Potentiation of direct antitumor cytotoxicity and production of tumor cytolytic factors in human blood monocytes by human recombinant interferon-gamma and muramyl dipeptide derivatives

Summary We investigated whether human peripheral blood monocytes isolated by centrifugal elutriation from healthy donors could be acitivated to become tumoricidal and release tumor cytolytic factor (TCF) subsequent to incubation with recombinant human interferon-gamma (r-IFN-) or a derivative of muramyl dipeptide (nor-MDP), or both. Blood monocytes incubated in endotoxin-free medium containing up to 1000 U/ml of r-IFN- or in medium containing less than 1 g/ml of nor MDP were not activated to lyse radiolabeled allogeneic human tumor cells. In contrast, the incubation of monocytes with various dose combinations of r-IFN- and nor-MDP generated significant direct cytotoxic activity as well as production of TCF. Preincubation of the r-IFN- and nor-MDP mixture with polymyxin B did not inhibit the synergism, thus ruling out the possibility that the process was due to endotoxin contamination. TCF harvested from monocyte culture supernatants was cytolytic against five allogeneic tumor targets, but not against a nontumorigenic cell line. Collectively, the data demonstrate that r-IFN- can prime human blood monocytes to allow their activation by synthetic nor-MDP.On leave from the Department of Internal Medicine, The University of Tokushima School of Medicine, Kuramoto-cho, Tokushima 770, Japan     

Analysis of two chloride requirements for sodium-dependent amino acid and glucose transport by intestinal brush-border membrane vesicles of fish

Intestinal brush border vesicles of a Mediterranean sea fish (Dicentrarchus labrax) were prepared using the Ca²⁺-sedimentation method. The transport of glucose, glycine and 2-aminoisobutyric acid is energized by an Na⁺ gradient ($\text{out > in}$). In addition, amino acid uptake requires Cl^? in the extravesicular medium (2-aminoisobutyric acid more than glycine). This Na⁺- and Cl^?-dependent uptake is electrogenic, since it can be stimulated by negative charges inside the vesicles. The specific Cl^? requirement of glycine and 2-aminoisobutyric acid transport is markedly influenced by pH, a change from 6.5 to 8.4 reducing the role played by Cl^?. In the presence of Cl^?, the $\text{K}{}_{\mathrm{<mtext>m</mtext>}}$ of 2-aminoisobutyric acid uptake is reduced and its $\text{V}{}_{\mathrm{<mtext>max</mtext>}}$ is enhanced. Cl^? affects also a non-saturable Na⁺-dependent component of this amino acid uptake. Amino acid transport is also increased by intravesicular Cl^? (2-aminoisobutyric acid less than glycine). This effect is more concerned with glucose uptake, which can be then multiplied by 2.3. A concentration gradient ($\text{in > out}$) as well as the presence of Na⁺ in the incubation medium seems to enter into this requirement. This intravesicular Cl^? effect is not influenced by pH between 6.5 and 8.4.     

Dimethylsulfoxide action on dark- and light-induced leaflet movements and its necrotic effects on excised leaves of Cassia fasciculata

Dimethylsulfoxide (DMSO) acts on dark- and light-induced movements exhibited by leaflets of isolated leaves of Cassia fasciculate Michx. The closing movement (scotonasty), induced when the leaves are placed in darkness during the normal period of daylight, was inhibited, whereas the opening movement (photonasty), when the leaves arc transferred to light during the normal period of darkness, was promoted. The concentration for significant effects of DMSO was 1% (v/v) when applied over a 3-h period. After five days, a necrosis of the leaflets was observed for DMSO concentrations as small as 0.1%, applied over a 6-h period. Complete abscission took place if 3% DMSO was applied for more than 30 min.     

A cDNA clone containing the entire coding sequence of a mouse H-2Kd histocompatibility antigen

We have isolated a cDNA clone carrying a 1560 bp long insert which contains the entire coding and 3' untranslated regions of an H-2K(d) mouse histocompatibility antigen. Its sequence and overal features are described. They point to the existence of unique properties of DNA sequences associated with the H-2K(d) antigen.     

Secondary and Apparent Primary Antibody Responses After Group A Streptococcal Vaccination of 21 Children

A partially purified M protein, extracted from a mouse-virulent strain of type 3, group A streptococcus, was administered subcutaneously in gradually increasing amounts at weekly intervals to 21 children in a Family Program. Seven children with type 3 bactericidal antibody in prevaccination sera showed a secondary response. Of 14 children with no detectable type 3 bactericidal antibody prior to vaccination, 13 developed definite type 3 antibody during or soon after vaccination. This response appeared to be of the primary variety in at least some of the 13 children because (i) the total incidence of antibody response (20 of 21) was greater than can be accounted for by the documented incidence of clinical and subclinical type 3 infections among children of our Family Program during a period of 14 years, (ii) the response in the 13 children with no detectable antibody prior to vaccination was more delayed than in those showing a definite secondary response, and (iii) on the average, the amount of vaccine needed for a response in these 13 children was 15 to 28 times greater than that required for the secondary response. Local skin reactions were variable among the vaccinated children. Systemic reactions were infrequent and not severe. The giving of multiple injections of partially purified M protein did not seem to cause cutaneous hypersensitivity.