Male reproductive defects caused by puromycin-sensitive aminopeptidase deficiency in mice.

Male reproductive performance is composed of two principal elements, copulation and spermatogenesis. A wealth of literature has described the intricate web of endocrine events underlying these biological processes. In the present study we show that puromycin-sensitive aminopeptidase (Psa)-deficient mice are infertile, lack copulatory behavior, and have impaired spermatogenesis. The reproductive deficits of the mutants are not restored by androgen administration, although no aberrant localization of the sex steroid receptors was detectable in their brains and testes. Considering the strong expression of the Psa gene in the brain and Sertoli cells and the degenerative morphology of Sertoli cells in Psa-deficient mice, Psa may participate in testosterone-mediated reproductive signal pathways in the brain and testis.

Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in transcatheter arterial embolization for urgent control of life-threatening massive bleeding from gastric or duodenal ulcer.

We estimated the usefulness of a mixture of N-butyl-2-cyanoacrylate (NBCA) with lipiodol for transcatheter arterial embolization (TAE) used to control massive bleeding from gastric or duodenal ulcer. Thirty patients who had gastric or duodenal ulcers and massive bleeding that was uncontrollable by endoscopic procedures were included in this study. All patients were subjected to TAE (without NBCA in 23 and with NBCA in seven patients). Coils and/or gelfoam were also used. The achievement of haemostasis, occurrence of rebleeding and the time taken for TAE were compared between patients who received TAE without and with NBCA. Eighteen of 23 patients (78.3%) who received TAE without NBCA and six of seven patients (85.7%) who underwent TAE with NBCA achieved complete haemostasis without rebleeding. The time for TAE was significantly shorter in patients who received NBCA compared with those who did not (P = 0.0095). TAE using NBCA or a combination of NBCA and coils achieved a rapid, complete embolization regardless of vascular distribution or arterial diameter. Thus NBCA is considered to be useful as a secondary embolization material in TAE that is urgently conducted to control massive bleeding from gastric or duodenal ulcers.

[The clinical evaluation of hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer employing an implanted port system].

Between 1986 and 1994, 66 patients with unresectable liver metastases from colorectal cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable port system. In this study, 44 patients who received intermittent hepatic arterial infusion of high dose 5-FU (1000mg/m2) were analysed according to a response rate, survival rates, developments of extrahepatic lesions, periods of hepatic arterial infusion, and the rates at home. Two cases (4.5%) achieved a complete response (CR) and 27 cases (61.4%) a partial response (PR). The overall one-year and two-year survival rates were 56.7% and 37.8% respectively. The 50% survival time for all patients was 17.2 months. During the course of observation, extrahepatic lesions developed in 16 of the 39 patients (41.0%) and many responders died due to deterioration of extrahepatic lesions. The over all rates at home were more than 85%. Hepatic arterial infusion of the 5-FU at 1000mg/m2 every week showed a high response rate in colorectal cancer patients with hepatic metastases, and the responders showed a low rate of death due to the hepatic metastases. However, in many patients the prognosis-determining-factor was extrahepatic lesions. Thus, countermeasures were necessary for extrahepatic lesions.

Endocytotic internalization of alpha-2-macroglobulin: alpha-galactosidase conjugate by cultured fibroblasts derived from Fabry hemizygote.

Endocytotic internalization of alpha-galactosidase by cultured fibroblasts derived from a patient with Fabry's disease was achieved via receptor-mediated endocytosis of alpha-2-macroglobulin (alpha-2-M). alpha-galactosidase of coffee beans was conjugated to alpha-2-M when the latter was treated with trypsin. Internalization of the conjugate resulted in an increase of alpha-galactosidase activity in the crude cell extracts. The observed internalization was blocked by the presence of bacitracin, an inhibitor of binding between alpha-2-M and its receptor on the cell surface. When the cells were incubated at 4 degrees C with the conjugate, internalization was also inhibited. The alpha-galactosidase activity in the cells was saturated when the concentration of the conjugate in the medium was 40 micrograms/ml. Since non-conjugated alpha-galactosidase was not effectively internalized, the observed internalization of the conjugate was mediated by recognition of alpha-2-M by its receptor. The effective internalization of alpha-galactosidase described in this paper has a potential use in the enzyme replacement therapy of Fabry's disease.