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J M Abrams

Publications and source records attributed to J M Abrams.

32 records · Page 2Linked to original sources
PubMed1996

grim, a novel cell death gene in Drosophila.

A genomic interval at 75C1,2 is required for programmed cell death in Drosophila. We identified a new activator of apoptosis, grim, which maps between two previously identified cell death genes in this region reaper (rpr) and head involution defective (hid). Expression of grim RNA coincided with the onset of programmed cell death at all stages of embryonic development, whereas ectopic induction of grim triggered extensive apoptosis in both transgenic animals and in cell culture. Cell killing by grim was blocked by coexpression of p35, a viral product that inactivates ICE-like proteases, and did not require the functions of rpr or hid. The predicted grim protein shares an amino-terminal motif in common with rpr. However, grim was sufficient to elicit apoptosis in at least one context, where rpr was not. The grim gene product might thus function in a parallel circuit of cell death signaling that ultimately activates a common set of downstream apoptotic effectors.

Amino Acid Sequence↗
PubMed1995

The head involution defective gene of Drosophila melanogaster functions in programmed cell death.

Deletions of chromosomal region, 75C1,2 block virtually all programmed cell death (PCD) in the Drosophila embryo. We have identified a gene previously in this interval, reaper (rpr), which encodes an important regulator of PCD. Here we report the isolation of a second gene in this region, head involution defective (hid), which plays a similar role in PCD. hid mutant embryos have decreased levels of cell death and contain extra cells in the head. We have cloned the hid gene and find that its expression is sufficient to induce PCD in cell death defective mutants. The hid gene appears to encode a novel 410-amino-acid protein, and its mRNA is expressed in regions of the embryo where cell death occurs. Ectopic expression of hid in the Drosophila retina results in eye ablation. This phenotype can be suppressed completely by expression of the anti-apoptotic p35 protein from baculovirus, indicating that p35 may act genetically downstream from hid.

Alleles↗
PubMed1994

Programmed cell death in Drosophila.

During Drosophila development, large numbers of cells undergo natural cell death. Even though the onset of these deaths is controlled by many different signals, most of the dying cells undergo common morphological and biochemical changes that are characteristic of apoptosis in vertebrates. We have surveyed a large fraction of the Drosophila genome for genes that are required for programmed cell death by examining the pattern of apoptosis in embryos homozygous for previously identified chromosomal deletions. A single region on the third chromosome (in position 75C1,2) was found to be essential for all cell deaths that normally occur during Drosophila embryogenesis. We have cloned the corresponding genomic DNA and isolated a gene, reaper, which is capable of restoring apoptosis when reintroduced into cell death defective deletions. The reaper gene is specifically expressed in cells that are doomed to die, and its expression precedes the first morphological signs of apoptosis by 1-2 h. This gene is also rapidly induced upon X-ray irradiation, and reaper deletions offer significant protection against radiation-induced apoptosis. Our results suggest that reaper represents a key regulatory switch for the activation of apoptosis in response to a variety of distinct signals.

Animals↗
PubMed1994

Genetic control of programmed cell death in Drosophila.

A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. Mutant embryos contained many extra cells and failed to hatch, but many other aspects of development appeared quite normal. Deletions that include reaper also protected embryos from apoptosis caused by x-irradiation and developmental defects. However, high doses of x-rays induced some apoptosis in mutant embryos, and the resulting corpses were phagocytosed by macrophages. These data suggest that the basic cell death program is intact although it was not activated in mutant embryos. The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis.

Amino Acid Sequence↗
PubMed1993

Programmed cell death during Drosophila embryogenesis.

The deliberate and orderly removal of cells by programmed cell death is a common phenomenon during the development of metazoan animals. We have examined the distribution and ultrastructural appearance of cell deaths that occur during embryogenesis in Drosophila melanogaster. A large number of cells die during embryonic development in Drosophila. These cells display ultrastructural features that resemble apoptosis observed in vertebrate systems, including nuclear condensation, fragmentation and engulfment by macrophages. Programmed cell deaths can be rapidly and reliably visualized in living wild-type and mutant Drosophila embryos using the vital dyes acridine orange or nile blue. Acridine orange appears to selectively stain apoptotic forms of death in these preparations, since cells undergoing necrotic deaths were not significantly labelled. Likewise, toluidine blue staining of fixed tissues resulted in highly specific labelling of apoptotic cells, indicating that apoptosis leads to specific biochemical changes responsible for the selective affinity to these dyes. Cell death begins at stage 11 (approximately 7 hours) of embryogenesis and thereafter becomes widespread, affecting many different tissues and regions of the embryo. Although the distribution of dying cells changes drastically over time, the overall pattern of cell death is highly reproducible for any given developmental stage. Detailed analysis of cell death in the central nervous system of stage 16 embryos (13-16 hours) revealed asymmetries in the exact number and position of dying cells on either side of the midline, suggesting that the decision to die may not be strictly predetermined at this stage. This work provides the basis for further molecular genetic studies on the control and execution of programmed cell death in Drosophila.

Acridine Orange↗
PubMed1992

Macrophages in Drosophila embryos and L2 cells exhibit scavenger receptor-mediated endocytosis.

Mammalian macrophage scavenger receptors exhibit unusually broad binding specificity and are implicated in atherosclerosis and host defense. Scavenger receptor-like endocytosis was observed in Drosophila melanogaster embryos and in primary embryonic cell cultures. This receptor activity was expressed primarily by macrophages. The Drosophila Schneider L2, but not the Kc, cell line also exhibited a scavenger receptor-mediated endocytic pathway similar to its mammalian counterpart. L2 receptors mediated high-affinity internalization and subsequent temperature- and chloroquine-sensitive degradation of 125I-labeled acetylated low density lipoprotein and displayed characteristic ligand specificity. These findings suggest that scavenger receptors mediate important, well-conserved functions and raise the possibility that they may be pattern recognition receptors that arose early in the evolution of host defense mechanisms. They also establish additional systems for the investigation of endocytosis in Drosophila and scavenger receptor function in disease, host defense, and development.

Animals↗
PubMed1990

Children's knowledge of sexuality: a comparison of sexually abused and nonabused children.

Sexually abused and nonabused children, matched for age and social class, were compared for knowledge of various aspects of sexuality. No differences between groups were found. Many of the abused children, however, gave unusual affective responses to the stimuli of the child interview, whereas none of the nonabused children did so. Implications for clinicians working with sexually abused children are discussed.

Attitude↗
PubMed1989

Intronic positioning maximizes co-expression and co-amplification of nonselectable heterologous genes.

The overproduction of heterologous gene products in mammalian cells is often a prerequisite for studies of protein structure, function, and therapeutic efficacy. We report that recombinant fusion of a nonselectable reporter template into the intronic sequences of an amplifiable minigene gives dramatically enhanced co-expression efficiency in stable, primary transformants. Further incremental selective pressure for marker gene amplification results in the rapid acquisition of very high expression levels from the intronically positioned reporter. Nested within a constitutively expressing gene, these templates can be independently regulated at moderate gene dosage levels. Intronic positioning may therefore be of general utility for a variety of recombinant studies.

Animals↗
PubMed1989

Deletion of stably integrated DNA is suppressed by cadmium and zinc.

The bacterial xanthine-guanine phosphoribosyltransferase (GPT) gene was fused to a metal-responsive promoter and transfected into a murine cell line. Clonal transformants harboring metal-responsive or nonresponsive GPT genes (using a thymidine kinase promoter) were then studied for the loss of transfected gene function either during periods of constitutive expression or during periods of induced activity. Nontoxic levels of cadmium and zinc markedly reduced the frequency of mutagenesis in all transfected lines irrespective of transcriptional status. A survey of 17 GPT-clones derived from two original transfectants showed partial or complete excisions of the transfected gene in every case. These studies show that quantities of cadmium and zinc that induce metallothioneins also suppress the incidence of deletions in murine cells.

Animals↗
PubMed1989

Chimeric 3-hydroxy-3-methylglutaryl coenzyme A reductase-dihydrofolate reductase genes display bidirectional expression and unidirectional regulation in stably transfected cells.

We have constructed hybrid dihydrofolate reductase (DHFR) genes which are controlled by the sterol-responsive hamster 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase promoter. Stable transfection frequencies of these chimeric templates into a DHFR-deficient Chinese hamster cell line indicate that the HMG CoA reductase promoter fragment confers DHFR transformation irrespective of its orientation relative to a downstream murine DHFR cDNA. Sterol-regulated levels of DHFR RNA and protein are detected from hybrid genes which carry a properly oriented promoter fragment. Constructions which invert this HMG CoA reductase promoter, however, generate DHFR RNA levels which do not respond to sterols. In the context of these transfected fusion genes, we present evidence of divergent opposite-strand transcription initiating from the HMG CoA reductase 5' fragment. In contrast, the endogenous HMG CoA reductase promoter region shows no apparent evidence of such bidirectional activity.

Animals↗
PubMed1985

Opposite-strand RNAs from the 5' flanking region of the mouse dihydrofolate reductase gene.

We have characterized a transcription unit in the 5' flanking region of the mouse gene encoding dihydrofolate reductase (EC 1.5.1.3) that is oriented in the opposite direction to that of dihydrofolate reductase transcription. These opposite-strand RNAs are 180-240 nucleotides long, differing in length at their 5' ends. They are abundant in nuclear RNA and are not polyadenylylated. We suggest that the promoter region of the dihydrofolate reductase gene functions in a bidirectional manner to produce both these RNAs and dihydrofolate reductase mRNAs.

Animals↗
PubMed1979

Two-dimensional echocardiographic features of bicuspid aortic valve.

The two-dimensional cross-sectional echocardiographic diagnosis of bicuspid aortic valves is described and compared with results of M-mode echocardiograms. Aortic valve anatomy was determined in 19 selected patients by angiography, and confirmed in five by direct surgical visualization. Using an eccentricity index (EI) of 1.3 or greater as diagnostic of bicuspid aortic valve, M-mode correctly identified anatomy in 14 of 19 valves (74 percent), although EI varied in several patients. For two-dimensional diagnosis of bicuspid aortic valve, short axis cross section was preferred, and criteria included number of cusps seen in real time motion, irregularity of folding of cusp margins, and location of commissural insertions. Two-dimensional echocardiography correctly identified anatomy in 18 of 19 valves (95 percent). Long axis cross section disclosed valvular doming in all 8 patients in whom doming was observed angiographically, correlating with hemodynamic findings. Two-dimensional echocardiography aids in the detection of bicuspid aortic valve in a suspected population, can give an estimate of valve gradients, and explains variability in M-mode findings. As such, two-dimensional echocardiography is a valuable tool in the noninvasive diagnosis of the bicuspid aortic valve.

Adolescent↗