Interferon-α, interferon-γ and sizofiran in the adjuvant therapy in ovarian cancer — a preliminary trial

The study included 24 cases of negative second-look laparotomy (SLL) after operation on ovarian cancer. 12 cases were treated with sizofiran and recombinant interferon-gamma before and after SLL and then with human lymphoblastoid interferon-alpha. The remaining 12 cases (controls) were followed up without any drug therapy after SLL. There were no recurrences in the treated group, but in 3 cases of the control group. Also significant difference in survival was noted in the treated group.     

Mouse/human chimeric anti-HIV-1 gp120 antibody to the principal neutralizing determinant: Tolerability and pharmacokinetics in cynomolgus monkeys,Macaca fascicularis

In preparing for testing a pharmaceutical grade preparation of chimeric (mouse/human) antibody CGP 47 439 in HIV-1 infected individuals, it was administered toMacaca fascicularis (cynomolgus) monkeys to study tolerability, immunogenicity and pharmacokinetics. Four groups of monkeys, three males and three females per group, received respectively four infusions of 0, 1.43, 4.3, and 14.3 mg of CGP 47 4391 kg body weight at one-week intervals. The chimeric antibody induced no fever, was tolerated well throughout the 50-day observation period, elicited no tissue damage and no anti-antibody response. The pharmacokinetic profile was similar at all dose levels with a mean T_1/2 of 14.2 h (range 11.8–19.3 h) and a mean T_1/2 of 172.6h (range 137.2–220.5h). Following four successive antibody infusions serum concentrations of CGP 47 439 increased without reaching a steady state, and its measured concentrations were comparable to the simulated values. Collectively the study has provided safety and pharmacokinetic data that would allow human studies with this antibody in AIDS patients.     

Targeting to the HIV-1 RRE of the influenza virus NS1 protein effector domain as a potent, specific anti-HIV agent

The Rev axis of HIV autoregulation is one of two critical viral regulatory pathways required for expression of viral genomic and mRNA and for replication. Consequently it is an attractive therapeutic target. Previous studies have investigated the anti-HIV efficacy of targeting to the RRE (the viral RNA target sequence of the Rev axis) a trans-dominant negative inhibitor mutant Rev, M10. In this study we have fused a portion of the influenza virus NS1 protein (which normally inhibits polyA(+) mRNA transport and splicing) to the Rev M10 gene while deleting the NS1 poly(A) binding region. The resulting chimera demonstrates specific and enhanced inhibition of viral-RRE-containing RNA expression.     

Coexistence of multiple peptides in small intensely fluorescent (SIF) cells of inferior mesenteric ganglion of the guinea pig

Summary Coexistence of peptides in the small intensely fluorescent cells was demonstrated by immunocytochemistry for met-enkephalin-Arg-Gly-Leu, vasoactive intestinal polypeptide, somatostatin, neuropeptide Y and dynorphin. In the extreme example, a single cell was immunoreactive to all 5 peptides examined. Four peptides coexisted in 8% and three peptides in 13% of SIF cells. In 10% of SIF cells no peptide immunoreactivity could be detected. The most prevalent peptide was met-enkephalin (in 46% of cells), then vasoactive intestinal polypeptide (45%), somatostatin (39%), neuropeptide Y (31%) and dynorphin (24%). Met-enkephalin and vasoactive intestinal polypeptide coexisted most commonly (25%).     

Early and late passage C-6 glial cell growth: Similarities with primary glial cells in culture

Earlier studies in our laboratory have shown that C-6 glial cells in culture exhibit astrocytic properties with increasing cell passage. In this study, we tested the responsiveness of early and late passage C-6 glial cells to various cultures conditions: culture substrata (collagen, poly-L-lysine, plastic), or supplements for the culture medium, DMEM, [fetal calf, or heat inactivated (HI) serum, or media conditioned from mouse neuroblastoma cells (NBCM) or primary chick embryo cultured neurons (NCM)]. Glutamine synthetase (GS) and cyclic nucleotide phosphohydrolase (CNP), astrocytic and oligodendrocytic glial markers, were used. Cell numer and protein content increased exponentially with days in culture regardless of the type of the substratum or cell passage. Differences in cell morphology among the three types of substratum were also reflected on GS activity, which rose by three-fold on culture day 3 for cells grown on collagen; thereafter, GS profiles were similar for all substrata. This early rise in GS is interpreted to reflect differential cell adhesion processes on the substrata; specifically, cell adhesion on the collagen stimulated differentiation into astrocytic phenotype.Analogous to immature glia cells in primary cultures, early passage C-6 glial cells responded to neuronal factors supplied either from NCM or NBCM by expressing reduced GS activity, the astrocytic marker and enhanced CNP activity, the oligodendrocytic marker. Thus, early passage cells can be induced to express either astrocytic or oligodendrocytic phenotype. In accordance with our previous reports on primary glial cells, late passage C-6 cells exhibit their usual astrocytic behavior, responding to serum factors with GS activity. Moreover, whereas NCM or NBCM alone markedly lowered GS activity, a combination with serum restored activity. The present findings confirm our previous observations and further establish the C-6 glial cells as a reliable model to study immature glia.Special issue dedicated to Dr. Paola S. Timiras.