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S Alonso

Publications and source records attributed to S Alonso.

At least 91 records · Page 5Linked to original sources
PubMed1997

Embryonic and fetal myogenic programs act through separate enhancers at the MLC1F/3F locus.

Embryonic and fetal stages of skeletal muscle development are characterized by the differential expression of a number of muscle-specific genes. These include the products of independent promoters at the fast myosin light chain 1F/3F locus. In the mouse embryo MLC1F transcripts accumulate in embryonic skeletal muscle from E9, 4-5 days before high-level accumulation of MLC3F transcripts. A 3' enhancer can activate MLC1F and MLC3F promoters in differentiated muscle cells in vitro and in transgenic mice; both promoters, however, are activated at the time of MLC1F transcript accumulation. We now demonstrate the presence of a second muscle-specific enhancer at this locus, located in the intron separating the MLC1F and MLC3F promoters. Transgenic mice containing the intronic, but lacking the 3' enhancer, express high levels of an nlacZ reporter gene from the MLC3F promoter in adult fast skeletal muscle fibers. In contrast to the 3' enhancer, the intronic element is inactive both in embryonic muscle cells in vivo and in embryonic myocyte cultures. The intronic enhancer is activated at the onset of fetal development in both primary and secondary muscle fibers, at the time of endogenous MLC3F transcript accumulation. Late-activated MLC3F transgenes thus provide a novel in toto marker of fetal myogenesis. These results suggest that temporal regulation of transcription at the MLC1F/3F locus is controlled by separate enhancers which are differentially activated during embryonic and fetal development.

Animals↗
PubMed1997

Short alleles revealed by PCR demonstrate no heterozygote deficiency at minisatellite loci D1S7, D7S21, and D12S11.

Short VNTR alleles that go undetected after conventional Southern blot hybridization may constitute an alternative explanation for the heterozygosity deficiency observed at some minisatellite loci. To examine this hypothesis, we have employed a screening procedure based on PCR amplification of those individuals classified as homozygotes in our databases for the loci D1S7, D7S21, and D12S11. The results obtained indicate that the frequency of these short alleles is related to the heterozygosity deficiency observed. For the most polymorphic locus, D1S7, approximately 60% of those individuals previously classified as homozygotes were in fact heterozygotes for a short allele. After the inclusion of these new alleles, the agreement between observed and expected heterozygosity, along with other statistical tests employed, provide additional evidence for lack of population substructuring. Comparisons of allele frequency distributions reveal greater differences between racial groups than between closely related populations.

Alleles↗
PubMed1997

[Primary stent treatment in the acute phase of myocardial infaction].

INTRODUCTION: Although direct balloon angioplasty has emerged as an alternative to thrombolytic therapy in patients with acute myocardial infarction, reocclusion and restenosis rates are limiting factors. We postulated that these limitations could be partly overcome by primary stenting of the responsible lesion. MATERIAL AND METHODS: Since January/94 we have studied 59 patients with acute myocardial infarction who were treated in the early phase (3.1 +/- 2 hours since the onset of symptoms) by elective Palmaz-Schatz stent implantation. No adjunctive thrombolytic therapy was associated. Two patients were in cardiogenic shock and were treated under percutaneous cardiopulmonary support. At cardiac catheterization a left ventriculography and coronary angiograms were obtained. Then, mechanical recanalization of the responsible lesion was performed. If the angiographic anatomy was considered suitable, a stent was implanted at the lesion. RESULTS: The infarct related artery was the left anterior descending in 29 patients, the circumflex in 14 and the right coronary artery in 16. At baseline conditions, 40 patients had a totally occluded artery and 19 showed a TIMI-grande 1 antegrade flow. One patient had an early clinical recurrence 4 days later, which required an additional divided Palmaz-Schatz stent at the distal portion of the lesion, in order to seal a residual dissection. All remaining patients had a favourable clinical course without major complications. Immediately after treatment the minimal lumen diameter was 3.2 +/- 0.4 mm and no residual stenosis was detectable at the treated segment. Six-month angiographic reevaluation was performed in all 29 (49%) eligible patients. Restenosis (> 50% stenosis) was detected in 6 out of the 29 evaluated patients (21%). CONCLUSIONS: Primary stent implantation in selected patients with an evolving myocardial infarction provides good initial and 6-month results.

Acute Disease↗
PubMed1996

[Characteristics and course of patients over 65 years of age with severe heart failure].

INTRODUCTION AND OBJECTIVES: Although there have been many studies on the prognosis of congestive heart failure, most of them have not provided specific data about older patients. The aim of our study is to evaluate general characteristics and short and medium-term evolution of patients older than 65 years with severe heart failure. PATIENTS AND METHODS: We have carried out a prospective study of all patients older than 65 years admitted to our Department during 1993 due to severe heart failure (functional class III or IV of the NYHA classification), regardless of the etiology. In that year, 84 patients who fulfilled those criteria were admitted. RESULTS: The mean age was 72 +/- 6 years, 56% were male and 44% female. Age distribution was as follows: 36 patients were between 65 and 70 years, 27 between 70 and 75, 8 between 75 and 80, and 13 older than 80. The etiology of heart failure was: ischemic heart disease 44%, valvular heart disease 36%, idiopathic dilated cardiomyopathy 8%, systemic arterial hypertension 7% and other etiologies 5%. Significant systolic dysfunction (left ventricular ejection fraction < 0.45) was present in 36% of the patients. Ten percent of the patients suffered from severe ventricular arrhythmias (ventricular tachycardia or fibrillation). Regarding treatment, 24% underwent valvular surgery, 74% received only medical treatment and coronary angioplasty was performed in one patient. In hospital mortality was 9% (8 patients). After a mean follow-up of 8 +/- 4 months, the probability of survival was 78% at 1 month, 71% at 6 months and 63% at 1 year. The survival rate was better in patients with higher ejection fraction (53% for patients with ejection fractions of less than 0.45, 64% for those with ejection fractions between 0.45 and 0.60 and 79% for those with ejection fractions greater than 0.60). Considering etiology, the survival rate was worse for patients with acute myocardial infarction (30%) and aortic valve stenosis (58%). CONCLUSIONS: Patients older than 65 years admitted to the hospital for severe congestive heart failure represent a heterogeneous population in respect to etiology, systolic function and prognosis. Nevertheless, from this study it appears that a worse prognosis was associated with the lower left ventricular ejection fractions and with certain etiologies; such as acute myocardial infarction or aortic stenosis.

Age Factors↗
PubMed1995

Heterotaxia syndrome and autosomal dominant inheritance.

Previous familial cases of recurrent heterotaxia have suggested an autosomal recessive or exceptionally X-linked or dominant inheritance. Here, we report six families including 18 affected members, consistent with autosomal dominant inheritance. Among these, four families have more than one case of heterotaxia. The other two families have one member with heterotaxia and at least one other affected member with an "isolated" heart malformation, which could be considered as a mild form of heterotaxia. In five families, the disorder is transmitted through two or three generations. In one family, the patients are of the same generation but are linked to each other by obligate carriers. We suggest a rule to classify these families with heart malformations, according to the etiologic factor involved (rule of precocity). This rule might be useful to other disruptions of morphogenetic processes.

Fatal Outcome↗
PubMed1995

Genetic typing with HUMTH01, HUMVWA31A and HUMFES/FPS short tandem repeat loci, D1S80 variable number tandem repeat locus and HLA-DQ alpha of recent and from XII-XIII centuries spongy bone.

The genetic analysis of ancient populations through DNA from bone remains, requires use of short sized loci that can be amplified by polymerase chain reaction (PCR) for which the short tandem repeat (STR) loci are most suitable. These techniques can also be applied to genetic identification in forensic casework. In this study three STR loci, HUMFES/FPS, HUMTH01, and HUMVWA31A, were selected to estimate their usefulness when applied to recent and ancient spongy bone DNA typing. In addition, loci D1S80 and HLA DQ alpha were also tested in the analysis of recent spongy bone DNA. The recent remains studied were constituted by ten spongy bone samples of postmortem material from one individual buried for 1 year. The ancient remains are composed by 8 spongy bone samples from the heads of left femurs from a XII-XIII Centuries Basque Country population. Adequate amplification and typing results could only be obtained with cetyltrimethyl ammonium bromide (CTAB)-extracted DNA, without any further purification after precipitation. Genotypes of the one year post-mortem material and those of his son and his wife were obtained at the D1S80, HLA-DQ alpha, and STR loci. In all these systems, no exclusion was observed, with a combined probability of paternity of 0.9997. This demonstrates the reliability of the obtained results. The genetic typing of HUMTH01 in spongy bone from the XII-XIII Centuries Basque Country individuals was also performed. This will allow the genetic analysis of ancient bone remains and therefore, to carry out evolutionary population studies.

Base Sequence↗
PubMed1995

Population study of 3 STR loci in the Basque Country (northern Spain).

The tetrameric STRs, HUMTH01, HUMVWA31A and HUMFES/FPS, were studied in a population from the Basque Country (northern Spain) for their frequency distribution and applicability to identity and paternity testing. All systems conformed to Hardy-Weinberg equilibrium; pairwise comparisons demonstrated the allelic independence between loci, and furthermore, all systems seemed to be in agreement with expectations from the Stepwise Mutation Model (SMM) of the mutation-drift theory, which indicates the homogeneity of the population and suggests a replication slippage mechanism as a possible model for generating alleles. A comparison with other population groups appeared to indicate that frequencies are well conserved in Caucasians, but differ from other racial groups. The calculated parameters "a priori probability of exclusion" (PEX) and "index of discrimination" (ID), show the informativeness of these loci for the determination of identity and relatedness of individuals.

Alleles↗
PubMed1995

Myosin light chain 3F regulatory sequences confer regionalized cardiac and skeletal muscle expression in transgenic mice.

The myosin light chain IF/3F locus contains two independent promoters, MLC1F and MLC3F, which are differentially activated during skeletal muscle development. Transcription at this locus is regulated by a 3' skeletal muscle enhancer element, which directs correct temporal and tissue-specific expression from the MLC1F promoter in transgenic mice. To investigate the role of this enhancer in regulation of the MLC3F promoter in vivo, we have analyzed reporter gene expression in transgenic mice containing lacZ under transcriptional control of the mouse MLC3F promoter and 3' enhancer element. Our results show that these regulatory elements direct strong expression of lacZ in skeletal muscle; the transgene, however, is activated 4-5 d before the endogenous MLC3F promoter, at the time of initiation of MLC1F transcription. In adult mice, transgene activity is downregulated in muscles that have reduced contributions of type IIB fibers (soleus and diaphragm). The rostrocaudal positional gradient of transgene expression documented for MLC1F transgenic mice (Donoghue, M., J. P. Merlie, N. Rosenthal, and J. R. Sanes. 1991. Proc. Natl. Acad. Sci. USA. 88:5847-5851) is not seen in MLC3F transgenic mice. Although MLC3F was previously thought to be restricted to skeletal striated muscle, the MLC3F-lacZ transgene is expressed in cardiac muscle from 7.5 d of development in a spatially restricted manner in the atria and left ventricular compartments, suggesting that transcriptional differences exist between cardiomyocytes in left and right compartments of the heart. We show here that transgene-directed expression of the MLC3F promoter reflects low level expression of endogenous MLC3F transcripts in the mouse heart.

Animals↗
PubMed1995

D1S80 locus typing by micro thermal cycler. Application to genetic identity testing.

Based on a micro thermal cycler apparatus, a new protocol for amplification of the D1S80 locus has been developed. The advantages of this system consist of a reduction in time and costs of the amplification process, which greatly facilitates the analysis of the D1S80 locus at the population level and considerably increases its applicability in forensic samples. Using this protocol, an allele distribution study of the D1S80 locus has been carried out in a sample of 257 individuals residing in the Basque Country. In this study, up to 22 different alleles, ranging from 17 to 40 repetitions have been observed; moreover, the 35 and 38-repetition alleles, not reported in the european populations analyzed to date, have been detected. The sample studied fits Hardy-Weinberg equilibrium, the observed heterozygosity being 0.74, and the expected heterozygosity 0.804 +/- 0.012. The Chance of Exclusion and Index of Discrimination are 0.638 and 0.072 respectively. Moreover, the gene frequency distribution from the Basque resident population does not show significant differences when compared to other European and U.S. Caucasian populations.

Alleles↗
PubMed1994

Deciphering the molecular genetics of congenital heart disease.

Congenital heart diseases are starting to benefit from the major advances provided by the advent of molecular biology methods. It is now possible to identify genes which are responsible for congenital heart diseases. The gene responsible for supravalvular aortic stenosis--an autosomal dominant trait--was cloned last year. It is the elastin gene. DiGeorge and Shprintzen syndromes, conotruncal anomaly face and some cardiac malformations have a common cause: a deletion of the 22q11 region resulting in a monosomy. Although the region of deletion is large, it is possible that monosomy of only one gene results in these conditions. Studies are underway to evaluate the impact of this new genetic factor on the incidence of congenital heart malformations. Studies on familial bundle branch block, and lateralization defect with midline anomalies are soon going to show a chromosomal region with the gene defect. Discovering the genes and their protein products which are implied in the cardiac morphogenesis will definitively change our understanding of these cardiac malformations.

Abnormalities, Multiple↗
PubMed1993

Re-localization of Actsk-1 to mouse chromosome 8, a new region of homology with human chromosome 1.

We present here the genetic mapping of the alpha-skeletal actin locus (Actsk-1) on mouse Chromosome (Chr) 8, on the basis of the PCR analysis of a microsatellite in an interspecific backcross. Linkage and genetic distances were established for four loci by analysis of 192 (or 222) meiotic events and indicated the following gene order: (centromere)-Es-1-11.7 cM-Tat-8.3 cM-Actsk-1-0.5 cM-Aprt. Mapping of ACTSK to human Chr 1 and of TAT and APRT to human Chr 16 demonstrates the existence of a new short region of homology between mouse Chr 8 and human Chr 1. Intermingling on this scale between human and mouse chromosomal homologies that occurred during evolution creates disorders in comparative linkage studies.

Actins↗
PubMed1993

A model of cholestasis in the rat, using a microsurgical technique.

An experimental model of extrahepatic cholestasis in the rat, using a microsurgical technique, is described. Sixteen days postoperatively all of the animals (n = 10) were alive and had hepatomegaly, splenomegaly, jaundice, and hyperbilirubinemia. The use of this technique prevents the development of hepatic cysts and other complications inherent in the surgical techniques of cholestasis, such as hepatopneumonic abscesses.

Animals↗
PubMed1993

[Mice SI/Col: a study model in the research of genes involved in situs inversus].

The SI/Col mouse is carrier of the i.v. mutation which expresses itself in an autosomal recessive mode. Fifty per cent of mice born of homozygotic i.v./i.v. parents are normal and 50% present an abnormality of lateralisation of the thoracic and abdominal organs with cardiac malformations involving the venous, atrial, ventricular and arterial segments. Identifying the i.v. mutation may improve our understanding of the genesis of the heterotaxic syndrome in man. With the help of return crossing with wild mice, the authors studied segregation of 10 makers of the murine, chromosome 12 of the situs inversus mice. The genetic map constructed from this data places the i.v. mutation near the telomeric extremity of the murine chromosome 12. Given the inter-species conservation between this region and the telomeric region of the human chromosome 14, it is a candidate region for the search of a homologous human gene in syndromes of heterotaxis.

Animals↗
PubMed1992

Synthesis of 3-[(2,3-dihydro-1,1,3-trioxo-1,2-benzisothiazol-2-yl)alkyl] 1,4-dihydropyridine-3,5-dicarboxylate derivatives as calcium channel modulators.

1,4-Dihydropyridine (DHP) derivatives with a 1,2-benzisothiazol-3-one 1,1-dioxide group, linked through an alkylene bridge to the C-3 carboxylate of the DHP ring, with both vasoconstricting and vasorelaxant properties were obtained. In blocking Ca(2+)-evoked contractions of K(+)-depolarized rabbit aortic strips, compounds 12 and 41 were 10-fold more potent than nifedipine; 27 other compounds were 1-4-fold more potent. Their vascular versus cardiac selectivity was very pronounced; for instance, the selectivity index for compound 41 was 70-fold higher than that of nifedipine. This was also true for the vasoconstricting compound 22, which was as potent as Bay K 8644 in enhancing the Ca(2+)-evoked contractions of rabbit aorta strips, yet it had poor inotropic activity in rabbit left atria. Oral administration of compounds 38, 40, 43, and 53 (20 mg/kg) caused a 35-37% decrease in systolic blood pressure in spontaneously hypertensive rats (SHR); these effects were similar to those of nifedipine. However, iv administration of these compounds to anesthetized SHR caused a decrease in blood pressure which was more pronounced and long-lasting than that of nifedipine. When administered iv at 100 micrograms/kg, the vasoconstricting compound 22 caused a 40% increase in systolic and diastolic blood pressure. Compound 22 exhibited an unusually interesting feature over the other five Ca2+ DHP agonists: it had diester substitutions at the C-3 and C-5 positions of the DHP ring. Overall, compounds possessing these properties might be useful in treating clinical cardiovascular conditions in which DHP Ca2+ antagonists or agonists are indicated.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

A detailed linkage map of subtelomeric murine chromosome 12 region including the situs inversus mutation locus IV.

A mouse model is an invaluable tool to tackle genesis of human congenital diseases that have so far eluded human studies. Homozygote for the i.v. mutation, the murine Si/Col strain presents a left-right lateralization defect of thoracic and abdominal organs and heart defects very similar to human ones. This i.v. mutation has been mapped to the region between the Aat and Igh-C loci, suggesting the presence of an equivalent human gene in the human syntenic 14q3 region. A precise linkage map of the region is, therefore, of great interest since it will contribute to the genetic approach of the i.v. gene. Analysis of 242 back-cross progeny from Mus musculus (MAI) or spretus strains of mice and SI/Col mice has allowed mapping of the i.v. gene to a linkage group of eight markers. It includes four genes: Aat (alpha 1-antitrypsin), Ckb (creatine kinase, brain form), Crip (cysteine-rich intestinal protein), and Igh-C (immunoglobulin heavy chain constant region complex); three murine microsatellites: D12Mit6, D12Mit7, and D12Mit8; and one new marker, D12Mtp1, defined by a minisatellite human probe, pYNZ2. After analysis of the data by the LINKAGE program, the following multilocus map has been constructed: centromere-D12Mit6-6.9 cM-D12Mit7-1.7 cM-D12Mtp1-2.6 cM-Aat-5.0 cM-(Ckb, Igh-C)-0.4 cM-D12Mit8-0.4 cM-Crip-11.2 cM-i.v.-telomere. This map differs from the previous map in placing i.v. locus telomeric to Igh-C. D12Mit6 and D12Mit7 are now precisely mapped centromeric to the locus Aat. In addition, a new locus D12Mtp1 is located between Aat and D12Mit7.

Animals↗