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Biomedical subjects

A Daniel

Publications and source records attributed to A Daniel.

At least 37 records · Page 2Linked to original sources

Complex regulatory region mediating tailless expression in early embryonic patterning and brain development.

tailless encodes a transcription factor expressed in multiple domains in the developing embryo. Early and transient expression at the posterior pole is required to establish a domain from which the eighth abdominal segment, telson and posterior gut arise. Just a few nuclear cycles later, a brain-specific domain is initiated at the anterior; expression in this domain is maintained with complex modulations throughout embryogenesis. Expression of tailless in this domain is required to establish the most anterior region of the brain. To understand the function and regulation of these different domains of expression, we provide a detailed description of tailless expression in brain neuroblasts and show that this expression is not detectably regulated by the head gap genes buttonhead or orthodenticle, by the proneural gene lethal of scute or by tailless itself. We show that approximately 6 kb of sequenced upstream regulatory DNA can drive lacZ expression in a pattern that mimics the full tailless embryonic expression pattern. Within this sequence we identify multiple modules responsible for different aspects of the tailless pattern. In addition to identifying additional torso response elements that mediate early blastoderm polar expression, we show that the complex brain expression pattern is driven by a combination of modules; thus expression at a low level throughout the brain and at a high level in the dorsal medial portion of the brain and in the optic lobe, as well as neuroblast-specific repression are mediated by different DNA regions.

Animals↗

Nasal mucosal cells in human immunodeficiency virus type 1-seropositive patients with sinusitis.

Recently, sinusitis has been recognized as a frequent clinical problem in human immunodeficiency virus (HIV-1)-infected individuals. We hypothesized that quantitative defects in immune cells in the nasal mucosa of HIV-positive subjects might mirror those in the peripheral blood and explain a predisposition to sinus disease in this population. Nasal mucosa biopsies were obtained from three different groups of patients-HIV-1 seropositive with sinusitis, HIV-1 seronegative with sinusitis, and HIV-1 seronegative without sinusitis (normal volunteer)-and phenotyped for cluster of differentiation antigen (CD) markers. In this study, we found patients with HIV-1 and sinus disease to have significantly lower numbers of both CD3 and CD4 nasal mucosa lymphocytes than seronegative controls in the nasal mucosa (P < 0.05, P < 0.01, respectively). A correlation between nasal mucosal CD4 cells and peripheral-blood CD4 cells was noted (R = 0.67, P < or = 0.01). No deficiency in the number of nasal mucosa T or TC type mast cells was noted for the HIV-1-positive sinusitis group. Further study is warranted to define more completely the pathophysiology and microbiology of, and therapy for, this important clinical problem.

Acquired Immunodeficiency Syndrome↗

A pseudoknot ribozyme structure is active in vivo and required for hepatitis delta virus RNA replication.

The ribozymes of hepatitis delta virus (HDV) have so far been studied primarily in vitro. Several structural models for HDV ribozymes based on truncated HDV RNA fragments, which are different from the hammerhead or the hairpin/paperclip ribozyme model proposed for plant viroid or virusoid RNAs, have been proposed. Whether these structures actually exist in vivo and whether ribozymes actually function in the HDV replication cycle have not been demonstrated. We have now developed an in vivo ribozyme self-cleavage assay capable of detecting self-cleavage of dimer or trimer HDV RNA in vivo. By site-directed mutagenesis and compensatory mutations to disrupt and restore potential base pairing in the ribozyme domain of the full-length HDV RNA according to the various structural models, a close correlation between the detected in vivo and the predicted in vitro ribozyme activities of various mutant RNAs was demonstrated. These results suggest that the proposed in vitro ribozyme structure likely exists and functions during the HDV replication cycle in vivo. Furthermore, the pseudoknot model most likely represents the structure responsible for the ribozyme activity in vivo. All of the mutants that had lost the ribozyme activity could not replicate, indicating that the ribozyme activities are indeed required for HDV RNA replication. However, some of the compensatory mutants which have restored both the cleavage and ligation activities could not replicate, suggesting that the ribozyme domains are also involved in other unidentified functions or in the formation of an alternative structure that is required for HDV RNA replication. This study thus established that the ribozyme has important biological functions in the HDV life cycle.

Base Sequence↗

Identification of marker chromosomes in thirteen patients using FISH probing.

Fourteen marker chromosomes were studied by FISH (fluorescence in-situ hybridization) in cytogenetic preparations from 13 patients. The derived markers were identified as one isodicentric bisatellited mar(22), one fragment sized r(X), one fragment sized r(Y), one i(18p), small autosomal ring markers in three different patients derived from chromosomes 2, 8, and 8, a marker comprised of 9p and part of 9qh, and 3 bisatellited apparently monocentric markers; one of each from chromosomes 13 or 21, 14 or 22, and 15. Two fragment sized small ring markers in one patient and a small ring marker in another were negative with all twenty-two different probes used. In addition, the small ring marker Y chromosome that was found in a boy with karyotype 46,X,-Y,+mar was negative with both pDXZ1 and pDYZ3. This anomaly of negative results with the battery of centromeric alphoid probes can be explained if one breakpoint for some small ring markers is very near to or within the centromere. Only some of the pericentromeric repetitive sequences in the normal chromosome would be represented in the chromosome specific alphoid probes, and presumably those corresponding to the currently available probes are truncated during the formation of the unidentified markers. In three of the small ring markers the FISH signal on the marker was much stronger than on the normal homologues in various proportions of cells, and this may indicate that some of the fragment sized small rings were multicentric. The literature was reviewed for Distamycin A/DAPI negative small ring markers that were present as extra chromosomes. There were only single published cases of most small rings but there were three r(8) cases, two r(1) cases, two r(12) cases, and two r(20) cases, uncomplicated by the presence of other chromosome abnormalities. Most cases with similar small rings were quite dissimilar phenotypically and syndrome identification was not possible, but in pooled data, 18/23 (about 80%) were developmentally and/or phenotypically abnormal. Some patients (5/23, about 20%) with small rings were dysmorphic without intellectual handicap. Of 28 such patients with small ring markers (Distamycin/Dapi negative) in pooled data there are 6 (about 20%) with multiple markers mostly derived from different chromosomes. This is a very high figure and would suggest that the ring formation events, although involving different chromosomes, must be related and must be an indicator of the mechanism of origin of this group of markers.

Adolescent↗

Bone marrow adherent layers inhibit apoptosis of acute myeloid leukemia cells.

Human acute myeloid leukemia (AML) cells, like normal hematopoietic progenitors, die rapidly by apoptosis when cultured under serum-free conditions. Apoptosis was demonstrated by electron microscopy and agarose gel electrophoresis and quantified by flow cytometry. Culturing AML blasts in the presence of a bone marrow fibroblast (BMF) monolayer reduced the percentage of AML blasts undergoing apoptosis in the majority of cases studied. The effect was more pronounced when AML cells were cultured in the presence of an adherent long-term bone marrow (LTBM) stroma rather than BMF. Overall, the mean percentage of AML cells with fragmented DNA fell from 85 +/- 8% in control cultures to 20 +/- 9% in cultures with adherent stroma (p = 0.0004, n = 7). Supplementation of serum-free medium with recombinant cytokines, including stem cell factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-alpha or with human placenta-conditioned medium (HPCM) matched the degree of inhibition of apoptosis induced by BMF in only 50% of cases. Granulocyte colony-stimulating factor (G-CSF), interleukin-1 beta (IL-1 beta), and IL-6 were completely ineffective. Consistent with this observation, direct contact between leukemic cells and adherent layers was essential for maximum inhibition of leukemic-cell DNA fragmentation. Separation by a porous membrane allowing passage of soluble growth factors, but interrupting direct cell contact, was associated with significantly greater DNA fragmentation and cell death. Inhibition of leukemic-cell apoptosis correlated with improved survival and growth of malignant clonogenic cells. Colonies grown in cultures were identified as leukemic by morphology and by fluorescence in in situ hybridization to demonstrate numerical chromosomal abnormalities identified at diagnosis. Close contact between leukemic cells and bone marrow inhibits blast cell apoptosis and directly promotes survival of clonogenic AML cells.

Acute Disease↗

The effect of interdialytic weight gain on predialysis blood pressure.

Interdialytic weight gain is believed to influence predialysis blood pressure. Since interdialytic weight gains vary among treatments for individual patients, blood pressure and weight gain data could be examined to determine how weight variations correlate with differences in blood pressure. Therefore, the quantitative effect on prehemodialysis blood pressure of typical interdialytic weight gains was prospectively studied in 19 nondiabetic patients on chronic hemodialysis. Over a mean of 23.6 treatments (range 17-25), the slope of each patient's prehemodialysis blood pressure versus excess weight (prehemodialysis weight minus baseline dry weight) was determined. The mean slope of the prehemodialysis mean blood pressure/excess weight regression line was 1.2 mm Hg/lb excess weight. No significant correlation was found between individual prehemodialysis blood pressure/excess weight slopes and patient age (r = 0.20), months on dialysis (r = 0.33), dry weight (r = 0.05), or mean excess weight (r = 0.19). Slopes did not differ for 3-day versus 2-day interdialytic intervals, hypertension-treated versus untreated patients, or men versus women. In 5 patients, individual prehemodialysis mean blood pressure/excess weight slopes were significantly greater than 0, averaging 2.4 mm Hg/lb excess weight (vs. 0.8 mm Hg/lb in the remaining patients). These 5 volume-responsive patients did not differ clinically from the 14 volume-resistant patients. The weight gains commonly observed in patients undergoing chronic hemodialysis have only a modest effect on prehemodialysis blood pressure in the majority of patients.

Adult↗

A spreadsheet program measuring laboratory productivity in several ways: an application of College of American Pathology scores and other data to assess the overall economics of clinical laboratories.

A spreadsheet has been designed that measures the productivity of hospital or other clinical laboratories using several methods, one of which, used as a yardstick, is based on College of American Pathology (CAP) workload test scores with some departures from CAP conventions. In this method the CAP-assessed proportion of a laboratory's time utilised in performing pathology or other tests is compared with the time allocated to non-testing departmental activities as a group. A premise in the approach is that variation in the time allocated to these latter activities, in addition to variation in the efficiency of testing, also contributes significantly to the productivity and economics of hospital laboratories. The workload measure of productivity used in the study is referred to as total staff-paid-productivity (TSPP)--allied to paid-productivity of the CAP Manual 1991--and it is suggested that it be used together with several other result parameters to assess laboratories. However, there are two differences from CAP in the TSPP parameter: the salaries and hours of all staff whether medical, technical or scientific are included; and the professional component (time necessary for test interpretation) is also included where applicable. Necessary data include the goods and services costs, the total test-generated income, the total number of full-time staff equivalents and their hours in each unit or work group, the numbers of tests and raw CAP scores and in addition, an estimation of the professional/interpretive component of each test until the generation of a report. The method is illustrated with examples from six different departments with total staff-paid-productivities covering a wide range beyond the typical values of 65 per cent to 75 per cent. When the data for the laboratories are compared, it is observed that the various admixtures of non-testing activities are a stronger influence on differences in total staff-paid-productivity than the interpretative components of tests, although the latter vary markedly from discipline to discipline. When the interpretative components are included in workload measurements, it enables the productivity of different laboratories to be compared across disciplines. It is suggested that for laboratories to generate ongoing productivity they should be staffed at a rate that produces approximately a maximum total staff-paid-productivity of about 75 per cent.

Australia↗

Milwaukee Prehospital Chest Pain Project--phase I: feasibility and accuracy of prehospital thrombolytic candidate selection.

This study prospectively determined the feasibility and accuracy of prehospital thrombolytic therapy candidate selection by base station emergency physicians. During a 6-month period, paramedics acquired and transmitted prehospital 12-lead electrocardiograms (ECGs) and then applied a thrombolytic therapy contraindication checklist. Emergency physicians interpreted prehospital ECGs and prospectively selected candidates for thrombolytic therapy. A safety committee of cardiologists reviewed prehospital ECGs, checklists and hospital records to determine accuracy independently. Six hundred-eighty stable adult prehospital patients with a chief complaint of nontraumatic chest pain were initially evaluated. Two hundred forty-one patients were excluded because of (1) unsuccessful electrocardiographic transmission (149), (2) transport to nonparticipating facilities (72), and (3) unavailable medical records (20). No prehospital thrombolytic therapy was administered in this study. Of 439 cases, 91 (21%) had the final diagnosis of acute myocardial infarction, 38 (8.7%) had diagnostic prehospital ECGs, and 12 (2.7%) were selected by emergency physicians as candidates for thrombolytic therapy. Seventy percent of patients with myocardial infarction had checklist exclusions for thrombolytic therapy. Prehospital evaluation increased mean scene time (paramedic arrival on scene to scene departure) by 4 minutes. The median time from chest pain onset to paramedic arrival in patients with myocardial infarction was 60 minutes. The estimated average time saved if prehospital thrombolytic therapy had been available was 101 +/- 81 minutes. The safety committee concluded that acceptable accuracy of emergency physician prehospital electrocardiographic interpretation, checklist and case selection was achieved. It is concluded that emergency physicians can accurately identify candidates for prehospital thrombolytic therapy.

Adult↗

A familial MCA/MR syndrome due to translocation t(10;16) (q26;p13.1): report of six cases.

A minute familial translocation t(10;16) (q26;p13.1) was detected in a family with 6 affected children in 2 generations and 9 carriers in 3 generations. This apparently unique translocation is associated with a deleterious syndrome which includes fetal hydrops, ascites, complex congenital heart defect, psychomotor retardation, failure to thrive, hypotonia, narrow palpebral fissures, abnormally modeled, apparently low-set ears, cleft palate, thumb abnormalities, hypogenitalism, inguinal hernia, and sparse hair. All children of known or presumed carriers have been either balanced or unbalanced carriers of this translocation.

Abnormalities, Multiple↗

[The role of chlorhexidine irrigation combined with ultrasonic root planing in treatment of periodontal disease. Preliminary study].

The beneficial effects of chlorhexidine on plaque formation have been well documented. This study was undertaken to evaluate the dual effects of chlorhexidine irrigation and root planing with an ultrasonic scaler. The parameters measured were plaque and gingival indices and bleeding on probing. A statistically significant decrease in all indices measured was demonstrated when compared with the test group of patients who received ultrasonic scaling and irrigation with sterile water.

Chlorhexidine↗

[Preprosthetic periodontal examination. Clinical observations].

A detailed and comprehensive clinical examination is an important and fundamental basis for establishing a proper diagnosis for prosthetic treatment. It is important to make an accurate diagnosis, a rational treatment plan and establishing a prognosis. A careful examination of teeth and periodontium must be done and the prosthetic plan must consider the periodontal status of the teeth. The prosthetic treatment plan must take into consideration problems of appliance retention, iatrogenic tooth injuries and other factors. A classification based on 6 different clinical situations suggested and their therapeutic solution proposed.

Dentures↗

Evaluation of indicators of erythropoiesis stimulated by recombinant human erythropoietin in renal anemia.

Recombinant human erythropoietin (rh-EPO) was administered to 11 anemic children with end-stage renal disease who were undergoing hemodialysis. Hematocrit (Hct), absolute reticulocyte count (retics), creatine concentration of red cells and erythrocyte density test (EDT) were chosen as indicators of rh-EPO effect on erythropoiesis. In the present report the first 9 weeks shall be presented in which all patients received an identical dosage of rh-EPO per kg body weight. The pre-EPO values of retics, creatine and EDT varied considerably. In 10 patients the Hct increased to 0.30 after 9 weeks of rh-EPO treatment. Retics and creatine rose in all cases above the normal range, rates of increase and maximal values differed. Retics, creatine and EDT respond faster to rh-EPO than Hct. Retics and creatine seem to be equally good indicators of rh-EPO stimulated erythropoiesis. The EDT showed an increase only up to the 4th week.

Adolescent↗