

The capacity of embryonic stem cells for virtually unlimited self-renewal and differentiation capacity has opened up the prospect of widespread applications in biomedical research and regenerative medicine. For the latter, the cells provide hope that it will be possible to overcome the problems of donor tissue shortage and also, by making the cells immunocompatible with the recipient, implant rejection. Four years after the first derivation of human pluripotent cell lines from pre-implantation embryos, a great deal has been learnt about their biology and how differentiation can be encouraged towards particular cell lineages. However, considerable research is needed, not least into means to enrich and purify derivative cell lineages, before clinical trials can be considered.

Cell Differentiation↗

PubMed2002

Derivation of type II alveolar epithelial cells from murine embryonic stem cells.

Embryonic stem (ES) cell pluripotency is being investigated increasingly to obtain specific cell lineages for tissue engineering. However, the possibility that ES cells can give rise to lung tissue has not been tested. We hypothesized that lung epithelial cells (type II pneumocytes) can be derived in vitro from murine ES cells. After withdrawal of leukemia inhibitory factor (LIF) and formation of embryoid bodies in maintenance medium for 10, 20, and 30 days, differentiating ES cells were kept in the same medium or transferred to serum-free small airway growth medium (SAGM) for a further 3 or 14 days of culture. The presence of type II pneumocytes in the resulting mixed cultures was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) of surfactant protein C (SPC) mRNA, immunostaining of SPC, and electron microscopy of osmiophilic lamellar bodies only at 30 days sampling time. SAGM appeared to be more favorable for type II cell formation than ES medium. No SPC transcripts were found in differentiating cells grown under the same conditions without formation of embryoid bodies. These findings could form the basis for the enrichment of ES cell-derived cultures with type II pneumocytes, and provide an in vitro system for investigating mechanisms of lung repair and regeneration.

Animals↗