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V Dhar

Publications and source records attributed to V Dhar.

32 records · Page 2Linked to original sources
PubMed1990

Erythroid-specific nuclease-hypersensitive sites flanking the human beta-globin domain.

Recent evidence suggests that DNA sequences from the region lying 5' of the human epsilon-globin gene are important for erythroid-specific expression of human beta-like globin genes. This region, as well as a region 20 kilobases (kb) downstream from the beta-globin gene, contains a set of developmentally stable, DNase I-superhypersensitive sites that are thought to reflect a chromatin structure supporting active globin gene expression. We have analyzed the chromatin structure in these two regions in a wide variety of nonerythroid and erythroid cells. The study included analysis of chromatin structure changes occurring during globin gene activation in mouse erythroleukemia-human nonerythroid cell hybrids. The results identified a hypersensitive site (III) 14.8 kb upstream of the epsilon-globin gene that was strictly correlated with active globin gene transcription. Interestingly, a multipotent human embryonal carcinoma cell line exhibited a hypersensitive site (IV) 18.4 kb upstream of epsilon-globin that was absent in all other nonerythroid cells examined, suggesting that chromatin structure changes at specific hypersensitive sites during embryonic development may also be important in globin gene repression.

Cell Line↗
PubMed1989

Activation and repression of a beta-globin gene in cell hybrids is accompanied by a shift in its temporal replication.

To investigate whether a switch in the transcriptional activity of a gene is associated with a change in the timing of replication during the S phase, we examined the replication timing of the beta-globin genes in two different types of somatic cell hybrids. In mouse hepatoma (Hepa 1a) x mouse erythroleukemia (MEL) hybrid cells, the beta-globin gene from the MEL parent is transcriptionally inactivated and is later replicating than in the parental MEL cell line. In human fibroblast (GM3552) x MEL hybrid cells, the human beta-globin gene is transcriptionally activated, and all of the sequences within the human beta-globin domain (200 kilobases) we have examined appear to be earlier replicating than those in the parental fibroblast cell line. The chromatin configuration of the activated human beta-globin domain in the hybrids is relatively more sensitive to nucleases than that in the fibroblasts. Furthermore, major nuclease-hypersensitive sites that were absent in the chromatin flanking the distal 5' region of the human beta-globin gene cluster in the parental fibroblast cell line are present in the transcriptionally activated domain in the hybrid cell line. These results suggest that timing of replication of globin genes has been altered in these hybrid cells and thus is not fixed during the process of differentiation.

Animals↗
PubMed1988

The coordinate replication of the human beta-globin gene domain reflects its transcriptional activity and nuclease hypersensitivity.

The temporal order of replication of DNA sequences in the chromosomal domain containing the human beta-globin gene cluster and its flanking sequences (140 kilobases) was measured and compared in two different human cell lines. In human erythroleukemia (K562) cells, in which embryonic and fetal globin genes are transcribed, all of the sequences we examined from the beta-globin domain replicated early during S phase, while in HeLa cells, in which globin genes are transcriptionally silent, these sequences replicated late during S. Potential sites of initiation of DNA replication within this domain were identified. The beta-globin gene domain was also found to differ with respect to the nuclease sensitivity of the chromatin in these two cell lines. In K562 cells, hypersensitive sites for endogenous nucleases and DNase I were present in the chromatin near the earliest-replicating segments in the beta-globin domain.

DNA Replication↗
PubMed1988

Replication program of active and inactive multigene families in mammalian cells.

In a comprehensive study, the temporal replication of tissue-specific genes and flanking sequences was compared in nine cell lines exhibiting different tissue-specific functions. Some of the rules we have determined for the replication of these tissue specific genes include the following. (i) Actively transcribed genes usually replicate during the first quarter of the S phase. (ii) Some immunoglobulin genes replicate during the first half of S phase even when no transcriptional activity is detected but appear to replicate even earlier in cell lines where they are transcribed. (iii) Nontranscribed genes can replicate during any interval of S phase. (iv) Multigene families arranged in clusters of 250 kilobases or less define a temporal compartment comprising approximately one-quarter of S phase. While these rules, and others that are discussed, apply to the tissue-specific genes studied here, all tissue-specific genes may not follow this pattern. In addition, housekeeping genes did not follow some of these rules. These results provide the first molecular evidence that the coordinate timing of replication of contiguous sequences within a multigene family is a general property of the mammalian genome. The relationship between replication very early during S phase and the transcriptional activity within a chromosomal domain is discussed.

Animals↗
PubMed1987

Contrasting effects of 5 alpha- and 5 beta-pregnane-3,20-dione on the motor activity of ovariectomized rats.

While progesterone metabolites have long been known to be potent anesthetics in pharmacological doses, there is no available information as to their effects on behaviour at physiological levels. In this study, 5 alpha- and 5 beta-pregnanediones in silastic capsules were implanted in ovariectomized rats. Approximately 4 mg/kg/day was absorbed over a 24-day period. Rats receiving 5 beta-pregnanedione had decreased motor activity (58% control, P less than or equal to 0.001) while those receiving the 5 alpha-isomer had increased activity (143% control, P = 0.01). These studies suggest that these progesterone metabolites may be responsible for some behavioural changes.

5-alpha-Dihydroprogesterone↗
PubMed1984

Transfer of Chinese hamster chromosome 1 to mouse cells and regional assignment of 7 genes: a combination of gene transfer and microcell fusion.

We have used a combination of chromosome-mediated gene transfer and microcell fusion techniques to transfer Chinese hamster chromosome 1 to mouse cells. Microcell hybrids containing a single hamster chromosome were analyzed to map genes on this chromosome. We have confirmed the assignment of seven markers (GSR, NP, EST-D, ADK, PEP-S, PGM2, and PEP-B) to hamster chromosome 1. Segregation among the linked markers was induced by X irradiation followed by selection for the retention or loss of human hprt. Cosegregation of markers in independent subclones made it possible to determine the gene order for the seven loci. The gene order proposed for these loci is as follows: pter-GSR-NP-EST-D-ADK-(PEP-S, PGM2)-PEP-B-qter. In addition GSR, NP, EST-D, and ADK have been assigned to pter-1q12; PEP-S and PGM2 to 1q12-1q21, and PEP-B to 1q32-1qter. These regional assignments and gene order on chromosome 1 have provided the information relevant to the linkages conserved between Chinese hamster, mouse, and man.

Adenosine Kinase↗
PubMed1982

Disseminated mucormycosis in a case of metastatic carcinoma.

A 50-year-old white woman who underwent bilateral mastectomy for fibrocystic disease of the breast in 1974 and laminectomy for lumbar disc fusion in 1979, was diagnosed early in 1980 at Roswell park Memorial Institute as a case of metastatic anaplastic carcinoma. She was started on platinum combination therapy, but in the course of her treatment she became increasingly jaundiced, then semi-comatose and died suddenly two months after the diagnosis of carcinoma. Histopathologic examinations revealed undifferentiated small-cell carcinoma in the lung, liver, lymph nodes, and bone. Mucormycosis, characterized by the presence of broad coenocytic hyphae associated with thrombosis, infarction, and necrosis, was unexpectedly discovered at postmortem examination in the brain, lung, and heart. The etiologic agent, Absidia corymbifera, was isolated from a lung specimen and was identified by its morphologic characteristics and by the formation of zygospores in crosses with a compatible tester strain of the mating type (-).

Carcinoma, Small Cell↗