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L Nagarajan

Publications and source records attributed to L Nagarajan.

64 records · Page 4Linked to original sources

Localization of the human pim oncogene (PIM) to a region of chromosome 6 involved in translocations in acute leukemias.

The human homolog, hpim, of the murine pim-1 gene, which is activated in murine T-cell lymphomas by insertion of retrovirus proviral genomes in the pim-1 region, has been molecularly cloned; the cloned probe has been used to map the hpim locus to human chromosome region 6p21 by somatic cell hybrid analysis and chromosomal in situ hybridization. The hpim gene is expressed as a 3.2-kilobase mRNA in various human cell lines of hematopoietic lineage, most dramatically in the K562 erythroleukemia cell line, which contains a cytogenetically demonstrable rearrangement in the 6p21 region. A characteristic chromosome anomaly, a reciprocal translocation t(6;9)(p21;q33), has been described in myeloid leukemias and could involve the hpim gene.

Chromosome Mapping↗

Production of insulin-like growth factor-II (MSA) by endoderm-like cells derived from embryonal carcinoma cells: possible mediator of embryonic cell growth.

The present study was carried out to determine if an insulin-like growth factor (IGF) type activity might be produced by embryonal carcinoma-derived cells. The cell line used to condition growth medium for the isolation of secreted growth factors was a newly established Dif 5 cell type. Dif 5 cells are a differentiated endoderm-like cell type derived from F9 embryonal carcinoma cells (which possess properties similar to mouse embryonic stem cells) following extensive exposure to retinoic acid. When growth medium conditioned by Dif 5 cells is chromatographed on Sephadex G-75 in 1 M acetic acid two peaks of activity are observed which compete for specific [125I]iodo multiplication stimulating activity (MSA) binding to PYS cells. MSA is the rat homologue of human IGF-II. The high molecular weight fraction (Mr approximately 60K) apparently corresponds to IGF-binding protein as determined by its ability to bind [125I]iodo-MSA. The low molecular weight fraction (Mr approximately 8K) is biologically active as this fraction stimulates [3H]thymidine incorporation into serum-starved chick embryo fibroblasts. Radioimmunoassay data indicate that the IGF-like activity produced by Dif 5 cells is more closely related to IGF-II than to IGF-I. Undifferentiated embryonal carcinoma stem cell lines (F9, Nulli, and PCC4) produced little of this MSA-like activity, while PYS-2 (parietal endoderm-like) cells produced about 16 ng MSA/10(6) cells/24 hr as determined by radioimmunoassay. Dif 5 and PSA-5E (visceral endoderm-like) cells, are found to secrete significant amounts of MSA into the growth medium (30-50 ng MSA/10(6) cells/24 hr). These findings offer further support to a proposal that MSA (IGF-II) produced by endoderm cells, particularly visceral endoderm, may serve as an early embryonic growth factor.

Animals↗

Increase in cell-surface N-acetylglucosaminide beta (1----4)galactosyltransferase activity with retinoic acid-induced differentiation of F9 embryonal carcinoma cells.

Exposure of F9 cells to all-trans-retinoic acid over a period of 6 days resulted in 4-fold induction of cell surface N-acetylglucosaminide beta (1----4)galactosyltransferase (GT) activity. The retinoic acid-induced GT activity was further enhanced by treatment of the cells with 8-bromo cyclic AMP. The ability of retinoic acid alone, or retinoic acid in combination with 8-bromo cyclic AMP, to induce GT activity was inhibited by both actinomycin D and cycloheximide. These findings indicate that the induction of galactosyltransferase activity noted with differentiation of F9 cells involves de novo synthesis of new enzyme protein.

8-Bromo Cyclic Adenosine Monophosphate↗

Activity of X-linked genes in stem and differentiated Mus musculus X Mus caroli hybrid cells.

Hypoxanthine phosphoribosyltransferase-deficient (HPRT-) F9-derived teratocarcinoma stem cells carrying an SV40 genome (12-16TG cells) were fused with Mus caroli (M. car.) spleen cells, and a stem cell hybrid containing reduced numbers of M. car. chromosomes was isolated (BC6 stem cell). The BC6 cells containing an active X chromosome from each parental cell were induced to differentiate in retinoic acid, and differentiated clones were isolated. Most differentiated clones retained both parental X chromosomes in active form. One differentiated clone, BC6-13, grew equally well in hypoxanthine/aminopterin/thymidine (HAT) selective medium (which requires an active M. car. HPRT (E.C.2.4.2.8) locus) or in 6-thioguanine (6TG, which would require either loss or inactivation of the M. car. HPRT locus). Using cDNA probes for HPRT and phosphoglycerate kinase (PGK) (E.C.2.7.2.3) loci and biochemical assays for HPRT and PGK enzymes, it was shown that BC6-13 cells, whether grown in nonselective medium, HAT medium, or 6TG-containing medium, retain the HPRT and PGK genes of both parental cells, but the M. car. forms of HPRT and PGK were inactivated in cells treated with 6TG. 6-Thioguanine seems to act as an inducer, one effect of which is X chromosome inactivation, which seems to be complete and irreversible as early as 24 h after addition of 6TG to BC6-13 cells.

Animals↗

A new differentiated cell line (Dif 5) derived by retinoic acid treatment of F9 teratocarcinoma cells capable of extracellular matrix production and growth in the absence of serum.

Treatment of F9 teratocarcinoma cells with all trans retinoic acid (RA) causes them to differentiate into two or three morphologically distinct cell types. Whereas the majority of these retinoid-derived cells exhibit properties resembling parietal endoderm, a small percentage of this differentiated cell population manifests properties distinct from the parietal endoderm cell type. The isolation and partial characterization of such a non-parietal endoderm cell line (Dif 5) derived from F9 cells following prolonged (44 days) exposure to 1 microM retinoic acid are described. Unlike the retinoid-induced parietal endoderm-like cell population, which exhibits a dramatic, characteristic morphological change upon treatment with 8-bromo cAMP, Dif 5 cells do not show any morphological change with exposure to this cAMP analog. Dif 5 cells synthesize and deposit an extracellular matrix consisting of several components of Reichert's membrane (fibronectin, laminin, and type IV collagen). This new cell line does not synthesize alpha-fetoprotein but does secrete plasminogen activator. An interesting property of these cells is their ability to grow in the absence of serum or other hormonal supplements. Yet the Dif 5 cells do exhibit density-dependent inhibition of growth. Unlike the parent F9 cells or parietal yolk sac (PYS-2) cells, these cells do possess specific cell surface receptors for epidermal growth factor (EGF). The growth-arrested Dif 5 cells can be reinitiated to proliferate by the addition of fetal calf serum (FCS) or EGF. The properties of Dif 5 cells determined fail to fulfill all the characteristics described for either parietal or visceral endodermal cells. This raises the possibility that Dif 5 cells might represent an endodermal cell type which is intermediate in differentiation to either parietal or visceral endoderm but which lacks the biochemical signal to complete this stage of differentiation. This new Dif 5 cell line should be of considerable value in studying the modulation of growth requirements and extracellular matrix formation during early embryonic development.

Animals↗

The amount of a specific cellular protein (p53) is a correlate of differentiation in embryonal carcinoma cells.

A specific cellular protein of molecular weight of 53-55,000 (p53) has been shown to be induced in all SV40 transformed cells. A similar protein has also been shown to be present in embryonal carcinoma cells and in midgestation murine embryo primary cells, which are not infected by SV40. In embryo cell primaries the amount of the protein was shown to decrease with the increase in the stage of embryo development. As differentiation or decrease in cell growth rate can account for this, and since the growth rate of embryo primary cells cannot be measured, we chose to investigate various embryonal carcinoma cells. We report that the p53 is present in a pluripotent embryonal carcinoma cell OTT6050, and in its differentiated parietal endoderm derivative, PYS-2 cells. The amount of p53 is higher in the undifferentiated EC stem cells than in the differentiated PYS-2 (parietal endoderm) cells. The amount of the protein decreases in F9 embryonal carcinoma cells induced to differentiate to a parietal endoderm cell type by treatment with retinoic acid, as it does following spontaneous differentiation of OTT6050 EC cells. To determine if a change in growth rate, rather than differentiation, might account for the diminished levels of this protein, the amount of p53 was measured in growing and in growth arrested cell populations. When the growth rate of F9 cells was reduced by treatment with 8-bromocyclic AMP there was no change in the amount of p53. The half life of the p53 was compared in the undifferentiated and the differentiated cell types to determine if a change in stability might account, in part, for the altered levels of this protein. The p53 is found to be most stable in the SV40 transformed established clonal cells. It is less stable in the fibroblast clonal cells which were not transformed by SV40. The results of these experiments indicate that a decrease in the amount of p53 primarily correlates with differentiation in the embryonal carcinoma cell lines studied and not with cell growth rate. Furthermore, the decrease appears to be related (in part) to the decreased stability of the p53.

Animals↗

Multiplication-stimulating activity stimulates the multiplication of F9 embryonal carcinoma cells.

The present study was designed to assess the effectiveness of multiplication-stimulating activity (MSA), an insulin-like growth factor, in supporting the growth of F9 cells (an embryonal carcinoma line with properties similar to embryonic stem cells). Under serum-free growth conditions in a medium supplemented with transferrin and fibronectin, MSA is an effective mitogen. At 100 ng/ml, MSA completely replaces the growth requirement for fetal calf serum. Biologically active MSA polypeptides II and III act as potent growth promoters of F9 cells, whereas MSA I appears to be somewhat less effective. Binding studies carried out with [125I]iodo-MSA indicate that F9 cells possess specific receptors for MSA. Scatchard analysis indicates a single class of MSA receptors with a Ka of 8.2 x 10(9) M-1; about 55,000 MSA molecules can bind per F9 cell. Insulin-like growth factor I and II both complete for MSA binding, whereas insulin does not compete. Since insulin is an effective promoter of F9 cell growth, these results indicate that the mitogenic action of insulin toward F9 cells is not mediated through MSA receptors. It is apparent from these results that MSA is capable of serving as an early embryonic growth factor.

Animals↗

Contralateral temporal hypometabolism on positron emission tomography in temporal lobe epilepsy.

INTRODUCTION: No detailed case studies report lateralised hypometabolism on positron emission tomography (PET) contralateral to the epileptogenic focus in temporal lobe epilepsy (TLE). MATERIAL AND METHODS: We performed 18F fluorodeoxyglucose (FDG) PET in two intractable TLE patients. RESULTS: One had right temporal interictal spikes on electroencephalography (EEG) and a right medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed decreased uptake in the left temporal lobe. Right temporal ictal onset, with bilateral interictal epileptiform activity, occurred on intracranial EEG. He is seizure free after right temporal lobectomy and ganglioglioma resection. The second had right temporal lobe interictal and ictal EEG activity. MRI demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal and lateral frontal hypometabolism. He is seizure free after right temporal lobectomy. CONCLUSION: These findings suggest that regional uptake asymmetry on FDG-PET may be give misleading lateralising information in TLE.

Adult↗

An enquiry into work environmental status and health of workers involved in production of incense sticks in city of Bangalore.

This preliminary study represents 10% of the workers in this occupation in Bangalore. The industry is highly commercial in nature and the city of Bangalore; has the largest number of units in Karnataka State. The study provides base line data relating to some morbidity conditions for future comparisons. Low back ache, tiredness, head ache, irritation in the eyes, sleeplessness, joint pains, chest pain, postural giddiness, persistent running nose, abdominal pain, cough and tremors of hands, were some of the common conditions elicited among the workers. Some of the conditions were identified to be possibly related to various processes within the industry. Particularly low back ache and irritation in the eyes (rolling and dipping), tremors of hands (packing). It is very likely that in the final stages when certain chemical ingredients are added which finally give the scent, the chances of pollutants entering either through skin or inhalation is possible. Environmental monitoring has not shown any appreciable dust hazard. The study has helped in identifying some of the areas in the work environment which required improvement. There is a need for social workers, medical personnel and industrial hygienists to explore the possibilities of minimizing possible hazards. A national sampling survey in other parts of the country might also be beneficial.

Aerosols↗