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Biomedical subjects

M Martinez

Publications and source records attributed to M Martinez.

At least 181 records · Page 10Linked to original sources
PubMed1996

Toxicity of cadmium species on luminescent bacteria.

The toxicity of cadmium compounds against luminescent bacteria has been measured using the Microtox(R) toxicity bioassay and has been related to the cadmium species. Since the Microtox(R) test is carried out in NaCl (2%) and cadmium forms stable chloro complexes, NaNO(3) and NaClO(4) have been tested successfully as alternative to sodium chloride to provide the adequate osmotic protection of the bacteria. The influence of medium and ionic strength as well as different exposure times on EC(50) values has been evaluated.

Journal Article↗
PubMed1996

[Genetics of Alzheimer's disease].

This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins.

Alzheimer Disease↗
PubMed1996

Scintigraphic detection of invasive cutaneous malignant melanoma with Tc-99m MIBI.

Malignant melanoma is a relatively uncommon cancer of increasing incidence. The authors report on two cases of malignant melanoma lesions (primary and lymph node metastasis) imaged with Tc-99m MIBI. One patient revealed intense accumulation of the radiotracer in a primary skin lesion of the thorax, whereas the other patient showed increased Tc-99m MIBI uptake in a lymph node metastasis of the neck. Tc-99m MIBI imaging could be helpful in the evaluation of patients with suspicious skin lesions and in patients with known cutaneous malignant melanoma, in the investigation of lymph nodal invasion, local recurrence, and metastatic spread.

Adult↗
PubMed1996

No founder effect in three novel Alzheimer's disease families with APP 717 Val-->Ile mutation. Clerget-darpoux. French Alzheimer's Disease Study Group.

We sequenced exons 16 and 17 of the APP (amyloid precursor protein) gene in 18 unrelated French Alzheimer's disease (AD) patients. These patients had an onset before the age of 60 and belonged to families with autosomal dominant transmission of the disease. We detected the APP 717 Val-->Ile mutation in three out of 18 (16.6%) families. In these three families, all affected subjects had the APOE 3/3 genotype, but their ages of onset ranged from 38 to 60 years, indicating that factors other than the APOE genotype influence age of onset. Analysis of two polymorphic loci adjacent to the APP gene showed that at least two independent mutational events had occurred within these pedigrees, in spite of their origin in the same region of France.

Adult↗
PubMed1996

Effect of HMG-CoA reductase inhibitors on red blood cell membrane lipids and haemorheological parameters, in patients affected by familial hypercholesterolemia.

Eighteen patients with familial hypercholesterolemia treated with lovastatin (40 mg/day) for three months were studied to find out whether the drug induces modifications in the lipid composition of the erythrocyte membrane and whether these induce changes in the rheological behaviour of the red blood cell. Our results show that the changes observed in plasma lipids correlate with a significant decrease in the cholesterol/phospholipid ratio of the red blood cell membrane. These changes in the lipid composition of the cell are statistically related to a decrease in the erythrocyte aggregability and an improvement in blood filterability probably due to an increase in the red blood cell deformability.

Adult↗
PubMed1996

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. I: nosology, sex and age of onset.

BACKGROUND: Little is known about the long-term outcome of schizophrenia that has its onset during childhood and early adolescence (early-onset schizophrenia, or EO-SZ). Whether or not EO-SZ is an aetiologically separate form of schizophrenia (SZ) is unresolved. METHOD: The study was a 14.8-year follow-up, using methods such as systematic sampling, evaluation of possible non-respondent bias, consensus best-estimate diagnoses (DSM-III-R) made independently in childhood and adulthood, measures of positive and negative dimensions, of non-psychotic behaviour disturbances (NPBD) and of developmental problems before the appearance of SZ. RESULTS: There was high stability of EO-SZ (n = 40) diagnoses (mean onset at 14.0 years) until adulthood (mean age at follow-up 28.8 years) but a lower stability of positive and negative schizophrenic dimensions. There was a poor outcome of EO-SZ, a strong over-representation of males but few gender differences, and no effect of age of onset on clinical features and outcome. CONCLUSIONS: EO-SZ taken as a whole shows no qualitative differences to adult-onset SZ. However, a distinction through the onset of preschizophrenic developmental problems or NPBD might be a way to investigate heterogeneity within EO-SZ.

Adolescent↗
PubMed1996

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: Postnegative distinction and childhood predictors of adult outcome.

BACKGROUND: The aim of this study was to verify the presence and stability across life of the positive/negative distinction in early-onset schizophrenia (EO-SZ) through a longitudinal factor analysis of the schizophrenic dimensions, and to identify the factors predicting several indices of long-term outcome for EO-SZ. METHOD: Forty children consecutively referred for DSM-III-R schizophrenia (SZ) in a specific catchment area comprised the sample. RESULTS: Across a 14.8-year follow-up, longitudinal factor analysis identified two separate factors corresponding to the positive and negative symptom dimensions. We also observed that: the GAS rated over the last three years of adult illness and the severity of negative symptoms during the stabilised interepisode intervals in adulthood were the indices of adult outcome that were most easily predicted; and the best childhood predictors of adult outcome were premorbid functioning and severity of positive and negative symptoms during acute episodes. CONCLUSIONS: The presence of premorbid non-psychotic behaviour disturbances (NPBD) and premorbid developmental problems was not related to severity of outcome, in contrast to the former variables.

Adolescent↗
PubMed1996

[A phase II study with mitoxantrone-vinorelbine association in the treatment of advanced breast cancer in elderly women].

To assess efficacy and toxicity of less toxic analogs for advanced breast cancer in elderly women, we performed a phase II study using the combination mitoxantrone (MTZ)-vinorelbine (VNR). From January 1991 to May 1993, 25 women older than 70 years received a chemotherapy consisting in 10 mg/m2 of MTZ on day 1, followed by 20 mg/m2 of VNR on day 1 and 8. Cycles were repeated every 21 days for a maximum of ten cycles in the case of an objective response. Sixteen women previously received first line hormonotherapy, eight with only one metastatic site. Twenty-three patients are evaluable for response and toxicity. An objective response was observed in five cases (22%), with a median time to progression of 13 months. More than 75% of the planned dose-intensity, for MTZ and VNR was received by 90 and 57.2% of patients, respectively. Dose-limiting toxicity was myelosuppression but no febrile neutropenia was observed. Extra haematologic toxicities were unfrequent. This combination is well tolerated by elderly women, but best results could be achieved by increasing delivered dose intensity.

Aged↗
PubMed1995

Evidence for apolipoprotein E epsilon 4 association in early-onset Alzheimer's patients with late-onset relatives.

Recently several reports have extended the apolipoprotein E (APOE) epsilon 4 association found in late-onset Alzheimer's disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset < or = 60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE epsilon 4 allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that for an individual, bearing at least one epsilon 4 allele increases both the risk of AD before age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases.

Adult↗
PubMed1995

Further evidence for anticipation in schizophrenia.

The term 'anticipation' is used to describe the increase in disease severity or the decrease in age of onset in succeeding generations within families. This phenomenon has been related to expansion of trinucleotide repeat DNA sequences in some genetic illnesses. We examined age of onset among two generations in familial schizophrenia. Twenty-six unilineal pedigrees previously ascertained for linkage studies were used. We defined the older generation as G1 and the younger generation as G2. Cumulative survival analysis for intergenerational pairwise comparisons in groups G1 and G2 showed a significantly earlier age of onset in G2 (10 years earlier). Additional analyses, which took into account some biases such as the censoring effect of age at interview and preferential ascertainment of late-onset parents, did not modify the results. No evidence for genomic imprinting was found in our sample. We conclude that anticipation occurs in our sample of familial schizophrenia.

Adolescent↗
PubMed1995

No evidence for linkage or association between the dopamine transporter gene and schizophrenia in a French population.

Pharmacological and clinical findings suggest that the dopamine transporter (DAT) gene may be involved in the genetic predisposition to schizophrenia. Linkage of a Taq I VNTR polymorphism in the DAT gene to schizophrenia was studied in multiplex schizophrenic families from Rouen, France (n = 10) and the Island of La Réunion (n = 21). Neither the lod score method nor nonparametric methods (the affected pedigree member method of Weeks and Lange [1988] and the sibling method of Green and Woodrow [1977]) provided any evidence for linkage. An association study, carried out within a group of 91 unrelated schizophrenic patients from Rouen and 91 matched control subjects, examined a 40 base-pair repeat polymorphism located in the 3' nontranslated end of the DAT mRNA. There was no significant difference in allelic or genotypic frequencies between the two groups. These results exclude any substantial involvement of the DAT gene in the pathogenesis of schizophrenia in the population studied.

Adult↗
PubMed1995

Yeast aminopeptidase I is post-translationally sorted from the cytosol to the vacuole by a mechanism mediated by its bipartite N-terminal extension.

Transport of aminopeptidase I (API) to the vacuole appears to be insensitive to blockage of the secretory pathway. Here we show that the N-terminal extension of the 61 kDa precursor of API (pAPI) is proteolytically processed in two sequential steps. The first step involves proteinase A (PrA) and produces a 55 kDa unstable intermediate (iAPI). The second step involves proteinase B (PrB) and converts iAPI into the 50 kDa stable, mature enzyme (mAPI). Reversion of the cup1 growth phenotype by a pAPI-CUP1 chimera indicates that pAPI is transported to the vacuole by a post-translational mechanism. Deletion of the first 16 amino acids results in accumulation of the truncated protein in the cytosol, indicating that pAPI is actively transported to the vacuole. The chimera pAPI-myc, constructed by fusing a myc tag to the C-terminus of pAPI, was exploited to dissect the mechanism of pAPI transport. Cell fractionation studies show the presence of iAPI-myc and mAPI in a fraction of vacuoles purified by density centrifugation. This and the sequential conversion of pAPI-myc into iAPI-myc and mAPI lacking the myc tag is consistent with insertion of pAPI into the vacuolar membrane through its N-terminal extension. The specific mechanism of API sorting demonstrates a new pathway of protein transport in vacuolar biogenesis.

Amino Acid Sequence↗
PubMed1995

Differential regulation of sphingomyelinase and ceramidase activities by growth factors and cytokines. Implications for cellular proliferation and differentiation.

Sphingosine is a product of sphingolipid metabolism that has been linked to a protein kinase C-independent mitogenic response. In previously published data, utilizing an in vitro model system for platelet-derived growth factor (PDGF)-induced vascular smooth muscle proliferation, we have demonstrated that sphingosine is increased at the expense of a concomitant decrease in ceramide formation, implicating an altered ceramidase activity. To explore mechanisms of growth factor-stimulated sphingosine formation, we have developed and investigated a cell-free model system assessing ceramidase activity. We now report that an alkaline, membrane-associated, ceramidase activity in the rat glomerular mesangial cell, a smooth muscle-like pericyte, is up-regulated by growth factors, apparently via a tyrosine kinase phosphorylation mechanism. PDGF also stimulated sphingomyelinase activity which generates sufficient substrate to drive the subsequent ceramidase reaction. Inflammatory cytokines, including interleukin-1, and tumor necrosis factor-alpha, stimulated sphingomyelinase but not ceramidase activity, a result consistent with the cellular accumulation of the ceramide, apoptidic, differentiating second messenger. Mitogenic vasoconstrictor peptides such as endothelin-1 stimulated neither sphingomyelinase nor ceramidase activities. An inhibitor of ceramidase activity, N-oleoylethanolamine, reduced PDGF- but not endothelin-1-stimulated proliferation. Thus, we conclude that, in mesangial cells, growth factors but not vasoconstrictor peptides or cytokines induce mitogenesis, in part, through ceramidase-mediated sphingosine formation.

Amidohydrolases↗
PubMed1995

Characteristics of familial aggregation in early-onset Alzheimer's disease: evidence of subgroups.

Characteristics of familial aggregation of Alzheimer's Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determination of early-onset Alzheimer's disease.

Adult↗
PubMed1995

Allelic association at the D14S43 locus in early onset Alzheimer's disease. French Alzheimer's Disease Collaborative Study Group.

The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer's disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer's disease (< 60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample.

Adult↗