Establishment of a tumor-specific immunotherapy model utilizing TNP-reactive helper T cell activity and its application to the autochthonous tumor system

Preinduction of potent hapten-reactive helper T cell activity and subsequent immunization with hapten-coupled syngeneic tumor cells result in enhanced induction of tumor-specific immunity through T-T cell collaboration between anti-hapten helper T cells and tumor-specific effector T cells. On the basis of this augmenting mechanism, a tumor-specific immunotherapy protocol was established in which a growing tumor regresses by utilizing a potent trinitrophenyl (TNP)-helper T cell activity. C3H/He mice were allowed to generate the amplified (more potent) TNP-helper T cell activity by skin painting with trinitrochlorobenzene (TNCB) after pretreatment with cyclophosphamide. Five weeks later, the mice were inoculated intradermally with syngeneic transplantable X5563 tumor cells. When TNCB was injected into X5563 tumor mass, an appreciable number of growing tumors, in the only group of C3H/He mice in which the amplified TNP-helper T cell activity had been generated were observed to regress (regressor mice). These regressor mice were shown to have acquired tumor-specific T cell-mediated immunity. Such immunity was more potent than that acquired in mice whose tumor was simply removed by surgical resection. These results indicate that in situ TNP haptenation of the tumor cells in TNP-primed mice can induce the enhanced tumor-specific immunity leading to the regression of a growing tumor. Most importantly, the present study further investigates the applicability of this TNP immunotherapy protocol to an autochthonous tumor system. The results demonstrate that an appreciable percent of growing methylcholanthrene-induced autochthonous tumors regressed by the above TNP immunotherapy protocol. Thus, the present model provides an effective maneuver for tumor-specific immunotherapy in syngeneic transplantable as well as autochthonous tumor systems.     

Correlations in one-dimensional fully developed chaos

Correlations in the baker map and the tent map as examples of one-dimensional, fully developed chaos are considered. It is shown, utilizing symbolic dynamical systems derived from these maps, that the vanishing second-order correlation function is not sufficient to guarantee uncorrelatedness. Importance of the higher-order, especially third-order, correlation functions is emphasized for chaotic systems. In search of the quantities that grasp correlational behaviors as a whole in chaotic systems, it is proposed to use the fixed-separation correlation integral, which is a modified quantity of the usual correlation integral devised to calculate the fractal dimension of strange attractors, for these maps. It is shown that the new quantity contains all the even-number orders of autocorrelation function that are commonly considered.     

Dispersion distance of queens from natal sites in the two haplometrotic paper waspsPolistes riparius andP. snelleni (Hymenoptera: Vespidae)

Dispersion capabilities of new queens were studied in the two haplometrotic paper wasps Polistes riparius and P. snelleni. New queens were marked on the nests in the late summer and located in the next spring. Dispersion distances greatly varied among queens: although a large part of recovered queens nested in close proximity to their natal sites, some did disperse over 100–300 m. This suggests that queens' emigration from and immigration into the censused areas occurred to a substantial extent. On the whole, these species exhibited a weaker “philopatric” tendency than those so far studied for dispersion distance, and seem to have the potential for a long-distance dispersion.     

Characterization of a chloroplast DNA sequence from Chlorella ellipsoidea that promotes autonomous replication in yeast

Summary An EcoRI 2.7 kbp fragment from Chlorella ellipsoidea chloroplast DNA (cpDNA) cloned in YIp5 was shown to promote autonomous replication in Saccharomyces cerevisiae. The fragment was localized in the small single copy region close to the inverted repeat. The ARS activity (autonomously replicating sequences in yeast) was found to be confined within a subclone of a ca. 300 bp HindIII fragment. Sequence analysis of this fragment revealed its high AT content and the presence of several direct and inverted repeats and a few elements that were related to the yeast ARS consensus sequence. Electron microscopic studies revealed that this sequence did not coincide with the primary replication origin of chloroplast DNA. The functioning of this sequence as a possible origin of plasmid replication in vivo is discussed. This is the first report on Chlorella cpDNA sequence. re]19850821 rv]19851211 ac]19851216     

Selective accumulation of heavy metals by microorganisms

Summary An investigation of the removal and recovery of urnnium from aqueous systems using microbial biomass has been described previously (Nakajima et al. 1982). To establish which microorganisms accumulate the most uranium, we extended our investigation of uranium uptake to 83 species of microorganisms, 32 bacteria, 15 yeasts, 16 fungi and 20 actinomycetes. Of these 83 species of microorganisms tested, extremely high uranium-absorbing ability was found in Pseudomonas stutzeri, Neurospora sitophila, Streptomyces albus and Streptomyces viridochromogenes.The selective accumulation of heavy metal ions by various microorganisms has also been examined. Uranyl, mercury and lead ions were readily accumulated by almost all the species of microorganisms tested. Actinomycetes and fungi differ from many bacteria and most yeasts in their selective accumulation of uranium and mercury.In addition to this fundamental research, uranium recovery was investigated in immobilized Streptomyces albus, a microorganism with high uranium-uptake ability. These immobilized cells adsorbed uranium readily and selectively. The immobilized cells recovered uranium almost quantitatively and almost all uranium absorbed was desorbed with 0.1 M Na₂CO₃. The dry weight of the free cells decreased by 50% during 5 adsorption-desorption cycles. However, the dry weight of the immobilized cells decreased by only 2% during 5 cycles. These results showed that microbial cells are more stable after immobilization and can be used repeatedly for the process of uranium adsorption-desorption.     

Fibrinolysis: Its initiation and regulation

Fibrinolytic system is one of the major proteolytic pathways in vivo and primarily responsible for dissolution of thrombi. Two enzymes are primarily involved in this proteolytic system; plasminogen activator (PA) and plasmin. Plasmin is formed by a limited proteolysis of plasminogen by PA, which is mainly synthesized by and secreted from vascular endothelial cells. This proteolytic process proceeds physiologically only on the surface of fibrin. Thus, initiation and progression of the fibrinolytic process depend on the function of endothelial cells and fibrin formation. Endothelial cells may also synthesize and excrete PA inhibitor (PAI) which inhibits immediately, PA once released. The rates of synthesis and excretion of PA and PAI by endothelial cells are regulated by various factors. Among them, thrombin stimulates the release of PA whereas activated protein C may decrease the release of PAI. Thus, both enzymes enhance fibrinolytic potential. PA which has escaped from inhibition by PAI binds to fibrin. ₂-Plasmin inhibitor (₂PI) inhibits the binding of plasminogen to fibrin, thereby suppressing this fibrin-associated plasminogen activation. A part of ₂PI is cross-linked to fibrin by activated factor XIII when fibrin is formed, and the ₂PI thus cross-linked to fibrin inhibits in situ plasmin formed on fibrin. Thus, ₂PI as well as PAI plays a central role in inhibition of fibrinolysis.     

The hemolymph coagulation system in invertebrate animals

A hemocyte lysate from horseshoe crab produced a gel, when exposed to Gram-negative bacterial endotoxins. This gelation reaction of the lysate, so-called Limulus test, has been widely employed as a simple and very sensitive assay method for endotoxins. Recent biochemical studies on the principle of Limulus test indicate that the hemocytes contain several serine protease zymogens, which constitute a coagulation cascade triggered by endotoxins, and that there is a (1 3)--d-glucan-mediated coagulation pathway which also results in the formation of gel. Up to now, six protein components, designated coagulogen, proclotting enzyme, factor B, factor C, factor G and anti-LPS factor, all of which are closely associated with the endotoxin-mediated coagulation pathway, have been purified and biochemically characterized. Among these components, the complete amino acid sequences of coagulogens isolated from one American and three Asian species of horseshoe crabs have been established. Moreover, the reconstitution experiment using the isolated clotting factors, C, B, proclotting enzyme and coagulogen in the presence of endotoxin, leads to the formation of coagulin get. Based on these results, we propose here a mechanism for the Limulus coagulation cascade.     

Postmortem changes in uric acid and ascorbic acid in human cerebral cortex tissues excised after cardiac death

There has been no report on the determination of uric acid (UA) in human brain and heart tissues. UA and ascorbic acid (AA) in human cerebral cortex and heart tissues excised after cardiac death have been studied by reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection (ECD). It has been found that the levels of AA and UA in the human cerebral cortex tissues tend to decrease and increase, respectively, after cardiac death as a function of time between death and forensic operation. In addition, it has been found that there is no special relationship between UA levels in human heart tissues and time after cardiac death, also that the UA levels in the heart are high as compared with those in human cerebral cortex tissues. We have emphasized that the HPLC-ECD method is useful in determining UA and AA in mammalian tissues by one-time chromatography to gain a better understanding of the relationship between disease and serum urate level.