Improved formulations of antisense oligodeoxynucleotides using wrapped liposomes.

Previously, we demonstrated that wrapping dextran fluorescein anionic/cationic lipid complexes with neutral lipids produced a stable formulation that markedly increased the duration of the compound in plasma after intravenous administration to rats. The improved drug-delivery properties of the wrapped liposomes (WL) relative to other formulations suggested that this technology could offer important advantages for the administration of other polyanionic drugs, including antisense oligodeoxynucleotides (ODN). In the present study, we investigated the value of WL for formulating fluorescence-labeled phosphorothioated ODN (F-ODN). WL encapsulating F-ODN/cationic lipid complexes were prepared efficiently using similar methodology to that used in our earlier study. Studies confirmed that these WL were stable in vitro. Following intravenous administration to mice, free F-ODN and naked F-ODN/cationic lipid complexes were rapidly eliminated whereas administration of the WL resulted in high blood concentrations of drug that were maintained for several hours. Additional studies were conducted in mice that were inoculated with tumor cells (Caki-1 xenograft model, human kidney); in these experiments, intravenous administration of WL delivered 13 times more F-ODN to the tumor site than achieved after injection of free F-ODN.     

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.     

Solitary fibrous tumor of the inguinal region

Solitary fibrous tumors (SFT) have recently been established to be of mesenchymal origin. Although there are numerous reports of SFTs arising from the pleura, reports of the tumor arising from extrapleural sites are comparatively rare [Fletcher CDM, Unni K, Mertens F (eds) World Health Organization classification of tumors, pathology & genetics, tumors of soft tissue and bone. IARC Press, Lyon, pp 86–901, 2002]. We report a case of SFT arising in the inguinal region.     

Anal metastasis from carcinoma of the lung: Report of a case

We report herein the case of a 75-year-old man who developed anal canal metastasis from squamous cell carcinoma of the lung. Initially, he underwent a right middle and lower lobectomy combined with left atrial wall resection under cardiopulmonary bypass. He presented 3 months later with an anal polyp which had prolapsed and bled, for which he underwent a transanal polypectomy. Histologically, the polyp was classified as squamous cell carcinoma and considered to be a metastasis from the primary lung cancer. He is presently well with no signs of recurrence 9 months after his initial operation. To our knowledge, there has been no other case of anal metastasis from lung cancer ever reported.     

Evaluation of renal first pass blood flow with a functional image technique in hypertensive patients

The renal circulation of patients with essential hypertension and renovascular hypertension was evaluated using ^99mTc-DTPA. The first renal peak count (the first C_max; FC_max), time phase distribution (the first T_max; FT_max), and blood velocity (the FC_max/FT_max) were calculated by digital imaging. This yields a visual image of the renal circulation. We consider that the increase in the renal first pass blood flow in patients with essential hypertension is best observed pixel by pixel. The FC_max and FC_max/FT_max images before and after treatment by percutaneous transluminal renal angioplasty in patients with renovascular hypertension clearly show its therapeutic effect. The FI technique, therefore, has the advantage that it can be performed at the same time as the conventional routine examinations of renal function. This makes it very useful clinically.     

The biphasic response of hepatic arterial blood flow caused by vasoactive substances--an experimental study in dogs]

In ten male mongrel dogs, blood flow was measured in the common hepatic artery (CHA), portal vein (PV) and liver tissue before and after the injection of vasoactive substances: angiotensin II (1.0 micrograms/kg), prostaglandin F2 alpha (1.0 micrograms/kg) and vasopressin (0.1 Unit/kg), under observation of the systemic circulation. Each injection caused a biphasic response in CHA blood flow, an initial decrease followed by a marked increase, while PV blood flow decreased. Liver tissue blood flow was reduced just after injection, but soon returned to a normal level. The duration of action was the shortest with prostaglandin F2 alpha and the longest with vasopressin. In using vasoactive substances in pharmaco-angiography, it is important to consider the biphasic response in CHA blood flow as well as the duration of action of these substances.