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Biomedical subjects

A Ragusa

Publications and source records attributed to A Ragusa.

At least 19 recordsLinked to original sources
PubMed2005

Evaluating the therapeutic approach in pregnancies complicated by borderline glucose intolerance: a randomized clinical trial.

AIMS: Most studies relating minor gestational metabolic alterations to macrosomia refer to glucose intolerance classified on the basis of the National Diabetes Data Group or previous World Health Organization diagnostic thresholds. Our aim was to evaluate the consequences of very mild forms of gestational glucose intolerance, defined by an elevated 50-g glucose challenge test followed by a normal oral glucose tolerance test, using the more restrictive Carpenter and Coustan's criteria (Borderline Gestational Glucose Intolerance, BGGI). METHODS: Three hundred BGGI women were randomly assigned to: Group A (standard management), Group B (dietary treatment and regular monitoring). A control group (C) was also considered. Newborns were classified as macrosomic, large (LGA), or small for gestational age (SGA). RESULTS: The three groups were similar in age, body mass index and parity. Therapy in Group B significantly improved fasting (from 4.68 +/- 0.45 to 4.28 +/- 0.45 mmol/l) and 2-h postprandial glycaemia (from 6.01 +/- 0.57 to 5.13 +/- 0.68 mmol/l). Fasting glycaemia at delivery was significantly lower in B (4.20 +/- 0.38 mmol/l) than in A (4.84 +/- 0.45 mmol/l), and was also lower than in C (4.31 +/- 0.39 mmol/l). Significantly fewer LGA babies were born to Group B (6.0%) than Group A (14.0%) and Group C (9.1%). No difference was found in the SGA rate. The neonatal Ponderal Index was higher (P = 0.030) in group A (2.73 +/- 0.35) than in C (2.64 +/- 0.30) and B (2.64 +/- 0.24). CONCLUSIONS: Even very mild alterations in glucose tolerance can result in excessive or disharmonious fetal growth, which may be prevented by simple, non-invasive therapeutic measures.

Adult↗
PubMed2004

Progesterone supplement in pregnancy: an immunologic therapy?

One of the most interesting functions of the placenta is the regulation of the maternal immune response such that the fetal semi-allograft is tolerated during pregnancy. Trophoblasts are presumed to be essential to this phenomenon because they lie at the maternal-fetal interface, where they are in direct contact with cells of the maternal immune system. Trophoblasts do not express classic major histocompatibility complex (MHC) class II molecules. Surprisingly, cytotrophoblasts express more HLA-G, a MHC class Ib molecule, as they invade the uterus. Progesterone plays an important role in postovulatory regulation of the menstrual cycle. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy. Progesterone has been named the 'hormone of pregnancy', because in preparing the endometrium for embryo implantation and facilitating endometrial development, it is critical to the very survival of a pregnancy. In addition, this key hormone inhibits the rejection of T cell-mediated tissue and also decreases myometrial activity and sensitivity throughout pregnancy. The cellular actions of progesterone are mediated through intracellular progesterone receptors (PRs), which are well studied gene regulators, not express classic major histocompatibility complex. The more used paradigm is relative to the alteration of relationship TH1/TH2, but the complexity of the respective distributions of cytokines at the materno-fetal interface, strongly suggest that, as useful as it certainly was for a while, the Th1/Th2 paradigm must now be considered as an oversimplification. Rather, the existing data point to sequential windows and are suggestive of a system where an extreme complexity is allied to very precise timing and tuning. They also suggest that the materno-fetal relationship is not simply maternal tolerance of a foreign tissue, but a series of intricate mutual cytokine interactions governing selective immune regulation and also control of the adhesion and vascularization processes during this dialogue. However, as shifting the immune response toward the Th2 pattern (IL-4, IL-5, IL-6) may benefit the fetus, whereas development of proinflammatory Th1 cells (secreting IL-2, IFN g, TNF a) may be harmful. Now we are working to open comprise the precise behaviour of NK populations, with the hope of obtaining a diagnostic test of the condition of abortion from 'immunological causes'.

Abortion, Habitual↗
PubMed2001

Incremental prognostic value of technetium-99m-tetrofosmin exercise myocardial perfusion imaging for predicting outcomes in patients with suspected or known coronary artery disease.

Technetium-99m (Tc-99m)-tetrofosmin is a radio isotope that has been shown to be an accurate alternative to thallium-201 for detecting coronary artery disease. However, its prognostic value is less well determined. To this end, 459 consecutive patients (mean age 58 +/- 10 years) with suspected or known coronary artery disease underwent exercise single-photon emission tomography Tc-99m-tetrofosmin scintigraphy. Follow-up, defined as the time from scanning until a soft event (revascularization procedures), a hard event (myocardial infarction and cardiac death), or patient response, lasted up to 78 months (median 38). An ischemic scintigraphic perfusion score, which takes into account both the extent and severity of reversible perfusion defects, was calculated to estimate the severity of perfusion abnormalities. Patients with normal scans were at low risk of events (yearly hard event rate 0.5% and soft event rate 0.9%). The rate of outcomes increased significantly with abnormal scans (yearly hard event rate 4.9% and soft event rate 10.3%). Statistical analysis using the Kaplan-Meyer survival curves showed a significant difference in event-free survival between patients with normal and abnormal scans. With use of Cox proportional-hazards analysis, after adjusting for prescan information, nuclear data provided incremental prognostic value for hard events (clinical and exercise data vs nuclear data; chi-square = 15.5 vs 33.4, p <0.001). Exercise single-photon emission tomographic scintigraphy using Tc-99m-tetrofosmin provides significant independent information on the subsequent risk of hard and soft events. The annual event rate for hard and soft events is <1% for patients with a normal scan. Furthermore, this tracer yields incremental prognostic information in addition to that provided by clinical and exercise data for hard events.

Coronary Disease↗
PubMed2001

Long-term angiographic follow-up after successful repeat balloon angioplasty for in-stent restenosis.

BACKGROUND: Coronary stent implantation is associated with improved angiographic short-term and mid-term clinical outcome. However, restenosis rate still remains between 20 and 30%. HYPOTHESIS: The purpose of the study, performed as a prospective angiographic follow-up to detect restenosis, was to evaluate the immediate and the 6-month angiographic results of repeat balloon angioplasty for in-stent restenosis. METHODS: From April 1996 to September 1997, 335 stenting procedures performed in 327 patients underwent prospectively 6-month control angiography. Of the 96 lesions that showed in-stent restenosis (> 50% diameter stenosis) (29%), 72 underwent balloon angioplasty. RESULTS: The primary success rate was 100%. Follow-up angiogram at a mean of 6.9 +/- 2.4 months was obtained in 54 patients. Recurrent restenosis was observed in 24 of the 55 stents (44%). Repeat intervention for diffuse and body location in-stent restenosis before repeat intervention was associated with significantly higher rates of recurrent restenosis (p < 0.001 and p < 0.05, respectively). Of the 19 patients who underwent further balloon angioplasty (100% success rate), coronary angiography was performed in 18 (95%) at a mean of 8.2 +/- 2.0 months and showed recurrent restenosis in 12 patients (67%). Further repeat intervention for diffuse and severe in-stent restenosis before the second repeat intervention was associated with significantly higher rates of further recurrent restenosis (p < 0.05 and p < 0.005, respectively). CONCLUSIONS: Although balloon angioplasty can be safely, successfully, and repeatedly performed after stent restenosis, it carries a progressively high recurrence of angiographic restenosis rate during repeat 6-month follow-ups. The subgroup of patients with diffuse, severe, and/or body location in-stent restenosis proved to be at higher risk of recurrent restenosis.

Aged↗
PubMed2001

Prenatal diagnosis of ATR-X syndrome in a fetus with a new G>T splicing mutation in the XNP/ATR-X gene.

The molecular cause of the alpha-thalassemia/mental retardation syndrome (ATR-X) resides in mutations affecting the XNP/ATR-X gene. Recently molecular defects in the gene have been found in singular cases of a discrete number of X-linked mental retardation (XLMR). ATR-X-affected males are characterised by severe mental retardation, distinct facial dysmorphisms and genital abnormalities, besides a wide spectrum of pathological features and an extremely limited biological fitness. Given that molecular investigation of XNP/ATR-X mutations is made onerous by the length of the gene transcript, we carried out a prenatal diagnosis in a fetus at risk for ATR-X syndrome by initially determining the XNP/ATR-X gene haplotype before considering gene sequencing. Disease-associated haplotype analysis was performed selecting five genic (CA)n repeats that showed high heterozygosity (Het>0.7) in the general population. The fetus segregated an identical allelic pattern to that of the affected child of the family under investigation who shows features suggestive of the ATR-X syndrome. Subsequent mutational analysis of the gene revealed a novel IVS3+1G>T splicing mutation confirming the diagnosis.

Adult↗
PubMed2001

Different geographic origins of Hb Constant Spring [alpha(2) codon 142 TAA-->CAA].

BACKGROUND AND OBJECTIVES: The occurrence of Hb CS is usually limited to the geographic area which includes Southern China and South East Asia. In 1968 Hb CS was also found to occur in the Mediterranean area where it was originally described as Hb Athens. We investigated the independent origin of these termination codon mutations of the alpha 2-globin gene by determining the alpha-cluster haplotype and comparing the hematologic data from Hb CS-Hb H patients and their family members. DESIGN AND METHODS: We studied one Hb CS-Hb H patient of Greek origin and a Sicilian family in which one individual was affected by Hb CS-Hb H. The haplotype of the Hb CS allele was determined and compared to the haplotype of an Hb CS-Hb H individual of Chinese origin. RESULTS: The haplotype found for the Greek and Sicilian Hb CS was the same but differed significantly from the Asiatic Hb CS mutation. INTERPRETATION AND CONCLUSIONS: The Hb CS mutation found in both Mediterranean patients arose independently in the Mediterranean area. The difference in clinical manifestation of the Hb CS-Hb H disease in both patients is less common but consistent with similar variation in the clinical expression of analogous Hb Icaria-Hb H disease patients.

China↗
PubMed2000

Evidence that a dodecamer duplication in the gene HOPA in Xq13 is not associated with mental retardation.

A recent study suggested that a dodecamer duplication in exon 42 of the HOPA gene in Xq13 may be a significant factor in the etiology of X-linked mental retardation. In an effort to investigate this possibility, we determined the incidence of the dodecamer duplication in cohorts of non-fragile X males with mental retardation from three countries, cohorts of fragile X males from two countries, 43 probands from families with X-linked mental retardation and control cohorts from three countries. The duplication was found in 3.6-4.0% of male patients from two non-fragile X groups (Italy and South Carolina), in 1.2% from another non-fragile X group (South Africa), but in no male patients from families with X-linked mental retardation (South Carolina). The dodecamer duplication was also found in several white males with fragile X syndrome from France (5%) and South Africa (22.2%). Additionally, the duplication was found in 1.5% of South Carolinian newborn males, 2.5% South Carolinian male college students, 5% Italian male controls and 4.5% of the white South African controls. None of the black South African non-fragile X individuals with mental retardation, the fragile X or the control samples tested carried the duplication, suggesting that the duplication is rare in the black South African population. The incidence of the duplication was not significantly different between any of the groups in the study. Therefore, results of our studies in four different populations do not corroborate the findings of the previous study, and indicate that the HOPA dodecamer duplication does not convey an increased susceptibility to mental retardation.

Adult↗
PubMed1999

Genetic variations in human fetal globin gene microsatellites and their functional relevance.

Short tandem repeats are abundantly present within the genome. They are commonly used as polymorphic markers but their potential functional role is poorly documented. Several of these microsatellites have been described within the beta-globin locus and some could be involved in controlling gene expression. Our purpose was to investigate the extent and significance of the (TG)n(CG)m dinucleotide repeat polymorphisms in the two gamma-globin gene IVS2s. Two groups of subjects were studied: a group of 63 beta-thalassaemic patients presenting either with a severe Cooley's anaemia (n=50) or with thalassaemia intermedia (TI, n=13), and a control group of 60 unrelated healthy individuals. A high heterogeneity of the polymorphic repeats was demonstrated, extending the range of the published alleles from 13 to 22 and allowing a first attempt at making a phenotype/genotype correlation. One specific allele, (TG)13 in the Agamma-gene, was highly enriched in the TI patients (46.1% vs 2.9% of the Cooley's anaemia cases, P < 0.0002, and 23.3% in the normal controls, P < 0.008) and preferentially observed in TI patients with a high haemoglobin F (Hb F). Transient transfection assays in K562 cells, with the growth hormone gene as a reporter, showed a positive regulatory action mediated by a (TG)13-containing 243 nt IVS2 fragment. Finally, a first set of mobility shift experiments with erythroid (K562 and MEL) and nonerythroid (HeLa) cell lines showed binding of erythroid component(s) in this DNA region and the binding pattern was modified upon induction of MEL cells by DMSO. Thus, our in vivo and in vitro data raise the question of a possible contribution of the gamma-gene IVS2s polymorphic microsatellites to the variable Hb F synthesis in the major haemoglobinopathies: a well known, puzzling and still unanswered question.

Cell Line↗
PubMed1999

Evaluation of a mutation screening strategy for sporadic cases of ATR-X syndrome.

We report on the evaluation of a strategy for screening for XNP/ATR-X mutations in males with mental retardation and associated dysmorphology. Because nearly half of the mutations in this gene reported to date fall into a short 300 bp region of the transcript, we decided to focus in this region and to extend the mutation analysis to cases with a negative family history. This study includes 21 mentally retarded male patients selected because they had severe mental retardation and a typical facial appearance. The presence of haemoglobin H or urogenital abnormalities was not considered critical for inclusion in this study. We have identified six mutations which represents a mutation detection rate of 28%. This figure is high enough for us to propose this strategy as a valid first level of screening in a selected subset of males with mental retardation. This approach is simple, does not require RNA preparation, does not involve time consuming mutation detection methods, and can thus be applied to a large number of patients at a low cost in any given laboratory.

Adolescent↗
PubMed1998

Network analyses of Y-chromosomal types in Europe, northern Africa, and western Asia reveal specific patterns of geographic distribution.

In a study of 908 males from Europe, northern Africa, and western Asia, the variation of four Y-linked dinucleotide microsatellites was analyzed within three "frames" that are defined by mutations that are nonrecurrent, or nearly so. The rapid generation and extinction of new dinucleotide length variants causes the haplotypes within each lineage to diverge from one another. We constructed networks of "adjacent" haplotypes within each frame, by assuming changes of a single dinucleotide unit. Two small and six large networks were obtained, the latter including 94.9% of the sampled Y chromosomes. We show that the phenetic relationships among haplotypes, represented as a network, result largely from common descent and subsequent molecular radiation. The grouping of haplotypes of the same network thus fits an evolutionarily relevant criterion. Notably, this method allows the total diversity within a sample to be partitioned. Networks can be considered optimal markers for population studies, because reliable frequency estimates can be obtained in small samples. We present synthetic maps describing the incidence of different Y-chromosomal lineages in the extant human populations of the surveyed areas. Dinucleotide diversity also was used to infer time intervals for the coalescence of each network.

Africa, Northern↗
PubMed1998

New mutations in XNP/ATR-X gene: a further contribution to genotype/phenotype relationship in ATR/X syndrome. Mutations in brief no. 176. Online.

The molecular causes of ATR-X syndrome reside in mutations involving the XNP/ATR-X gene, which maps in the Xq13.3 region. Mutational analysis of this gene in two unrelated affected patients allowed us to identify two new molecular defects in two distinct regions of the gene. The first is a A-->G splice mutation in the acceptor site of the intron 11 that removes most of the 3' part of the protein, including the helicase domains and the glutamic acid stretch. Three cryptic acceptor splice sites are activated by this point mutation with consequent production of three types of abnormal mRNA: two with intronic insertions and a smaller one, approximately 10% of the total transcript, which is shorter than normal mRNA by one amino acid residue (E). Since the physiopathological characteristics of the patient carrying the splice mutation do not exhibit severe urogential abnormalities despite the lack of the -COOH end of the protein, a residual function of this third transcript is to be suspected. The second encountered nucleotide change (G-->T) leads to an R246L amino acid substitution in the putative zinc finger DNA-binding domain in the -NH2 terminal part of the protein.

DNA Helicases↗
PubMed1997

Molecular basis of alpha-thalassemia in Sicily.

To evaluate the allelic frequency and genetic diversity of alpha-thalassemia defects in Sicily, both epidemiological and patient-oriented studies were carried out. For the epidemiological study, phenotypic data were collected on more than 1000 Sicilian individuals. Among them, 427 were explored at the molecular level for nine alpha-thalassemic variants known to be common in the Mediterranean region. Our data reveal an allele frequency of 4.1% for alpha(+)-thalassemia matching that of beta-thalassemia in this region. The presence of alpha0-thalassemia (--MEDI and --CAL) was observed only in the group of referred patients. Newly acquired nucleotide sequence data on the deletional breakpoint of --CAL allowed us to design a simple PCR-based procedure for exploring this allele. The data also provide additional information concerning the genetic mechanisms involved in such large deletions.

Adolescent↗
PubMed1996

Celiac disease in Down's syndrome with HLA serological and molecular studies.

The association between Down's syndrome (DS) and celiac disease (CD) has been confirmed by several authors. The sensitivity and specificity of antigliadin antibodies (AGAs), the clinical features of subjects with DS and CD (DS-CD+), the incidence of CD, and the results of serological and molecular class I and II HLA typing were determined in a sample of 57 Sicilian subjects with DS. Six (10.5%) and 17 subjects (29.8%) showed high levels of IgA AGAs and IgG AGAs, respectively. AGAs sensitivity and specificity were lower than in the population without DS. Ten people with DS were submitted to jejunal biopsy, and seven (12.2%) showed CD according to ESPGAN criteria. All seven patients were put on gluten-free diet, followed by rapid disappearance of symptoms. Class I and II HLA serological and molecular typing was carried out in seven DS-CD + subjects, 22 people with DS without CD (DS-CD-), five subjects with CD without DS, and 20 controls. Between DS-CD + and DS-CD- subjects, no statistically significant difference regarding serum HLA class I antigens was found. DQA1*0101 allele appears significantly in DS-CD + patients and deserves to be searched for in a larger sample to assess its meaning in the DS-CD association.

Adolescent↗