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Biomedical subjects

M Martinez

Publications and source records attributed to M Martinez.

At least 199 records · Page 11Linked to original sources
PubMed1995

How can maximum likelihood methods reveal candidate gene effects on a quantitative trait?

Different maximum likelihood approaches were used to explore the role of candidate genes in the variability of quantitative trait Q1 while accounting for the effects of age, Q2, and Q3. Segregation analysis, under the class D regressive model, provides evidence for a Mendelian gene effect on the adjusted trait Q1. Results of gene mapping through lod-score analyses remain puzzling. Pairwise lod scores indicate a possible linkage with the candidate gene C5 which is excluded when using tightly linked informative marker loci. Finally, our combined segregation and linkage analysis clearly shows that a C5 linked gene is involved in Q1 variability. However, given the lod-score results within the C5 region, we postulate a more complex mechanism for Q1 than a single di-allelic C5 linked gene. The knowledge of the true model (C5 is MG1 and has three alleles) permits a partial explanation of our results. This study demonstrates the advantages of using complementary approaches to reveal the role of candidate genes in complex traits, and the value of simultaneous estimation of linkage and segregation parameters.

Alleles↗
PubMed1995

Cloning and expression of FECV spike gene in vaccinia virus. Immunization with FECV S causes early death after FIPV challenge.

The spike gene of the feline enteric coronavirus (FECV), strain FECV-1683, was PCR amplified from total RNA extracted from FECV-infected cells and its sequence determined. A primary translation product of 1454 amino acids is predicted from the nucleotide sequence, containing a N-terminal signal sequence, a C-terminal transmembrane region and 33 potential N-glycosylation sites. The sequence shares 92% homology with the previously published feline infectious peritonitis virus, strain WSU-1146; however, several regions were identified that distinguished FECV from Feline Infectious Peritonitis virus, FIPV. The full length FECV S gene was cloned and expressed in vaccinia virus. Recombinants produced a 200 kD protein which was recognized by sera from cats infected with FIPV. When kittens were immunized with the vaccinia/FECV S recombinant, neutralizing antibodies to FIPV were induced. After challenge with a lethal dose of FIPV, the recombinant vaccinated animals died earlier than control animals immunized with vaccinia virus alone.

Animals↗
PubMed1995

Polyunsaturated fatty acids in the developing human brain, erythrocytes and plasma in peroxisomal disease: therapeutic implications.

Patients with Zellweger syndrome and related peroxisomal disorders have profound changes in the polyunsaturated fatty acid (PUFA) patterns in brain and other tissues, with a constant decrease in docosahexaenoic acid (DHA, 22: 6omega3) concentration. Arachidonic acid (AA, 20: 4omega6) concentration is normal or increased and linoleic acid (LA, 18: 2omega6) is increased in the brain of Zellweger patients. In the retina of these patients, the levels of DHA are extremely low. Since these alterations are reflected elsewhere, they can be detected in vivo in patients with generalized peroxisomal disorders by measuring the PUFA content of plasma and erythrocytes, which show very low concentrations of DHA. The concentration of AA is low in plasma in generalized peroxisomal patients, although it is within normal limits in erythrocytes. Patients with X-linked adrenoleukodystrophy (X-ALD) or adrenomyeloneuropathy (AMN) have a normal DHA and AA content in both plasma and erythrocytes, unless they receive extremely low-PUFA diets. Given the probable role of DHA deficiency in the pathogenesis of Zellweger syndrome (ZS), it is important to normalize concentrations of DHA, at least in blood, in an attempt to correct the DHA deficiency in brain. DHA ethyl ester was given orally to two infants with a peroxisome deficiency disorder for a year, and some favourable biochemical changes were produced in erythrocytes and plasma. Normalization of the DHA concentrations in erythrocytes was obtained in about 2 months, and the ratios 26: 0/22: 0 and 26: 1/22: 0 decreased markedly in plasma in the two patients. The plasmalogen ratio 18: 0 dimethyl acetal/18: 0 in erythrocytes increased to virtually normal values in both patients. There was a clear clinical improvement in the two patients, which paralleled the increase in blood DHA. The concentrations of AA and other PUFAs were closely monitored and, when necessary, AA was added to the diet. Such a DHA therapy, given under close biochemical and clinical control, and accompanied by a diet rich in other long-chain PUFA, is strongly recommended in all patients with peroxisomal disorders in whom a DHA deficiency is detected in blood.

Brain↗
PubMed1995

Anaesthetic induction in a child with end-stage cardiomyopathy.

The purpose of this clinical report is to discuss the anaesthetic management of a patient with end-stage cardiomyopathy. An eight-year-old boy sustained electro-mechanical dissociation following a "standard anaesthetic induction" but was subsequently successfully anaesthetized using a combination of etomidate, midazolam, lidocaine, vecuronium and glycopyrrolate. Anaesthetic techniques and their relationship to the specific category of cardiomyopathy (dilated, hypertrophic or restrictive) are discussed. The potential detrimental effects of anaesthetic sympatholysis, myocardial depression and negative chronotropy on cardiac output are explained.

Anesthesia, Intravenous↗
PubMed1995

A pharmacologically guided phase I study of carboplatin in combination with methotrexate and vinblastine in advanced urothelial cancer.

Carboplatin is an alternative for cisplatin in the treatment of urothelial cancers. A pharmacologically guided phase I study of carboplatin in combination with methotrexate (30 mg/m2) and vinblastine (4 mg/m2) was conducted in ten patients by increment of the area under the plasma concentration versus time curve (AUC) for ultrafilterable carboplatin using the Calvert formula. The maximal tolerated AUC was 5 mg ml-1 min, with neutropenia being the dose-limiting toxicity. There was a significant linear correlation between the percentage of decrease in neutrophil count and the carboplatin AUC. Determination of the glomerular filtration rate by the isotopic method allowed us to adapt the dose of carboplatin given to patients suffering from urothelial cancer, who frequently have impaired renal function. The recommended AUC for phase II study is 4 mg ml-1 min.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Efficacy, safety, and immunogenicity of a meningococcal group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile. Chilean National Committee for Meningococcal Disease.

A meningococcal group B (15:P1.3) outer membrane protein vaccine was tested for efficacy in a randomized, double-blind controlled study in Iquique, Chile. A total of 40 811 volunteers, ages 1-21 years, enrolled in the study. Volunteers received two doses of vaccine six weeks apart by jet injector. Both the experimental vaccine and the control vaccine (Menomune, A, C, Y and W135 meningococcal polysaccharide vaccine) were well tolerated with minor side-effects. Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique. Eighteen cases of group B meningococcal disease were confirmed during the 20 months. Efficacy was estimated to be 51% (p = 0.11) for all ages combined. In children aged 1-4 no protection was evident, but in volunteers aged 5-21 vaccine efficacy was 70% (p = 0.045). The IgG antibody response by ELISA was characterized by a large booster effect after the second dose, followed by a substantial drop in antibody levels by 6 months. The youngest children had the highest responses. The bactericidal antibody response, on the other hand, was characterized by the lack of a significant booster response, higher responses in the older children, and an increase in the geometric mean titer in the later months of the study in the older children.

Adolescent↗
PubMed1995

Genetic changes and bioassays in bleomycin- and phleomycin-treated cells, and their relationship to chromosomal breaks.

The recombinogenicity of damaged chromosomes in diploid Saccharomyces cerevisiae cells treated with bleomycin and structurally related phleomycin was measured, along with aneuploidy and mutation events. Phleomycin was substantially (up to 26-fold) more effective than bleomycin in producing genetic changes at all concentrations, even when colony-forming abilities of cells growing in the presence of bleomycin or phleomycin were similar. These results suggest that the DNA lesions produced by the two structurally related analogs could differ in their nature or frequency, or could be processed differently by the cells. Bioassays were developed and used to compare the cytotoxicities of freshly dissolved bleomycin and phleomycin with the cytotoxicities of lysates prepared from bleomycin- and phleomycin-treated cells. Unexpectedly, lysates prepared from bleomycin-treated cells were 1.5-3.5 times more cytotoxic than freshly dissolved bleomycin after 45-min treatments (3-33 x 10(-6) M). In contrast, lysates prepared from phleomycin-treated cells were 3-38 times less cytotoxic than freshly dissolved phleomycin (0.5-6.4 x 10(-6) M). Cytotoxicities of all lysates were higher after 36-h treatments than after 45-min treatments. At 3.3 x 10(-6) M, this increase was eightfold for bleomycin and 15-fold for phleomycin. Nevertheless, lysates from phleomycin-treated cells were considerably more cytotoxic than lysates from bleomycin-treated cells or freshly prepared bleomycin, consistent with the higher effectiveness of phleomycin than bleomycin in producing chromosomal breaks, genetic changes, and cell killing.

Aneuploidy↗
PubMed1995

Posterior probability of linkage and maximal lod score.

To detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(theta 1) at a given value theta 1 of the recombination fraction. If z(theta 1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0.5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined theta 1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16.4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than +3. Given a Zmax of +2.5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.

Genetic Markers↗
PubMed1995

Negative, psychoticism, and disorganized dimensions in patients with familial schizophrenia or bipolar disorder: continuity and discontinuity between the major psychoses.

OBJECTIVE: This study aimed to answer the following questions: 1) Can we reliably measure the psychopathologic dimensions of schizophrenia by using a lifetime frame and by rating acute and interepisode periods separately? 2) Can we reproduce in subjects with familial schizophrenia the characteristic three-factor structure of schizophrenic symptoms that has been found previously in general groups of schizophrenic patients? 3) Is the factor structure also present in familial bipolar disorder? METHOD: Lifetime measures of psychotic symptoms were taken through a slightly modified version of the Comprehensive Assessment of Symptoms and History for 138 patients with highly familial DSM-III-R schizophrenia (N = 51), bipolar disorder (N = 44), or spectrum disorders (N = 43). Symptoms were rated separately in the acute episodes and in the stabilized interepisode intervals across the patients' lives. RESULTS: A satisfactory level of reliability was obtained. In this highly familial study group, the positive/negative factorial distinction was replicated, as was a three-factor model similar to that observed in prior general groups of schizophrenic patients. These factors were also present in bipolar affective disorder. The negative, psychoticism, and disorganized factor model applied more to the acute phase of illness than to the stabilized state. CONCLUSIONS: These findings offer an empirical basis for testing biological or genetic variables in relation to negative/positive symptom dimensions, rather than diagnoses. Observations of a shared structure for schizophrenia and bipolar disorder suggest some continuity in the causes of these disorders.

Acute Disease↗
PubMed1995

A large pedigree with early-onset Alzheimer's disease: clinical, neuropathologic, and genetic characterization.

We present clinical, neuropsychological, and neuropathologic data on a large pedigree including 34 subjects with early-onset progressive dementia. The mean (+/- SD) age at onset was 46 +/- 3.5 years and the mean age at death 52.6 +/- 5.7 years. Twelve patients were clinically diagnosed as having probable Alzheimer's disease (AD) according to the NINCDS-ADRDA criteria. Neuropsychological evaluation, performed at a moderate stage of the disease, was available in six subjects and showed a classic pattern of cognitive deficit. Myoclonus and extrapyramidal signs were common, and seizures were present in all affected subjects. There were neuropathologic changes typical of AD in two brains. A significant lod score of 5.48 was observed at a recombination fraction of theta = 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. These results suggest that epilepsy could represent a particular feature in AD families linked to chromosome 14q.

Age of Onset↗
PubMed1995

A rare allele of a microsatellite located in the tyrosine hydroxylase gene found in schizophrenic patients.

We investigated the frequency of a rare variant of a common microsatellite tetrarepeat allele in the tyrosine hydroxylase gene in 2 independent ethnic groups of schizophrenic patients and their matched controls. In a French population we found the rare variant allele in 5 of 94 (5%) unrelated chronic schizophrenic patients and in none of 145 unaffected controls, thus yielding a significant association (p < 0.01) between schizophrenia and the tyrosine hydroxylase gene. Similarly, in a replication study, we found the rare allele in 4 of 44 (9%) unrelated chronic schizophrenic patients and in none of 44 unaffected controls in a Tunisian population. Albeit the reason of this association is at the moment unknown, it is possible that this polymorphism in the tyrosine hydroxylase gene may be involved in the regulation of its activity.

Adult↗
PubMed1995

A mutant approach and molecular strategy to study fungal cell walls.

The current study describes recombinant plasmids which complement the hypersusceptibility to killing bleomycin of blm1-1 mutant cells of Saccharomyces cerevisiae, and a strategy developed and used to recover active clones from a stable yeast genomic library. The resistance of a spontaneous revertant isolated from the original blm1-1 mutant strain and of mutant cells transformed with each of several recombinant plasmids which complemented the recessive blm1-1 mutation was comparable to the resistance of the parental (non-mutant) strain from which the original blm1-1 mutant was derived. The strategy for cloning S. cerevisiae DNA was based on complementation and in situ hybridization. This strategy employed 32P-labelled 6.6-kb BamHI and 3.8-kb BamHI-ClaI probes from a cloned DNA fragment to recover clones which either fully or partially complemented the hypersensitivity of mutant cells to killing by bleomycin. This method considerably reduced the time and effort required to recover biologically active clones from a genomic library.

Bleomycin↗
PubMed1995

[Granular cell tumor localized in the glottis in children. Apropos of a case].

We report the first case of adult granular cell tumor form localized in the glottis in a 8 year-old girl. The first symptom was a chronic dysphonia. Examination with rigid optic demonstrated an irregular yellow hypertrophic lesion in the posterior third of the left vocal fold. The lesion was removed by CO2 laser micro-spot under general anesthesia. There has been no recurrence after 15 months of follow-up and the postoperative voice quality is satisfactory regarded both objectively as subjectively. Granular cell tumors are rare. The histogenesis is still badly known. Enzymological and electron microscopy studies seem to indicate a nervous origin (Schwann cells). Treatment is surgical. Wide local excision is the general rule for limited lesions with easy access. When bigger lesions are present in more vital structures such as trachea or oesophagus, surgery has to be more cautious.

Child↗
PubMed1995

[Phenotype of familial forms of early-onset Alzheimer's disease linked to chromosome 14. Clinical and neuropsychological characteristics of a large group].

We report the clinical features and neuropsychological data of chromosome-14 linked early-onset Alzheimer's disease in a large family (FAD-RO1). Information available in the literature from eight additional chromosome 14-linked Alzheimer's disease kindreds was compared with the data obtained from six kindreds with amyloid precursor protein gene mutations (APP). In the chromosome 14-linked families the disease has an earlier onset and a shorter duration than in families with APP mutations, with an age at death lower than sixty years of age. Seizures, myoclonus and extra pyramidal signs were frequently present in the cases of FAD-RO1 as in six chromosome 14-linked kindreds, but these features were absent in two other ones. The high frequency of seizures (> 80%) in FAD-RO1 and two other chromosome 14-linked kindreds is remarkable. Seizures and myoclonus were encountered at a lower prevalence in APP kindreds. This review suggests that some clinical features are more prevalent in chromosome 14-linked than in APP kindreds but a phenotypic heterogeneity does exist within and between families. The profile of deterioration of the neuropsychological performances, as illustrated by the FAD-RO1 members, shows that chromosome 14-linked kindreds do not demonstrate a specific expression in comparison to APP kindreds. Memory was first impaired. Deficits in visuo-spatial and visuopractic abilities were then noted. Finally the verbal performance deteriorated.

Adult↗
PubMed1995

Endonasal dacryocystorhinostomy: indications, technique and results.

Dacryocystorhinostomy (DCR) allows an obstructed lachrymal drainage system to be drained into the nasal fossa. Since the development of endonasal microsurgical techniques, the endonasal approach presents itself as an alternative choice to the conventional external approach. It is far less traumatic, yet as efficacious as the conventional approach, and avoids the need for a skin incision and the disruption of the medial canthal structures. Twenty-six patients suffering from lachrymal system obstruction underwent 28 endonasal dacryocystorhinostomies under microscopical (n = 25) or endoscopic control (n = 3). Pre-operative assessment included clinical symptoms (sac swelling, purulent secretions, epiphora) and outflow obstruction on X-rays (conventional dacryocystography and/or subtraction macrodacryocystography). Post-operatively, 23 DCR were free of symptoms. Two presented occasional epiphora and three were unsuccessful. The presence of pre-operative purulent secretions was significantly correlated with post-operative success and with lachrymal sac patency, which is also confirmed by X-ray examination (p<0.001). Thus in cases of purulent secretion with epiphora, X-ray examination is redundant and may be avoided. On the contrary, when epiphora is an isolated symptom, X-rays must be performed in order to determine where the obstruction is located and to provide information on lachrymal sac morphology.

Adolescent↗