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Biomedical subjects

D Coen

Publications and source records attributed to D Coen.

At least 19 recordsLinked to original sources

Home care prevents cognitive and functional decline in frail elderly.

Today home health care (HHC) programs have been developed in numerous Western countries, in order to answer the questions regarding the care of frail elderly suffering from polypathologies and, therefore, being at high risk of disability. The HHC program of the Israelite Hospital of Rome has been planned as a complementary model, and not as a substitute of hospitalization, being able to offer flexible services, suitable for each elderly patient. The present study has established that taking care of old patients in their home allows us to prevent the deterioration of cognitive performance and functional impairments,as measured by the mini mental state examination (MMSE), the scales of activity of daily living (ADL), and the instrumental activity of daily living (IADL), respectively. We found considerable improvements also in the mood disorders during HHC, as measured by the geriatric depression scale (GDS). All psychometric tests were administered at the beginning of home care and after almost 1 year. Moreover, we formulated some questions regarding the quality of the offered services, and the answers revealed great satisfaction of both the patients and their caregivers.

Activities of Daily Living↗

Prevalence and association of the factor V Leiden and prothrombin G20210A in healthy subjects and patients with venous thromboembolism.

AIM: To determine the prevalences of factor V Leiden and the G20210A mutation in the prothrombin gene (PT20210A) and the frequency of their association in healthy subjects and in patients with venous thromboembolism (VTE). METHOD: We studied 160 Croatian patients with at least one episode of VTE and 155 healthy subjects as a control group. Genomic DNA was extracted according to standard procedures and the presence of factor V Leiden and PT20210A were determined by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The prevalences of factor V Leiden and PT20210A were in VTE patients 21% and 8% respectively, and 4% in controls for both mutations. Additionally, 4 patients were affected by double heterozygous defects, corresponding to a frequency of 3%, whereas none of the controls were double heterozygotes. The coexistence of the PT20210A in heterozygous carriers of factor V Leiden was 15% in VTE group. The results obtained for different subgroups of VTE patients showed that the carriers of analyzed mutations were identified only in subgroups of patients with deep venous thrombosis of lower extremities (in 30 patients with factor V Leiden and in 13 patients with PT20210A) and superficial venous thrombosis (in 3 patients with factor V Leiden). CONCLUSION: The prevalences of factor V Leiden and PT20210A in analyzed population of VTE patients are higher than in the group of healthy subjects. High frequency of association between both mutations supports the need to perform simultaneous genetic analyses of factor V Leiden and PT20210A in all VTE patients.

Adolescent↗

P-element transposition in Drosophila melanogaster: influence of size and arrangement in pairs.

In Drosophila melanogaster, several factors have been suggested to influence the rates of P-element transposition and excision, including position effects, size and structure of the elements and differences in transposase source. We have investigated the effect of the size of the starting P-element on the rates of excision and transposition. Four transgenes localized at the same insertion site on the X chromosome and which differ by the number of copies of an internal repeated sequence, were studied. Transgenes with sizes ranging from 11 kb to 22 kb excise at similar rates, and size does not correlate with the differences in transposition rate between them. We also studied the behavior of double P-elements, located at the same site and arranged in various configurations: nested, contiguous or separated by a few base pairs, in the same or reverse orientation. These double P-elements display different mobilities depending on the arrangement of the two transgenes. Transposition and excision rates were also studied for an insertion bearing four transgenes in very close proximity. Our results suggest that several neighboring elements could excise together. We also propose a new model to explain the formation of all the double P-elements we describe.

Animals↗

white+ transgene insertions presenting a dorsal/ventral pattern define a single cluster of homeobox genes that is silenced by the polycomb-group proteins in Drosophila melanogaster.

We used the white gene as an enhancer trap and reporter of chromatin structure. We collected white+ transgene insertions presenting a peculiar pigmentation pattern in the eye: white expression is restricted to the dorsal half of the eye, with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and heritable, indicating that phenotypic expression of the white reporter reflects positional information in the developing eye. Localization of these transgenes led us to identify a unique genomic region encompassing 140 kb in 69D1-3 subject to this D/V effect. This region contains at least three closely related homeobox-containing genes that are constituents of the iroquois complex (IRO-C). IRO-C genes are coordinately regulated and implicated in similar developmental processes. Expression of these genes in the eye is regulated by the products of the Polycomb-group (Pc-G) and trithorax-group (trx-G) genes but is not modified by classical modifiers of position-effect variegation. Our results, together with the report of a Pc-G binding site in 69D, suggest that we have identified a novel cluster of target genes for the Pc-G and trx-G products. We thus propose that ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin structure in a manner similar to that of the homeotic gene complexes, perhaps by local compaction of the region into a heterochromatin-like structure involving the Pc-G products.

ATP-Binding Cassette Transporters↗

Serum amyloid A protein in the prediction of postburn complications and fatal outcome in patients with severe burns.

Fifty adults hospitalized with extensive burns formed the basis of the present study. Serum amyloid A protein, C-reactive protein, alpha 1-antichymotrypsin and alpha 1-acid glycoprotein were measured in serum samples taken on admission, and 3 and 7 days later. Fatal outcome was observed in 13 out of 14 (93%) patients with serum amyloid A protein over 100 mg/l on admission and in only 2 of the remaining 36 (6%) patients with serum amyloid A protein below 100 mg/l. The median serum amyloid A protein concentration on admission in 15 patients with fatal outcome was 134 mg/l, and only 30 mg/l in 35 patients who recovered (p < 0.00005). As a reference value, the level of 100 mg serum amyloid A protein per litre on admission gave an evident predictive value (93%) and sensitivity (87%) for fatal outcome. The difference between serum amyloid A protein concentrations in patients with complications (median 642 mg/l) and those without complications (median 250 mg/l) was statistically very significant (p = 0.0003) three days after burn injury. The level of 400 mg/l as a reference value 3 days after burn injury gave a reasonable predictive value (80%) and sensitivity (74%) for the development of postburn complications, but patients who died did not develop a hypermetabolic reaction and their serum amyloid A protein concentration remained below 400 mg/l, despite high serum amyloid A protein concentrations observed on admission (above 100 mg/l). No statistical significance was observed for the other 3 acute phase proteins investigated in this study.

Adult↗

Prevalence of localized rearrangements vs. transpositions among events induced by Drosophila P element transposase on a P transgene.

We have studied P transposase-induced events on a P[w] transgene, P[wd1], harboring the whole white gene with a 3.44-kb direct duplication of its 5' regulatory sequences (containing the ZESTE-binding region, ZBR). We have recovered mutations leading to an increase or a decrease of zeste1 repression, generally as the consequence of modifications of number of ZBR in close physical proximity and/or jumps to other sites. We describe mutants displaying deletions of the original duplicated sequence or increases in the number of repeats from two to three or four. Internal deletions are more frequent than amplifications. Both require the integrity of P-element ends. We have also observed a high frequency of double P elements localized at the original P[wd1] insertion site. These double P elements are arranged in nonrandom configurations. We discuss the frequencies and the possible mechanisms leading to the various types of derivatives, in light of the current models for P excision and transposition. We propose that the P transposase induces mainly localized events. Some of these could result from frequent changes of template during gap-repair DNA synthesis, and/or from abortive transposition.

Animals↗

Maternal inheritance of P cytotype in Drosophila melanogaster: a "pre-P cytotype" is strictly extra-chromosomally transmitted.

In Drosophila melanogaster, transposition of the P element is under the control of a cellular state known as cytotype. The P cytotype represses P transposition whereas the M cytotype is permissive for transposition. In the long-term, the P cytotype is determined by chromosomal P elements but over a small number of generations it is maternally inherited. In order to analyse the nature of this maternal inheritance, we tested whether a maternal component can be transmitted without chromosomal P elements. We used a stable determinant of P cytotype, linked to the presence of two P elements at the tip of the X chromosome (1A site) in a genome devoid of other P elements. We measured P repression capacity using two different assays: gonadal dysgenic sterility (GD) and P-lacZ transgene repression. We show that zygotes derived from a P cytotype female (heterozygous for P (1A)/balancer devoid of P copies) and which inherit no chromosomal P elements from the mother, have, however, maternally received a P-type extra-chromosomal component: this component is insufficient to specify the P cytotype if the zygote formed does not carry chromosomal P elements but can promote P cytotype determination if regulatory P elements have been introduced paternally. We refer to this strictly extra-chromosomally inherited state as the "pre-P cytotype". In addition, we show that a zygote that has the pre-P cytotype but which has not inherited any chromosomal P elements, does not transmit the pre-P cytotype to the following generation. The nature of the molecular determinants of the pre-P cytotype is discussed.

Animals↗

Maternal repression of the P element promoter in the germline of Drosophila melanogaster: a model for the P cytotype.

The transposition of P elements in Drosophila melanogaster is regulated by products encoded by the P elements themselves. The P cytotype, which represses transposition and associated phenomena, exhibits both a maternal effect and maternal inheritance. The genetic and molecular mechanisms of this regulation are complex and not yet fully understood. In a previous study, using P-lacZ fusion genes, we have shown that P element regulatory products were able to inhibit the activity of the P promoter in somatic tissues. However, the repression observed did not exhibit the maternal effect characteristic of the P cytotype. With a similar approach, we have assayed in vivo the effect of P element regulatory products in the germline. We show that the P cytotype is able to repress the P promoter in the germline as well as in the soma. Furthermore, this repression exhibits a maternal effect restricted to the germline. On the basis of these new observations, we propose a model for the mechanism of P cytotype repression and its maternal inheritance.

Animals↗

P regulatory products repress in vivo the P promoter activity in P-lacZ fusion genes.

The transposition of P elements in Drosophila melanogaster is regulated by products encoded by the P elements themselves. The molecular mechanisms of this regulation are complex and still unclear. We have assayed in vivo the effects of P regulatory products on the P promoter itself by using P-lacZ fusion genes. We have found that all the P-lacZ insertions are repressed in a P background. This repression occurs in all the tissues observed and at all the developmental stages. The amount of transcripts specific for P-lacZ is substantially reduced in a P background. These results suggest that P trans-acting products can exert a direct repression on the P promoter transcription.

Animals↗

P element regulatory products enhance zeste repression of a P[white duplicated] transgene in Drosophila melanogaster.

Drosophila P element mobilization is subject to a complex array of regulatory mechanisms. A fruitful approach to study them is the use of insertion mutations whose expression is influenced by P regulation. In the present report, it is shown that P element somatic products may influence the expression of an unrelated gene inserted in a P transposon. The P[wdl9.3]19De transgene carriers an in vitro modified white gene harboring a duplication of the 5' regulatory sequences. Expression of this transgene is repressed in a P background. No maternal effect is detected and repression can be relieved as soon as P chromosomes are replaced by M ones. The amplitude of repression is correlated to the P transposase activity of the individuals examined. Repression appears to be exerted by somatic products of complete autonomous P elements or of in vitro modified P elements lacking the capacity to express the fourth P exon. The P repression of P[wdl9.3]19DE is strongly dependent on the insertion site of this transgene. This P repression effect occurs only in the presence of the zeste allele and is suppressed by Su(z)2 mutations. No qualitative differences of transcription pattern are observed between white+ and P[wdl9.3]19DE in any backgrounds. P repression acts to reduce the amount of the major white transcript. This suggests that P regulatory products may act through cis-interactions at a distance of over 3 kb.

Animals↗

Are "routine" clinical and laboratory examinations of any help in the treatment of chronic hemodialysis patients?

The relevance of routine physical examinations, laboratory tests, and x-rays in guiding therapeutic decisions was investigated in 54 patients on hemodialysis. Patients were observed for 1 year, while recording all therapeutic interventions and tracing the procedures that had determined them. In no case did a variation in treatment follow the routine physical examination of a patient who was not symptomatic or already signaled for BP or dialytic problems by the hemodialysis nurses. A number of major therapeutic interventions were conversely necessary for acute illnesses that could not be foreseen during the routine physician-patient encounter. Of the many laboratory tests, only the determination of complete blood cell count, serum electrolytes, and calcium and phosphorus levels were frequently associated with therapeutic decisions. No intervention was directly related with x-ray bone examination. On the whole, a subgroup of 11 "high-risk" patients who required frequent and multiple therapeutic interventions was identified, the remaining 43 needing only rare and minor adjustments. It is concluded that routine physical examinations are probably useless in identifying and treating intercurrent problems of patients with chronic end-stage renal failure and that only very few hematochemical laboratory tests should be regularly performed. On the basis of a benefit/risk and benefit/cost examination, it is suggested that personally tailored follow-up schemes would probably be a more appropriate way of monitoring patients on maintenance hemodialysis.

Diagnostic Tests, Routine↗