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D Acampora

Publications and source records attributed to D Acampora.

At least 73 records · Page 4Linked to original sources
PubMed1991

HOX gene activation by retinoic acid.

Vertebrate homeobox genes of the Hox family are, like Drosophila homeotic genes, organized in gene clusters and show a strict correspondence, or collinearity, between the order of the genes (3' to 5') within the chromosomal cluster and that of their expression domains (anterior to posterior) in the embryo. Recent data obtained from embryonal carcinoma cells induced to differentiate by retinoic acid cast some light on the molecular mechanisms underlying the collinear expression of the Hox genes.

Amino Acid Sequence↗
PubMed1991

EVX2, a human homeobox gene homologous to the even-skipped segmentation gene, is localized at the 5' end of HOX4 locus on chromosome 2.

We isolated and mapped three new human homeoboxes located on chromosome 2 upstream from the reported seven HOX4 homeobox sequences. Two of them, HOX41 and HOX4H, clearly belong to the HOX gene family, in particular to homology groups 1 and 2, and possibly represent the most 5' HOX4 homeoboxes. A third homeobox 13 kb upstream from HOX41 was identified. Sequencing data show that this is the human homolog of the murine Evx-2 homeobox. Both homeoboxes are closely related to the murine Evx-1 and to the frog Xhox-3 homeoboxes. The four genes represent vertebrate homologs of Drosophila even-skipped (eve), a segmentation gene of the pair-rule class. Human EVX2 sequences belong to an active gene because they are transcribed and properly processed in cells and tissues. We have identified for the first time a homeogene of a different class at a HOX locus. These findings are relevant to the understanding of the evolution of HOX gene clusters and their regulation.

Amino Acid Sequence↗
PubMed1991

Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells.

We studied the expression of 38 human homeobox genes belonging to the four HOX complex loci in embryonal carcinoma (EC) cells induced to differentiate by culturing them in a medium containing retinoic acid (RA). Genes located at the 3' end of each one of the four HOX loci are activated by RA in a sequential order colinear with their 3' to 5' arrangement in the cluster: 3' HOX genes respond early to the drug while upstream genes respond progressively later. Among the genes located at the 5' end of HOX loci RNase protection analysis reveals that one HOX3 gene and four HOX4 genes are weakly expressed in EC stem cells and downregulated upon treatment with 10(-5) M RA. While activation of early responding genes does not require continuous protein synthesis, the observed timing and polarity of gene activation is disrupted in the absence of protein synthesis.

Amino Acid Sequence↗
PubMed1990

Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells.

RETINOIC acid had been implicated as a natural morphogen in chicken and frog embryogenesis, and is presumed to act through the gene regulatory activity of a family of nuclear receptors. Homeobox genes, which specify positional information in Drosophila and possibly in vertebrate embryogenesis, are among the candidate responsive genes. We previously reported that retinoic acid specifically induces human homeobox gene (HOX) expression in the embryonal carcinoma cell line NT2/D1. We now show that the nine genes of the HOX2 cluster are differentially activated in NT2/D1 cells exposed to retinoic acid concentrations ranging from 10(-8) to 10(-5) M. Genes located in the 3' half of the cluster are induced at peak levels by 10(-8) M retinoic acid, whereas a concentration of 10(-6) to 10(-5) M is required to fully activate 5' genes. At both high and low retinoic acid concentrations, HOX2 genes are sequentially activated in embryonal carcinoma cells in the 3' to 5' direction.

Antigens, Surface↗
PubMed1990

Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci.

We studied the expression of 33 human homeobox genes belonging to four complex HOX loci in embryonal carcinoma NT2/D1 cells. These cells can be induced to differentiate by culturing them in media containing retinoic acid. Northern blot analysis reveals that no expression of these genes was detectable in NT2/D1 stem cells, whereas 22 HOX genes are well expressed in NT2/D1 cells treated with 10 microM retinoic acid for 14 days. The 11 HOX genes the expression of which remained undetectable in NT2/D1 cells after this treatment are located at the 5' end of their loci: four in HOX1, five in HOX3 and two in HOX4. The boundary between induced and silent genes roughly corresponds to the HOX genes constituting the homology group 5, related to the Abdominal-B homeotic gene of Drosophila. All nine identified HOX2 genes are well expressed in fully induced NT2/D1 cells and none of them maps 5' genes of this homology group. We conclude that HOX genes are differentially activated by retinoic acid in these cells according to their physical location within the four chromosomal loci.

Amino Acid Sequence↗
PubMed1990

Expression of HOX homeogenes in human neuroblastoma cell culture lines.

Mammalian genes containing a class-I homeobox (HOX genes) are highly expressed in the embryonic nervous system. As a first step towards the molecular analysis of the role these genes play in neural cells, we studied the expression of four human HOX genes in five neuroblastoma (NB) cell lines - SK-N-BE, CHP-134, IMR-32, SK-N-SH and LAN-1 - during the process of differentiation induced by treatment with retinoic acid (RA). The four genes, HOX1D, 2F, 3E and 4B, located at corresponding positions in the four HOX loci, share a high degree of sequence similarity with the Drosophila Deformed homeotic gene and constitute a homology group, group 10. One of these genes, HOX1D, is not expressed in the cells used, whereas the other three are highly expressed in untreated and RA-induced NB cells, even though the expression pattern in the various lines is slightly different for the three genes. Our analysis reveals a complex and specific expression pattern in these lines, paving the way to an identification of different NB-cell populations by means of specific HOX gene expression schemes. On the other hand, in every line studied, morphological maturation toward a neuronal differentiated phenotype appears to be associated with increased HOX gene expression.

Amino Acid Sequence↗
PubMed1989

The human HOX gene family.

We report the identification of 10 new human homeobox sequences. Altogether, we have isolated and sequenced 30 human homeoboxes clustered in 4 chromosomal regions called HOX loci. HOX1 includes 8 homeoboxes in 90 kb of DNA on chromosome 7. HOX2 includes 9 homeoboxes in 180 kb on chromosome 17. HOX3 contains at least 7 homeoboxes in 160 kb on chromosome 12. Finally, HOX4 includes 6 homeoboxes in 70 kb on chromosome 2. Homeodomains obtained from the conceptual translation of the isolated homeoboxes can be attributed to 13 homology groups on the basis of their primary peptide sequence. Moreover, it is possible to align the 4 HOX loci so that corresponding homeodomains in all loci share the maximal sequence identity. The complex of these observations supports and extends an evolutionary hypothesis concerning the origin of mammalian and fly homeobox gene complexes. We also determined the coding region present in 3 HOX2 cDNA clones corresponding to HOX2G, HOX2H and HOX2I.

Amino Acid Sequence↗
PubMed1989

New epidemiologic evidence confirming that bias does not explain the aspirin/Reye's syndrome association.

To determine the validity of the aspirin/Reye's syndrome association, we developed an epidemiologic investigation to assess the effects of five potential sources of bias. A case-control study incorporated procedures to avoid temporal precedence and susceptibility bias. These included classifying cases as having monophasic or biphasic patterns of illness and matching for severity of symptoms at zero-time. To evaluate the effect of a potential recall bias, an "alternate-condition" control group was enrolled. A medical record review study was conducted to assess the potential for diagnostic bias, and a blanket surveillance of all hospitals in a region was conducted to evaluate reporting bias. Twenty-four case subjects and 48 matched controls were enrolled. Eight-eight percent of case subjects and only 17% of controls had received aspirin prior to the onset of Reye's syndrome (matched odds ratio, 35; 95% confidence interval, 4.2 to 288). Further analyses demonstrated that the association could not be attributed to the five potential sources of bias.

Adolescent↗
PubMed1989

Posttranscriptional control of human homeobox gene expression in induced NTERA-2 embryonal carcinoma cells.

We have studied the expression of four human homeobox genes representative of four different clusters (i.e., HOX-1, HOX-2, HOX-3 and HOX-5) in the embryonal carcinoma (EC) cell line NT2/D1. Following treatment with retinoic acid (RA), these cells differentiate into several cell types, including neurons, and steadily accumulate polyadenylated transcripts derived from the genes in a period ranging from 18 hr to 14 days of RA treatment. The sizes of major transcripts in differentiated EC cells coincide with those previously detected by the same probes in human embryos. Nuclear run-on transcriptional analysis showed no difference in the transcription rate of the four homeobox genes in differentiated vs. undifferentiated EC cells. Inhibition of protein synthesis by 5-18 hr of treatment of undifferentiated cells with cycloeximide causes accumulation of some homeobox transcripts at levels comparable to those observed after 18 hr of RA induction, although it does not cause superinduction in fully differentiated cells. These data suggest that the activation of homeobox gene expression in RA-induced EC cells is controlled, at least in part, by posttranscriptional mechanisms.

Amino Acid Sequence↗
PubMed1989

Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system.

We have investigated the structure of the human HOX-2 locus, which encompasses a 90-kb region on chromosome 17q21. Five new human HOX-2 homeoboxes, termed HOX-2.5, 2.4, 2.6, 2.7 and 2.8, have been identified, and their nucleotide sequences are reported. They have the same 5'-3' transcriptional orientation and are clustered with three previously described HOX-2 homeoboxes (5'-2.5-2.4-2.3-2.2-2.1-2.6-2.7-2.8-3'). We have also investigated the region-specific expression of HOX-2 genes in human embryonic-fetal life by Northern-blot analysis. All genes are expressed in whole embryos and fetuses at 5-9 weeks from conception. Their major site of expression lies within the central nervous system (CNS), although they are transcribed at a lower level in body structures other than the CNS. Their relatively abundant expression in CNS has been analyzed along the anterior-posterior axis by dissecting the brain, the medulla oblongata and the spinal cord proper. HOX-2.5, 2.4 and 2.3 transcripts are markedly more abundant in spinal cord than in medulla, whereas 2.2, 2.1, 2.6 and 2.7 mRNAs are progressively more abundant in the medulla. Additionally, expression in brain was detected, although at lower level, for HOX-2.1, 2.6, 2.7, 2.8. Thus, the relative position of HOX-2 homeobox genes along the chromosome in the 5'-3' direction appears to correlate with the relative position of their expression domains along the CNS longitudinal axis in the caudal-cephalic direction.

Amino Acid Sequence↗
PubMed1989

Organization of human class I homeobox genes.

We report the genomic organization of 20 human class I homeoboxes and the predicted primary sequence of the encoded homeodomains. These homeoboxes are clustered in four complex HOX loci on chromosomes 2, 7, 12, and 17. The homeoboxes of one HOX locus can be aligned to the homeoboxes of the other HOX loci so that corresponding homeodomains in all loci can share the maximal peptide sequence identity. This correspondence of individual homeoboxes in different chromosomal loci suggests the hypothesis of large-scale duplications of a single complex locus. The existence of an ancestral complex locus might have predated the divergence of vertebrates and invertebrates.

Amino Acid Sequence↗
PubMed1988

Relation of peak creatine kinase levels during acute myocardial infarction to presence or absence of previous manifestations of myocardial ischemia (angina pectoris or healed myocardial infarction).

The hypothesis that acute myocardial infarction (MI) is more extensive in patients without previous angina or healed MI was evaluated in 177 patients with documented recent acute MI. Ninety-nine patients (56%) had no previous angina or healed MI (negative history group), and the remaining 78 patients (44%) had a previous history of angina or healed MI (positive history group). The mean peak creatine kinase (CK) level in the negative history group was 784 compared with 419 IU in the positive history group (p less than 0.0001). The mean peak CK-MB level in the negative history group was 128 compared with 76 IU in the positive history group (p less than 0.001). The mean peak CK-MB level was higher in the negative history group after controlling for age, streptokinase administration, previous coronary artery bypass grafting or treatment with beta-blocking agents. Despite the high frequency of healed MI in the positive history group (73%), the rates of in-hospital complications were similar for the 2 groups. Patients with acute MI without previous angina or healed MI have substantially higher peak CK and CK-MB levels; this implies a larger MI than in patients with previous angina or healed MI.

Aged↗
PubMed1988

At least three human homeoboxes on chromosome 12 belong to the same transcription unit.

Mammalian homeoboxes show a clustered chromosomal organization. In the mouse, at least seven homeoboxes on chromosome 6 and at least six on chromosome 11 identify the murine Hox-1 and Hox-2 loci, respectively. A number of homeoboxes on chromosome 7 define the human HOX-1 locus and homeoboxes on chromosome 17 define the human HOX-2 locus. We studied the genomic organization of three homeobox sequences of the HOX-3 locus on chromosome 12 and analyzed transcripts from this region. Structural characterization and sequencing of several cDNA clones reveal that the three homeobox sequences present in this chromosomal region identify a single transcription unit. Primary transcripts are alternatively processed to give mature messengers with a common 5' noncoding exon encoding different proteins containing one of the three homeodomains.

Amino Acid Sequence↗
PubMed1988

A computer protocol to predict myocardial infarction in emergency department patients with chest pain.

To achieve more appropriate triage to the coronary care unit of patients presenting with acute chest pain, we used clinical data on 1379 patients at two hospitals to construct a simple computer protocol to predict the presence of myocardial infarction. When we tested this protocol prospectively in 4770 patients at two university hospitals and four community hospitals, the computer-derived protocol had a significantly higher specificity (74 vs. 71 percent) in predicting the absence of infarction than physicians deciding whether to admit patients to the coronary care unit, and it had a similar sensitivity in detecting the presence of infarction (88.0 vs. 87.8 percent). Decisions based solely on the computer protocol would have reduced the admission of patients without infarction to the coronary care unit by 11.5 percent without adversely affecting the admission of patients in whom emergent complications developed that required intensive care. Although this protocol should not be used to override careful clinical judgment in individual cases, the computer protocol for the most part yields accurate estimates of the probability of myocardial infarction. Decisions about admission to the coronary care unit based on the protocol would have been as effective as those actually made by the unaided physicians who cared for the patients, and less costly. Whether physicians who are aided by the protocol perform better than unaided physicians cannot be determined without further study.

Angina Pectoris↗
PubMed1988

Organization of human homeobox genes.

The chromosomal localization of 17 human homeoboxes and the predicted primary sequence of the encoded homeodomains is reported. These homeoboxes are clustered in four complex HOX loci on chromosomes 2, 7, 12 and 17. Although the identification of human homeoboxes has not been completed, existing data permit preliminary conclusions on the origin and evolution of these complex loci to be drawn. The homeo-domains of one HOX locus can be unambiguously aligned to the homeodomains of the other HOX loci, so that corresponding homeodomains in all loci can share the maximal peptide sequence identity. This one-to-one correspondence of individual homeodomains in different chromosomal loci suggests the hypothesis of large-scale duplications of a single complex locus and subsequent spreading in different chromosomes. The existence of an ancestral complex locus might have predated the divergence of the arthropod/annelid and vertebrate evolutive lineages.

Amino Acid Sequence↗
PubMed1987

Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room.

In a prospective multicenter investigation of emergency room patients with acute chest pain, physicians admitted 96% of patients with acute myocardial infarction (AMI) and discharged 4%. Of 35 patients who were sent home with AMI, only 11 (31%) returned to the same hospital because of persistent symptoms. Compared with a control group of 105 randomly selected patients with AMI who were admitted from the emergency room, patients in whom AMI was missed were significantly younger, had less typical symptoms and were less likely to to have had prior AMI or angina or to have electrocardiographic evidence of ischemia or infarction not known to be old. Despite the less typical presentations of patients in whom AMI was missed, after controlling for age and sex, the short-term mortality rate was significantly higher among patients in whom AMI was missed but in whom it was detected through our follow-up procedures than in admitted AMI patients. As determined by independent reviewers, 49% of the missed AMIs could have been diagnosed through improved electrocardiographic reading skills or by admission of patients with recognized ischemic pain at rest or ischemic electrocardiographic changes not known to be old.

Age Factors↗
PubMed1987

Two human homeobox genes, c1 and c8: structure analysis and expression in embryonic development.

Two human cDNA clones (HHO.c1.95 and HHO.c8.5111) containing a homeobox region have been characterized, and the respective genomic regions have been partially analyzed. Expression of the corresponding genes, termed c1 and c8, was evaluated in different organs and body parts during human embryonic/fetal development. HHO.c1.95 apparently encodes a 217-amino acid protein containing a class I homeodomain that shares 60 out of 61 amino acid residues with the Antennapedia homeodomain of Drosophila melanogaster. HHO.c8.5111 encodes a 153-amino acid protein containing a homeodomain identical to that of the frog AC1 gene. Clones HHO.c1 and HHO.c8 detect by blot-hydridization one and two specific polyadenylylated transcripts, respectively. These are differentially expressed in spinal cord, backbone rudiments, limb buds (or limbs), heart, and skin of human embryos and early fetuses in the 5- to 9-week postfertilization period, thus suggesting that the c1 and c8 genes play a key role in a variety of developmental processes. Together, the results of the embryonic/fetal expression of c1 and c8 and those of two previously analyzed genes (c10 and c13) indicate a coherent pattern of expression of these genes in early human ontogeny.

Amino Acid Sequence↗