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Biomedical subjects

J L Diez

Publications and source records attributed to J L Diez.

At least 19 recordsLinked to original sources
PubMed2005

Long-term outcome of allogeneic PBSC transplantation in pediatric patients with hematological malignancies: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) and the Spanish Group for Allogeneic Peripheral Blood Transplantation (GETH).

We analyzed the clinical outcome in 90 children undergoing allogeneic PBSC transplantation from HLA-identical relative for leukemia. GvHD prophylaxis was CsA+ methotrexate in 50 and CsA+/-steroids in 40. Median CD34+ cells infused were 6 x 10(6)/kg (range, 1.4-32). Median follow-up was 60 months (range, 6-115). CI of transplant-related mortality (TRM) was 18.4+/-4%. On multivariate analysis, high Lansky score (>80) at transplantation was associated with lower TRM (HR, 0.9; P<0.0002). Relapse incidence (RI) was 33.6+/-6%. On multivariate analysis, high Lansky score at transplantation and cGvHD were associated with lower RI (HR, 0.04; P<0.0005 and HR, 0.23; P<0.03, respectively). Disease-free survival (DFS) was 57.8+/-5%. Disease status at transplantation (HR, 0.33; P<0.02), steroid treatment at day +90 (HR, 5.61; P<0.005) and cGvHD (HR, 0.23; P<0.005) had a significant impact on DFS in multivariate analysis. CI of cGvHD was 63.7+/-7%. Patients with cGvHD had better DFS (65+/-5%) because of lower RI (15.7+/-6%) and similar TRM (27.4+/-4%). These data suggest acceptable long-term outcomes after allogeneic PBSC transplantation in children despite the high incidence of cGvHD. These patients had a lower risk of relapse and a better DFS.

Adolescent↗
PubMed2004

Risk assessment and outcome of chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell transplantation in pediatric patients.

We retrospectively evaluated the incidence, risk factors for chronic graft-versus-host disease (cGvHD) and outcome in 80 pediatric patients (36 male) (median age 13 years) who underwent allogeneic peripheral blood progenitor cell transplantation. Patients were grafted from an HLA-identical sibling after myeloablative conditioning (total body irradiation (TBI) based 52; non-TBI 28). GvHD prophylaxis used were: cyclosporin A (CsA)+ short methotrexate (MTX) in 52 and CsA+/-prednisone in 28. The median number of CD34+ cells infused were 5.8 x 10(6)/kg (range: 1.4-32.8). The median follow-up was 24 months (range: 3-94). In all, 28 patients had cGvHD (confidence interval (CI): 54.2+/-10%). Factors that were significant on univariate analysis were diagnosis (P=0.03) and GvHD prophylaxis administered (P=0.04). On multivariate analysis, only GvHD prophylaxis used was associated with a significant risk of cGvHD (hazard ratio (HR): 3.94; 95% CI: 1.41-10.91, P=0.009). The CI of cGvHD for patients receiving CsA+MTX was 40.9+/-12 vs 76.5+/-18% for patients who did not (P=0.03). The probability of relapse was 36+/-6% for all patients (12.5+/-8% for patients with cGvHD vs 47.9+/-8% without cGvHD). The probability of disease-free survival was better for patients with cGvHD (69.9+/-10 vs 37.9+/-7%; HR: 3.59, 95% CI: 1.47-5.56; P=0.001). Our data suggest that the GvHD prophylaxis used is the most relevant predictor of cGvHD. Patients with cGvHD had a lower risk of relapse and a better survival.

Adolescent↗
PubMed2001

Heat shock regulatory elements are present in telomeric repeats of Chironomus thummi.

As in other Diptera, the telomeres of Chironomus thummi lack canonical short telomerase-specified repeats and instead contain complex sequences. They react to heat shock and other stress treatments by forming giant puffs at some chromosome termini, which are visible in polytene cells. All telomeres, except the telocentric end of chromosome four (4L), consist of large blocks of repeats, 176 bp in length. Three subfamilies of telomeric sequences have been found to show different distribution patterns between chromosome ends. TsA and TsC are characteristic of telomeres 3R and 4R, respectively, whereas TsB is present in the other non-telocentric telomeres. Heat shock transcription regulatory elements have been identified in the telomeric sequences, appearing differentially represented in the three subfamilies, but otherwise rather similar in size and sequence. Interestingly, TsA and TsB repeats share the well-conserved heat shock element (HSE) and GAGA motif, while the TATA box is only present in the former. Neither a HSE nor a TATA box appear in TsC repeats. Moreover, experimental data indicate that the HSE is functionally active in binding heat shock transcription factor (HSF). These results provide, for the first time, a molecular basis for the effect of heat shock on C.thummi telomeres and might also explain the different behaviour they show. A positive correlation between the presence of HSE and telomeric puffing and transcription under heat shock was demonstrated. This was also confirmed in the sibling species Chironomus piger. The significance of heat shock activation of telomeric repeats in relation to telomeric function is unknown at present, but it might be compared to the behaviour of other non-heat shock protein coding sequences, such as SINE-like and LINE-like retroelements, which have been reported to be activated by stress.

Animals↗
PubMed2001

Telomeres in Chironomus thummi are characterized by different subfamilies of complex DNA repeats.

Members of the genus Chironomus, as well as other Diptera, lack the highly conserved structure of most telomeres, characterized by short repeats generated by telomerase, and have long repeats at their chromosome ends. Among Chironomus species with characterized telomeres Chironomus thummi is of particular interest because one of the telomeres, 3R, forms a giant puff in response to heat shock and other stress treatments. The puff contains nucleoprotein granules in which transcripts of the telomeric repeats are present. Most other nontelocentric telomeres irregularly form less pronounced heat shock puffs. One, the 4R telomere is, however, exceptional in being completely refractory to heat shock. We now pose the question whether the repeats in 3R and 4R have special sequence features. We find three different subfamilies of telomeric repeats in C. thummi, named TsA, TsB and TsC. They have an identical length (176 bp) and display base differences in defined regions, V1 and V2, connected by conserved segments. The TsA subfamily is localized exclusively at 3R, TsC only at 4R, whereas TsB repeats are shared by the remaining nontelocentric telomeres: 1R, 1L, 2R, 2L and 3L. Consequently both 3R and 4R have unique types of telomeric repeats. The 176 bp type repeats are absent from the telocentric, left end of chromosome 4. These results allowed us to differentiate in polytene chromosomes four types of telomeres characterized by tandemly repeated specific sequences.

Animals↗
PubMed2001

Favourable effect of the combination of acute and chronic graft-versus-host disease on the outcome of allogeneic peripheral blood stem cell transplantation for advanced haematological malignancies.

To assess the influence of graft-versus-host disease (GVHD) on the outcome of patients with advanced haematological malignancies (AHM) who received a primary, unmodified allogeneic peripheral blood progenitor cells transplant (allo-PBT) from a human leucocyte antigen (HLA) identical sibling donor, we analysed 136 patients with myeloid neoplasms (n = 70) or lymphoproliferative disorders (n = 66), transplanted at 19 Spanish institutions. Median age was 35 years (range 1-61). The cumulative incidence of relapse for all patients was 34% (95% CI, 26-42%), 41% (95% CI, 33-49) for patients without GVHD and 14% (95% CI, 3-25) (P = 0.001) for patients with acute and chronic GVHD. After a median follow-up of 11 months (range 2-49), 60 (44%) patients remained alive with an actuarial probability of overall survival and disease-free survival (DFS) at 30 months of 31% (95% CI, 21-41%) and 28% (95% CI, 17-39%) respectively. In patients surviving > 100 d, the low incidence of relapse in those with acute and chronic GVHD led to a DFS of 57% (95% CI, 38-76%) compared with a DFS of 34% (95% CI, 17-51%) in the remaining patients (P = 0.03). Our results indicate a reduced incidence of relapse for patients with AHM receiving an unmodified allo-PBT and developing acute and chronic GVHD, which results in an improved DFS.

Acute Disease↗
PubMed2000

Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Español de Citogenética Hematológica.

Recently, a consensus International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in the myelodysplastic syndromes (MDS) has been developed. However, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities for which real prognosis at present is uncertain. The main aims of this study were to evaluate in an independent series the prognostic value of the IPSS and to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in 640 patients. In univariate analyses, cases with single 1q abnormalities experienced poor survival, whereas those with trisomy 8 had a higher risk of acute leukaemic transformation than the remaining patients (P = 0.004 and P = 0.009 respectively). Patients with single del(12p) had a similar survival to patients with a normal karyotype and showed some trend for a better survival than other cases belonging to the IPSS intermediate-risk cytogenetic subgroup (P = 0.045). Multivariate analyses demonstrated that IPSS cytogenetic prognostic subgroup, proportion of bone marrow blasts and haemoglobin level were the main prognostic factors for survival, and the first two characteristics and platelet count were the best predictors of acute leukaemic transformation risk. A large international co-operative study should be carried out to clarify these findings.

Adult↗
PubMed1993

HSP90 associates with specific heat shock puffs (hsr omega) in polytene chromosomes of Drosophila and Chironomus.

The heat shock protein HSP90, which is mainly cytoplasmic, has recently been reported to be present in the nucleus. We have found a specific chromosomal localization of HSP90 in different species of Drosophila and Chironomus using immunocytochemical techniques with different mono- and polyclonal antibodies for this hsp. HSP90 was found associated with heat shock-induced puffs at 93D and 48B in salivary gland chromosomes of Drosophila melanogaster and Drosophila hydei, respectively. The localization of HSP90 to locus 93D occurred rapidly after the onset of heat shock and disappeared during recovery, concomitant with puff regression. The association of HSP90 with the 93D locus was strictly heat shock dependent as shown by the absence of HSP90 in puff 93D induced by either benzamide or colchicine. No specific nuclear staining was observed in unstressed control cells. HSP90 was also found in the temperature-induced telomeric Balbiani ring puffs (T-BRs) in Chironomus thummi and in one heat shock puff at I-1C in Chironomus tentans. Other heat shock puffs also appeared lightly stained with the HSP90 polyclonal antibody in both species of Chironomus. HSP90 was absent from the T-BRs when RNA synthesis was inhibited with Actinomycin D suggesting that the localization of HSP90 is dependent on transcription. Inhibition of protein synthesis did not prevent association of this hsp with the T-BRs, indicating that pre-existing HSP90 can associate with this locus. HSP90 did not associate with any telomeric chromosomal regions of unstressed cells. The present observations suggest that heat shock gene products such as HSP90 may somehow be involved in the regulation at the chromosomal level of other members of the heat shock gene family. Puffs 93D (D. melanogaster) and 48B (D. hydei) are equivalent and correspond to homologous gene loci (hsr omega) that have unusual features that distinguish them from other heat shock puffs. The binding of HSP90 at T-BRs and at puff I-1C in the genus Chironomus is the first demonstration, albeit indirect, of the existence of hsr omega analogous loci in species other than Drosophila.

Animals↗
PubMed1989

Epidemiology of fractures of the proximal femur associated with osteoporosis in Barcelona, Spain.

We studied the epidemiology of osteoporotic fractures of the proximal femur (cervical and trochanteric fractures) in residents of Barcelona, aged 45 years or over, for a 1-year period. Fractures resulting from metastases were not included. During the period of observation, a total of 1,358 patients with hip fractures were treated at acute-care hospitals in Barcelona. Of those, 1,163 were researched. For each case, age, sex, and home address were registered. The incidence of hip fractures per 100,000 inhabitants aged 45 years or over was 115.6 in men and 252.2 in women. Age was the most influencing factor in the occurrence of hip fractures. Women presented fractures of the proximal femur more frequently than men. The epidemiological curve was similar to that reported in other western countries, although the crude rate was lower than that found in northern countries. We conclude that osteoporotic fractures of the proximal femur are common processes in the Mediterranean area, and reflect the impact of osteoporosis in our environment; however, the lower incidence compared with northern geographical areas may probably reflect the influence of climatic, ethnic, or other factors.

Aged↗
PubMed1986

A BASIC program on heterokaryosis and survival in Phycomyces.

We have written a BASIC program about survival and heterokaryosis in Phycomyces for APPLE II series. Surviving and heterokaryotic unit fraction of spores as a consequence of several lethal effects such as mitotic, dominant and recessive lethals can be computed by the system, and also the uninucleate fraction of spores which were originated by mitotic and recessive lethals. The probability of a mitotic lethal per nucleus can be also computed starting from the only surviving unit fraction of spores. The program can also compute the relationship between the mutation rates due to mitotic and recessive lethals acting together concurrently, introducing surviving and heterokaryotic unit fraction of spores. The program can be easily modified to run on different microcomputers with similar versions of BASIC.

Algorithms↗
PubMed1984

Ultrastructure of a temperature-induced Balbiani ring in Chironomus thummi.

A Balbiani ring-like structure (T-BR III) is induced at the right telomere on chromosome III by a 35 degrees C heat-shock. The location of T-BR III was identified in 3 micron-semithin sections that were afterwards resectioned to obtain ultrathin sections. These were stained either by uranyl acetate-lead citrate or PTA. The puff appeared composed of different structures: small compact chromatin bodies, loose chromatin with an apparently fibrillar organization, and granules. The granules, 200-250 A in diameter, appeared either in linear arrays or in a clustered form. The three components described above were interspersed within the T-BR without a compartmentalized organization. EDTA preferential ribonucleoprotein staining technique evidenced an EDTA-positive material within the T-BR that corresponded to 200-250 A granules as well as apparently fibrillar structures. However, EDTA did not completely stain some clustered granules. Neither free nor clustered granules were found in T-BRs formed in the presence of actinomycin D. The significance of the different T-BR structures in relation to the transcriptional activity of the puff is discussed.

Animals↗
PubMed1982

[Anemia with hypochromia and decreased serum iron in malignant tumours of the small intestine. Two case-reports (author's transl)].

The authors report two cases of malignant tumours of the small intestine (one adenocarcinoma and one lymphoma). In both patients, longstanding anemia with hypochromia and decreased serum iron remained unexplained for some time. Iron was prescribed without definite diagnosis. These two cases demonstrate the extreme latency of these tumours and the necessity for detailed intestinal investigations in patients presenting with isolated hypochromic hyposideremic anemia. Among these investigations, doubla contrast roentgenographic study of the small intestine appears to be an adequate diagnostic procedure for disclosing even very small lesions.

Adenocarcinoma↗
PubMed1981

Modification of transcriptional activity induced by protein synthesis inhibitors in salivary gland cells of Chironomus thummi.

Uridine incorporation in salivary gland cells of Chironomus thummi may be increased by short treatments with cycloheximide, anisomycin or emetine. Accordingly, the rate of UTP incorporation in drug pre-treated permeabilized glands is higher than in control glands. Electrophoretical analyses indicate that when the aforementioned inhibitors are given to whole larvae, the synthesis of glandular giant-heterogeneous RNA and, to a higher extent, that of low molecular weight (4-5S) RNA, are enhanced, while nucleolar 38S pre-rRNA synthesis is generally depressed. On the contrary, when the inhibitors are directly applied to excised glands, the the synthesis of all RNAs, including the pre-ribosomal one, is higher than in control glands. These results suggest that the transcription of various RNA species in polytene cells of C. thummi appears to be specifically regulated by mechanisms in which newly synthesized proteins are involved. In addition, the response of nucleolar genes transcription to treatments with protein synthesis inhibitors seems to be dependent on the environmental conditions of the glands.

Animals↗
PubMed1980

The influence of ascites on the pharmacokinetics of amikacin.

The pharmacokinetics of Amikacin are studied after the administration of 7.5 mg/kg body weight to 10 ascitic patients diagnosed with various hepatic disorders. The antibiotic was determined microbiologically in plasma and in the ascitic fluid. The antibiotic follows a two-compartment kinetic model, and it may be seen that once the rapid disposition phase has ended, an inflexion in the plasma-time levels curve takes place, with a passing increase in the plasma concentrations. From the pharmacokinetic study of Amikacin in these patients, it may be deduced that the ascitic liquid forms part of the central compartment for the effects of distribution, though not for the effects of elimination. The plasma half-life of the slow disposition phase is analogous to that obtained from non-ascitic patients with normal renal function. In one of the patients, the antibiotic was administered intraperitoneally; following this, the plasma concentrations of Amikacin were detected. In the last of the 10 patients included in the survey, the evolution of the plasma concentrations of the antibiotic were studied while the patient was undergoing a multiple dosage regimen with the aim of determining the accumulation of Amikacin in the ascitic fluid. A dosage regimen of multiple doses is programmed which should guarantee the efficiency and safety of the antibiotic.

Amikacin↗
PubMed1980

Naproxen disposition in hepatic and biliary disorders.

The pharmacokinetics of Naproxen have been studied in 11 patients diagnosed with various hepatic and biliary disorders after oral administration of a single dose of 250 mg of the drug. The drug is seen to follow an open two-compartment model. In relation to the values obtained from healthy volunteers, it may be seen that in these patients there are modifications in the absorption, distribution and elimination of the drug. In certain of the patients with cholestasis, a significant delay in absorption may be observed. In most of the patients studied, elimination is clearly diminished due to a decrease in the capacity to biotransform the drug within the organism. In healthy volunteers, the plasma half-life of the beta-phase has an average value of 14.14 hrs while in patients it reaches a value of 20.36 hrs.

Cholestasis↗
PubMed1977

Effect of cycloheximide on RNA synthesis in Chironomus polytene chromosomes.

Modifications in the synthesis of salivary gland RNA were induced by treatments with 10 microgram/ml cycloheximide (CHM) on 4th instar larvae of Chironomus pallidivitattus. After 3, 6 and 24 h CHM treatment, RNA was labeled "in vitro", by incubating the salivary glands in a medium containing H3-uridine. The electrophoretical analyses corresponding to the 3 and 6 h treatment showed a stimulation of the non-ribosomal components of the newly synthesized RNA, while preribosomal RNA synthesis appeared depressed. This fact was also confirmed at cytological level, since autoradiograms made after 3 h of CHM treatment showed a reduced H3-uridine label over the nucleolus and an increase of diffuse labeling over the chromosomes. Longer treatments (24 h) causes a considerable inhibition of the synthesis of all RNA species. The role played by protein synthesis inhibition in the aforementioned effects is discussed.--Some of the morphological implications of CHM treatment, such as modifications of the nucleolar structure (nucleolar segregation) are also reported. The use of a squash technique based on glutaraldehyde fixation of the salivary glands, considerably facilitates such studies.

Animals↗