Enhanced delivery to target cells by heat-sensitive immunoliposomes.

Heat-sensitive immunoliposomes are capable of releasing the entrapped content at the target cell surface upon a brief heating to the phase transition temperature of the liposome membrane. In this study we have examined the delivery efficiency of drugs entrapped in heat-sensitive immunoliposomes. Immunoliposomes composed of dipalmitoyl phosphatidylcholine with entrapped [3H]uridine were incubated with target cells at 4 degrees C. The cell-liposome mixture was then heated to 41 degrees C and the uptake of [3H]uridine into the intracellular pool of phosphorylated uridine-containing molecules was measured. The immunoliposomes showed maximal release of the uridine at 41 degrees C, the phase transition temperature of dipalmitoyl phosphatidylcholine liposomes. The largest accumulation of [3H]uridine in the target cells also took place at 41 degrees C. The initial level of uptake of [3H]uridine released from immunoliposomes by heating was greatly enhanced over that observed for free [3H]uridine and [3H]uridine released from liposomes without attached antibody. The nucleoside uptake inhibitors nitrothiobenzylinosine, dipyridamole, and unlabeled uridine were able to inhibit uptake of [3H]uridine released from immunoliposomes. This supports the hypothesis that the enhanced uptake is due to a heat-induced release of [3H]uridine at the cell surface followed by transport and phosphorylation of [3H]uridine by the target cells. These results indicate the feasibility of using the heat-sensitive immunoliposomes as a target-specific drug delivery system.     

Seroepidemiologic study of giardiasis patients and high-risk groups in a midwestern city in the United States.

Serum antibodies to Giardia lamblia were measured in giardiasis patients, in groups at high risk for intestinal parasite infection, and in controls by an indirect fluorescent antibody (IFA) technique. Symptomatic patients had the highest antibody titers, and antibodies remained present for up to 18 months in persons with chronic infection. Indochinese refugees and male homosexuals with the acquired immunodeficiency syndrome (AIDS) and pre-AIDS had higher mean antibody levels than did healthy controls, whereas sewer and highway maintenance workers had levels similar to those of controls. Serum antibodies to Entamoeba histolytica measured by an indirect hemagglutination antibody technique were detected in only a few Indochinese refugees. We conclude that serology is a promising tool in G. lamblia epidemiology and that further population studies would be of interest.     

Adriamycin response of two human tumor xenografts using a double-radiolabel organ culture method

A double-radiolabel method of quantitating drug response in a simple organ culture system was used to study the effects of adriamycin on two human tumor xenografts in vitro. Explants of X56, an adenocarcinoma of colon, and HXG2, an amelanotic melanoma, both maintained by serial transplantation in athymic mice, were sequentially incubated in vitro with 14C-thymidine, one of several concentrations of adriamycin, and then 3H-thymidine. The ratios of second to first radiolabel incorporation declined as a function of adriamycin concentration. HXG2 was significantly more responsive to adriamycin than X56 in the double-radiolabeled assay. Greater sensitivity of HXG2 was confirmed by three additional methods: The human tumor stem cell assay (HTSCA), chemotherapy trials in tumor-bearing athymic mice, and a double-radiolabel protocol in vivo in tumor-bearing athymic mice. An organ culture method of this type may be useful in screening individual patients' tumors for drug resistance.     

A twenty-five year review of laboratory-acquired human infections at the National Animal Disease Center

The National Animal Disease Center's experience with personnel exposure or infection with pathogenic agents is summarized. A total of 128 laboratory-associated exposures to infectious disease agents were reported. Of these exposures, 103 resulted from known accidents. The other 25 were identified only after the development of clinical or serological manifestations of infection. Thirty-four cases of laboratory-acquired infections were reviewed. Class 3 organisms--Chlamydia sp., Brucella sp. and Mycobacterium sp.--were responsible for 76% of the infections encountered, with Brucella sp. incriminated most frequently. The most commonly reported cause of exposure was associated with hypodermic syringe use. Unknown routes of exposure, presumed to be aerosol related, were the overwhelming explanation involved in the laboratory-associated infections.     

MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

Background  

MFSD2A (major facilitator superfamily domain containing 2) gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer.