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E Moro

Publications and source records attributed to E Moro.

At least 37 records · Page 2Linked to original sources
PubMed2001

CDY1 analysis in infertile patients with DAZ deletions.

The DAZ (deleted in azoospermia) gene family is considered the major AZFc ("azoospermia factor" c) candidate responsible for male infertility. However, other genes have been recently mapped to this region and they could contribute to the AZFc phenotype. In particular, the testis-specific CDY1 (chromadomain protein 1) gene has one copy within the DAZ cluster and another one at its distal end. Therefore, this gene could be associated with the spermatogenic damage observed in DAZ-deleted patients since at least one CDY1 copy is invariably absent in these patients. In this study, we investigated whether selected infertile patients affected by different testiculopathies caused by DAZ deletions retained CDY1 and if a genotype-phenotype relation could be demonstrated. We found 3 out of 17 patients with absence of both CDY1 copies, while 14 patients have only one CDY1 copy absent. Two out of the 3 patients with deletion of both copies of CDY1 were affected by severe hypospermatogenesis while one patient presented Sertoli cell-only syndrome. Therefore, there was no clear relation between genotype and phenotype, and the loss of the distal copy of CDY1 does not seem to worsen the phenotype of infertile patients with deletion of the DAZ gene cluster. However, a possible contribution of CDY1 in determining the spermatogenic alteration could not be excluded.

Deleted in Azoospermia 1 Protein↗
PubMed2001

Different insulin-like 3 (INSL3) gene mutations not associated with human cryptorchidism.

Cryptorchidism is the most frequent congenital anomaly of the urogenital tract in the male, but its etiology is for the most part unknown. Evidence suggests that a possible genetic cause may be involved. Animal models support this hypothesis, and in particular INSL3 (Leydig insulin-like 3 hormone) has been proposed as putative gene for cryptorchidism, since male mice mutant for Insl3 exhibit bilateral abdominal cryptorchidism due to alteration of gubernaculum development. In this study, we analyzed whether mutations in INSL3 could be associated with human cryptorchidism. Heteroduplex analysis and sequencing of both exons of INSL3 in 65 ex-cryptorchid patients and a group of control subjects allowed us to find four nucleotide changes in the sequence of exon I. These mutations are all single base substitutions from G to A at position 27, 96, 126 and 178. Only the 178G-->A substitution changes codon 60 from alanine to threonine (A60T). All mutations were found in comparable distribution in ex-cryptorchid patients and non-cryptorchid men. Therefore, all mutations represent neutral polymorphisms not associated with phenotype. This study confirms previous observations and demonstrates a novel polymorphism in the INSL3 gene. In contrast to that described for the mutant mouse, these data indicate that mutations of INSL3 do not seem to represent a frequent cause of cryptorchidism.

Adult↗
PubMed2001

Deep brain stimulation in the treatment of severe dystonia.

A retrospective study of a consecutive series of 19 patients with medically intractable dystonia treated with uni- or bilateral deep brain stimulation (DBS) is reported. A minimal follow-up of 6 months was available, up to eleven years in one patient. The first twelve consecutive patients (4 with primary and 8 with secondary dystonia) were treated with chronic stimulation of the posterior part of the ventrolateral thalamic nucleus (VLp). In this group global functional outcome was improved in 8 patients, although dystonia movement and disability scale scores did not show significant improvement. Of the 12 patients treated first by VLp DBS, three (1 primary and 2 secondary dystonia) underwent pallidal (GPi) DBS after the VLp DBS failed to improve their symptoms. The last seven consecutive patients (5 primary and 2 secondary dystonia) were treated directly with GPi DBS. Extracranial infection prevented chronic GPi DBS in one patient. In another GPi patient, preliminary negative tests with the electrodes discouraged implantation of the stimulators, and the patient was not treated with chronic DBS. In the remaining group of eight patients including those previously treated with VLp DBS, chronic GPi DBS resulted in a significant improvement in the dystonia movement scale and disability scores. Although this is a retrospective study dealing with dystonia of heterogeneous etiology, the results strongly suggest that GPi DBS has a better outcome than VLp DBS.

Adolescent↗
PubMed2001

Intestinal motor stimulation by the 5-HT4 receptor agonist ML10302: differential involvement of tachykininergic pathways in the canine small bowel and colon.

5-Hydroxytryptamine (5-HT)4 receptor agonists stimulate gut motility through cholinergic pathways, although there are data suggesting that noncholinergic (tachykininergic) excitatory pathways may also be involved. Differences may exist between the small bowel and colon. Our aims were: (i) to compare the prokinetic effect exerted by the 5-HT4 receptor agonist ML10302 in the canine small bowel and colon in vivo; and (ii) to investigate the role of tachykininergic pathways in mediating this response. In fasting, conscious dogs, chronically fitted with electrodes and strain-gauge force transducers along the small bowel and colon, intravenous injection of ML10302 (35 microg kg-1) immediately stimulated spike activity and significantly increased propagated myoelectrical events at both intestinal levels. In the small bowel, the effects of ML10302 were unchanged by previous administration of the selective NK1 tachykinin receptor antagonist SR140333, the NK2 tachykinin receptor antagonist SR48968, or the NK3 tachykinin receptor antagonist SR142801. In the colon, all tachykinin receptor antagonists significantly inhibited stimulation of spike and mechanical activity by ML10302, without affecting ML10302-induced propagated myoelectrical events. Atropine (100 microg kg-1 i.v.) suppressed the stimulatory effect of ML10302 at both intestinal levels. In conclusion, the 5-HT4 receptor agonist ML10302 induced significant prokinesia both in the small bowel and colon through activation of cholinergic pathways. Tachykininergic pathways are not involved in the ML10302-induced prokinesia in the small bowel, but they play an important role in mediating the colonic motor response to ML10302.

Algorithms↗
PubMed2001

Prognostic value of Y deletion analysis. The role of current methods.

Y chromosome microdeletions represent the most frequent genetic alteration in azoospermic and severely oligozoospermic men, and screening for microdeletions in AZFa, b and c are routinely performed in the major andrology and infertility centres. Since patients with Y microdeletions often require intracytoplasmic sperm injection (ICSI), the question of whether the type of the microdeletion present could have prognostic value for the presence of spermatozoa in the ejaculate or in the testes [by testicular sperm extraction (TESE)] is an interesting one. The review of the literature on this topic showed that there is still no clear genotype--phenotype relationship, i.e. similar testicular alterations may be caused by different types of microdeletions, and apparently identical microdeletions may be associated with diverse tubular damage. Even in azoospermic men, the localization of the microdeletion cannot be used as a valid prognostic parameter before TESE--ICSI to identify patients with spermatozoa in their testes. The only finding with absolute negative prognostic value is the presence of complete AZFa--c deletions, which are invariably associated with an absence of spermatozoa. Microdeletions in AZFa or AZFb seem to have promising prognostic value, but more data and gene-specific deletions have to be provided to draw clear conclusions. The absence of a clear genotype--phenotype relationship, and therefore of a prognostic value of Y deletion analysis, is probably due to the current methods used for the screening of the microdeletions. In fact, to date most centres do not use gene-specific markers but instead use anonymous primers that contribute little information to the pathogenic role of the microdeletions.

Gene Deletion↗
PubMed2001

Y chromosome microdeletions and alterations of spermatogenesis.

Three different spermatogenesis loci have been mapped on the Y chromosome and named "azoospermia factors" (AZFa, b, and c). Deletions in these regions remove one or more of the candidate genes (DAZ, RBMY, USP9Y, and DBY) and cause severe testiculopathy leading to male infertility. We have reviewed the literature and the most recent advances in Y chromosome mapping, focusing our attention on the correlation between Y chromosome microdeletions and alterations of spermatogenesis. More than 4,800 infertile patients were screened for Y microdeletions and published. Such deletions determine azoospermia more frequently than severe oligozoospermia and involve especially the AZFc region including the DAZ gene family. Overall, the prevalence of Y chromosome microdeletions is 4% in oligozoospermic patients, 14% in idiopathic severely oligozoospermic men, 11% in azoospermic men, and 18% in idiopathic azoospermic subjects. Patient selection criteria appear to substantially influence the prevalence of microdeletions. No clear correlation exists between the size and localization of the deletions and the testicular phenotype. However, it is clear that larger deletions are associated with the most severe testicular damage. Patients with Y chromosome deletions frequently have sperm either in the ejaculate or within the testis and are therefore suitable candidates for assisted reproduction techniques. This possibility raises a number of medical and ethical concerns, since the use of spermatozoa carrying Y chromosome deletions may produce pregnancies, but in such cases the genetic anomaly will invariably be passed on to male offspring.

Chromosome Aberrations↗
PubMed2001

Sertoli cell function in infertile patients with and without microdeletions of the azoospermia factors on the Y chromosome long arm.

Deletions of the azoospermia factors on the Y chromosome long arm are an important cause of male infertility, and they may involve germ cell-specific genes or ubiquitously expressed genes. To date, no clinical or hormonal parameters have yet been found to distinguish patients with and without Yq microdeletions. In particular, Sertoli cell function, as evaluated by inhibin B, has not yet been described. Our hypothesis was that microdeletions involving genes specifically expressed in germ cells should not alter Sertoli cell function. To do this, we have evaluated the testicular hormonal function in infertile patients affected by severe testiculopathies with and without Yq microdeletions, with particular emphasis on Sertoli cell function. We studied 102 well-characterized infertile patients; 27 had Yq microdeletions, and 75 were classified as idiopathic infertiles. Patients with Yq microdeletions had lower FSH and higher inhibin B plasma concentrations with respect to patients without microdeletions, suggesting that Sertoli cell function in Yq-deleted men is only partially altered. Furthermore, patients with deletions involving germ cell-specific genes had higher concentrations of inhibin B with respect to patients with deletions of ubiquitously expressed genes. These results suggested that a specific alteration of germ cells only partially influences Sertoli cell function. Hormonal status of patients without deletions suggested that in such cases the cause that has determined the spermatogenic defect may have damaged both Sertoli and germ cells. Inhibin B production in patients with Yq deletions was about 70% higher than the nondeleted patients, and the functional relationship between FSH and inhibin B was normally preserved. This study elucidated the multifactorial mechanisms underlying spermatogenic defects, where Sertoli cells may be normally functioning or damaged depending on the primary cause that has determined the testicular damage.

Chromosome Mapping↗
PubMed2000

Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility.

Three distinct regions, designated AZFa, b and c from proximal to distal Yq, are required for normal spermato-genesis in humans. Deletions involving AZFa (deletion interval 5C/D) seem to occur less frequently in infertile men and to be associated with a more severe testicular phenotype, with almost complete absence of germ cells. AZFa contains three genes, named USP9Y, DBY and UTY, and presents high homology with the mouse Delta Sxr (b) interval, deletion of which causes a severe spermatogenic impairment. However, the specific role of these genes in human spermatogenesis is still unknown and it is not clear which of them is responsible for the AZFa phenotype. Here we describe a complete sequence map of the AZFa region, the genomic structure of AZFa genes and their deletion analysis in a large number of infertile men characterized by well-defined spermatogenic alterations. Both USP9Y and DBY may cause severe testiculopathies, but DBY appears to be the major AZFa candidate. DBY is frequently deleted in infertile patients and its absence produces severe spermatogenic damage leading to a significant reduction of germ cells or even to their complete absence. Expression analysis of AZFa genes and their X-homologues revealed ubiquitous expression for all of them except DBY; this gene produces a long transcript which is ubiquitously expressed in addition to a shorter transcript which is only expressed in the testis, suggesting a specific role for DBY in the spermatogenic process. This hypothesis is further supported by the high similarity of DBY to other DEAD box proteins belonging to the PL10 subclass.

Animals↗
PubMed2000

Y chromosome microdeletions in infertile men with varicocele.

The pathogenic mechanisms by which varicocele disrupt spermatogenesis are not clearly understood and it is possible that when varicocele is associated with a severe bilateral testiculopathy, other causes may represent the actual aetiological factor. Since microdeletions in the Y chromosome long arm (Yq) have become in last years a major cause of male infertility, we perform a Yq microdeletion screening in infertile men with varicocele. We selected 40 patients with severe oligozoospermia (sperm count<5x10(6)/ml, group 1) and 80 with varicocele and mild oligozoospermia (sperm count 10-20x10(6)/ml, group 2). Deletions of Yq was observed in seven out of 40 patients (17.5%) of group 1, while no deletions were found in patients of group 2, suggesting that the bilateral testicular damage observed in patients of group 1 is due to the underlying genetic anomaly, and not to varicocele itself. The finding of a genetic aetiology in infertile men with varicocele suggests that in such patients a Yq microdeletion screening should be performed, both for a proper diagnosis and to avoid unnecessary treatments that will probably not improve the sperm count.

Biopsy, Needle↗
PubMed2000

Y chromosome.

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Chromosome Deletion↗
PubMed2000

Role of the AZFa candidate genes in male infertility.

The AZFa region on the Y-chromosome long arm has been recently assembled in a complete sequence map contained in a contig and shown to span more than 1 Mb. It contains three genes, USP9Y, DBY and UTY, but only the former two can be at present considered candidate genes for the infertile phenotype associated with deletion of this interval. These genes have X-homologues and are expressed in many tissues, even if DBY has a shorter transcript expressed in the testis only, strengthening its role in spermatogenesis. Only few patients with gene-specific deletion have been reported and a clear genotype-phenotype relation is still lacking. While deletions or even smaller mutations in USP9Y seem to be associated with a testicular phenotype of severe hypospermatogenesis, patients with deletions of DBY may present both Sertoli cell-only syndrome and severe hypospermatogenesis. On the contrary, the phenotype of patients with deletion of both USP9Y and DBY seem to be invariably azoospermia with a testicular histology of Sertoli cell-only.

Chromosome Mapping↗
PubMed2000

Y-chromosomal DNA haplotypes in infertile European males carrying Y-microdeletions.

We have determined Y-chromosomal DNA haplotypes in 73 infertile European males carrying Y microdeletions and compared them with the haplotypes of 299 infertile males lacking microdeletions. Chromosomes were typed with a set of 11 binary Y markers, which identified 8 haplogroups in the sample. Haplogroup frequencies were compared between 3 microdeletion classes and the non-deleted infertile males. Deletions arise on many different haplotypic backgrounds. No statistically significant differences in frequency were seen, although the small number of AZFa deletions lay predominantly on one branch of the Y haplotype tree.

DNA↗
PubMed2000

The impact of deep brain stimulation on executive function in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) improves Parkinson's disease and increases frontal blood flow. We assessed the effects of bilateral DBS on executive function in Parkinson's disease patients, seven with electrodes implanted in the STN and six in the GPi. Patients were assessed off medication with stimulators off, on and off again. The groups showed differential change with stimulation on the Reitan Trail-Making test (TMT B) (STN more improved) and on some measures of random number generation and Wisconsin Card Sorting (STN improved, GPi worse with stimulation). Across the groups, stimulation speeded up responding (Stroop control trial, TMT A) and improved performance on paced serial addition and missing digit tests. Conversely, conditional associative learning became more errorful with stimulation across the two groups. In general, change in performance with stimulation was significant for the STN but not the GPi group. These results support two opposite predictions. In support of current models of Parkinson's disease, 'releasing the brake' on frontal function with DBS improved aspects of executive function. Conversely, disruption of basal ganglia outflow during DBS impaired performance on tests requiring changing behaviour in novel contexts as predicted by Marsden and Obeso in 1994.

Association Learning↗
PubMed2000

Roughening and super-roughening in the ordered and random two-dimensional sine-gordon models

We present a comparative numerical study of the ordered and the random two-dimensional sine-Gordon models on a lattice. We analytically compute the main features of the expected high-temperature phase of both models, described by the Edwards-Wilkinson equation. We then use those results to locate the transition temperatures of both models in our Langevin dynamics simulations. We show that our results reconcile previous contradictory numerical works concerning the super-roughening transition in the random sine-Gordon model. We also find evidence supporting the existence of two different low-temperature phases for the disordered model. We discuss our results in view of the different analytical predictions available and comment on the nature of these two putative phases.

Journal Article↗
PubMed2000

Continuous time dynamics of the thermal minority game

We study the continuous time dynamics of the thermal minority game. We find that the dynamical equations of the model reduce to a set of stochastic differential equations for an interacting disordered system with nontrivial random diffusion. This is the simplest microscopic description which accounts for all the features of the system. Within this framework, we study the phase structure of the model and find that its macroscopic properties strongly depend on the initial conditions.

Journal Article↗
PubMed2000

Acute challenge with apomorphine and levodopa in Parkinsonism.

BACKGROUND: The diagnosis of different parkinsonian syndromes and the ability to predict long-term drug efficacy constitute important clinical issues. DESIGN: Motor responses to the acute administration of levodopa and apomorphine were analyzed in a series of 134 parkinsonian patients, including 83 patients with a clinical diagnosis of idiopathic Parkinson's disease (PD), 28 patients with multiple-system atrophy (MSA), 6 with progressive supranuclear palsy, and 17 with an unclassified parkinsonian syndrome. METHODS: The patients received oral levodopa/carbidopa (250/25 mg) and subcutaneous apomorphine (1.5, 3 and 4.5 mg). Clinical variations of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score were evaluated 1 h following levodopa administration or 20 min following apomorphine. The motor improvement produced by each acute challenge was matched with the clinical diagnosis and with the response to chronic levodopa treatment. The diagnosis was verified by repeated clinical assessments or by autopsy in 2 cases. A receiver operating characteristics curve was plotted comparing PD vs. non-PD, PD vs. MSA and chronic responders vs. nonresponders. Cutoff threshold improvement was defined as the value closest to the crossing point for 80% sensitivity and 80% specificity, corresponding to the best trade-off for a predictive evaluation. RESULTS: UPDRS motor score improvement was on average higher in PD than in non-PD patients (levodopa: 29.8 vs. 12.2%; apomorphine 1.5 mg: 27.1 vs. 10.5%; apomorphine 3 mg: 27.7 vs. 9.7%; apomorphine 4.5 mg: 28.8 vs. 11.8%; p < 0.01 with Student's t test). When PD patients were compared to non-PD patients, levodopa challenge had the best diagnostic accuracy with a threshold improvement of 16%. Apomorphine had the best diagnostic accuracy with a threshold improvement of 13.5% for 1.5 mg, 13% for 3 mg, and 16% for 4.5 mg. This meant that patients improving at least 16% in all tests had the highest probability of having PD. When PD patients were compared to MSA patients, levodopa acute challenge had the best diagnostic accuracy with a threshold improvement of 17%. Apomorphine had the best diagnostic accuracy with an improvement of 13% for 1.5 mg, 15% for 3 mg, and 18% for 4.5 mg. This meant that patients improving at least 18% in all tests had the highest probability of having PD rather than MSA. When patients who responded to chronic levodopa treatment were compared to those who did not, acute challenge with levodopa had the best predictive accuracy with a threshold improvement of 14.5%. Apomorphine had the best predictive accuracy with an improvement of 13% for 1.5 mg, and 14% for 3 and 4.5 mg. This meant that patients improving at least 14.5% in all tests had the highest probability of responding to chronic treatment. CONCLUSION: A good agreement was found between acute challenges with levodopa/carbidopa and apomorphine, and the use of both improved the reliability of the test. Different threshold improvements after acute challenges would support a diagnosis of PD or the exclusion of MSA, and would have a predictive value for subsequent response to chronic levodopa therapy.

Age of Onset↗
PubMed2000

Male infertility caused by a de novo partial deletion of the DAZ cluster on the Y chromosome.

Deletions in distal Yq interval 6 represent the cause of 10-15% of idiopathic severe male infertility and map to a region defined AZFc (azoospermia factor c). The testis-specific gene DAZ is considered a major AZFc candidate, and its deletion has been associated with a severe disruption in spermatogenesis. However, DAZ is actually a multicopy gene family consisting of seven clustered copies spanning about 1 megabase. Only deletions removing the entire DAZ gene cluster together with other genes have been reported in infertile males. Because no case of spermatogenic failure has been traced to intragenic deletions, point mutations, or even deletions not involving all the DAZ copies, the definitive proof for a requirement of DAZ for spermatogenesis is still debatable. Here we report the first case of a partial deletion of the DAZ cluster removing all but one of the copies. This deletion is present in a patient affected with severe oligozoospermia who had a testicular phenotype characterized by a great quantitative reduction of germ cells (severe hypospermatogenesis). The absence of this deletion in the fertile brother of the patient suggests that this de novo mutation indeed caused the spermatogenic failure.

Adult↗