Effect of thymosin alpha 1 on the antitumor activity of tumor-associated macrophage-derived dendritic cells

We have previously suggested that thymosin ₁ (thy1), an immunomodulating thymic hormone, can activate tumor-associated macrophages to a tumoricidal state in a murine model bearing a transplantable T-cell lymphoma of spontaneous origin designated as Dalton's lymphoma (DL). Since tumor-infiltrating dendritic cells (DC) also play an important role in the host's antitumor response and are as such in an immunocompromised state in a tumor-bearing host, in the present investigation we studied if thy1 is able to influence the differentiation of tumor-associated macrophages (TAM) into DC with granulocyte macrophage colony stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF) and whether these TAM-derived DC show enhanced antitumor activity. It was observed that DC generated from thy1-administered tumor-bearing mice showed augmented antitumor activity in vitro. Adoptive immunotherapy using TAM-derived DC showed a significant delay in the tumor growth and a prolongation of the survival time in tumor-bearing mice. DC obtained from TAM of thy1-administered mice also produced an enhanced amount of cytokines like IL-1 and TNF-. This is the first study of its kind regarding the effect of thy1 on the differentiation of DC from TAM and the role of TAM-derived DC in tumor progression.     

Tumor-derived Fas ligand induces toxicity in lymphoid organs and plays an important role in successful chemotherapy

 Recent studies have suggested that Fas ligand (FasL⁺) tumor cells can induce apoptosis in Fas⁺ T cells. However, the effect of growth of FasL⁺ tumors in vivo, on lymphoid tissues of the host is not clear and therefore was the subject of this investigation. Injection of FasL⁺ LSA tumor caused a significant decrease in cellularity of the thymus and spleen, resulting from marked apoptosis, in syngeneic C57BL/6+/+ (wild-type) but not C57BL/6-lpr/lpr (Fas-deficient) mice. The tumor-induced toxicity resulted from tumor-derived rather than host-derived FasL, inasmuch as LSA tumor growth in C57BL/6-gld/gld (FasL-defective) mice, induced marked apoptosis and toxicity in the thymus and spleen. The LSA tumor growth induced a significant decrease in the percentage of CD4⁺CD8⁺ T cells in the thymus of C57BL/6+/+ mice and an increase in the percentage of CD4⁺, CD8⁺ and CD4⁻CD8⁻ T cells. Of the four subpopulations tested, the CD4⁺CD8⁺ T cells showed maximum apoptosis. The LSA (FasL⁺) but not P815(FasL⁻) tumor cell lysates and culture supernatants induced marked apoptosis in Fas⁺ thymocytes, when tested both in vitro and in vivo. The LSA-tumor-induced apoptosis in vitro was inhibited by antibodies against FasL or by caspase and other inhibitors of apoptosis. Chemotherapy of LSA-tumor-bearing C57BL/6+/+ mice at advanced stages of tumor growth failed to cure the mice, whereas, more than 80% of LSA-tumor-bearing C57BL/6-lpr/lpr mice, similarly treated, survived. Together, the current study demonstrates that FasL produced by LSA tumor cells is functional in vivo and can cause severe toxicity in lymphoid organs of the host. Also, Fas/FasL interactions may play an important role in the successful chemotherapy of FasL-bearing tumor. Received: 31 August 1999 / Accepted: 12 November 1999     

Assessing Genetic Differentiation in Geographic Populations of Labeo calbasu Using Allozyme Markers

The population structure of Labeo calbasu from 11 rivers belonging to the Indus, Ganges, Bhima, Mahanadi, and Godavari basins was investigated using allozyme marker systems. Seven out of 20 allozyme loci (35%) were polymorphic (P < 0.99). Both probability and score tests indicated significant deviation of genotype proportions from Hardy–Weinberg expectations at two loci, XDH* (Mahanadi, Bhima, and Godavari) and G6PDH* (Mahanadi). A pairwise genetic homogeneity test and F _ST values indicated a low-to-moderate level (0.0515) of genetic structuring in the wild population of L. calbasu. AMOVA analysis also indicated moderate differentiation among the samples from different river basins. Analysis for genetic bottleneck was performed under the infinite allele model. The study revealed nine genetic stocks of L. calbasu from the natural population across Indian rivers. Evidence of genetic bottlenecks in some rivers was also revealed.     

Starch phosphorus content in potato (Solanum tuberosum L.) cultivars and its effect on other starch properties

The research presented herein provides valuable data with respect to the phosphorus content of starches from many potato (Solanum tuberosum L.) cultivars using an energy-dispersive X-ray fluorescence technique. In all starches examined, the phosphorus content ranged from 308 to 1244 ppm. Furthermore, the estimation of the starch characteristics of representative samples differing manifestly in their phosphorus content indicated that enhancing the starch phosphate resulted in significant increases in the swelling power, peak viscosity, and breakdown and significant but small increases in the onset and peak temperatures of gelatinization. Other starch quality parameters, such as the amylose content, median granule size, and the gelatinization enthalpy, did not change significantly due to the degree of phosphate substitution of starch.     

Genetic identification of three species of the genus Clarias using allozyme and mitochondrial DNA markers

Genetic variability in three clariid species, Clarias batrachus, C. gariepinus and C. macrocephalus, were investigated by allozyme electrophoresis and mitochondrial DNA (ND 5/6) RFLP markers. The catfish species C. batrachus and C. macrocephalus are native to the Indian subcontinent and Southeast Asia, respectively, while the African catfish C. gariepinus was introduced to Asian countries for culture. Sixteen gene loci from 12 enzyme systems were analyzed. Fixed allelic differences were evident between pairs of species at least at four loci. In mtDNA RFLP analysis, eight composite haplotypes were observed and each species was characterized by a set of haplotypes. The UPGMA phylogenetic tree revealed three distinct clusters: C. batrachus; C. gariepinus (India and Thailand); and C. macrocephalus.