[Hemoglobinopathies in Spanish and emigrant population].
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Emigration and Immigration↗
Biomedical subjects
A Villegas
Publications and source records attributed to A Villegas.
[New therapeutic perspectives in iron overload].
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Clinical Trials as Topic↗
Response of the haematocrit to body condition changes in Northern Bald Ibis Geronticus eremita.
We study the usefulness of the haematocrit as a predictor of body condition in birds, using a captive population of the endangered species Northern Bald Ibis (Geronticus eremita). This population is 14% of the worldwide captive population, which is far greater than the known free-living population. The haematocrit, body mass and body condition index responded in the same sense to two different nutritional periods, and there was a statistically significant relationship between changes in condition index and haematocrit of individual birds between the two periods. We discuss the relationship of these parameters with subcutaneous fat and muscle mass, and analyse the individuals' nutritional status in each of the periods studied. The conclusion was that the haematocrit is sensitive to variations in body condition since it responds to mass-loss processes corresponding to phases of mobilization of fat reserves, a situation prior to the mobilization of muscle proteins when there is a manifest deterioration of the individual's aspect.
Adipose Tissue↗
Two new mutations in cis on (G)gamma chain of fetal hemoglobin: Hb F-Madrid [G gamma 50(D1)Ser-->Cys] and [G gamma 75(E19)Ile-->Thr].
We describe a new structural hemoglobin variant of (G)gamma with two amino acid replacements in cis found in the umbilical cord blood of a neonate in Madrid, Spain. The substitutions were identified on exon 2 of the (G)gamma globin gene, at codon 50 (T CT-->T GT) and at codon 75 (A TA-->A CA). We have named it Hb F-Madrid. The father of the propositus was the carrier of the same (G)gamma chain variant and, moreover, molecular study of alpha genes revealed the loss of an alpha gene (-alpha(3.7)/alpha alpha) both in the propositus and his mother.
Base Sequence↗
[HFE gene mutations, hepatic iron content, and histological severity in hepatitis C virus-induced chronic hepatitis].
OBJECTIVE: To study whether any relationship exists between the C282Y and H63D mutations of the HFE gene, iron liver content, and the severity of histological damage in patients with hepatitis C virus (HCV)-induced chronic hepatitis. MATERIAL AND METHODS: In 72 patients diagnosed with HCV-chronic infection, naïve for antiviral therapy, and undergoing liver biopsy, the Knodell index was established, a morphometric evaluation of hepatic hemosiderin deposits was performed by using a semiautomatic method of image analysis, and mutations of the HFE gene were identified through a polymerase chain reaction on leukocyte genomic DNA by using specific restriction enzymes. The control group for the distribution of HFE genetic variants was composed of 181 healthy individuals with the same ethnic and geographical (white Spaniards) origin. RESULTS: (Cases/controls): 1. Genotype distribution: a) mutation C282Y: no homozygotes, 6/23 heterozygotes, 66/158 without the mutation (not significant, n.s.); b) mutation H63D: 2/5 homozygotes, 26/52 heterozygotes, 44/124 without the mutation (n.s.). compound heterozygotes 2/6. 2. Allele frequencies: a) mutation C282Y: 0.042/0.064 (n.s.); b) mutation H63D: 0.208/0.171 (n.s.). Four C282Y heterozygous patients had stainable liver iron (p=0.015 vs patients without mutations). Sixty-six patients were not carriers of the C282Y mutation; among them, 26.9% of 26 carriers and 15% of 40 non-carriers of the H63D mutation had liver stainable iron (n.s.). Knodell index score, gender, age at diagnosis, mode of transmission, and serum and liver iron values were not related to the HFE genotype. CONCLUSIONS: our results suggest that the C282Y mutation, but not the H63D mutation, of the HFE gene is frequently associated with stainable iron in the liver in HCV-related chronic hepatitis. The HFE genotype is not related to the histological severity of the disease.
Adult↗
C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the notch3 epidermal growth factor-like repeats. A Colombian kindred carries a novel C455R mutation located in the predicted ligand-binding domain. Stroke occurred in the patients at an unusually early age (median age: 31 years) in comparison to the more frequent onset in the fourth decade of life in other CADASIL populations, including a second Colombian kindred with an R1031C mutation.
Adult↗
Characterization of a new hemoglobin variant: Hb Badalona (beta31[B13]Leu-->Val).
Hemoglobin (Hb) Badalona was identified in a 35-year-old Spanish female and two other family members. All affected subjects presented erythrocytosis and increased oxygen affinity (P(50): 21 mmHg). Hemoglobinopathy was not detected with electrophoretic methods. It was, however, separated and quantified by cation exchange and reverse-phase high-performance liquid chromatography. Hb Badalona accounted for 35% of the total Hb. No significant clinical symptoms were found to be related to this hemoglobinopathy. This is the first case of a Leu-->Val replacement at position beta31(B13) reported in the world literature.
Adolescent↗
Blood chemistry and haematocrit of the black vulture (Aegypius monachus).
We determined the values of haematocrit and blood chemistry of the black vulture (Aegypius monachus) in Extremadura (Spain). We analysed 57 nestlings, five feral adults, seven captive individuals in their first year and five captive adults. Free-living adults had a higher haematocrit and lower calcium and alkaline phosphatases concentrations than captive birds. There were differences in haematocrit and in the concentrations of glucose, uric acid, total proteins, alkaline phosphatases, phosphorus and aspartate aminotransferase between nestlings and young in their first year and adults. The estimated age of the nestlings was significantly correlated with haematocrit, plasma glucose and total protein concentrations. The physical condition of nestlings was significantly correlated with plasma alkaline phosphatases levels.
Aging↗
Disease activity during the premenopausal and postmenopausal periods in women with systemic lupus erythematosus.
PURPOSE: Cyclophosphamide-induced ovarian failure has been reported to be protective against flares of systemic lupus erythematosus (SLE). We studied whether patients with SLE experience a decrease in disease activity after natural menopause. SUBJECTS AND METHODS: We studied 30 SLE patients with natural menopause who had been observed at least 2 years before and after menopause and who did not receive hormone replacement therapy or danazol. Menopause was defined as the date of the last self-reported menstrual period. Disease activity was assessed retrospectively by medical chart review using standard measures (the SLE disease activity index) during the immediate premenopausal and postmenopausal periods, and 2 (n = 30 patients), 3 (n = 19), and 4 (n = 13) years before and after menopause. We also compared the use of health services and medications. RESULTS: Patients were studied for a mean (+/- SD) of 6.4 +/- 1.7 years (premenopausal, 3.3 +/- 0.9 years; postmenopausal, 3.2 +/- 0.9 years). During the premenopausal periods, the mean disease activity score was 2.3 +/- 2.3 (range, 0 to 9 on a 0 to 105 scale), compared with 2.3 +/- 2.9 (range, 0 to 12; P = 0.37) after menopause. The maximum disease activity score was somewhat greater in the premenopausal period (7.9 +/- 6.0 [range, 0 to 22] vs. 5.8 +/- 5.1 [range, 0 to 22]; P = 0.04). The incidence rates of flares (0.56 per year vs. 0.43 per year, P = 0.20) and severe flares (0.17 per year vs. 0.12 per year, P = 0.33) were similar in the premenopausal and postmenopausal periods. Differences in disease activity scores (mean and maximum) and the number of visits to a rheumatologist's office were only significant when the fourth year before menopause was compared with the fourth year after menopause. CONCLUSIONS: Disease activity is mild during the premenopausal and postmenopausal periods in women with SLE. A modest decrease, especially in the maximum disease activity, is seen after natural menopause.
Anti-Inflammatory Agents↗
Deletion of BCR region 3' in chronic myelogenous leukemia.
The t(9;22)(q34;q11) produces the BCR/ABL fusion gene which codifies a 210 kb protein with a strong tyrosine kinase activity and is involved in cellular development and growth. Because this translocation is a reciprocal event, it could give rise to a second fusion gene, ABL-BCR, on the derivative 9q+. We analyzed the influence of the 3' M-BCR deletion on the clinical picture at diagnosis and disease outcome in 57 patients with a clinical diagnosis of CML. Molecular studies were done on DNA from peripheral blood leukocytes or bone marrow with the restrictions enzymes BglII, EcoRI, HindIII, and BamHI, and the BCR 3' probe (transprobe 1) (Oncogene Science Inc.), which encompasses almost all of the 5.8 Kb of the M-BCR gene area. In 18 patients Southern blot analysis showed deletion of the 3' end of BCR gene (32.7%). There were no significant differences between patients with or without deletion, either in the clinical and laboratory data at the disease diagnosis or at the disease outcome. The absence of differences between the patients with and without 3' BCR deletion supports the hypothesis that the hybrid gene ABL-BCR does not have an important role in leukemogenesis in CML cases.
Fusion Proteins, bcr-abl↗
Intragraft cytokine expression in heart transplants with mild or no histological rejection.
UNLABELLED: The study of pro-inflammatory cytokines produced in situ in heart allografts may help to understand the mechanisms of rejection and open new possibilities to control graft rejection. METHODS: A total of 23 endomyocardial biopsies obtained from 16 transplanted patients treated with triple-drug therapy (azathioprine, prednisone, and cyclosporine) were studied. mRNA expression for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-10, IL-12, IL-15, transforming growth factor (TGF)-beta, and beta-actin was determined by reverse transcription polymerase chain reaction (RT-PCR) and Southern blotting. Semiquantitative analysis was done by establishing the ratio between densitometric integrated value of each cytokine with the beta-actin and correlated with the histopathologic findings. RESULTS: Three groups of biopsies were determined according to the International Society for Heart and Lung Transplantation criteria: grade 0 (control group, n=12), grade 1A (sub-clinical rejection, n=6) and 'quilty effect' (n=5). An increased expression of mRNA for TNF-alpha and IL-6 (p=0.0091 and 0.0075, respectively) was found associated with rejection grade 1A episodes, mRNA for IL-1 beta was nonspecifically expressed in all the study groups, while IL-10 mRNA was not detected in any of the biopsies studied. mRNA for IL-12 and IL-15 was not associated with rejection. Interestingly, TGF-beta was not detected in any of the biopsies with the 'quilty pattern'. CONCLUSION: The association of TNF-alpha and IL-6 mRNA in situ expression with mild histologically probed rejection episodes may be used in the monitoring of heart transplants.
Adult↗
Monosomy for the most telomeric, gene-rich region of the short arm of human chromosome 16 causes minimal phenotypic effects.
We have examined the phenotypic effects of 21 independent deletions from the fully sequenced and annotated 356 kb telomeric region of the short arm of chromosome 16 (16p13.3). Fifteen genes contained within this region have been highly conserved throughout evolution and encode proteins involved in important housekeeping functions, synthesis of haemoglobin, signalling pathways and critical developmental pathways. Although a priori many of these genes would be considered candidates for critical haploinsufficient genes, none of the deletions within the 356 kb interval cause any discernible phenotype other than alpha thalassaemia whether inherited via the maternal or paternal line. These findings contrast with previous observations on patients with larger (> 1 Mb) deletions from the 16p telomere and therefore address the mechanisms by which monosomy gives rise to human genetic disease.
Adolescent↗
Pretreatment characteristics and clinical outcome of acute promyelocytic leukaemia patients according to the PML-RAR alpha isoforms: a study of the PETHEMA group.
Of 167 newly diagnosed acute promyelocytic leukaemia patients, 83 patients were long (L)-form (50%), eight variable (V)-form (5%) and 76 short (S)-form (45%). The V-form and S-form groups presented a significantly higher percentage of patients with white blood cell counts > 10 x 10(9)/l (P < 0.05). The S-form cases displayed a significantly higher number of cases with M3v microgranular features (P = 0.005) and CD34 expression (P < 0.0001). There were no differences between the three isoforms in complete remission (CR) rate (overall CR 90%), but the 3-year disease-free survival was lower for V-form cases than it was for L- and S-form cases (62% vs. 94% and 89%, P = 0.056). We conclude that the V-form and S-form types are associated with some negative prognostic features at diagnosis. However, our data were only able to demonstrate an association with adverse prognosis in the V-form type and, moreover, as the number of cases was limited, needs to be confirmed in large, uniformly treated series.
Adolescent↗
The thalassemia syndromes: molecular characterization in the Spanish population.
This work compiles the results of our research on alpha- and beta-thalassemias, and includes a literature review of the molecular genetics of alpha- and beta-thalassemias in Spain. We studied 1,564 subjects with thalassemia (294 with beta-thalassemia and 1,264 with alpha-thalassemia) by molecular biology techniques. In relation to beta-thalassemia, a total of 15 different mutations were characterized in a study of 308 chromosomes belonging to 294 unrelated subjects. Eleven were homozygotes (22 alleles), three compound heterozygotes (6 alleles), and the remaining 280 were heterozygotes (280 alleles). A total of 86.6% of the alleles identified can be grouped into five different mutations [IVS-I-1 (G-->A), IVS-I-6 (T-->C), IVS-I-110 (G-->A), codon 39 (C-->T), codons 8/9 (+G)]. In 14 subjects (4.5%), all heterozygotes, it was not possible to identify the alteration responsible for the beta-thalassemia. For alpha-thalassemia, 911 subjects showed heterozygous alpha(+)-thalassemia (872 with -3.7 kb; 14 with -4.2 kb; two with the deletion of 3.5 kb of DNA, and 23 with nondeletional alpha-thalassemia). Two hundred and thirty-three subjects had homozygous alpha(+)-thalassemia (223 for -alpha(-3.7)/-alpha(-3.7)); one for -alpha(-4.2)/-alpha(-4.2); six for -alpha(-3.7)/-alpha(-4.2); one for -alpha(-3.5)/-alpha(-3.7); one for alphaalpha(Nco)/alphaalpha(Nco); one for alpha(HPh)/alpha(Hph)). One hundred patients presented with heterozygous alpha(0)-thalassemia (18 of whom were progenitors of patients with Hb H disease). The alpha(0) determinant was found in 20 patients with Hb H disease associated with -alpha(-3.7). From the DNA analysis were identified the - -(MED), - -(SEA), - -(SPAN) deletions and the - -(MA) mutations; in three cases, a break that affects the distal portion of the short arm of chromosome 16; one of these was associated with the ATR-16 (alpha-thal with mental retardation) syndrome. Triplication of the alpha genes (alphaalphaalpha(-3.7)/alphaalpha) was found in 25 subjects, 16 of whom were associated with a heterozygous beta-thalassemia. Only one patient was homozygous for the triplication of alpha genes (alphaalphaalpha(-3.7)/alphaalphaalpha(-3.7)) that was associated with a heterozygous beta-thalassemia. In the Mediterranean region preventive programs for thalassemia, based on the detection of heterozygote carriers and genetic advice, are not sufficient to reduce the incidence of newborns with major thalassemia. Prenatal diagnosis of thalassemias has given a new dimension to the prevention of these, but in order to implement this, a knowledge of the mutations and the incidence of these, is essential. This study, therefore, aims to give a general picture of the molecular genetics of thalassemia and its geographical distribution in our area.
Alleles↗
A novel splice acceptor site mutation of the alpha2-globin gene causing alpha-thalassemia.
A novel nondeletional alpha-thalassemia mutation that affects RNA processing, changing the alpha2 IVS-II-142 splice acceptor consensus sequence from AG to AA, has been detected in an Argentinian patient with Hb H disease and her daughter.
Adult↗
Variability in the levels of PML-RAR alpha fusion transcripts detected by the laboratories participating in an external quality control program using several reverse transcription polymerase chain reaction protocols.
BACKGROUND AND OBJECTIVES: The detection of PML-RAR by reverse transcription (RT) polymerase chain reaction (PCR) in acute promyelocytic leukemia (APL) patients who are in hematologic remission influences therapeutic decision making in several trials. In the light of this, the Spanish group has recently designed an external quality assessment program (EQAP) of RT-PCR detection of PML-RAR, which includes a study of sensitivity of the participating laboratories. DESIGN AND METHODS: Eighteen laboratories were involved in the program. Ten laboratories followed the method of Biondi et al., 5 employed that of Borrow et al. and the 3 remaining used other protocols. The sensitivity was studied in five rounds of quality control. The first two shipments consisted of dilutions of NB4 RNA into non-APL RNA. The third round consisted of serial dilutions of the NB4 cell line into HL60 cells. The fourth and five rounds consisted of plasmid dilutions containing the bcr1 and bcr3 PML-RAR isoforms. RESULTS: The results showed that the distinct methods allow detection of the PML-RAR hybrid up to a dilution of 10(-4), and exceptionally, up to 10(-5). The laboratories following the method of Biondi et al. usually detected the 10(-3) dilution and less frequently the 10(-4) one, whereas those using other methods usually detected PML-RAR transcript in the 10(-4) dilution, and less commonly in the 10(-5) dilution. However, each of the PCR methods used by EQAP participating laboratories successfully detected at least 50 copies of PML-RAR alpha fusion transcript in plasmid dilution controls. INTERPRETATION AND CONCLUSIONS: The results point to heterogeneous sensitivity amongst participating laboratories. This may reflect differences in methodology, although variations in sample quality may also account for discrepant findings.
Humans↗
Association of t(9;11)-MLL AF9 and trisomy 8 in an AML-M5 preceded by pancytopenia.
The implication of MLL gene rearrangements in the prognosis of acute myeloblastic leukemia is an issue of considerable current interest. We report a case of a young man who initially presented with a pancytopenia and went on to develop a highly-aggressive acute myeloblastic leukemia. At this time, the karyotypic study revealed trisomy 8, a t(9;11) was demonstrated by fluorescence in situ hybridization (FISH) and the MLL/AF4 rearrangement by reverse transcriptase-polymerase chain reaction (RT-PCR).
Adult↗
Hb Johnstown [beta 109 (G11) Val-->Leu]: second case described and associated for the first time with beta(0)-thalassemia in two Spanish families.
Hb Johnstown, a high oxygen affinity hemoglobin, was identified in four members from two unrelated Spanish families with erythrocytosis and left-shifted hemoglobin-oxygen dissociation curve. This hemoglobin variant, electrophoretically silent, was analyzed by reverse-phase high-performance liquid chromatography, and the mutation was characterized at the DNA level by beta gene sequencing. In one of these families, two members are affected with Hb Johnstown in association with beta(0)-thalassemia. In these cases the erythrocytosis and low values for P(50) due to Hb Johnstown remain in spite of the beta-thalassemia.
Adult↗