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At least 613 records · Page 34Linked to original sources
PubMed1992

A nephritogenic rat monoclonal antibody to mouse aminopeptidase A. Induction of massive albuminuria after a single intravenous injection.

Antibodies directed against antigens present on renal epithelial cells can cause membranous glomerulonephritis in experimental animals, which closely resembles the human form of this disease. However, most antibodies produced so far fail to cause the persistent and severe proteinuria that is seen in humans. In our search for new antibodies of this kind, we have now produced a monoclonal antibody (mAb) against mouse aminopeptidase A, a hydrolase that is present in the mouse kidney. The mAb (ASD-4) was prepared by fusion of mouse myeloma cells with splenocytes of Lou rats immunized with brush border (BB) membranes from mouse kidneys. ASD-4 is of the IgG1 subclass and reacts with a 140-kD protein as demonstrated by immunoprecipitation on radiolabeled BB membranes. In indirect immunofluorescence and immunoelectronmicroscopy of normal mouse kidneys, ASD-4 was diffusely present on the BB of the S1 and S2 segments of the proximal tubules, and on the cell membranes of the glomerular visceral epithelia. It also bound to cell membranes of nonglomerular endothelia, smooth muscle cells of arteries, and juxtaglomerular cells. After injection of ASD-4 into normal mice, an immediate homogeneous binding to the capillary wall was seen that gradually changed into a fine granular pattern after 1 d. This glomerular binding was followed by binding to the BB and basolateral membranes of the convoluted proximal tubules. Immediately after injection of ASD-4, a dose-dependent albuminuria occurred that lasted for at least 16 d. ASD-4 is thus a new rat mAb against a well-defined renal epithelial antigen that causes not only membranous glomerulonephritis after a single injection in the mouse, but also severe albuminuria.

Albuminuria↗
PubMed2000

Intravenous injection of naked DNA encoding secreted flt3 ligand dramatically increases the number of dendritic cells and natural killer cells in vivo.

The trace number of dendritic cells (DCs) present in tissues has limited the study of DC biology and development of clinical applications utilizing DCs. Here we show that hydrodynamics-based gene delivery of naked DNA encoding secreted human flt3 ligand (hFLex) can dramatically increase the number of functional DCs and natural killer (NK) cells. After a single injection of the hFLex gene, hFLex levels in mouse serum reached approximately 40 microg/ml and remained above 1 microg/ml for 5-6 days. Sustained levels of serum hFLex correlated with significant increases in the size of the lymphoid organs and in the proportion of dendritic cells and NK cells in both lymph nodes and spleen. The increase in DC and NK cell numbers started from day 5, and reached peak levels between day 8 and day 12. The levels then returned to normal on day 20. These DCs and NK cells were functional as evidenced by mixed leukocyte reactions and lysis of YAC-1 cells, respectively. These results suggest that delivery of the hFLex gene provides a simple, efficient, and inexpensive way of increasing DC and NK cell populations in vivo, and may have broad applications in the further study of DC and NK cell biology and in the development of immunotherapy strategies.

Animals↗
PubMed1991

The clearance and degradation of oligodeoxynucleotides following intravenous injection into rabbits.

A 32P-labeled oligodeoxynucleotide of 20 bases was found to be quite stable in freshly drawn rabbit or human blood and no degradation was apparent within 2 hr. In contrast, following injection into rabbits, the same oligodeoxynucleotide was cleared from the blood rapidly and at least 17% was completely degraded within 5 min. After 90 min, 16% of the oligonucleotide was found largely intact in the urine. At this time, radioisotope was also found in all the solid tissues tested but probably not as intact oligonucleotide.

Animals↗
PubMed1976

Reactions to intravenous injections of diazepam.

Local reactions during and after i.v. injection of two different formulations of diazepam were studied. Two-thirds of the patients felt pain during the injection. Verfied or probable thrombophlebitis occurred with increasing frequency following operation, indicating a late onset. One month after discharge, 29% of those who had received diazepam in glycoferol-alcohol-benzoic acid complained of tender injection sites, compared with only 10% of the patients who received diazepam in cremophor EL. The difference is significant, indicating an influence of the solvent system.

Diazepam↗
PubMed1986

Carcinogenicity of N-alkyl-N-(1-hydroperoxyalkyl) nitrosamines after intravenous injections in F344 rats.

As model compounds of alpha-hydroxy N-nitrosamines, four alpha-hydroperoxy N-nitrosamines were tested for their carcinogenic potential in F344 rats by i.v. injections. Correlation between chemical structure and carcinogenic potencies with respect to target organs was examined. Compounds used in this study were N-methyl-N-(hydroperoxymethyl)nitrosamine (MHPMN), N-ethyl-N-(1-hydroperoxyethyl)nitrosamine (EHPEN), N-propyl-N-(1-hydroperoxypropyl)nitrosamine (PHPPN) and N-butyl-N-(1-hydroperoxybutyl)nitrosamine (BHPBN). All chemicals were dissolved in distilled water and rats received 10 X 1 weekly i.v. injections of these chemicals (10 X 1 weekly injection of 5 mg/kg of MHPMN or equimolar amounts of other chemicals). Lung tumors were detected in all groups of both sexes and the incidences were 100% in each group. Thyroid tumors were also observed with relatively high incidences in treated groups except BHPBN. In the control group, tumors were observed mainly in the testis or uterus, and only two lung tumors and one thyroid tumor were observed in females. Histologically, all lung tumors in the MHPMN group were adenocarcinomas, squamous cell carcinomas or a mixture of both types. In the EHPEN, PHPPN and BHPBN groups, especially in females, incidences of carcinomas decreased as the length of the alkyl chain of the compounds, and most of lung tumors in females of the PHPPN and BHPBN groups were adenomas. Many of the thyroid tumors observed in the treated groups were follicular adenomas/carcinomas, whereas C-cell adenomas were the most common type of spontaneous thyroid tumors in this strain of rats. These target organs were similar to those of alpha-acetoxy N-nitrosamines reported previously. The results indicate that the carcinogenic activities of these chemicals depend on the length of the alkyl chain and that organ specificity of these chemicals may differ from those of their mother compounds.

Animals↗
PubMed1989

Therapy for osteosarcoma in dogs with intravenous injection of liposome-encapsulated muramyl tripeptide.

Canine osteosarcoma is a spontaneous malignancy in dogs, characterized by micrometastasis to pulmonary and extrapulmonary tissues at the time of diagnosis. Standard treatment involves amputation of the affected leg, but median survival time is 3-4 months with death due to metastasis. A randomized double-blind trial was conducted to evaluate liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (liposome/MTP-PE) as a treatment for metastasis in dogs undergoing amputation for osteosarcoma. Fourteen dogs were treated with liposome/MTP-PE, and 13 were treated with empty liposomes. Median survival time was 222 days for dogs treated with liposome/MTP-PE, compared to 77 days for dogs treated with empty liposomes (P less than .002). In the liposome/MTP-PE-treated group there were still four dogs alive and free of metastasis at greater than 1 year post surgery. Treatment was well tolerated; no significant toxic effects were noted except for mild elevations in body temperature (1-2 degrees C) for 2-6 hours post injection.

Acetylmuramyl-Alanyl-Isoglutamine↗