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D Acampora

Publications and source records attributed to D Acampora.

At least 55 records · Page 3Linked to original sources
PubMed1995

Developmental analysis of murine Promyelocyte Leukemia Zinc Finger (PLZF) gene expression: implications for the neuromeric model of the forebrain organization.

Promyelocyte Leukemia Zinc Finger (PLZF) is a Kruppel-like zinc finger gene previously identified in a unique case of acute promyelocytic leukemia (APL) as the counterpart of a reciprocal chromosomal translocation involving the retinoic acid receptor alpha gene (RAR alpha). PLZF is highly conserved throughout evolution from yeast to mammals. To elucidate its role, we isolated the murine PLZF gene and studied its expression during embryogenesis. PLZF is expressed in an extremely dynamic pattern with transcripts appearing at E 7.5 in the anterior neuroepithelium and quickly spreading to the entire neuroectoderm until E 10. At E 8.5, PLZF is transcribed in most of the endoderm. During mid to late gestation PLZF is expressed in restricted domains of the developing CNS as well as in specific organs and body structures. We have focused our attention on the developing forebrain where PLZF is transcribed in a transverse, segment-like domain corresponding to the anterior pretectum, in the alarmost part of the dorsal thalamus, in the epithalamus, and in the hypothalamus along a defined longitudinal subdomain. Furthermore, PLZF is expressed in several segmentary boundaries, among them, the zona limitans intrathalamica. Combined analysis with other regionally restricted genes, such as Orthopedia and Dlx1, indicates that in the hypothalamus the PLZF domain is contained within that of Orthopedia and both are complementary to that of Dlx1. Our data suggest a role for PLZF in the establishment and maintenance of transverse identities, longitudinal subdomains, and interneuromeric boundaries, providing additional evidences in favor of the neuromeric organization of the forebrain.

Animals↗
PubMed1994

Chromosome locations of human EMX and OTX genes.

We have determined the chromosomal localization of four human homeobox-containing genes, EMX1, EMX2, OTX1, and OTX2, related to Drosophila genes expressed in the developing head of the fly. Murine homologs of these genes are expressed in specific nested domains in the developing rostral brain of midgestation embryos. DNAs from a panel of 19 rodent-human hybrids, each carrying one or a few human chromosomes such that most human chromosome regions were represented, were tested for the presence of the four gene loci by filter hybridization to radiolabeled probes. Regional chromosomal localization was determined by similarly testing DNAs from hybrid mapping panels for each of the candidate chromosomes. Finally, fluorescence in situ hybridization of cosmid clones for these loci refined the locations, two of which were in the vicinity of previously mapped orphan homeobox genes and two of which were near each other. OTX2, the earliest and most widely expressed gene, maps to chromosome region 14q21-q22; the OTX1 locus maps to 2p13; EMX2 maps to 10q26.1; and EMX1, the most narrowly and lately expressed, maps to 2p14-p13. Thus, these homeobox-containing genes involved in brain development are not linked to any of the four HOX clusters on 7p15-p14, 17q21-q22, 12q12-q13, and 2q31. However, the OTX1 and EMX1 loci may be closely linked on or near 2p13, prompting speculation that a clustered gene structure could have functional significance, as is presumably the case for the HOX clusters.

Animals↗
PubMed1994

Cloning and characterization of two members of the vertebrate Dlx gene family.

A number of vertebrate genes of the Dlx gene family have been cloned in mouse, frog, and zebrafish. These genes contain a homeobox related to that of Distalless, a gene expressed in the developing head and limbs of Drosophila embryos. We cloned and studied the expression of two members of this family, which we named Dlx5 and Dlx6, in human and mouse. The two human genes, DLX5 and DLX6, are closely linked in an inverted convergent configuration in a region of chromosome 7, at 7q22. Similarly, the two human genes DLX1 and DLX2 are closely linked in a convergent configuration at 2q32, near the HOXD (previously HOX4) locus. In situ hybridization experiments in mouse embryos revealed expression of Dlx5 and Dlx6 mRNA in restricted regions of ventral diencephalon and basal telencephalon, with a distribution very similar to that reported for Dlx1 and Dlx2 mRNA. A surprising feature of Dlx5 and Dlx6 is that they are also expressed in all skeletal structures of midgestation embryos after the first cartilage formation. The expression pattern of these genes, together with their chromosome localization, may provide useful cues for the study of congenital disorders in which there is a combination of craniofacial and limb defects.

Amino Acid Sequence↗
PubMed1994

Orthopedia, a novel homeobox-containing gene expressed in the developing CNS of both mouse and Drosophila.

A novel homeobox-containing gene has been identified. Its name, Orthopedia (Otp), exemplifies the homology shared by both the orthodenticle and Antennapedia homeodomains. Otp is highly conserved in evolution. In mouse, Otp is expressed only in restricted domains of the developing forebrain, hindbrain, and spinal cord. In Drosophila, otp first appears at gastrulation in the ectodermal proctodeum and later in the hindgut, anal plate, and along the CNS. Here, we compare the Otp-, Distal-less homeobox 1-(DIx1-), Orthodenticle homolog 1-(Otx1-), Otx2-, and Empty spiracles homolog 2-expressing domains. Our results indicate that Otp is expressed along the CNS both in mouse and Drosophila; Otp could specify regional identities in the development of the forebrain and spinal cord; transcription of Otp and DIx1 takes place in alternating hypothalamic regions reminiscent of a segment-like pattern; and the structural and functional conservation could correspond to a conserved function maintained in evolution.

Amino Acid Sequence↗
PubMed1994

Expression of the neuron-specific FE65 gene marks the development of embryo ganglionic derivatives.

The major transcript of the FE65 gene is a neuron-specific mRNA that encodes a nuclear protein whose aminoterminal domain strongly activates the transcription of a reporter gene when fused to a heterologous DNA-binding domain. FE65 gene expression is regulated during neuronal differentiation of the NTERA-2 cell line, and it is temporally and spatially restricted during mouse embryo development. It is first detected around day 10 of gestation in the basal plate of the neural tube, and then, at the subsequent stages of development and in the newborn animals, it is found solely in neural structures. Its expression is most abundant in the neural crest derivatives (e.g. spinal and encephalic ganglia), ganglionic structures of sense organs (ganglionic layer of the retina and olfactory epithelium), as well as the ganglionic structures of the autonomic nervous system. Thus FE65 gene expression can be considered a marker of the development of embryo ganglionic derivatives.

Animals↗
PubMed1993

A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo.

We studied the expression of two vertebrate homeobox genes, Otx1 and Otx2, related to orthodenticle, a gene expressed in the developing head of Drosophila. Both genes are expressed in restricted regions of the developing rostral brain including the presumptive cerebral cortex and olfactory bulbs. The expression patterns of the two genes in diencephalon suggest that they both have a role in establishing the boundary between presumptive dorsal and ventral thalamus. They are also expressed in regions of the developing olfactory, auricolar and ocular system, including the covering of the optic nerve. Otx1 expression is detectable from day 8 of gestation in telencephalic, diencephalic and mesencephalic regions. From day 10.5 of gestation its expression extends to some metencephalic areas. Otx2 appears to be already expressed in the epiblast of prestreak embryos. It persists in the entire embryonic ectoderm for some time after the onset of gastrulation. In midstreak embryos its expression appears progressively restricted to the anterior embryonic ectoderm corresponding to presumptive fore- and mid-brain. In early midgestation embryos it is expressed in telencephalic, diencephalic and mesencephalic regions but from day 11.75 of gestation its expression disappears from dorsal telencephalon and is confined to diencephalic and mesencephalic regions. Otx2 is one of the earliest genes expressed in the epiblast and immediately afterwards is expressed in anterior neuroectoderm, demarcating rostral brain regions even before headfold formation. Its gene product contains a homeodomain of the bicoid class and is able to recognize and transactivate a bicoid target sequence.

Amino Acid Sequence↗
PubMed1993

A predictive index for functional decline in hospitalized elderly medical patients.

OBJECTIVE: To prospectively develop and validate a predictive index to identify on admission elderly hospitalized medical patients at risk for functional decline. DESIGN: Two prospective cohort studies, in tandem. The predictive model developed in the initial cohort was subsequently validated in a separate cohort. SETTING: General medical wards of a university teaching hospital. PATIENTS: For the development cohort, 188 hospitalized general medical patients aged > or = 70 years. For the validation cohort, 142 comparable patients. MEASUREMENT AND MAIN RESULTS: The subjects and their nurses were interviewed twice weekly using standardized, validated instruments. Functional decline occurred among 51/188 (27%) patients in the development cohort. Four independent baseline risk factors (RFs) for functional decline were identified: decubitus ulcer (adjusted relative risk [RR] 2.7; 95% confidence interval [CI] 1.4, 5.2); cognitive impairment (RR 1.7; CI 0.9, 3.1); functional impairment (RR 1.8; CI 1.0, 3.3); and low social activity level (RR 2.4; CI 1.2, 5.1). A risk-stratification system was developed by adding the numbers of RFs. Rates of functional decline for the low- (0 RF), intermediate- (1-2 RFs), and high- (3-4 RFs) risk groups were 8%, 28%, and 63%, respectively (p < 0.0001). The corresponding rates in the validation cohort, of whom 34/142 (24%) developed functional decline, were 6%, 29%, and 83% (p < 0.0001). The rates of death or nursing home placement, clinical outcomes associated with functional decline in the hospital, were 6%, 19%, and 41% (p < 0.002) in the development cohort and 10%, 32%, and 67% (p < 0.001) in the validation cohort, respectively, for the three risk groups. CONCLUSIONS: Functional decline among hospitalized elderly patients is common, and a simple predictive model based on four risk factors can be used on admission to identify elderly persons at greatest risk.

Activities of Daily Living↗
PubMed1993

The Yale Geriatric Care Program: a model of care to prevent functional decline in hospitalized elderly patients.

OBJECTIVE: To describe the structure and implementation of the Yale Geriatric Care Program, an innovative, nursing-centered model for developing geriatric nursing expertise throughout an acute-care hospital. DESIGN: Descriptive study of an intervention in a prospective cohort of patients. SETTING: University teaching hospital. PATIENTS: Two hundred forty four patients aged 70 years and older on four non-intensive care intervention units during the study period (July 9, 1990 to July 31, 1991). INTERVENTION: The Geriatric Care Program involved an integrated model of primary nurses, specially trained unit-based geriatric resource nurses, gerontological nurse specialists, and geriatric physicians. The intervention included surveillance and identification of frail older patients, unit-based geriatric educational programs for all nurses, special education and support for the geriatric resource nurses, and twice-weekly rounds of the Geriatric Care Team. RESULTS: The Geriatric Care Program has been successfully implemented on four units. The interventions ranged from general clarification of goals in 226 (92%) to specific recommendations for management of immobility in 100 (41%), bladder/bowel problems in 99 (41%), pressure ulcer treatment or prevention in 61 (25%), confusion evaluation or management in 62 (25%), and adjustment of medications in 43 (18%). Overall, 68% of the specific recommendations were documented to have been implemented. Barriers to implementation of the program have included initial difficulties with recruitment and retainment of geriatric resource nurses (due to high nursing turnover and the increased time commitment required), breakdown in communication and carryover of recommendations between nursing shifts, and obstacles to communication between the nursing and medical staff. CONCLUSIONS: An innovative model of care, in which geriatric nursing was integrated as part of standard nursing care on selected medical and surgical units, has been designed and implemented. Evaluation of the effectiveness and costs of this intervention are currently underway.

Activities of Daily Living↗
PubMed1993

A controlled trial of a nursing-centered intervention in hospitalized elderly medical patients: the Yale Geriatric Care Program.

OBJECTIVE: To test the effectiveness of a nursing-centered intervention to prevent functional decline among hospitalized elderly medical patients. DESIGN: Prospective cohort study with stratified and matched cohort analyses. SETTING: General medicine wards of a university teaching hospital. PATIENTS: Two hundred sixteen patients aged > or = 70 years (85 intervention and 131 control patients). INTERVENTION: The intervention included identification and surveillance of frail older patients, twice-weekly rounds of the Geriatric Care Team, and a nursing-centered educational program. MAIN OUTCOME MEASURE: Functional decline, defined as a net decline in five activities of daily living (ADLs). RESULTS: In stratified analyses, the intervention resulted in a beneficial effect with a relative risk of 0.82 (95% confidence interval [CI] 0.54 to 1.24) in patients (n = 106) with one of four geriatric target conditions at baseline (eg, delirium, functional impairment, incontinence, and pressure sores). The intervention had no effect in patients without target conditions at baseline (n = 110); thus, this subgroup was excluded from further analyses. When patients were matched on number of target conditions and risk for functional decline at baseline (n = 66), the intervention resulted in a significant beneficial effect, with a reduction in functional decline from 64% in controls to 41% in the intervention group, for a relative risk of 0.64 (95% CI, 0.43 to 0.96). The intervention group had significantly less decline in ADL score and in individual ADLs than control subjects. Specific interventions aimed at maximizing function, such as physical therapy, were received more often by intervention patients; however, the beneficial effects of the intervention were achieved without increasing per-day hospital costs. CONCLUSIONS: The intervention appears effective to decrease functional decline in targeted elderly hospitalized medical patients.

Activities of Daily Living↗
PubMed1993

Predictors of formal home health care use in elderly patients after hospitalization.

OBJECTIVE: To prospectively study the incidence of and risk factors for home health care (HHC) use in a cohort of elderly medical and surgical patients discharged from acute care. Although HHC is commonly received by patients in this group, its predictors have not been well studied. DESIGN: Prospective cohort study. SETTING: Medical and surgical wards at a university teaching hospital, followed by 23 Medicare-certified HHC agencies in the study catchment area. PATIENTS: 226 medical and surgical patients aged 70 years and older immediately after discharge from acute care. MEASUREMENTS: HHC initiated within 14 days after hospital discharge, measured by direct review of HHC agency records. RESULTS: The incidence of HHC initiated within 2 weeks post-discharge was 75/226 (34%). The median duration of service was 30 days (range 3-483) with a median of 3 visits per week. Four independent predictors of HHC were identified through multivariate analysis: educational level < or = 12 years (relative risk (RR) 3.3; 95% confidence interval (CI) 1.6 to 6.6); less accessible social support (RR, 1.7; CI 0.9 to 3.1); impairment in at least one instrumental activity of daily living (RR, 1.9; CI, 1.0, 3.4); and prior HHC use (RR, 2.1; CI, 1.2 to 3.6). Risk strata were created by adding one point for each risk factor present: with 0-1 risk factors, 8% used HHC; with two risk factors, 28%; with three risk factors, 45%, with four risk factors, 76%. This trend was statistically significant (P < 0.001). CONCLUSIONS: HHC use is common among elderly patients after discharge from acute care. A simple predictive model based on four risk factors can be used on admission to predict HHC use. This model may be useful for discharge planning and health care utilization planning for the elderly population.

Activities of Daily Living↗
PubMed1993

The murine cripto gene: expression during mesoderm induction and early heart morphogenesis.

The murine cripto gene encodes a 171-aminoacid epidermal growth factor-related protein, with 93% similarity to its human counterpart in the 'EGF-like' domain. The murine cripto mRNA contains two B1 repeats in its 3' non-coding region and a 163-nucleotide homology to the human mRNA. The mouse cripto gene is expressed at low level in specific organs of the adult animal such as spleen, heart, lung and brain. In situ hybridization analysis during murine embryogenesis (day 6.2 to day 10.5) reveals a very restricted expression pattern. cripto transcripts are first detected in a few epiblastic cells at day 6.5. During gastrulation, the transcripts are expressed in the forming mesoderm and later during development cripto gene expression is restricted to the truncus arteriosus of the developing heart. This expression pattern suggests a role for cripto gene in the determination of the epiblastic cells that subsequently give rise to the mesoderm.

Amino Acid Sequence↗
PubMed1993

Homeobox genes in the developing central nervous system.

A number of genes containing sequences coding for DNA-binding domains homologues to homeobox sequences in Drosophila have been isolated in vertebrate and their mechanism of action have been studied. In Particular Hox family genes share with Drosophila homeotic genes a genomic organization in gene clusters and an expression pattern that is similar in a number of important respects. In situ hybridization experiment have shown that there is a strict correspondence, or colinearity, between the order of the Hox genes (3' to 5') within the chromosomal cluster and that of their expression domains (anterior to posterior) in the embryo. Recent data obtained in embryonal carcinoma (EC) cells induced to differentiate by retinoic acid (RA) cast some light on the molecular mechanisms underlying the colinear expression of the Hox genes.

Amino Acid Sequence↗
PubMed1992

Nested expression domains of four homeobox genes in developing rostral brain.

Insight into the genetic control of the identity of specific regions along the body axis of vertebrates has resulted primarily from the study of vertebrate homologues of regulatory genes operating in the Drosophila trunk, but little is known about the development of most anterior regions of the body either in flies or vertebrates. Three Drosophila genes have been identified that are important in controlling the development of the head, two of which, empty spiracles and orthodenticle, have been cloned and shown to contain a homeobox. We previously cloned and characterized Emx1 and Emx2, two mouse genes related to empty spiracles that are expressed in restricted regions of the developing forebrain, including the presumptive cerebral cortex and olfactory bulbs. Here we report the identification of Otx1 and Otx2, which are related to orthodenticle. We have compared the expression domains of the four genes in the developing rostral brain of mouse embryos at a developmental stage, day 10 post coitum, when they are all expressed. Otx2 is expressed in every dorsal and most ventral regions of telencephalon, diencephalon and mesencephalon. The Otx1 expression domain is similar to that of Otx2, but contained within it. The Emx2 expression domain is comprised of dorsal telencephalon and small diencephalic regions, both dorsally and ventrally. Finally, Emx1 expression is exclusively confined to the dorsal telencephalon. Thus at the time when regional specification of major brain regions takes place, the expression domains of the four genes seem to be continuous regions contained within each other in the sequence Emx1 less than Emx2 less than Otx1 less than Otx2.

Amino Acid Sequence↗
PubMed1992

Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex.

We cloned two homeobox genes, Emx1 and Emx2, related to empty spiracles, a gene expressed in very anterior body regions during early Drosophila embryogenesis, and studied their expression in mouse embryos. Emx1 expression is detectable from day 9.5 of gestation whereas Emx2 appears to be already expressed in 8.5 day embryos. Both genes are expressed in the presumptive cerebral cortex and olfactory bulbs. Emx1 is expressed exclusively there, whereas Emx2 is also expressed in some neuroectodermal areas in embryonic head including olfactory placodes in earlier stages and olfactory epithelia later in development.

Amino Acid Sequence↗
PubMed1992

Alternative splicing of PML transcripts predicts coexpression of several carboxy-terminally different protein isoforms.

The acute promyelocytic leukaemia (APL)-specific chromosome 15;17 translocation leads to the fusion of a newly identified putative transcription factor, PML, and the retinoic acid receptor alpha. We have characterized the structure of the PML genomic locus and preliminarily characterized its expression pattern. The PML locus spans a minimum of 35 kb and is subdivided into nine exons. The putative PML DNA binding site is encoded by exons 2 and 3. We isolated a large number of alternatively spliced PML transcripts that encode numerous PML isoforms. Two groups of isoforms were identified that differed either in their C-terminal region or in the length of their central region, but retained the putative DNA-binding and dimerization domains. RNAase protection experiments revealed that the different PML isoforms are equally expressed in established cell lines of different histological origin.

Amino Acid Sequence↗
PubMed1991

Isolation and mapping of EVX1, a human homeobox gene homologous to even-skipped, localized at the 5' end of HOX1 locus on chromosome 7.

We isolated and mapped the human homeobox gene EVX1. This gene encodes a protein of 407 amino acid residues containing a homeodomain closely related to the Drosophila even-skipped (eve) segmentation gene of the pair-rule class. EVX1 belongs to a small family of vertebrate eve-related homeobox genes including human EVX1 and EVX2 genes, their murine homologs, Evx 1 and Evx 2, and the frog Xhox-3 gene. We previously reported that EVX2 is localized at the 5' end of the HOX4 locus on chromosome 2. We show here that EVX1 is localized at the 5' end of the HOX1 locus on chromosome 7, 48 kb upstream from the most 5' of the eleven HOX1 genes, namely HOX1J. Both EVX genes are transcribed in an opposite orientation as compared to that of adjacent HOX genes. Human HOX1 and HOX4 complex loci appear to be both closely linked to a homeobox gene of the EVX family.

Amino Acid Sequence↗