The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives

Summary A new haptenic compound, a muramyl dipeptide (MDP) derivative (designated as L4-MDP-ONB) cross-reactive with Bacillus Calmette Guerin (BCG) was synthesized. The cross-reactivity of L4-MDP hapten to BCG was demonstrated from the following evidence; (a) lymph node cells from BCG-primed C3H/HeN mice exhibited appreciable L4-MDP-specific proliferative responses to the in vitro stimulation of L4-MDP-modified syngeneic cells (L4-MDP-self); (b) inoculation of L4-MDP-self into footpads of BCG-primed C3H/HeN mice elicited ample delayed type-hypersensitivity (DTH) responses in vivo as measured by footpad swelling; and (c) BCG-primed mice contained L4-MDP-reactive helper T cell activity which functions to augment the generation of effector T cell responses to cell surface antigens. This crossreactivity between L4-MDP hapten and BCG as measured by the helper T cell activity was applied to enhanced induction of tumor-specific immunity. When BCG-primed C3H/HeN mice were immunized with L4-MDP-modified syngeneic X5563 tumor cells, these mice could generate augmented tumor-specific in vivo protective (tumor neutralizing) immunity as well as in vitro cytotoxic T cell responses. These results indicate the effectiveness of L4-MDP hapten in augmenting tumor-specific immunity. The present approach is discussed in the context of potential advantages of this new hapten for its future application to clinical tumor systems.     

Allelic variants of Ly-5 in inbred and natural populations of mice

Allelic variants of Ly-5 in inbred commensal and other natural populations of mice were analyzed by patterns of restriction fragment length polymorphisms (RFLP) and Southern hybridization using an Ly-5 cDNA probe and by cell-surface staining with a panel of antibodies directed against polymorphic and nonpolymorphic Ly-5 determinants. New Ly-5 alleles were defined by RFLPs generated by both Eco RI and Bam HI restriction enzyme digests. The Mus musculus subspecies and other species within the genus Mus showed a strong correlation between allelic variants defined by restriction enzymes and serologic specificities. The data also suggest the conservation of the Ly-5 gene throughout the genus Mus.     

Dynamics of appearance and disappearance of the ripple structure in multilamellar liposomes of dipalmitoylphosphatidylcholine

The physical properties of the pretransition (P beta'----L beta') of dipalmitoylphosphatidylcholine liposomes were investigated using freeze-fracture electron microscopy. The kinetics of pretransition examined in the previous paper using TEMPO spin probe (Tsuchida, K., et al. (1985) Biochim. Biophys. Acta 812, 249-254) was extensively studied by observing the ripple structures in the freeze-fractured surfaces at different time intervals. When the temperature is decreased from 38 degrees C to 30 degrees C, the ripple structure disappears in the following steps. The intervals between ripples begin to expand with the decrease of ripple density upon the temperature shift, and this process continues for several tens minutes. Then, each ripple disappears gradually and changes into a completely smooth surface at 3 h after the temperature shift. The comparison of relaxation times between the previous ESR measurement and the present experiment suggests that the fast relaxation observed in the previous study corresponds to the expansion of the intervals between ripples. On the other hand, the ripple structure of regular intervals appears rapidly in some places and then spreads over the whole area of fractured surface when the temperature is increased from 23 degrees C to 35 degrees C. The results obtained in this work and the previous ESR work strongly suggest that the formation and disappearance of ripple structure is closely related to the relaxation processes near the pretransition temperature.     

Interleukin-1 inhibits the secretion of gastric acid in rats: possible involvement of prostaglandin

To examine the hypothesis that interleukin-1 may inhibit the secretion of gastric acid, the present study was carried out using pylorusligated rats. Based upon three lines of evidence, we report here that interleukin-1, both endogenously released and exogenously administered, suppresses gastric acid secretion and that the interleukin-1-induced inhibition of acid output is possibly mediated by prostaglandin. First, lipopolysaccharide, a potent stimulant of the release and production of endogenous interleukin-1, caused the suppression of gastric acid, and this response was dose-related. Second, the intraperitoneal injection of interleukin-1 resulted in a dose-related inhibition of gastric acid output. Third, the administration of indomethacin completely blocked the suppression of gastric acid secretion induced by interleukin-1. These results demonstrated for the first time that IL-1 might be involved in the regulation of gastric secretion.     

Electron microscopic observations on tracheal epithelia of mice infected with Bordetella bronchiseptica

To clarify the pathogenesis of Bordetella in vivo infection, the tracheal epithelia of mice were examined in detail by electron microscopy at various intervals after intranasal inoculation with graded doses of phase I Bordetella bronchiseptica. In mice infected with a lethal dose (6 to 7 x 10(7) CFU), a remarkable rupture of the cell membranes of cilia and microvilli of the middle trachea was found on day I postinfection. The rupture of the membrane was observed over the entire tracheal epithelia, on day 2 after infection. The affected cilia were constricted at the transitional region and were broken off. In the ciliated cells the adherence of organisms to ciliary apexes and colonization in the interciliary spaces were also remarkable. In both the ciliated and nonciliated epithelial cells, the cytoplasmic vacuolation and pyknosis or karyorrehexis were also notable. In mice infected with one-tenth of the lethal dose, similar findings were seen, but appeared more slowly and the bacteria were not seen attaching to ciliary apexes. In mice receiving one-hundredth of the lethal dose, only mild cilial abnormality such as aggregation of cilia, and slight cytoplasmic vacuolation were found 6 days postinfection. Based on these findings, a possible mechanism of the ciliary damages produced by B. bronchiseptica was postulated.     

Neural coding of speech sound in the telencephalic auditory area of the mynah bird

Summary The responses of neurons in field L in the auditory neostriatum of the mynah bird, Gracula religiosa, were recorded during presentation of intact or manipulated mimic voices. A typical mimic voice konnichiwa elicited responses in most of the neurons. Neurons in the input layer (L2) of field L showed many peaks on peristimulus time histograms while those in other layers (L1 and L3) exhibited only one or two peaks. Several neurons in L1 and L3 responded only to the affricative consonant /t/ in the intact mimic voices. They did not respond to the affricative consonant in the isolated segment or to the one in the playbacked voice in reverse. Forty-five percent of the neurons (33/ 73) decreased in firing rates at the affricative consonant in the isolated segment compared with in the intact voice. Some of these neurons, in which neither the affricative consonant in the isolated segment nor bursts of noise alone elicited responses, exhibited clear phasic responses to /t/ in the case when bursts of noise with particular central frequencies preceded the affricative consonant. The responsiveness of these neurons appears to receive temporal facilitation. These results suggest that these neurons code the temporal relationship of speech sound.Abbreviations HVc hyperstriatum ventrale, pars caudale - TFN temporally facilitated neuron - TSN temporally suppressed neuron     

Diurnal rhythms of proopiomelanocortin-derived N-terminal peptide, beta-lipotropin, beta-endorphin and adrenocorticotropin in normal subjects and in patients with Addison's disease and Cushing's disease

In order to clarify the diurnal pattern of secretion of plasma immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides, IR-N-terminal peptide (Nt), IR-beta-endorphin (Ep), IR-beta-lipotropin (LPH), and IR-ACTH (ACTH) in normal subjects and in patients with Addison's disease and Cushing's disease, we measured these 4 peptides in the same plasma obtained at 0900 h and then every three hours until 0600 h at the next day. All four peptides showed diurnal rhythms with the peaks at 0600 h, and the nadirs of ACTH, LPH, Ep and Nt were at 0000 h, 0000 h, 1800 h and 0300, respectively in normal subjects. In patients with Addison's disease, these four peptides also showed diurnal rhythms with the peaks at 0600 h for ACTH and Ep and at 0900 h for LPH and Nt, and the nadirs at 2100 h for ACTH and Ep and at 0000 h for LPH and Nt. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in plasma also presented diurnal variations in normal subjects and in patients with Addison's disease. On the other hand, in patients with Cushing's disease, ACTH, LPH and Nt showed no rhythmicity or change in molar ratios of Ep/ACTH, LPH/ACTH or Nt/ACTH. Only Ep showed diurnal variation. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in patients with Cushing's disease were significantly higher than those in normal subjects and in patients with Addison's disease at 0000 h.(ABSTRACT TRUNCATED AT 250 WORDS)