Biomedical subjects

M Martinez

Publications and source records attributed to M Martinez.

At least 163 records · Page 9Linked to original sources

PubMed1997

The existence of human immunodeficiency virus resistance to nucleoside-analog drugs has not been shown.

Human immunodeficiency virus is thought to develop resistance to the common nucleoside-analog drugs by undergoing certain mutations in the pol gene. However, laboratory techniques which test for viral sensitivity to the drugs fail to provide direct evidence for the existence of the phenomenon. Available clinical and laboratory evidence indicates that drug resistance is entirely an artifact of the laboratory and most likely does not take place under natural circumstances. A method to directly confirm or disprove this notion is outlined.

Anti-HIV Agents↗

PubMed1997

Detection of two new polymorphic sites in the human interleukin-1 beta gene: lack of association with schizophrenia in a French population.

The pathogenesis of schizophrenia might involve abnormal development of the human brain. Interleukin-1 beta is a cytokine implicated in the development of the central nervous system and therefore its gene is a candidate gene in schizophrenia. Polymorphisms within the coding sequence and the 3'UTR of the IL1 beta gene were searched for using PCR-SSCP. Two polymorphisms, 1B-175/1B-173 and 1B-1765/1B-1763 were found in addition to the previously published TaqI site. Furthermore, a mutant was found in codon 106 (exon 5) of the IL1 beta gene located next to the published polymorphism at the TaqI site and abolishing this site. This novel mutation encodes an Asp in place of an Asn and was only observed in one patient in our French population. Association studies were conducted with the polymorphisms 1B-175/1B-173 and TaqI. There was no allelic or genotypic association between either of the two polymorphisms and schizophrenia. In our population, there is no evidence that the IL1 beta gene is involved in schizophrenia.

Adult↗

PubMed1997

No effect of the alpha1-antichymotrypsin A allele in Alzheimer's disease.

The apolipoprotein E (ApoE)-epsilon4 allele is associated in a dose dependent manner to an increased risk for Alzheimer's disease. However, the ApoE-epsilon4 allele effect does not account for all patients with Alzheimer's disease, and the existence of other genetic risk factors has been postulated. Kamboh et al reported an association between Alzheimer's disease and the A allele of alpha1-antichymotrypsin (Aact) gene, which was not confirmed in a larger series more recently analysed. The ApoE and Aact genotypes were analysed in 314 patients with Alzheimer's disease and 173 healthy controls, confirming the dose dependent effect of the ApoE-epsilon4 allele. Nevertheless, even using odds ratios adjusted for age and sex, there was no significant effect of the Aact genotype on Alzheimer's disease or on the ApoE-epsilon4 allele associated risk for Alzheimer's disease.

Alleles↗

PubMed1997

The Washington Heights-Inwood Genetic Study of Essential Tremor: methodologic issues in essential-tremor research.

Essential tremor (ET) is the most prevalent movement disorder. It is unknown to what extent ET clusters within families, and the role of genetic susceptibility in etiology of ET has not been adequately investigated at the population level. The problem is largely methodological, with few well-designed studies. The Washington Height-Inwood Genetic Study of ET, begun in 1955, is designed to investigate the genetics of ET using a methodology that has not been applied to ET research to date. Part of the design includes a new set of clinical and electrophysiological diagnostic criteria for ET; the present paper describes this novel study design.

Case-Control Studies↗

PubMed1997

Childhood/early adolescence-onset and adult-onset schizophrenia. Heterogeneity at the dopamine D3 receptor gene.

BACKGROUND: The dopamine D3 receptor gene (DRD3) is a meaningful candidate gene because it unifies the dopamine and the limbic hypotheses for schizophrenia. We tested for an allelic association between schizophrenia and the DRD3 Mscl alleles, hypothesising heterogeneity between childhood/early adolescence-onset schizophrenia (CO-SZ) and adult-onset schizophrenia (A-SZ). METHOD: The frequencies of the DRD3 alleles were compared between 70 DSM-III-R schizophrenics (35 CO-SZ and 35 A-SZ) and 79 controls. RESULTS: Compared with the controls, the subsample of A-SZ, but not CO-SZ, showed an over-proportion (P = 0.025) of allele 1. The association was not found in the total sample, combining the two subsamples. CONCLUSIONS: Consistently with former studies, our data suggest an aetiological heterogeneity between CO-SZ and A-SZ and a possible specificity of the excess of allele 1 to the familial form of schizophrenia and to schizophrenia with a better outcome.

Adolescent↗

PubMed1997

Albendazole therapy for neurocysticercosis: a prospective double-blind trial comparing 7 versus 14 days of treatment. Cysticercosis Working Group in Peru.

OBJECTIVE: To compare the effectiveness of two regimens of albendazole therapy for neurocysticercosis. DESIGN: Randomized, double-blind clinical trial. SETTINGS: Patients admitted to neurologic wards in Lima, Peru. PATIENTS: Adult patients with active neurocysticercosis demonstrated by CT and Western blot (immunoblot). INTERVENTION: One week (n = 25) versus 2 weeks (n = 25) of albendazole therapy. MEASUREMENTS: Decrease in the number of cysts on CT. RESULTS: Effectiveness of albendazole was 78%, with no difference between the groups when compared 3 months after therapy. Complete cure was obtained in only 38% of patients. Patients with more than 20 cysts had poorer responses to therapy. The clinical course and EEG evolution improved in most patients. Side effects were present in 38% of patients, mainly mild, transient gastrointestinal symptoms. Therapy was also associated with exacerbation of neurologic symptoms. Two patients died in the first year after therapy, both because of aggregated infections of ventricle-peritoneal shunts. One-year follow-up CT showed lesions in three of 10 patients presumed to be cured 3 months after therapy. CONCLUSIONS: Extension of albendazole therapy for more than 7 days adds no benefits for the patients.

Adult↗

PubMed1997

Subjective symptomatology of asthma: validation of the asthma symptom checklist in an outpatient Spanish population.

The objective of this study was to validate the Asthma Symptom Checklist (ASC) so that it could be reliably used to assess the subjective symptomatology of asthma attacks in our context. Subjective symptomatology of asthma was examined in a group of 100 adult Spanish outpatients (57 women, 43 men; 17-69 years of age) with asthma. All of them completed the modified version of the ASC as well as questionnaires of depression, anxiety, and self-management of asthma (self-efficacy expectancies and health care utilization). Data about duration and severity of asthma, as well as dyspnea and %FEV1, were also recorded. The highest reliability Cronbach alpha indexes were for the panic-fear and fatigue scales. The oblique rotation of the ASC revealed five correlated factors (53% of the total variance explained): 1) panic-fear, 2) airways obstruction, 3) airways obstruction and panic-fear, 4) fatigue and irritability, 5) hyperventilation. The structure of factors was revalidated using orthogonal (varimax) rotation. Construct validity was examined by Person product-moment coefficient correlations, ANOVAs (asthma severity x ASC scores), and t-tests (sex by ASC scores). Panic-fear showed the best construct validity, as it was related to the severity of the asthma and the use of high-cost health care resources. There were no differences in ASC scores either on the basis of the asthma severity or on the sex of patients. The ASC factors represent stable components of subjective symptomatology of asthma attacks, especially with regard to the panic-fear and the hyperventilation subscales; however, the structure of the checklist as a whole was not identical to those reported in other studies. Correlations of the ASC with clinical variables related to asthma severity support the construct validity of the instrument and confirm its utility to evaluate the subjective symptomatology of asthma attacks in outpatients.

Adolescent↗

PubMed1997

Apolipoprotein E and Alzheimer disease: genotype-specific risks by age and sex.

The distribution of apolipoprotein E (APOE) genotypes as a function of age and sex has been examined in a French population of 417 Alzheimer disease (AD) patients and 1,030 control subjects. When compared to the APOE epsilon3 allele, an increased risk associated with the APOE epsilon4 allele (odds ratio [OR] [epsilon4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a protective effect of the APOE epsilon2 allele (OR[epsilon2] = 0.5 with 95% CI = 0.3-0.98; P = .012) were retrieved. An effect of the epsilon4 allele dosage on susceptibility was confirmed (OR[epsilon4/epsilon4] vs. the epsilon3/epsilon3 genotype = 11.2 [95% CI = 4.0-31.6]; OR[epsilon3/epsilon4] vs. the epsilon3/epsilon3 genotype = 2.2 [95% CI = 1.5-3.5]). The frequency of the epsilon4 allele was lower in male cases than in female cases, but, since a similar difference was found in controls, this does not lead to a difference in OR between sex. ORs for the epsilon4 allele versus the epsilon3 allele, OR(epsilon4), were not equal in all age classes: OR(epsilon4) in the extreme groups with onset at < 60 years or > 79 years were significantly lower than those from the age groups 60-79 years. In epsilon3/epsilon4 individuals, sex-specific lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85 years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09-0.28) for women.

Age of Onset↗

PubMed1997

Morphologic changes in the vesical transition epithelium of alcoholic rats.

Few studies are available about the effect of alcohol on the epithelium of the urinary bladder. In the present investigation we studied the ultrastructure of the vesical transition epithelium of normal rats and of rats submitted to experimental chronic alcoholism. Adult rats were submitted to experimental chronic alcoholism by the ingestion of sugar cane liquor. The vesical epithelium was examined after 60, 120, 180 and 240 days of alcohol treatment by transmission electron microscopy. Surface cells presented nuclear and cytoplasmic changes and marked cellular desquamation. There was an increase in multivesicular bodies and lysosomes suggesting cell degeneration. Mast cell infiltration was observed, possibly related to increased epithelial sensitivity. Intracellular spaces were frequently observed. The transmission epithelium of the urinary bladder was found to be sensitive to the action of alcohol, as demonstrated by the changes in the components of the blood-urine barrier, the greater sensitivity to inflammation, the increase in cell desquamation and the greater recycling of the apical membrane and of the fusiform vesicles of surface cells observed in alcoholic rats.

Alcoholism↗

PubMed1997

Social, familial and medical aspects of Usher syndrome in Colombia.

A psycho-social study was performed in 19 Colombian families with 40 affected individuals with Usher syndrome, identified through our national screening program for this disease in Colombia. The study was aimed to understand their needs, kind of familial inter-relationships, and social and familial implications of the patients' double sensorial limitation, in order to provide enough information to support the importance of early diagnosis, appropriate genetic counseling, and the establishment of adequate educational and rehabilitation programs in Colombia.

Adolescent↗

PubMed1997

A morphometric ultrastructural study of the seminal vesicle of rats submitted to experimental chronic alcoholism.

The effects of chronic alcohol ingestion on the secretory epithelium of the seminal vesicle were studied in rats (Rattus norvegicus). Male adult albino Wistar rats were divided into two groups: alcoholic and control. Tips of the seminal vesicle were removed and prepared for light and electron microscopy. Ultrastructural observations on the epithelial cells of the seminal vesicle showed reduced epithelial cell size, decreased apical secretory vacuoles, irregularly shaped nuclei with deep infoldings, increased lipid droplets and dense bodies, a small number of microvilli covering the cell surface, and signs of degeneration. In addition to the hormonal effects, alcohol may act on the secretory epithelium of the seminal vesicle.

Alcoholism↗

PubMed1997

Cloning, characterization and identification of the gene encoding phosphatidylinositol 4-kinase.

The vast majority of AIDS-related deaths are associated with opportunistic infections. For fungal infections, there are few effective antifungals, particularly for systemic use. The discovery that very low doses of the bleomycin family of anticancer chemical congeners compromise the integrity of fungal cell walls led to our approach to identify genes that complement-cell wall defects, and develop methods to facilitate the identification of new antifungals targeted to fungal cell walls. This report describes one of the genes cloned by complementation of the blm1-1 mutation of S. cerevisiae using a YCp50-based yeast genomic library. Characterization and identification of the gene were carried out using drug screening tests, Southern hybridization analyses, DNA sequencing and DNA sequence similarity searches in databases. The gene STT4, is essential for viability and encodes a phosphatidylinositol 4-kinase that plays an important role in the phosphatidylinositol-mediated signal transduction pathway required for cell wall integrity. Like blm1-1 mutant strains, stt4 cells arrest mostly in the G2/M phase of the cell cycle. Further studies using this approach should help us understand the role of PI4-K in maintaining fungal cell-wall integrity, identify additional genes affecting potential target structures in cell walls of opportunistic fungal pathogens in AIDS patients, and assist in drug discovery and antifungal drug design.

1-Phosphatidylinositol 4-Kinase↗

PubMed1996

Age-related increase in oxidized proteins in mouse synaptic mitochondria.

Since it has been proposed that oxidized protein accumulation plays a critical role in brain aging, we have investigated their contents in synaptic mitochondria from five age groups of mice. Protein carbonyl content in synaptic mitochondria showed a significant positive correlation with age (r = 0.95, P = 0.01). A linear inverse relationship was observed between protein carbonyl content and complex IV/complex I ratio (which was used as an index of imbalance between mitochondrial respiratory complexes) in synaptic mitochondria in the five age groups (r = -0.99, P < 0.001). We suggest that age-related accumulation of oxidized proteins in synaptic mitochondria may be the result of an age-dependent increase in reactive oxygen species generation because of a disarrangement of mitochondrial oxidative phosphorylation.

Aging↗

PubMed1996

Expression and regulation of the lipoprotein lipase gene in human adrenal cortex.

Lipoprotein lipase (LPL), an enzyme which hydrolyzes triglycerides and participates in the catabolism of remnant lipoproteins, plays a crucial role in energy and lipid metabolism. The goal of this study was to analyze the expression and regulation of the LPL gene in human adrenals. Reverse transcriptase-polymerase chain reaction amplification and sequence analysis demonstrated the presence of LPL mRNA in fetal and adult human adrenal cortex. Furthermore, the human adrenocortical carcinoma cell line, NCI-H295, expresses LPL mRNA and protein, which is localized to the outer cellular membrane as demonstrated by immunofluorescence confocal microscopy and can be released in the medium by heparin addition. To asses whether the LPL gene is regulated by agents regulating adrenal steroidogenesis, NCI-H295 cells were treated with activators of second messenger systems. Whereas the calcium-ionophore A23187 did not affect LPL gene expression, treatment with phorbol 12-myristate 13-acetate decreased LPL mRNA levels in a time- and dose-dependent manner. This decrease after phorbol 12-myristate 13-acetate was associated with diminished heparin-releasable LPL mass and activity in the culture medium. Addition of the cAMP analog 8-Br-cAMP to NCI-H295 cells resulted in a rapid, but transient dose-dependent induction of LPL mRNA. Treatment with the protein synthesis inhibitor cycloheximide gradually induced, whereas simultaneous addition of cAMP and cycloheximide superinduced LPL mRNA levels. Nuclear run-on analysis indicated that the effects of cAMP and cycloheximide occurred at the transcriptional and post-transcriptional level, respectively. Transient co-transfection assays demonstrated that the first 230 base pairs of the proximal LPL promoter contain a cAMP-responsive element activated by protein kinase A and transcription factors belonging to the CREB/CREM family. These data indicate that LPL is expressed in human adrenal cortex and regulated in NCI-H295 adrenocortical carcinoma cells by activators of the protein kinase A and protein kinase C second messenger pathways in a manner comparable to P450scc, which catalyzes the first step in adrenal steroidogenesis. These observations suggest a role for LPL in adrenal energy and/or lipid metabolism and possibly in steroidogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1996

A novel presenilin 1 mutation resulting in familial Alzheimer's disease with an onset age of 29 years.

We have identified a novel Alzheimer's disease family in which affected subjects had a very young age of onset (range 29-35 years). Neuropathological confirmation of the diagnosis was obtained for one patient. Molecular analysis shows that within this family the disease results from a missense mutation at codon 235 of the presenilin 1 (PS-1) gene. Two patients had exhibited generalized tonico-clonic seizures several years before the onset of dementia. Whether this particular clinical feature is a consequence of the PS-1 mutation remains to be established. The Leu235Pro mutation is, to our knowledge, the PS-1 mutation associated with the youngest age of AD onset, which suggests that it has a drastic effect on PS-1 function.

Adult↗

PubMed1996

Segregation analysis of Alzheimer pedigrees: rare Mendelian dominant mutation(s) explain a minority of early-onset cases. French Alzheimer Collaborative Group.

Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ( < or = age 60 years) AD (EOAD) probands has been carried out, allowing for a mixture in AD inheritance among probands. The goal was to quantify the proportion of probands that could be explained by autosomal inheritance of a rare disease allele "a" at a Mendelian dominant gene (MDG). Our data provide strong evidence for a mixture of two distributions; AD transmission is fully explained by MDG inheritance in < 20% of probands. Male and female age-of-onset distributions are significantly different for "AA" but not for "aA" subjects. For "aA" subjects the estimated penetrance value was close to 1 by age 60. For "AA" subjects, it reaches, by age 90, 10% (males) and 30% (females). We show a clear cutoff in the posterior probability of being an MDG case.

Age Factors↗

PubMed1996

Ultrastructural study of the coagulating gland of Wistar rats submitted to experimental chronic alcohol ingestion.

Morphological changes of coagulating gland of Wistar rats submitted to the experimental chronic alcoholism were noted. Ultrastructurally, it was observed reduction of the granular endoplasmic reticulum cisternae and nuclei with basal position and irregular shape. The epithelial cells presented pycnotic nuclei and the mitochondrial cristae disappeared, characteristic of cellular degeneration.

Animals↗

PubMed1996

Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis.

A patient with classic Zellweger syndrome was treated with docosahexaenoic acid ethyl ester (DHA-EE) for three months. Five other patients with Zellweger variants (four of them less than one-year-old and a five-year-old) were treated with DHA-EE until normalization of the DHA levels in erythrocytes. When arachidonic acid (AA) concentration decreased, AA was added to the diet. Thereafter, a combined treatment with DHA plus AA followed, in a variable proportion that allowed the high levels of DHA in erythrocytes to be maintained. In the patient with Zellweger syndrome, DHA therapy produced an increase in plasmalogen and a decrease in 26:0 and 26:1. No clear clinical improvement could be detected in this patient during the short period of treatment with DHA-EE. The most consistent clinical effect produced by DHA therapy in the other patients with disorders of peroxisomal biogenesis was visual improvement, even in those patients that were virtually blind before the treatment. In general, the developmental curve began to accelerate. The infants became more alert, acquired better visual and social contact and muscular tone improved, with the beginning of good head control. The liver tests tended to normalize and some patients showed a reduction of hepatomegaly. All these favorable changes occurred when the patients were taking the DHA-EE alone. In some of the patients, muscular tone seemed to improve further after introducing AA supplements. From the biochemical point of view, the plasmalogen levels increased in most cases in erythrocytes, and the two ratios 26:0/22:0 and 26:1/22:0 decreased in plasma. In some patients there was a tendency for 26:1 to increase in plasma and for 18:0 plasmalogen to decrease in erythrocytes when AA was introduced in the diet. The significance of these findings remains to be elucidated, but they stress the importance of strict monitoring and control of the polyunsaturated fatty acids status during DHA therapy.

Docosahexaenoic Acids↗