A hepatocyte growth factor (HGF) that stimulates DNA synthesis of adult rat hepatocytes in primary culture was purified as a homogeneous material from platelets of 1000 rats by a four-step procedure: stimulation of its release from platelets by thrombin, cation-exchanger fast protein liquid chromatography (FPLC) on a Mono S column, heparin-Sepharose CL-6B chromatography, and reverse-phase HPLC on a C 4 column. The purified HGF stimulated DNA synthesis of adult rat hepatocytes in primary culture at 1 ng/ml and was maximally effective at 5 ng/ml, being about twice as potent as EGF at this concentration. HGF did not stimulate DNA synthesis of Swiss 3T3 cells. It was found to be a heat-and acid-labile protein that was inactivated by reduction with dithiothreitol. The purified HGF had a molecular mass of 82 kDa, as estimated by SDS-PAGE, and was found to be a heterodimer which dissociated into a large subunit of 69 kDa and a small one of 34 kDa by SDS-PAGE under reducing conditions. These biological and chemical properties showed that HGF was not identical with any known growth factors, including platelet-derived growth factor (PDGF).

These results indicate that (1) more than half the patients who developed hypothyroidism within 6 months after 131I treatment for Graves' disease recovered spontaneously, (2) TSAb activity might play some role in the recovery of transient hypothyroidism, and (3) the development of transient hypothyroidism may influence long-term thyroid function.

To investigate the efficacy of intravenous methylprednisolone pulse therapy on Graves' ophthalmopathy (GO), fifteen patients with severe GO were treated with large dose intravenous methylprednisolone (at a daily dosage of 1 g for 3 successive days). This treatment was repeated 3-5 times for 3-5 weeks. They were monitored before, 2 weeks after and 6 months after therapy by ophthalmological assessment, orbital magnetic resonance imaging (MRI), and by measuring serum antibodies to rat eye muscle (EMAB) in an enzyme linked immunosorbent assay and peripheral blood lymphocyte subsets by flow cytometry. Diplopia and periorbital edema markedly improved after treatment in 9 patients. Mean proptosis values and intraocular pressure measurements significantly decreased after pulse therapy. In 12 patients enlarged eye muscles significantly reduced in size after treatment, as determined by MRI. The overall ophthalmopathy index was improved from 4.8 +/- 2.4 to 2.5 +/- 1.6 at the end of pulse therapy (P < 0.01) and 2.4 +/- 1.5 six months after therapy (P < 0.01). Serum EMAB were detected in 8 out of 10 patients tested and their level significantly decreased after pulse therapy (from 3.3 +/- 1.4 to 2.5 +/- 1.2, P < 0.01). A significant increase in peripheral blood CD4+CD45RA+ cells was observed after pulse therapy. Increased numbers of CD11-CD8+ cells and decreased numbers of CD11+CD8++ cells were found prior to treatment and were normalized after pulse therapy. Our study indicates that methylprednisolone pulse therapy can be considered as a choice for the treatment of GO. The improvement in eye muscle involvement in these patients may be due to the effects of infused methylprednisolone on both humoral and cellular immune functions.

No abstract

The outcome of 131I therapy for 109 patients with Graves' disease was analysed according to pretreatment laboratory data including thyrotropin receptor antibody (TRAb) activities. Forty-five percent of patients became euthyroid, and 13% of patients became hypothyroid within one year after 131I therapy. Forty-two percent of patients remained hyperthyroid one year after 131I therapy. Pretreatment values for serum T4, T3, and the estimated weight of the thyroid were significantly higher in the hyperthyroid group. The mean for the TRAb index of the hyperthyroid group was significantly higher than that of the euthyroid group. Life table analysis revealed a significant effect of the TRAb index on the rate of hyperthyroidism after 3 months or later. These results appear to suggest that the TRAb index is one of the factors which influence the outcome of 131I therapy for Graves' disease.