Pretibial myxoedema associated with Hashimoto''s thyroiditis

Pretibial myxoedema is a cutaneous mucinosis typically associated with Graves' disease, although it may also develop in subjects with non-thyrotoxic thyroid pathologies. This report presents a rare case of pretibial myxoedema occurring in a 58-year-old woman with biopsy-proven Hashimoto's thyroiditis. The hypothetical pathogenetic link between the two disorders is discussed with particular attention to the role of thyroid stimulating hormone receptor antibodies.     

Selective nuclear protein phosphorylation/dephosphorylation in subpopulations of human colonic carcinoma cells

The nuclear protein and phosphoprotein profiles from 3 subpopulations of human colonic carcinoma cells which expressed different levels of neoplastic properties were characterized by two-dimensional electrophoresis. The silver stained nuclear protein profiles were found to be remarkably similar among the subpopulations. However, 2 types of nuclear proteins were found to be selectively modified by phosphorylation/dephosphorylation reactions. The dephosphorylation of type I and the phosphorylation of type II nuclear proteins were found to be associated with the HCT 116a subpopulation which expressed a high level of neoplastic properties. Conversely, the phosphorylation of type I and the dephosphorylation of type II nuclear proteins were found to be associated with the HCT 116b subpopulation, which expressed a low level of neoplastic properties. The HCT 116 subpopulation, which expressed an intermediate level of neoplastic properties, was found to possess an intermediate phosphoprotein profile relative to that of the other two subpopulations. Selective modification of cellular proteins by phosphorylation/dephosphorylation reactions may be involved in the generation of tumor cell diversity and heterogeneity.     

Rapid and simultaneous typing of hemoglobin S, hemoglobin C, and seven Mediterranean beta-thalassemia mutations by covalent reverse dot-blot analysis: application to prenatal diagnosis in Sicily

The molecular lesions causing beta-thalassemia in Sicily can be subdivided into two groups. One that occurs at a 71% frequency and consists of the beta 39, IVS 1,110 and IVS 1,6 mutations and the other group at a 20% frequency comprising the -87, beta s, IVS 1,1 and IVS 2,745 mutations. The identification of all these mutations by polymerase chain reaction (PCR) and conventional dot-blot hybridization has been time consuming and expensive. In this article, we describe the implementation of the reverse dot-blot (RDB) hybridization as a rapid nonradioactive method for the identification of the nine most frequent molecular lesions in the beta-globin gene (-87, beta s, beta c, IVS 1,1, IVS 1,6, IVS 1,110, beta 39, IVS 2,1, IVS 2,745) in Sicily. Sixty prenatal diagnoses were performed by this RDB assay, each of which was confirmed by dot-blot/ASO hybridization; thus demonstrating the accuracy of the RDB. The main advantage of this assay is the rapid typing of an individual's DNA for many mutations in a single working day. Because the mutations in this assay are representative for the Mediterranean region, this mutational panel can also be extended to the screening of beta-thalassemia from other Mediterranean regions.     

Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component

A study was carried out to explore requirements for the inhibition of tissue factor-factor VIIa enzymatic activity in plasma. Reaction mixtures contained plasma, 3H-factor IX or 3H-factor X, tissue factor (vol/vol 2.4% to 24%), and calcium. Tissue factor-factor VIIa activity was evaluated from progress curves of activation of factor IX or factor X, plotted from tritiated activation peptide release data. With normal plasma, progress curves exhibited initial limited activation followed by a plateau indicative of loss of tissue factor-factor VIIa activity. With hereditary factor X-deficient plasma treated with factor X antibodies, progress curves revealed full factor IX activation. Adding only 0.4 micrograms/mL factor X (final concentration) could restore inhibition. Inhibition was not observed in purified systems containing 6% to 24% tissue factor, factor VII, 0.5 micrograms/mL, factor IX, 13 micrograms/mL, and factor X up to 0.8 micrograms/mL, but could be induced by adding barium-absorbed plasma to the reaction mixture. Thus, both factor X and an additional material in plasma were required for inhibition. The amount of factor X needed appeared related to the concentration of tissue factor; adding more tissue factor at the plateau of a progress curve induced further activation. These results also indicate that inhibited reaction mixtures contained active free factor VII(a). Preliminary data suggest that inhibition may stem from loss of activity of the tissue factor component of the tissue factor- factor VII(a) complex.     

Restoration of normal growth control and membrane antigen composition in malignant cells by N,N-dimethylformamide

The effects of the differentiation agent, N,N-dimethylformamide (DMF), on malignant AKR-MCA cells were studied. The properties of DMF-treated AKR-MCA cells were compared to those of the normal parental AKR-2B mouse embryo fibroblasts. AKR-MCA cells grown in 1% DMF were found to be more similar to their normal counterparts than to untreated AKR-MCA cells by several criteria. These criteria included the loss of the transformed morphology, a 2-fold reduction of doubling time, a 10-fold reduction of saturation density, and the complete loss of the ability to grow with anchorage independence. The expression of high-molecular-weight membrane antigens (Mr 110,000 to 450,000), which was found to be greatly reduced in AKR-MCA cells in comparison to normal AKR-2B cells, was restored by treatment of AKR-MCA cells with DMF. The expression of a low-molecular-weight AKR-MCA cell-associated membrane antigen, on the other hand was found to be suppressed. Studies on the mitogenic response of these cells indicated that AKR-MCA and AKR-2B cells may be regulated by different types of growth control. Growth-arrested AKR-MCA cells did not respond to epidermal growth factor, but responded to nutrient replenishment. AKR-2B cells, on the other hand, responded to epidermal growth factor, but did not respond to nutrient replenishment. Treatment of AKR-MCA cells with DMF restored their ability to respond to epidermal growth factor, while their ability to respond to nutrient replenishment was lost. The results of this study indicated that DMF treatment induced the normalization of malignant AKR-MCA cells with regard to membrane antigen composition and growth control properties.