Search PubMed⌕ Search

Biomedical subjects

M Martinez

Publications and source records attributed to M Martinez.

At least 271 records · Page 15Linked to original sources

Isolation of two hemorrhagic toxins from Crotalus basiliscus basiliscus (Mexican west coast rattlesnake) venom and their effect on blood clotting and complement.

1. Two hemorrhagic toxins of mol. wt 27,000 (B1) and 27,500 (B2) and pI 9.8 and 5.2 respectively were isolated from Crotalus basiliscus venom. 2. The two proteinases did not cross-react antigenically. 3. Both toxins caused hemorrhage in mice and each was capable of hydrolyzing hide power azure, casein, collagen and fibrin. 4. B1 hydrolyzed the A alpha, B beta and gamma chains of fibrinogen. B2 hydrolyzed the A alpha and B beta chains of fibrinogen, but not the gamma chain. 5. Both proteinases inactivated guinea pig complement.

Animals↗

Isolation of a hemorrhagic toxin from Mojave rattlesnake (Crotalus scutulatus scutulatus) venom.

A hemorrhagic toxin was isolated from Mojave rattlesnake venom. The isoelectric point of the toxin was 4.7 and its mol. wt was 27,000. Concentrations as low as 2 micrograms injected s.c. in mice caused hemorrhage greater than 5 mm in diameter. The toxin was fibrinogenolytic and hydrolyzed hide powder azure, casein and collagen. The toxin also partially inactivated complement. It had no activity against elastin, fibrin, and the chromogenic substrates S-2805, S-2302 and S-2238. Its esterolytic activity was 3% of the activity of the unfractionated venom. The enzymatic and hemorrhagic activities were inhibited by EDTA. The hemorrhagic toxin was absent or in low quantities in Mojave rattlesnake venoms containing Mojave toxin. Chromatography by HPLC easily distinguishes Mojave rattlesnake venoms into two types by the presence or absence of the hemorrhagic toxin.

Animals↗

Genetic mapping of common diseases: the challenges of manic-depressive illness and schizophrenia.

Advances in genetic mapping of human diseases have led to the identification of single locus susceptibility for several common disorders. There have been a number of reports of linkage for the psychiatric disorders manic-depressive illness and schizophrenia, but none of these linkage reports is uncontested. Nonetheless, it appears promising to continue attempts to map these psychiatric disorders, since linkage can now be detected even when the inheritance is complex and includes genetic heterogeneity and variable penetrance.

Bipolar Disorder↗

Prevention of adult respiratory distress syndrome with plasminogen activator in pigs.

Death from traumatic shock has been associated with loss of blood externally or internally. However, many patients die after trauma, even though blood volume restoration is adequate. Death is often due to pulmonary failure (adult respiratory distress syndrome [ARDS]). Death and ARDS have been associated with disseminated intravascular coagulation (DIC) and microclots in the lungs. Dissolution of the microclots after trauma can be achieved by activation of endogenous plasmin. Nine pigs were anesthetized for 48 h. Trauma was administered by 60 standard blows to each thigh resulting in a bruise of muscle but no skin, bone, or major vessel injury. Nutrition and respiration were maintained at normal levels. All nine pigs died with severe lung pathology and low PaO2. Ten other traumatized pigs were treated with a plasminogen activator iv 4 h after trauma. Five of these were treated with tissue plasminogen activator (tPA) and five with urokinase. All treated pigs survived 48 h and maintained a normal PaO2. Autopsy showed minimal lung pathology.

Animals↗

Deteriorating ischemic stroke: risk factors and prognosis.

To determine a risk profile of deterioration in cerebral infarction of less than 8 hours' duration, we studied prospectively a series of clinical and radiologic data in 98 patients. We evaluated the Canadian Neurological Scale Score and Barthel index during a follow-up period of 3 months. There was deterioration in the 1st 48 hours in 40.8% of the patients. High systolic blood pressure, elevated blood sugar concentration at admission, and carotid territory involvement were independently related with deterioration in the logistic regression analysis. Death occurred in 35% of the patients with deteriorating infarcts and in 8.6% of those with stable infarcts. At the end of the study, functional capacity was lower in those with deteriorating infarcts, but the 2 groups improved in parallel from the 4th day onward.

Blood Glucose↗

Performance of linkage analysis under misclassification error when the genetic model is unknown.

Linkage analysis of complex diseases raises a number of important methodological problems. One of them concerns the clinical classification of disease phenotypes. In this study, we investigate the effects of false positive misclassification on the estimation of the recombination fraction and on the power and the robustness of tests for linkage. These effects are investigated 1) when the genetic model of the trait locus is known; and 2) when it is unknown, by maximizing the likelihood of the marker configuration given the disease status in the family. Results show that linkage analysis of misclassified data leads to an overestimation of the recombination fraction and a loss of power of the linkage test. The results are quite similar in both situations. However, the linkage test itself is robust to this kind of misclassification error.

Affective Disorders, Psychotic↗

Polyunsaturated fatty acid changes suggesting a new enzymatic defect in Zellweger syndrome.

The fatty acid composition of red blood cells, fibroblasts, forebrain, liver and kidney were studied in a 3-month-old infant who died from Zellweger Syndrome, and the results were compared with those of age-matched controls. Besides a typical increase in the very long chain fatty acids 26:0 and 26:1 and a great reduction in the plasmalogen levels, confirming the diagnosis of Zellweger Syndrome, some striking changes in the polyunsaturated fatty acid patterns were discovered. The most important was a very drastic decrease in the values of 22:6 omega 3 and 22:5 omega 6, the two products of delta 4-desaturation. In the kidney, the level of 22:6 omega 3 fell below that of 26:0. Consequently, the ratio 26:0/22:6 omega 3 (and 26:1/22:6 omega 3) was most useful in emphasizing the fatty acid anomalies, especially in renal tissue, where the 26:0/22:6 omega 3 ratio increased to almost 200 times the normal values. Other significant, although less consistent fatty acid alterations were increases in 18:2 omega 6, 18:3 omega 6, 20:3 omega 6, 18:4 omega 3 and 20:4 omega 3, and a decrease in 20:4 omega 6 in some tissues. The existence is proposed of a new enzyme defect in peroxisomal disorders, involving the desaturase system of long chain polyunsaturated fatty acids.

Brain↗

Lipid abnormalities in the brain in adult Down's syndrome and Alzheimer's disease.

Quantitative analysis by HPTLC of the major lipid classes and dolichol, and of fatty acyl groups of separated phosphoglycerides by capillary GLC, has been carried out on the gray matter of frontal cerebral cortex of brains from six Down's syndrome (DS) and six Alzheimer's disease (AD) adults, and six each of two corresponding sets of age-matched controls; specimens of DS and control cerebellum and corpus callosum were also analyzed. In DS frontal cortex, but not in AD frontal cortex, compared to their respective controls there was a decrease in the fraction of phosphatidylethanolamine (PE) and an increase in the fractions of sphingomyelin (SPM) and phosphatidylserine (PS). Abnormalities were not found in the proportions of major lipid classes in DS cerebellum or corpus callosum. The concentration of dolichol was elevated for age in the frontal cortex of DS and of AD. In the phosphoglycerides of DS frontal cortex, the fatty acyl composition showed small, but statistically significant, differences from those of age-matched controls, and some slight abnormalities were also detected in DS corpus callosum. The alterations in DS frontal cortex included decreases in (n-6) and increases in (n-3) groups in choline and ethanolamine phosphoglycerides (CPG and EPG), as had previously been found in EPG and serine phosphoglyceride (SPG) of the DS fetal brain. In DS frontal cortex, the proportion of 22:4(n-6) groups was decreased in SPG, and in inositol phosphoglyceride (IPG) 18:1(n-9) was increased. There were also small but significant alterations in DS frontal cortex in the fractions of shorter chain groups in CPG. In marked contrast, most of the fatty acyl abnormalities seen in DS were absent in the AD frontal cortex. It is therefore suggested that some abnormalities in the composition of cerebral membranes present prenatally in DS may persist into adulthood, and are not directly related to AD-type pathology.

Acetals↗

Comparative enzymatic study of HPLC-fractionated Crotalus venoms.

1. Ten venoms of the genus Crotalus (Crotalus adamanteus, Crotalus atrox, Crotalus durissus durissus, Crotalus horridus horridus, Crotalus lepidus, Crotalus polystictus, Crotalus molossus molossus, Crotalus pusillus, Crotalus scutulatus scutulatus, venom B, and Crotalus viridis lutosus) were fractionated using HPLC anion and cation exchange chromatography. 2. HPLC venom fractions were tested for hemorrhagic, hemolytic, and proteolytic activities. 3. Crude Virginia opossum (Didelphis virginiana) serum neutralized the hemorrhagic activity of HPLC fractions.

Animals↗

Excimer laser ablation of the human lens at 308 nm with a fiber delivery system.

A 308 nm excimer laser has been used with a fiber delivery system to perform ablation of the human lens. Preliminary results demonstrate the system's ability to ablate lens nucleus and cortex selectively, preserving the anterior and posterior capsules. The total delivered energy necessary to ablate a human lens ranged from 35 to 63 joules. Laser tissue interaction and ablation rates were computed for the different components of the human lens (capsule, cortex, nucleus) for the operatively useful energy densities (fluences). Operative experience suggests that cortex and nucleus can be ablated while preserving the capsule if an adequate irrigation and aspiration system is developed. These results also suggest that this modality may be adequate for performing endocapsular cataract extraction. Laser tissue interactions were also computed at variable distances between the fiber tip and tissue. As this distance increased, the spread of the beam increased and a significant increase in energy was necessary to induce tissue ablation. This was due to the decrease in fluence with increasing distance to the target tissue and/or the absorption and scattering of the delivered energy within a short distance from the fiber tip by the ablated material. Evidence of a sonic effect was also present.

Aged↗

The influence of cytochrome P-450 induction on the disposition of carcinogenic benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide in isolated cells.

The disposition of the carcinogenic (+)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] has been studied in isolated hepatocytes obtained from 3-methylcholanthrene-pretreated rats. In these cells different routes are acting in concert and contribute to diol-epoxide elimination. Conjugation of (+)-anti-BPDE with glutathione (GSH) and cytochrome P-450c-mediated metabolism of the diol-epoxide to 1- and 3-hydroxy-anti-BPDE (triol-epoxides) appears to be equally important. The reactive triol-epoxides undergo a number of secondary reactions, including covalent binding to cellular constituents, e.g. protein and GSH, and hydrolysis to pentahydroxyderivatives. The effective intracellular lifetime of (+)-anti-BPDE is approximately 1 min and comparable to that previously observed in hepatocytes obtained from uninduced animals.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Genetic heterogeneity between two clinical forms of cystic fibrosis evidenced by familial analysis and linked DNA probes.

CF heterogeneity has been evidenced from both clinical and genetic observations. At least two clinical forms of CF are easily distinguishable: CF with meconium ileus and CF without meconium ileus. The results of prenatal diagnosis have shown that the recurrence rates of CF are different in these two clinical forms. Molecular analysis of Restriction Fragment Length Polymorphisms (RFLPs) tightly linked to the cystic fibrosis (CF) gene defined several types of CF and normal chromosomes in a French sample of 64 families with CF. The CF mutation is tightly linked to one XV-2C and KM19 RFLPs haplotype but is differently linked to J3.11 RFLP alleles, depending on whether or not the clinical form of CF is associated with ileus. A distortion of the segregation ratio observed between normal and CF haplotypes in the families with ileus could explain the high recurrence rate of CF in such families.

Alleles↗

Effect of peptide AS-48 on Enterococcus faecalis subsp. liquefaciens S-47.

The enterococcal peptide AS-48 exerts a concentration-dependent bactericidal effect on Enterococcus faecalis subsp. liquefaciens S-47; cell rescue by cardiolipin and trypsin can be effected only in the first few minutes after antibiotic addition. Gramicidin-exposed cells are protected from killing by AS-48. Long-term and pulse incorporation of radiolabeled substrates into trichloroacetic acid-precipitable material, O2 consumption, and the ability to maintain intracellular potassium levels are impaired shortly after addition of AS-48.

Anti-Bacterial Agents↗

Detection of marker associations with a dominant disease gene in genetically complex and heterogeneous diseases.

Linkage disequilibrium of a marker allele with disease may characterize a chromosomal region containing the disease gene. In several diseases, only a limited number of pedigrees are linked to a particular region, because of linkage heterogeneity. Disequilibrium in this situation is more easily detected when the association is positive (an infrequent marker allele associated with disease mutation), and sampling is conditional on presence or absence of illness in individuals or gametes. Defining H as the marker frequency in illness-transmitting gametes, and Q the marker frequency in normal chromosomes, we compute the power of a given sample (of ill persons/gametes) to detect association in a disease that is genetically heterogeneous, with a dominantly transmitted form linked to a marker. The estimation of Q and the effects of linkage heterogeneity (when unrelated individuals are examined) are also analyzed. Two linked pedigrees give acceptable power to detect association when the allele is frequent enough in illness gametes (H greater than or equal to .6) and infrequent enough in normals (Q less than or equal to .01). If H greater than or equal to .2, 14 pedigrees are needed to give the same power. From the analysis of different values of Q and H, it appears that even in the presence of considerable genetic heterogeneity and complex inheritance (where some normals carry the disease mutation), association may be detected with clinically feasible sample sizes.

Alleles↗

Genetic analysis of human breast cancer: implications for family study designs.

Genetic analysis of human breast cancer, as with many common diseases, raises several problems including sampling strategies, genetic heterogeneity, and gene-environment interactions. A reanalysis of 200 Danish breast cancer pedigrees, under the unified mixed model, was conducted to investigate more specifically these three points. We found that use of different sampling schemes leads to similar conclusions: familial transmission of breast cancer in this whole Danish sample cannot be accounted for by the Mendelian segregation of a dominant gene. Homogeneity tests, based on an a priori subdivision of the sample, were all nonsignificant under a given genetic model. However, it was possible to isolate a particular subgroup of pedigrees displaying only breast cancer, which was compatible with the segregation of a dominant gene. We have also shown that correct specification of a liability indicator according to epidemiological factors is of major importance to detect a major effect under the mixed model. Our results emphasize the need to design family studies including various types of information in the probands and family members to permit some progress in the understanding of complex diseases.

Breast Neoplasms↗