In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

Skull metastasis of thyroid papillary carcinoma.

Skull metastasis of thyroid carcinoma is rare. The majority of skull metastases of thyroid carcinoma are of the follicular subtype, rather than thyroid papillary carcinoma. In this report, a 55-year-old woman with skull metastasis from thyroid papillary carcinoma is presented. The metastatic lesion of the skull was hypervascular and osteolytic, and the bleeding was profuse during resection. There have been only four reports of skull metastasis from thyroid papillary carcinoma. The mean period from the initial diagnosis of thyroid carcinoma until the detection of skull metastasis is 23.3 years, whereas in this patient, it was about 2 years. Therefore, in the clinical course of thyroid papillary carcinoma, skull metastasis should be considered, and the patient should be meticulously followed up.     

Clinical investigation of carbohydrate antigen CA-50

The CA-50 enzyme immunoassay kit (EIA kit) that has been developed with the use of C-50 monoclonal antibody prepared by L. Lindholm et al. was evaluated for diagnosis of human cancer. The levels of CA-50 in the sera were determined using this kit supplied from Mitsui Pharmaceuticals, Inc. Co. in 759 healthy donors, 728 patients with benign disease and 1,263 untreated patients with cancer. A CA-50 concentration of 40 U/ml of serum was used as the cut-off value. Patients with pancreatic cancer and patients with bile duct cancer had high positive incidence of 75% and 68%, respectively, compared with a low positive incidence of under 40% in patients with other cancers. On the other hand, positive rates in patients with benign disease were as low as 13%. Comparison of the serum levels of CA-50 with CA19-9 in the same samples did not exhibit complete positive correlation in patients with pancreatic cancer, patients with bile duct cancer and patients with liver cancer. These findings indicated that C-50 antibody reacted with two epitopes of CA19-9 and sialosyllactotetraose. From the above results, the usefulness of CA-50 as a tumor marker for pancreatic cancer and bile duct cancer was recognized with this EIA kit.     

The suppressive effects of smoking on antibody production in experimental hypersensitivity pneumonitis in rabbits]

Farmer's lung disease is one type of hypersensitivity pneumonitis (HP) in dairy farmers, and is usually caused by Micropolyspora faeni (Mf). It has been reported that the positive rate of precipitin antibody to Mf in smoking dairy farmers is one-eighth to one-half of that in nonsmoking dairy farmers. To clarify the mechanism of this phenomenon, by using an experimental HP model in rabbits, we investigated 1) the effects of short (5 weeks) and long (20 weeks)-term cigarette smoke exposure on the antibody formation, 2) the effects of 30 weeks of smoke exposure on the accessory cell function of alveolar macrophages (AM). Smoking exerted variable influences on antibody production, depending on the duration of smoke exposure, and we confirmed that long-term smoke exposure had suppressive effects. In addition AM from smoked rabbits suppressed lymphoproliferative response to autologous spleen cells. It was concluded that in this experimental HP, smoking affects the functions of both AM and lymphocytes, and that it suppresses antibody production as long as the smoke exposure continues.