Desensitization of the insulin receptor by antireceptor antibodies in vivo is blocked by treatment of mice with beta-adrenergic agonists.

In previous studies we reported that immunization of mice with ungulate insulins induced the development of antiinsulin antibodies, which include an idiotype that appeared to recognize the part of the insulin molecule recognized by the hormone receptor. The antiinsulin antibodies of this idiotype were replaced spontaneously by antiidiotypic antibodies. The antiidiotypic antibodies, which persisted for about 14 d, mimicked insulin and functioned as antibodies to the insulin receptor. They induced down regulation, desensitization and refractoriness of the insulin receptor and disturbances in glucose homeostasis in vivo (Shechter, Y., D. Elias, R. Maron, and I.R. Cohen., 1984; Elias, D., R. Maron, I.R. Cohen, and Y. Shechter. 1984, J. Biol. Chem. 259: 6411-6419). We now report that effects of the antiidiotypic antibodies on the insulin receptor effector system can be modified pharmacologically. Administration of the beta-adrenergic agonist isoproterenol during the period of insulin resistance (days 26-40 after primary immunization), largely restored fat cell responsiveness to insulin, and eliminated the appearance of fasting hyperglycemia. This restoration appeared to be caused by inhibition of both insulin receptor desensitization and refractoriness. In contrast, down regulation of insulin receptors was not reversed by isoproterenol treatment in vivo. The effects of treatment with isoproterenol persisted for 2-4 d after termination of treatment. The beta-antagonist, propranolol and more so, the beta 1a-antagonist metoprolol, specifically blocked the effect of isoproterenol at a molar ratio of 3-10:1. Oral administration of the cAMP phosphodiesterase inhibitor, aminophylline, was also effective in inhibiting the development of desensitization in fat cells. These results indicate that treatment with beta 1-adrenergic agonists in vivo, or other agents that elevate cellular cAMP levels, can inhibit the development of the "postbinding" defects induced by insulin-mimicking, antireceptor antibodies. These observations have both basic and clinical implications.     

Schistosomiasis: an unusual cause of tubal infertility

A case report of a Nigerian woman having an unusual cause oftubal infertility is presented. On histological examinationof the Fallopian tube, ova of Schistosoma haematobium enclosingliving miracidia were found in the smooth muscle layer of theFallopian tube and its mesosalpinx. Mechanisms of tubal involvementare analysed. The case indicates the need to consider schisto-somiasisas a possible aetiological factor in patients with tubal infertilitycoming from areas where the disease is endemic.     

A master curve for tensile properties of thermoplastics

Ultimate mechanical properties of polymers can be characterized by a dimensionless Hooke number He ≡ σ_b/(E?_b), where σ_b is the ultimate tensile strength, E the tensile modulus, and ?_b the elongation at break. Hooke numbers are found to be a smooth function of ultimate elongations, independent of the chemical and physical structure of common thermoplastics. This master curve for fracture strengths and elongations can be described by He = [1 + (?_b/?_crit)^ab]^?1/b with empirically found parameters ?_crit = 0,0168, a = 0,918, and b ≈ 4. The decrease of He with increasing ?_b at ?_b > ?_crit reflects the shear flow on deformation. Hooke numbers depend on entanglement densities v_e according to He = 1,285·10³⁶ (v_e/cm^?3)^?1,846 for v_e > 3,65·10¹⁹ cm^?3. A correction for additional segment orientation during tensile testing brings the exponent to ?1,846/0,918 = ?2,01; i. e., a dependence of Hooke numbers on the reciprocal square of entanglement densities.     

Massive haemorrhagic necrosis of the liver after liver transplantation.

Six of the first 85 patients who received the first 100 liver transplantations carried out in Birmingham developed a syndrome of fulminant liver failure with distinctive clinical and pathological features. The typical clinical presentation was of an uneventual initial postoperative period, followed by a sudden deterioration in graft function, progressing rapidly to graft failure. All six patients died. The characteristic pathological changes were those of massive haemorrhage and hepatocyte necrosis with only mild inflammation and without occlusive lesions in large arteries or veins. These distinctive features differed from other recognised patterns of graft damage and seemed to comprise a specific post-transplant syndrome. The pathogenesis was not clear and in the absence of any definite aetiology it is suggested that the term "massive haemorrhagic necrosis" be used to describe these cases. Additional findings seen in five of the six cases were venoocclusive lesions (n = 4) and a combination of ductopenia and foam cell arteriopathy (n = 2). The presence of these associated lesions suggests that there may be an overlap with other types of graft damage.