Search PubMed⌕ Search

Biomedical subjects

M Crossley

Publications and source records attributed to M Crossley.

47 records · Page 3Linked to original sources
PubMed1994

Regulation of the erythroid Kruppel-like factor (EKLF) gene promoter by the erythroid transcription factor GATA-1.

Erythroid Kruppel-like factor (EKLF) is an erythroid-specific transcription factor that binds a CACCC motif found in the human beta-globin gene promoter. We have studied the promoter of the EKLF gene and identified binding sites for the transcription factors GATA-1 and CCAAT-binding Protein 1 (CP1). We show that both types of binding sites are required for full activity, and that the GATA motif at -60 is essential. The EKLF promoter can be directly activated in nonerythroid cells in cotransfection experiments by forced expression of GATA-1. These results suggest that EKLF is dependent on GATA-1 for its expression and lies downstream of, or coincident with, GATA-1 in a regulatory hierarchy in erythroid development.

3T3 Cells↗
PubMed1993

Diagnostic utility of the MCMI-I and MCMI-II with psychiatric outpatients.

Research indicates that the Millon Clinical Multiaxial Inventory (MCMI-I) lacks diagnostic accuracy when compared to clinically generated DSM-III-R diagnoses. This shortcoming is most evident for the identification of psychotic disorders. The MCMI-II was designed to reflect more accurately the DSM-III-R diagnostic formulation, but its diagnostic efficacy has yet to be determined with clinical samples. In the present investigation, two consecutive samples of psychiatric patients who were attending an outpatient day treatment program were administered either the MCMI-I (N = 39) or the MCMI-II (N = 37). MCMI diagnoses were compared with clinician-generated DSM-III-R diagnoses. Relative to clinical judgment, both versions of the MCMI underestimated the incidence of psychotic disorders and overestimated the incidence of nonpsychotic disorders and personality disorders.

Adult↗
PubMed1993

Regulation of the beta-globin locus.

Transcription of the human beta-globin gene cluster depends upon upstream regulatory sequences, which are collectively termed the locus control region. Recent studies have provided new insights into how the individual genes of the cluster are regulated through development. The crux of transcriptional activation is how the locus control region communicates with the gene-proximal regulatory elements.

Animals↗
PubMed1992

Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter.

One form of the inherited, X-linked, bleeding disorder, hemophilia B, resolves after puberty. Mutations at -20 and -26 in the clotting factor IX promoter impair transcription by disrupting the binding site for the liver-enriched transcription factor LF-A1/HNF4. The -26 but not the -20 mutation also disrupts an androgen-responsive element, which overlaps the LF-A1/HNF4 site. This explains the improvement seen in patients with the -20 mutation and the failure of the -26 patient to recover.

Base Sequence↗
PubMed1992

Age-related differences in concurrent-task performance of normal adults: evidence for a decline in processing resources.

A concurrent-task paradigm was used to investigate age-related differences in the attentional capacity of 92 right-handed adults. Young, middle-aged, and elderly Ss were compared as they performed speeded, unimanual finger tapping with and without concurrent silent reading, speaking, and maze completion. There were 2 levels of difficulty for each cognitive task. The decrement in tapping rate from the single- to dual-task condition increased linearly with age. Concurrent-task tapping was slowed more by difficult than by easy tasks, and difficult tasks had a disproportionately disruptive effect on the concurrent performance of elderly Ss. The heightened vulnerability of the elderly to concurrent-task effects cannot be attributed parsimoniously to either general slowing or diminution of a specific resource. Instead the results suggest a reduction in a general-purpose processing resource with increasing age.

Adult↗
PubMed1991

Simulated scaphoid proximal pole fracture.

Five fresh cadaver upper extremities were studied with use of a static positioning frame, pressure-sensitive film, a microcomputer-based videodigitizing system, and a Sun station image analysis system to assess the load bearing characteristics of the scaphoid in the proximal carpal joint. Specimens were studied in their normal condition, after a proximal pole osteotomy of the scaphoid, and after resection of the proximal pole of the scaphoid. The amount of contact area born through the scaphoid fossa was essentially the same whether the scaphoid was intact, or after a simulated scaphoid fracture of its proximal pole, or after resection of the proximal pole. The scaphoid contact area and pressure, although overall relatively constant, was redistributed after osteotomy, resulting in increased contact area under the distal fragment and no change or a slight decrease in the contact area under the proximal fragment of the scaphoid. After resection of the proximal fragment, all scaphoid contact area and pressure was born by the distal scaphoid fragment. The contact area and pressure characteristics of the lunate remained unchanged in all conditions compared with the normal condition. There were no significant changes in the locations of the centroids of the scaphoid segments and the lunate in any of the conditions tested.

Adult↗
PubMed1991

The fourth carpometacarpal joint.

The base of the fourth metacarpal and the corresponding hamate/capitate articulation were the areas of most significant variation in 142 cadaveric wrists that were dissected to assess the variation of the shapes of the second through the fifth carpometacarpal joints. Five different shapes of the fourth metacarpal base were identified. The base of the fourth metacarpal was generally either flat (85.9%) or conical (14.1%). There was a fourth metacarpal/capitate articulation present in 81.7% of the specimens. The presence or absence of a fourth metacarpal/capitate articulation and whether or not the fourth metacarpal base was flat or conical were easily identifiable on radiographs. Specific types of fourth metacarpal bases could not, however, be identified by radiography.

Adult↗
PubMed1991

The silicone scaphoid: a biomechanical study.

Five fresh cadaver upper extremities were studied by use of a static positioning frame, pressure-sensitive film, and a microcomputer-based videodigitizing system, to assess the load-bearing characteristics of a scaphoid silicone implant within the radioulnarcarpal joint. Specimens were studied in their "normal" condition, after resection of the scaphoid, after placement of a scaphoid implant, and with a scaphoid implant and a simulated capitate-lunate-triquetrum-hamate fusion. The scaphoid silicone implant bore significant, although less, load than the normal scaphoid. Decreasing the size of the scaphoid implant decreased the load born by the implant. Decreased load through the scaphoid implant was compensated by the lunate. The addition of a limited carpal fusion did not significantly decrease the load born by a scaphoid implant. Therefore, the silicone scaphoid implant is a load-bearing implant even when undersized or placed in association with a limited carpal fusion.

Adult↗
PubMed1990

Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B.

Haemophilia B (or Christmas disease) is an inherited, X-linked bleeding disorder caused by mutations in the gene for clotting factor IX. There is a rare class of patients, exemplified by haemophilia B Leyden, who suffer from haemophilia B as children but improve after puberty. In these patients, plasma factor IX concentrations are less than 10% of normal during childhood, but after puberty they gradually rise to between 40 and 80% of normal. Mutations clustered around the main transcription start point (defined as +1 (ref.2)) have been reported in seven of these patients (at -20 (refs 1, 3, 4); -6 (refs 5, 6) and +13 (refs 7, 8)). To determine how these mutations interfere with factor IX expression, we have assayed for transcription factors binding to this area and have identified a nuclear factor-1 liver (NF1-L) binding site (-99 to -76) and a binding site for the CCAAT/enhancer binding protein (C/EBP) (+1 to +18). We show that the A----G mutation at +13 prevents the binding of C/EBP to this site. Furthermore, we show that C/EBP is capable of transactivating a cotransfected normal factor IX promoter but not the mutant promoter. This is the first natural mutation to be reported which disrupts a C/EBP binding site and is an illustration of the importance of this transcription factor in humans.

Age Factors↗