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Biomedical subjects

R Pinto

Publications and source records attributed to R Pinto.

At least 55 records · Page 3Linked to original sources
PubMed1996

Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma.

BACKGROUND: Global DNA hypomethylation has been found in the premalignant stages of some neoplasms and has been implicated as an important factor for tumour progression. AIMS: The aim of this study was to evaluate whether DNA hypomethylation occurs during the process of gastric carcinogenesis. METHODS: Gastric specimens were obtained from 49 patients and histologically classified as: normal 10, superficial gastritis 14, chronic atrophic gastritis with intestinal metaplasia 15, and intestinal type of gastric carcinoma 10. Global DNA methylation was assessed by incubating DNA with (3H)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (3H) methyl groups reflects a lower degree of intrinsic methylation. RESULTS: A graduated increase in (3H) methyl group incorporation into DNA was found over the range extending from normal gastric mucosa, to superficial gastritis and to chronic atrophic gastritis (136,556 (24,085) v 235,725 (38,636) v 400,998 (26,747 dpm/micrograms/DNA respectively; p = 0.0002). No further increase was found in specimens from patients with carcinoma. No differences were found between extent of DNA methylation in neoplastic or non-neoplastic mucosa from patients with gastric carcinoma. Hypomethylation of DNA increased substantially with severe atrophy (p = 0.01) or with type III intestinal metaplasia (p = 0.15). CONCLUSIONS: Global DNA hypomethylation occurs in the early stages of gastric carcinogenesis, and it may be a novel biomarker of gastric neoplasia, useful in monitoring the response to chemopreventive agents.

Adenocarcinoma↗
PubMed1996

LASIK for high myopia: one year experience.

BACKGROUND AND OBJECTIVE: Laser in situ keratomileusis (LASIK) is a technique combining the advantages of lamellar corneal surgery (not disturbing Bowman's layer) with the precision of excimer laser surgery. It can be used to correct myopia in a wide range of diopters. In this study we present our data on the first 34 consecutive cases of myopia correction by LASIK. PATIENTS AND METHODS: Thirty four eyes of 27 patients with myopia ranging from -10.00 to -22.50 diopters (D) were operated with LASIK. The follow-up was from six months to one year. The mean age was 33.02 +/- 7.98 years, 32.4% were males and 67.6% were females. Surgery was always performed with the Chiron Automated corneal shaper resecting a corneal flap of 160 mu and then ablating the stromal bed (OZ 4.50 mm) with the Summit OmniMed 5.0 excimer laser. The parameters used to assess the results were predictability, safety (variation of spectacle corrected visual acuity), stability, and patient satisfaction. RESULTS: Of the patients, 67.65% were between -1.00 and +1.00 at 6 months; 44.11% of eyes retained the same spectacle corrected visual acuity, 11.76% gained 1 line, 26.47% gained 2 lines, 8.82% lost 1 line and 8.82% lost 2 lines. Refraction at 1 month was 0.07 +/- 1.99 (range, -4.00 to +4.00); at 3 months 0.61 +/- 1.69 (range, -4.25 to +2.25); and at 6 months 0.81 +/- 1.71 (range, -4.75 to +2.25). Of the patients, 85.3% were happy with the procedure. Complications included two dislocated caps in the immediately post-operative period and two cases of epithelial ingrowth under the cap. Two eyes developed irregular astigmatism. These complications were found in the first two sessions of surgery and are related to the learning curve of the method. CONCLUSION: Results suggest that LASIK is a viable method for correction of high myopia with few complications and may have advantages over keratomileusis and PRK as it combines the best features of both methods--it preserves Bowman's layer and has the excimer laser precision. Refining the nomogram of ablation should result in even better results.

Adult↗
PubMed1995

Tay-Sachs disease: intron 7 splice junction mutation in two Portuguese patients.

A single nucleotide transversion (G-->C) in the 5' donor site of intron 7 of the beta-hexosaminidase alpha-chain gene was identified in two Portuguese patients with infantile Tay-Sachs disease. One patient was found to be homozygous and the other a compound heterozygote with the four-base insertion in exon 11 on the other allele. In fibroblasts from the homozygous patient the beta-hexosaminidase alpha mRNA was observed as a nearly undetectable fast migrating band. Through cDNA-PCR amplification and hybridization with full length alpha cDNA several fragments of smaller size than the normal transcript were detected, most of them lacking exon 7. We propose that this point mutation in the 5' donor site of intron 7 of the beta-hexosaminidase alpha-chain gene is responsible for an inefficient and abnormal processing of the mutant transcript, resulting in functional abnormality.

Base Sequence↗
PubMed1995

Prenatal diagnosis of GM2-gangliosidosis B1 variant.

Prenatal diagnosis in a pregnancy at risk for a juvenile B1 variant of GM2-gangliosidosis was carried out. The biochemical study of the cultured amniocytes and the affected fetal brain is reported. The results obtained show that the sulphated artificial substrate can be used in the diagnosis of B1 variant, but not the neutral one. The accumulation of GM2-ganglioside in the fetal brain of the B1 juvenile form and an infantile form of GM2-gangliosidosis (0 variant) was compared.

Amniocentesis↗
PubMed1995

[Lipid peroxidation, production of PGE2 and cellular mortality induced by UV in cultured human skin fibroblasts].

UV irradiation induces lipid peroxidation (LPO) and cell damage. The aim of the present work was the study of UVB radiation effects on cultured human skin fibroblasts, concerning LPO, prostaglandine E2 (PGE2) formation and cell viability. The cells were exposed to 50, 100, and 150 mJ/cm2 of UVB irradiation. Cellular TBARS and supernatant fluorescent substances were measured spectrofluorimetrically. PGE2 was measured using an immunoenzymatic method. Cell viability was evaluated by the MTT test. All determinations were done after a 2 h incubation period post-irradiation. TBARS were increased for all doses of irradiation (p < 0.001). Fluorescent substances differed from controls at 50 mJ/cm2 (p < 0.001). UVB at 100 and 150 mJ/cm2 decreased cellular viability (p < 0.001). An increase of PGE2 was observed with UVB at 150 mJ/cm2 (p < 0.001). These results confirm the occurrence of LPO and cytotoxicity after UV irradiation; on the other hand, this study showed the formation of PGE2 induced by UV light on cultured human skin fibroblasts. We propose a relationship between these phenomena.

Cell Death↗
PubMed1994

The N370S mutation in the glucocerebrosidase gene of Portuguese type 1 Gaucher patients: linkage to the PvuII polymorphism.

The mutation N370S accounts for 63% of the mutated glucocerebrosidase alleles of Portuguese type 1 Gaucher patients. It has been shown previously that this mutation is linked to the Pv1.1- form of the PvuII polymorphism and suggested that the N370S mutation in glucocerebrosidase alleles has an Ashkenazi Jewish origin. We have found that in Portuguese type 1 Gaucher patients this mutation is also invariably associated with the Pv1.1- haplotype, despite the fact that there is no evidence of Ashkenazi Jewish background in this population.

DNA↗
PubMed1994

X-linked adrenoleukodystrophy in patients with idiopathic Addison disease.

UNLABELLED: The two main causes of primary adrenal disease are tuberculosis and auto-immune adrenal destruction. The latter is responsible for about 70% of the cases of primary adrenal insufficiency (Addison disease). Commonly referred to as a rare cause of adrenal failure is X-linked adrenoleukodystrophy (ALD), a demyelinating peroxisomal disorder affecting 1: 20,000 Caucasian males. Albeit primary adrenal insufficiency is a rare entity per se, we decided to study patients with idiopathic Addison disease and establish the frequency of ALD as a cause of adrenal insufficiency. The biochemical defect of ALD was found in 5 out of 24 patients. The small number of cases in our series led us to include in our analysis the published results of two other groups of investigators. This analysis indicates that the proportion of cases in which Addison disease is attributable to ALD is age dependent. It is highest when the adrenal insufficiency manifests before 15 years. This study clearly demonstrates that the proportion of ALD in patients presenting primary adrenal insufficiency has been under-estimated. CONCLUSION: Addison disease manifesting during the first decade of life has a high likelihood of being the first sign of X-linked adrenoleukodystrophy.

Addison Disease↗
PubMed1994

Gaucher disease: N370S glucocerebrosidase gene frequency in the Portuguese population.

In the Portuguese population the most frequent form of Gaucher disease is type 1. The N370S glucocerebrosidase gene mutation accounts for 63% of mutated alleles. The frequency of this mutation was accurately determined in the Portuguese population, which does not present an Ashkenazi Jewish genetic background. A gene frequency of 0.0043, with 95% confidence limits between 0.0023 and 0.0063, was obtained studying the genomic DNA of 2000 blood cards randomly sampled from the national neonatal screening program. On the basis of this frequency a significantly high number of homozygotes for the N370S mutation should be expected in the Portuguese population. This finding supports the idea that the majority of homozygotes for this mutation present a very mild clinical phenotype and remain undiagnosed.

Chi-Square Distribution↗
PubMed1994

Molecular characterisation of type 1 Gaucher disease families and patients: intrafamilial heterogeneity at the clinical level.

Type 1 Gaucher disease families were studied in an attempt to establish a phenotype/genotype correlation in affected persons and also to identify carriers accurately. In the Portuguese type 1 Gaucher patients, screening for mutations N370S, L444P, R463C, and 1066 + 1 G-->A allowed the identification of 85% of the alleles among unrelated patients. A subclinical case with genotype N370S/1066 + 1 G-->A was identified in one family in which there were three other symptomatic sibs. To our knowledge this is the first subclinical case with a genotype other than N370S/N370S. No genotype-phenotype correlation could be established and considerable clinical heterogeneity was found even among sibs with the same genotype. The data collected on the origins of the Gaucher families indicated two areas in northern Portugal where a higher frequency of the disease may be expected to exist.

Adult↗
PubMed1993

Identification of Gaucher disease carriers: glucocerebrosidase antigen and DNA analysis.

Detection of Portuguese carriers for Gaucher disease with urine samples as a source of enzyme was carried out using an immunological procedure employing an anti-glucocerebrosidase monoclonal antibody and by DNA analysis for the presence of the two glucocerebrosidase mutations most frequently found in Portuguese Gaucher patients. Patients, obligate and putative carriers, and individuals unrelated to patients were analyzed. It was found that the vast majority of carriers for the two tested mutations (N370S and L444P), as well as obligate carriers for as yet unidentified mutations, could be distinguished from control subjects with this relatively easy and economic immunological procedure. Furthermore, results obtained for control subjects suggested a high frequency of carriers for the N370S mutation in the Portuguese population. It is concluded that this procedure may be useful in mass screening for carrier detection prior to DNA analysis, particularly in the study of non-Ashkenazi populations in which a significant number of mutations associated with Gaucher disease remain unidentified.

Adolescent↗
PubMed1993

Identification of GM2-gangliosidosis B1 variant carriers.

GM2-gangliosidosis B1 variant, considered a rare disorder with a wide geographical and ethnic distribution, appears to be exceptionally frequent in Portugal. In order to establish a carrier detection method for this disease we have determined the ratio of enzymatic activities against 4MUGS and 4MUG in urine from B1 variant obligate carriers and controls, using the total extract and the Hex A immunobound to a monoclonal antibody. The Hex A immunoassay was applied to the identification of carriers in B1 variant families and the results obtained were compared with those from DNA analysis. The reliability and feasibility of the Hex A immunoassay make it a suitable method for B1 variant carrier screening, which is particularly important for the prevention of this severe neurological disease in the population at risk.

Adolescent↗
PubMed1993

Management of chronic myeloid leukemia in chronic phase with autologous stem cell transplantation and alpha-2 interferon: cytogenetic and clinical results.

Forty-eight patients with chronic myeloid leukemia (CML) in chronic phase (CP) were treated by autologous stem cells transplantation (ASCT) and alpha Interferon (IFN) with three approaches: 1) ASCT at diagnosis followed by IFN, 2) ASCT post IFN with cells collected after an interval from IFN discontinuance, followed by IFN, 3) ASCT in patients selected by cytoconversion obtained with IFN, performed soon after IFN discontinuance. Following ASCT, a major karyotype response (more than 65% Ph1 negative cells, MKR) was observed at least once in 40%, 53% and 83% of patients from the three groups, respectively. At last follow-ups (median 39, 40 and 21 months, respectively) 19%, 13% and 67% of patients still present a MKR with 2 patients from group 1 and 4 patients from group 3 being 100% Ph' negative. Projected survival from diagnosis is 77% at 52 months for patients from group 1 and 47% at 75 months for patients from group 2. Present data indicate that 1) IFN can stabilize results obtained with ASCT, 2) ASCT can potentiate responses to IFN, 3) combined ASCT and IFN can improve survival. Longer follow-up of patients and randomized studies are required to define the real impact on disease outcome by these treatment approaches.

Adult↗