Monoclonal antibody-mediated tumor regression by induction of apoptosis

To characterize cell surface molecules involved in control of growth of malignant lymphocytes, monoclonal antibodies were raised against the human B lymphoblast cell line SKW6.4. One monoclonal antibody, anti-APO-1, reacted with a 52-kilodalton antigen (APO-1) on a set of activated human lymphocytes, on malignant human lymphocyte lines, and on some patient-derived leukemic cells. Nanogram quantities of anti-APO-1 completely blocked proliferation of cells bearing APO-1 in vitro in a manner characteristic of a process called programmed cell death or apoptosis. Cell death was preceded by changes in cell morphology and fragmentation of DNA. This process was distinct from antibody- and complement-dependent cell lysis and was mediated by the antibody alone. A single intravenous injection of anti-APO-1 into nu/nu mice carrying a xenotransplant of a human B cell tumor induced regression of this tumor within a few days. Histological thin sections of the regressing tumor showed that anti-APO-1 was able to induce apoptosis in vivo. Thus, induction of apoptosis as a consequence of a signal mediated through cell surface molecules like APO-1 may be a useful therapeutic approach in treatment of malignancy.     

Similarity of clover yellow vein virus and pea necrosis virus

There still is confusion concerning the relationships between clover yellow vein virus (ClYVV), pea necrosis virus (PNV) and bean yellow mosaic virus (BYMV). Therefore, three Swedish isolates of ClYVV and its type strain have now been compared with three isolates of PNV. A bean mosaic isolate and three pea necrosis isolates of BYMV have been used for reference. Based on host range tests, serology, and light microscope studies of inclusion bodies, ClYVV and PNV isolates are now considered to be strains of one virus, with the first name having priority. ClYVV (including the original PNV) especially differs from BYMV in its ability to infect white clover, to produce local lesions on cucumber cotyledons (at least two cultivars), to go systemic inChenopodium quinoa (the two local selections used at Wageningen and at Uppsala), to be rather virulent onNicotiana clevelandii, and to provoke extensive nucleolar enlargements in its host cells. Serologically the two viruses are more or less distinct.     

RABBIT HEMORRHAGIC DISEASE VIRUSES DETECTED IN PET RABBITS IN A COMMERCIAL LABORATORY IN EUROPE

Rabbit hemorrhagic disease (RHD) is an important cause of disease and mortality in wild and domestic European rabbits (Oryctolagus cuniculus) throughout the world. Testing for 2 distinct RHD virus types (RHDV/RHDVa and RHDV2) was carried out on samples collected from 684 rabbits submitted from veterinary practices and private owners throughout Europe between January 2015 and June 2017. Four (0.6%) were positive for RHDV/RHDVa and 257 (37.4%) were positive for RHDV2. RHDV/RHDVa was detected in individual samples from Germany and the Netherlands, while RHDV2 was found in animals from Germany, Great Britain, Luxembourg, The Netherlands, Spain, Switzerland, Poland, Belgium, Austria, Sweden, and Finland.     

First Record of A and B Type Beet necrotic yellow vein virus in Sugar Beets in Sweden

Natural infections of sugar beet with Beet necrotic yellow vein virus (BNYVV), the causal agent of rhizomania, have been detected for the first time in Sweden in two small areas, one on the island of Öland and one in the Southeastern part of Scania. Single strand conformation polymorphism analyses of PCR products revealed that the infections on Öland were produced by A type BNYVV, whereas those in Scania were caused by the B type. This suggests that BNYVV has been introduced into Sweden at least twice. Alternatively, the virus may have invaded sugar beet from unknown native hosts. BNYVV RNA 5 was not detected in the samples investigated.     

Role of EphA4 and EphrinB3 in local neuronal circuits that control walking

Local circuits in the spinal cord that generate locomotion are termed central pattern generators (CPGs). These provide coordinated bilateral control over the normal limb alternation that underlies walking. The molecules that organize the mammalian CPG are unknown. Isolated spinal cords from mice lacking either the EphA4 receptor or its ligand ephrinB3 have lost left-right limb alternation and instead exhibit synchrony. We identified EphA4-positive neurons as an excitatory component of the locomotor CPG. Our study shows that dramatic locomotor changes can occur as a consequence of local genetic rewiring and identifies genes required for the development of normal locomotor behavior.     

Serum concentrations of buprenorphine after oral and parenteral administration in male mice

Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post-administration serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24 h serum concentration: 110 ng h/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained in the circulation for a substantially shorter time (24 h serum concentration for IV and SC were 40 ng h/mL and 30 ng h/mL, respectively). This marked difference was probably due to the higher dose used for oral administration, which is regarded necessary for sufficient analgesic effect, and to the slower absorption of the oral boli, as well as saturation of the hepatic buprenorphine metabolising pathways. Voluntary ingestion of buprenorphine was found to constitute a practical way to provide laboratory mice with efficient pain relief.