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Biomedical subjects

A Chandrasekhar

Publications and source records attributed to A Chandrasekhar.

4 recordsLinked to original sources

Biological and molecular correlates between induced dedifferentiation and spore germination in Dictyostelium.

When developing cultures of Dictyostelium discoideum are disaggregated at any time prior to cell wall formation and challenged to reinitiate development, amoebae will progress through the original sequence of morphogenetic stages, but the second time through they will do so in roughly one-tenth the original time, a process known as 'rapid recapitulation'. However, if disaggregated cells are suspended in nutrient medium, they enter a program of dedifferentiation during which they lose the capacity to rapidly recapitulate after an 80 minute lag period in a process known as 'erasure'. Here we show that cells that have completed the morphogenetic program and emerge from spore coats in the process of germination have also erased. In addition, the germination-specific 270 gene family is expressed during induced dedifferentiation in a unique fashion, and a germination-defective mutant exhibits a dramatic delay in erasure without concomitant defects in the program of gene regulation accompanying induced dedifferentiation. These results suggest for the first time that induced dedifferentiation and spore germination share some common processes in converting cells from a developmental to vegetative state.

Animals

Induction chemotherapy in non-metastatic high grade osteo sarcomas--results of pilot study at Cancer Institute (WIA), Madras.

Twelve patients with high grade osteosarcomas of the extremities were treated with two cycles of induction chemotherapy using adriamycin and cis-platinum and sandwich radiation between the two cycles (4000 rads). Ten patients underwent amputation or disarticulation, two patients had wide excision followed by endoprosthesis. The specimen was assessed for grade of necrosis. The Disease Free Survival at a minimum follow-up period of 26 months and median follow-up period of 35.5%. All the five patients who developed distant metastases had shown only a grade I necrosis in the tumour.

Adolescent

Developmental mechanisms regulating the rapid decrease in a cohesion glycoprotein mRNA in Dictyostelium function primarily at the level of mRNA degradation.

During the morphogenetic program in Dictyostelium discoideum, the transcript of the gene encoding the cohesion glycoprotein gp80 accumulates to a maximum level between 4 and 6 hr, (just prior to the onset of aggregation), remains high between 6 and 10 hr (the ripple to loose aggregate stages), and then decreases to less than 10% of the maximum level between 10 and 12 hr (the tight aggregate stage). The level of gp80 transcript also decreases precipitously at the time of the erasure event in the program of dedifferentiation, or when cAMP is added to a dedifferentiating cell population prior to the erasure event. In the dedifferentiation-defective mutant HI4, the cAMP-stimulated system for rapidly reducing the level of gp80 transcript is intact, but the mechanism functioning at the time of the erasure event is defective, demonstrating that the two reduction mechanisms are dissociable. By comparing the levels of gp80 transcript with the levels of in vitro transcription of the gene in isolated nuclei, it is demonstrated that the rapid reduction of gp80 transcript immediately after aggregation and immediately after addition of 10(-4) M cAMP are the result of increased transcript degradation. The rapid reduction of gp80 transcript at the erasure event may also be due to increased transcript degradation, but transcriptional regulation cannot be completely ruled out in this case.

Cell Adhesion Molecules

Dictyostelium erasure mutant HI4 abnormally retains development-specific mRNAs during dedifferentiation.

The Dictyostelium mutant HI4 progresses through morphogenesis normally, but is defective in the reverse program of dedifferentiation. In contrast to dedifferentiating wild-type cells, HI4 cells retain the capacity to rapidly reaggregate well after the "erasure event" employing a nonchemotactic aggregation mechanism involving random collisions and cohesion. They also do not lose contact sites A (gp80) at the prescribed time in the dedifferentiation program. HI4 cells accumulate transcripts of the cysteine protease gene CP2 (formerly referred to as 16G1) and the cohesion glycoprotein gene gp80 at the correct times in the morphogenetic program, but abnormally retain these transcripts at high levels well after the prescribed times at which they are lost in wild-type cells during the reverse program of dedifferentiation. The retention of these mRNAs in HI4 cells after the erasure event is not due to abnormal maintenance of a high level of intracellular cAMP during dedifferentiation. The rapid reduction in the level of gp80 transcript which can be effected by the addition of cAMP prior to the erasure event in wild-type cells is also retained by HI4 cells well after the erasure event. The results suggest that cells possess at least two mechanisms for the reduction of gp80 transcript. One involves the immediate response to cAMP and may function during the forward program of development. The second functions specifically during the reverse program of dedifferentiation. It is this latter, erasure-specific mechanism which is selectively defective in the HI4 variant.

Blotting, Northern