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Biomedical subjects

A Aguilera

Publications and source records attributed to A Aguilera.

At least 91 records · Page 5Linked to original sources
PubMed1996

Epidemiology of human T-lymphotropic virus type II (HTLV-II) infection in Spain. HTLV Spanish Study Group.

The human T-lymphotropic virus type II (HTLV-II) has recently been associated with the genesis of some subacute neurological syndromes and, rarely, with atypical T-lymphoid malignancies. The virus is endemic in some Amerindian and African tribes, and among intravenous drug users (IDUs) in North America and Europe. Given that HTLV-II is transmitted by the same routes as other human retroviruses, the screening of antibodies to HTLV-II in blood donors has became a matter of controversy in some countries. Herein, we describe the clinical, epidemiological and virological features of 113 individuals with HTLV-II infection identified in Spain up to September 1995. Most of them (94/113; 83%) were male, and all but seven were natives. Four were African immigrants living in Madrid and 3 had been born in other European countries. All but six subjects were IDUs, and sexual transmission of HTLV-II and transfusion were involved in five and one individual, respectively. Eighty-four percent of the IDUs infected with HTLV-II were co-infected by HIV-I (93/107). Clinical manifestations potentially linked to HTLV-II were absent, although an IDU male co-infected by HIV-1 and HTLV-II developed a severe non-inflammatory proximal myopathy. In conclusion, HTLV-II infection is present in Spain, mainly among IDUs, with a growing incidence and a current overall prevalence of 2.0 percent.

Adult↗
PubMed1996

Epidemiology of HIV-2 infection in Spain. The HIV-2 Spanish Study Group.

Human immunodeficiency virus type 2 (HIV-2) infection is endemic in West Africa, where it is responsible for many cases of AIDS. HIV-2-infected subjects have been described in other countries, mainly African immigrants, although infection in native individuals has been reported as well. The first cases of HIV-2 infection in Spain were identified in 1988. Through December 1995, 56 HIV-2 infected individuals have been diagnosed, primarily in large urban areas (23 cases in Madrid and 18 in Barcelona). All are African immigrants, except for 12 natives (21.4%), six of whom acquired the infection in endemic areas; the remaining six (2 women with numerous sexual partners and 4 homo/bisexual men) acquired the infection in Spain. Heterosexual transmission was probable in all but seven cases: five homo/bisexual males, a subject who likely acquired infection through parenteral exposure, and a child born to an HIV-2-infected mother. Nine patients (all Spanish born) have developed AIDS (16%), six of whom have died. In conclusion, HIV-2 infection is present in Spain at a low rate, and there is little evidence supporting an emerging ongoing transmission outside the population of African immigrants.

AIDS Serodiagnosis↗
PubMed1996

The yeast HRS1 gene encodes a polyglutamine-rich nuclear protein required for spontaneous and hpr1-induced deletions between direct repeats.

The hrs1-1 mutation was isolated as an extragenic suppressor of the hyperrecombination phenotype of hpr1 delta cells. We have cloned, sequenced and deleted from the genome the HRS1 gene. The DNA sequence of the HRS1 gene reveals that it is identical to PGD1, a gene with no reported function, and that the Hrs1p protein contains polyglutamine stretches typically found in transcription factors. We have purified a His(6) tagged version of Hrs1p protein from E. coli and have obtained specific anti-Hrs1p polyclonal antibodies. We show that Hrs1p is a 49-kD nuclear protein, as determined by indirect immunofluorescence microscopy and Western blot analysis. The hrs1 delta null mutation reduces the frequency of deletions in wild-type and hpr1 delta backgrounds sevenfold below wild-type and rad52 levels. Furthermore, hrs1 delta cells show reduced induction of the GAL1,10 promoter relative to wild-type cells. Our results suggest that Hrs1p is required for the formation of deletions between direct repeats and that it may function in gene expression. This suggests a connection between gene expression and direct repeat recombination. In this context, we discuss the possible roles of Hrs1p and Hpr1p in initiation of direct-repeat recombination.

Amino Acid Sequence↗
PubMed1996

Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair.

We have obtained genetic and molecular evidence that the hrs2-1 mutation, isolated as a suppressor of the hyperrecombination phenotype of hpr1 delta, is in the SRB2 gene, which encodes a component of the RNA polII holoenzyme. A newly constructed srb2 delta allele restores the wild-type levels of deletions in hpr1 delta cells, indicating that the lack of a functional SRB2 transcription factor suppresses recombination between direct repeats. These results suggest a direct connection between transcription and recombination between DNA repeats. On the other hand, the hrs2-1 mutation (renamed srb2-101), in which Gly150 has been changed to Asp, makes cells sensitive to long MMS treatments, a phenotype observed for the srb2 delta null allele only in a hpr1 delta background. This indicates that mutations in the basal transcription factor SRB2 impair DNA repair of MMS-induced damage, which adds a new connection between transcription and DNA repair. We discuss the possibility that hpr1-induced deletions occurred as a consequence of a SRB2-dependent stalled or blocked transcription complex.

Alleles↗
PubMed1996

Epidemiology of HTLV-I infection in Spain. HTLV Spanish Study Group.

BACKGROUND: The human T-lymphotropic virus type I (HTLV-I) has been implicated in the genesis of tropical spastic paraparesis (TSP), adult T-cell lymphoma (ATL), and some cases of uveitis, subacute arthropathies, chronic dermatitis and lymphocytic alveolitis. The virus is endemic in some areas of the Caribbean basin, Japan, subSaharan Africa, Central and South America, Middle East and Melanesia. Given that HTLV-I is transmitted through similar ways to HIV, screening in blood donors is recommended in some countries. MATERIALS AND METHODS: The clinical, epidemiological and virological characteristics of 27 patients with HTLV-I infection were identified in Spain up to September 1995. RESULTS: Eighteen cases were Spanish natives and 9 were immigrants from endemic areas. Fifteen were male and 12 were female. The majority (12/18; 66.7 percent) of subjects born in Spain had resided in endemic areas or had had sexual partners from these regions. Four patients had TSP, three had ATL and one developed lymphomatous granulomatosis and T-cell lymphoma. The remaining HTLV-I subjects were asymptomatic at the time of diagnosis. Four cases were identified from screening of blood donors. CONCLUSION: HTLV-I is present in Spain, affecting natives and, less frequently, immigrants from endemic areas. Both neurological and lymphoproliferative diseases have been recognized in a quarter of patients.

Adolescent↗
PubMed1996

Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study.

According to this facility's protocol for the treatment of anemia in hemodialyzed patients, androgens were administered to male patients aged over 50 yr and recombinant human erythropoietin was administered to male patients below 50 yr of age and to female patients. In the study presented here, both therapeutic approaches have been prospectively analyzed. Patients were divided into two groups. Group A was composed of 18 patients, aged 62 +/- 12 yr, treated with nandrolone decanoate (200 mg/wk im) for 6 months; Group B was composed of 22 patients (6 men, 16 women) aged 47 +/- 15 yr, treated with subcutaneous recombinant human erythropoietin (initial dose, 6000 IU/wk) for 6 months. The increases of hemoglobin were similar in both groups; Group A, from 7.3 +/- 0.8 to 10.8 +/- 1.7 g/dL (P < 0.001), and Group B, from 7 +/- 0.6 to 10.4 +/- 1 g/dL (P < 0.001). In Group A, increases of triglycerides (159 +/- 71 versus 267 +/- 153 mg/dL, P < 0.001), serum albumin (3.9 +/- 0.3 versus 4.2 +/- 0.3 g/dL, P < 0.05), and dry weight (62.1 +/- 9.8 versus 64.9 +/- 10.1 kg, P < 0.001) were observed, which remained unmodified in Group B. Blood pressure control worsened in one patient (6%) from Group A, and in ten patients (45%) from Group B (P < 0.05). In conclusion, androgens produced an improvement in anemia in selected patients, similar to that achieved by use of recombinant human erythropoietin but at a lower cost. Androgens also have an appreciable anabolic effect and did not increase the blood pressure.

Aged↗
PubMed1996

Effects of androgen therapy on prostatic markers in hemodialyzed patients.

We have prospectively studied the evolution of serum levels of the prostatic-specific antigen and prostatic acid phosphatase in 14 male hemodialyzed patients, receiving a cycle of nandrolone decanoate (200 mg intramuscularly, once a week, for six months) as treatment for anemia. Androgen administration did not produce significant increases in serum concentrations of both tumor markers (basal: 0.9 +/- 0.5 and 0.7 +/- 0.3 ng/ml; at six months: 1.3 +/- 1.1 and 0.8 +/- 0.7 ng/ml respectively). Only one patient had a value of prostatic-specific antigen over the normal range: 4.2 ng/mol at the sixth month period, with a rapid decrease after the withdrawal of androgens. All the remaining values of both markers were within the normal range. In another six patients undergoing a prolonged treatment with androgens (between 9 to 24 months), the serum levels of prostatic-specific antigen and prostatic acid phosphatase were within the normal range in all of them. Nandrolone decanoate administration does not induce increases in prostate tumor markers when it is used as treatment for anemia in hemodialyzed patients.

Acid Phosphatase↗
PubMed1996

Androgen therapy for anaemia of chronic renal failure. Indications in the erythropoietin era.

The high cost of recombinant human erythropoietin has led us to consider the existing indications for androgen treatment of anaemia in patients with chronic renal failure. In the present work, we have tried to identify those patients on haemodialysis for whom androgens could constitute a therapeutic alternative. The evolution of haemoglobin concentration was analysed in 84 patients (67 males and 17 females) treated with a cycle of nandrolone decanoate (200 mg per week given intramuscularly, for six months). In the total group of patients, haemoglobin rose from 69 g/L to 87 g/L (p < 0.01). The increment in haemoglobin was not related to sex, basal haemoglobin, primary renal disease, or dose of nandrolone decanoate corrected by body weight. However, we observed a relationship between this increment in haemoglobin and patient age. Haemoglobin increased by 8 g/L in patients younger than 46 years (n = 29), by 18 g/L in patients aged between 46 and 55 years (n = 28), and by 27 g/L in patients older than 55 years (n = 27) (p < 0.01 between groups). In the last group, haemoglobin concentration at the end of androgen treatment was 101 +/- 16 g/L. The haemoglobin level reached during androgen treatment was maintained for over a year after androgen withdrawal in 55% of the responder patients. A reversible rise in the serum concentration of triglycerides was the main side-effect observed. Nandrolone decanoate therapy was not associated with hepatotoxicity or an increase in blood pressure. Voice change and mild hirsutism were observed in most of the women receiving nandrolone decanoate, and these secondary effects constitute a real disadvantage to its use in females. In conclusion, our results showed that androgens are a useful alternative in the treatment of anaemia in male haemodialysis patients older than 55 years. Furthermore, the response obtained was similar to that observed with erythropoietin, but at a lower cost.

Adolescent↗
PubMed1995

[Type 2 human immunodeficiency virus infection (HIV-2) in Spain: analysis of the first 50 cases. Spanish Group for the Study of HIV-2].

BACKGROUND: Infection by the human immunodeficiency virus type 2 (HIV-2) is endemic in West Africa where it is responsible for many AIDS cases. HIV-2 has been described in subjects in other countries, mainly in African immigrants, although it may also be found in natives. The first cases of HIV-2 infection were identified in Spain in 1988. METHODS: The clinical, epidemiologic and virologic characteristics of the subjects with HIV-2 infection identified in Spain up to November 1994 are described. RESULTS: Fifty people have been diagnosed with HIV-2 infection, being found mainly around the large urban centers (20 cases in Madrid and 16 in Barcelona). All the cases were African immigrants except for 10 Spaniards (20%), 6 of whom had acquired the infection in endemic areas while the other 4 (one prostitute from Barcelona and 3 bisexual males from Guipúzcoa) had acquired the infection in Spain. Heterosexual transmission was implicated in all the cases except in 6 subjects (4 bisexual males, one case of probable intravenous transmission and one vertically infected child). Eight (all Spanish) patients have developed AIDS and 5 have died to date. At least 10 other subjects have a CD4+ lymphocyte count lower than 0.2 x 10(9)/l, one being the only pediatric patient (6-year-old male). CONCLUSIONS: HIV-2 infection is present in Spain, although there is no evidence for a rapid dissemination of the virus outside the collective of African immigrants. The Spaniards with HIV-2 infection represent 20% of the cases having contracted the virus through sexual relations with natives from endemic areas.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[HTLV-I infection in Spain. Analysis of 24 cases identified until November, 1994. Spanish Group for the Study of HTLV-I/II)].

BACKGROUND: HTLV-I is a human retrovirus which has been implicated in the genesis of tropical spastic paraparesia (TSP), adult T-cell leukemia (ATL) and some patients with uveitis, subacute arthropathies and lymphocytary alveolitis. The virus is endemic in some zones of the Caribbean countries, Japan, subsaharian Africa, Middle East and Melanesia. Given that HTLV-I is transmitted by similar routes as HIV, anti-HTLV-I antibody screening is carried out in blood donors in some countries. METHODS: The clinical, epidemiologic and virologic characteristics of the patients with HTLV-I infection identified in Spain up to November 1994 are described. RESULTS: Twenty-four Spanish residents have been identified with HTLV-I infection including 16 Spaniards and 8 immigrants from endemic areas. Thirteen (53%) are males and 11 (47%) females. Most of the persons born in Spain (12/16; 75%) have lived in endemic areas or have maintained sexual relations with natives of them. Four patients were diagnosed with TSP, three with ATL and another with lymphomatoid granulomatosis and angiocentric T-cell lymphoma. The remaining patients were asymptomatic at the time of diagnosis. Two HTLV-I carriers were identified on blood donation. CONCLUSIONS: HTLV-I infection is present in Spain being found in Spanish natives and, to a lesser degree, in immigrants from endemic areas. It is therefore recommendable to analyze the cost-benefit of anti-HTLV-I screening in blood donors.

Adult↗
PubMed1995

Genetic evidence for different RAD52-dependent intrachromosomal recombination pathways in Saccharomyces cerevisiae.

Mutations in the RecA-like genes RAD51 and RAD57 reduce the frequency of gene conversion/reciprocal exchange between inverted repeats 7-fold. However, they enhance the frequency of deletions between direct repeats 5-12-fold. These induced deletions are RAD1- and RAD52-dependent. On the basis of these results it is proposed that there are several RAD52-dependent pathways of recombination: the recombinational repair pathway of gene conversion/reciprocal exchange dependent on RAD51 and RAD57; a RAD1- and RAD52-dependent pathway exclusively responsible for deletions that are induced in rad51 and rad57 mutants; and finally, it is possible that the gene conversion/reciprocal exchange events observed in rad51 and rad57 strains represent another RAD52-dependent recombination pathway of gene conversion/reciprocal exchange that does not require Rad51 and Rad57 functions. It is also shown that the RAD10 excision-repair gene is involved in long gene conversion tracts in homologous recombination between inverted repeats, as previously observed for RAD1. Finally, an analysis of meiotic recombination reveals that deletions are induced in meiosis 100-fold above mitotic levels, similar to intrachromosomal gene conversion/reciprocal exchange, and that, in contrast to intrachromosomal meiotic gene conversion (50% association), intrachromosomal meiotic gene conversion is not preferentially associated with reciprocal exchange (12-30% of association).

Adenosine Triphosphatases↗
PubMed1995

Precision and accuracy of in vivo bone mineral measurement in rats using dual-energy X-ray absorptiometry.

The aim of this study was to evaluate the precision and accuracy of dual-energy X-ray absorptiometry (DXA) for measuring bone mineral content at different sites of the skeleton in rats. In vitro the reproducibility error was very small (< 1%), but in vivo the intra-observer variability ranged from 0.9% to 6.0%. Several factors have been shown to affect in vivo reproducibility: the reproducibility was better when the results were expressed as bone mineral density (BMD) rather than bone mineral content (BMC), intra-observer variability was better than the inter-observer variability, and a higher error was observed for the tibia compared with that for vertebrae and femur. The accuracy of measurement at the femur and tibia was assessed by comparing the values with ash weight and with biochemically determined calcium content. The correlation coefficients (R) between the in vitro BMC and the dry weight or the calcium content were higher than 0.99 for both the femur and the tibia. SEE ranged between 0.0 g (ash weight) and 2.0 mg (Ca content). Using in vitro BMC, ash weight could be estimated with an accuracy error close to 0 and calcium content with an error ranging between 0.82% and 6.80%. The R values obtained between the in vivo and in vitro BMC were 0.98 and 0.97 respectively for femur and tibia, with SEE of 0.04 and 0.02 g respectively. In conclusion, the in vivo precision of the technique was found to be too low. To be of practical use it is important in the design of experimentation to try to reduce the measurement error.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes.

We have constructed novel DNA substrates (one inverted and three direct repeats) based on the same 0.6-kb repeat sequence to study deletions and inversions in Saccharomyces cerevisiae. Spontaneous deletions occur six to eight times more frequently than inversions, irrespective of the distance between the repeats. This difference can be explained by the observation that deletion events can be mediated by a recombination mechanism that can initiate within the intervening sequence of the repeats. Spontaneous and double-strand break (DSB)-induced deletions occur as RAD52-dependent and RAD52-independent events. Those deletion events initiated through a DSB in the unique intervening sequence require the Rad1/Rad10 endonuclease only if the break is distantly located from the flanking DNA repeats. We propose that deletions can occur as three types of recombination events: the conservative RAD52-dependent reciprocal exchange and the nonconservative events, one-ended invasion crossover, and single-strand annealing (SSA). We suggest that one-ended invasion is RAD52 dependent, whereas SSA is RAD52 independent. Whereas deletions, like inversions, occur through reciprocal exchange, deletions can also occur through SSA or one-ended invasion. We propose that the contribution of reciprocal exchange and one-ended invasion crossover vs. SSA events to overall spontaneous deletions is a feature specific for each repeat system, determined by the initiation event and the availability of the Rad52 protein. We discuss the role of the Rad1/Rad10 endonuclease on the initial steps of one-ended invasion crossover and SSA as a function of the location of the initiation event relative to the repeats. We also show that the frequency of recombination between repeats is the same independent of their location (whether on circular plasmids, linear minichromosomes, or natural chromosomes) and have similar RAD52 dependence.

Chromosome Inversion↗
PubMed1995

Isolation and genetic analysis of extragenic suppressors of the hyper-deletion phenotype of the Saccharomyces cerevisiae hpr1 delta mutation.

The HPR1 gene of Saccharomyces cerevisiae is involved in maintaining low levels of deletions between DNA repeats. To understand how deletions initiate in the absence of the Hpr1 protein and the mechanisms of recombination leading to deletions in S. cerevisiae, we have isolated mutations as suppressors of the hyper-deletion phenotype of the hpr1 delta mutation. The mutations defined five different genes called HRS for hyper-recombination suppression. They suppress the hyper-deletion phenotype of hpr1 delta strains for three direct repeat systems tested. The mutations eliminated the hyper-deletion phenotype of hpr1 delta strains either completely (hrs1-1 and hrs2-1) or significantly (hrs3-1, hrs4-1 and hrs5-1). None of the mutations has a clear effect on the levels of spontaneous and double-strand break-induced deletions. Among other characteristics we have found are the following: (1) one mutation, hrs1-1, reduces the frequency of deletions in rad52-1 strains 20-fold, suggesting that the HRS1 gene is involved in the formation of RAD52-independent deletions; (2) the hrs2-1 hpr1 delta mutant is sensitive to methyl-methane-sulfonate and the single mutants hpr1 delta and hrs2-1 are resistant, which suggests that the HPR1 and HRS2 proteins may have redundant DNA repair functions; (3) the hrs4-1 mutation confers a hyper-mutator phenotype and (4) the phenotype of lack of activation of gene expression observed in hpr1 delta strains is only partially suppressed by the hrs2-1 mutation, which suggests that the possible functions of the Hpr1 protein in gene expression and recombination repair can be separated. We discuss the possible relationship between the HPR1 and the HRS genes and their involvement in initiation of the events responsible for deletion formation.

Chromosomes, Fungal↗
PubMed1995

Interference between Neisseria meningitidis and PC-KLH induced anti-phosphorylcholine PFC responses in NZB/W autoimmune mice.

In this work, we demonstrate that the simultaneous injection of PC-KLH and Neisseria meningitidis-derived antigens [NMB or PC-(NMB)HI] induced in old NZB/W mice defective responses as does PC-KLH challenge. On the other hand, the simultaneous injection of both immunogenic preparations of N. meningitidis evoked responses similar to those shown by old mice challenged with NMB alone. Alteration in PC-specific PFC responses also affected hapten-free inhibition profiles and their heterogeneities. The increase in PC50s of anti-phosphorylcholine PFC responses and their heterogeneities induced by certain antigens with aging is correlated with a decrease in T15 idiotype expression, suggesting that after the T15 dominant clone disappears no other clone takes control of the anti-PC response. These results suggest that the mechanism(s) involved in the regulation of T15 marker expression play an important role in the inability of old NZB/W mice to mount good anti-PC responses and suggest that regulatory mechanisms induced by PC-KLH dominate those elicited by NMB.

Aging↗