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Biomedical subjects

M Martinez

Publications and source records attributed to M Martinez.

At least 307 records · Page 17Linked to original sources
PubMed1985

Segregation analysis of a marker localised Xp21.2-Xp21.3 in Duchenne and Becker muscular dystrophy families.

A DNA marker C7, localised Xp21.1-Xp21.3, has been studied in kindreds segregating for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). In DMD families four crossovers were observed in 38 informative meioses between C7 and the DMD locus (theta = 0.12, z max = +2.72). In BMD families no recombinants were observed in the 16 informative meioses studied. These data are consistent with the localisation of the mutations in these disorders being in the same region of Xp21. Studies in families also segregating for the DNA marker 754 support the previously reported physical order of these loci as X centromere-754-DMD-BMD-C7-X telomere. A recombination fraction of 0.11 (z max = +5.58) was found between DMD-754 by combining our previously published data with the data presented here. C7 and 754 thus provide good bridging markers for the diagnosis of DMD and BMD.

Chromosome Banding↗
PubMed1985

Glutathione conjugation of the carcinogenic and mutagenic electrophile (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetra hydrobenzo[a]pyrene catalyzed by purified rat liver glutathione transferases.

The kinetics of the enzyme-catalyzed conjugation of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]-pyrene [(+/-)-anti-BPDE] with glutathione (GSH) by the following purified soluble rat liver GSH transferases: 1-1, 1-2, 2-2, 3-3, 3-4 and 4-4 have been studied. When BPDE concentration was varied while GSH concentration remained constant (1 mM), linear Lineweaver-Burk plots were obtained: maximum rates of conjugation mediated by GSH transferases 1-1, 1-2, 2-2, 3-3, 3-4 and 4-4 were 105, 72, 83, 35, 179 and 357 nmol/min/mg protein, respectively. When GSH concentration was varied while BPDE concentration remained constant (40 microM), biphasic Lineweaver-Burk plots were obtained in each case with a break point of 0.2 mM GSH below which the affinity of these enzymes for GSH was apparently greater. These results are discussed with respect to the detoxication of benzo[a]pyrene (BP) in vivo.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Altered composition of polyunsaturated fatty acyl groups in phosphoglycerides of Down's syndrome fetal brain.

We have observed recently that in vitro lipoperoxidation is enhanced in Down's syndrome brain homogenates of prenatal age. As this may relate to the composition of polyunsaturated acyl groups (PUFA) in phospholipids, we have examined the PUFA of ethanolamine and serine phosphoglycerides (EPG and SPG), which are particularly rich in PUFA, in the same series of cerebral cortex specimens of Down's syndrome and age-matched control fetuses. Although the total percentages of PUFA in the two phosphoglycerides were not altered, compared with controls the ratio of PUFA of the (n-3) series to those of the (n-6) series was very significantly elevated in Down's syndrome, from 0.32 to 0.55 in EPG and from 0.60 to 0.97 in SPG. In particular, docosahexaenoyl, 22:6(n-3), groups were uniformly increased in Down's syndrome compared with controls by 54% and 33% in EPG and SPG, respectively, while arachidonoyl, 20:4(n-6), groups were decreased by 16% and 30%, respectively. Similar changes occur during normal development, but the (n-3) to (n-6) ratio of PUFA in these phosphoglycerides of Down's syndrome at the fifth month of gestation resembled that of normal human cerebral grey matter at term. However, other developmental indices related to PUFA composition were not significantly affected. It seems therefore that in the developing Down's syndrome brain there may be a distortion of the normal transformations of essential fatty acids and of their incorporation into phosphoglycerides. The disproportion between docosahexaenoyl and arachidonoyl groups in membrane phosphoglycerides during prenatal development in Down's syndrome may also result in disturbances of the proper functioning, and the ontogenetic integration, of membrane enzymes and transport processes.

Brain↗
PubMed1984

Metabolic activation of benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to protein-binding products and the inhibitory effect of glutathione and cysteine.

Trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) and the anti-isomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) were found to be activated by microsomes isolated from 3-methylcholanthrene (MC)-treated rats to reactive intermediates that bound covalently to microsomal proteins. The extent of binding was markedly reduced by the presence of reduced glutathione (GSH) or cysteine. Fluorescence spectroscopic studies on the products derived from BP-7,8-diol and BPDE after microsomal activation in presence of GSH or cysteine revealed the formation of a common reactive intermediate with unique fluorescence properties. The involvement of cytochrome P-448 in the activation of BP-7,8-diol and BPDE to protein-binding products was inferred by the requirement for NADPH and almost complete inhibition by alpha-naphthoflavone. Furthermore, microsomes from MC-treated rats could be replaced by a reconstituted system containing purified cytochrome P-448, NADPH-cytochrome reductase and co-factors. The conjugation of the reactive intermediates from BP-7,8-diol and BPDE with GSH or cysteine did not require the presence of either microsomes or cytosol, thus indicating a non-catalytic reaction. These results emphasize the importance of cellular nucleophiles such as GSH and cysteine in the deactivation of reactive benzo[a]pyrene (BP) intermediates and also provides evidence for the further activation of the ultimate carcinogen BPDE to more reactive electrophiles and may thus have relevance concerning the regulation of BP-induced carcinogenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1984

Induction of hepatic glutathione S-transferase activity by butylated hydroxyanisole and conjugation of benzo[a]pyrene diol-epoxide.

Dietary administration of 2(3)-tert-butyl-4-hydroxyanisole (BHA) to mice caused an increase in the hepatic soluble glutathione S-transferase activity towards (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) of approximately 5-fold whereas that towards 1-chloro-2,4-dinitrobenzene (CDNB) was increased by approximately 14-fold. Whereas with either substrate the catalytic capacity of the enzyme was elevated by BHA treatment, there was little effect on the Km for CDNB but an increase in the Km for BPDE as substrates. The results thus suggest that BHA-induced GSH S-transferase activity may be of limited importance for protection from certain reactive intermediates of polycyclic aromatic hydrocarbons.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1984

Metabolism of benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to protein-binding products and glutathione conjugates in isolated rat hepatocytes.

Isolated hepatocytes from 3-methylcholanthrene (MC)-treated rats metabolized trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) to water soluble conjugates including glutathione (GSH) conjugates. Under the conditions employed 35% of total water soluble products derived from BP-7,8-diol could be accounted for by GSH conjugates. The corresponding figure for anti-BPDE was estimated to be greater than or equal to 80%. Isolated hepatocytes metabolized BP-7,8-diol and anti-BPDE to GSH conjugates at maximal rates of 0.5 and 9 nmol per 10(6) cells per min, respectively. Thus, identifying the rate limiting step in the reaction sequence as the metabolism of BP-7,8-diol to the GSH conjugating intermediates. In addition to the direct conjugation of anti-BPDE with GSH, anti-BPDE but not the corresponding BP-tetraols, was further metabolized to reactive intermediates that subsequently bound to cellular proteins or reacted with GSH forming water soluble conjugates. The identity or identities of these novel reactive intermediates is discussed.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1983

Synthesis and structural study of N-substituted nortropane spirohydantoins.

A series of N8-alkyloxycarbonylalkyl-nortropane-3-spiro-5'-hydantoins has been synthesized and studied by spectral and crystallographic methods. The crystal and molecular structure of one [8(gamma-ethoxycarbonyl)nortropane-3-spiro-5'-hydantoin, VI] was determined by X-ray diffraction. The preferred conformations of these compounds and subsequent changes on protonation were determined from 1H-NMR and 13C-NMR data.

Chemical Phenomena↗
PubMed1983

Malfunction of ventriculoperitoneal shunts during pregnancy.

Two cases of successful pregnancy in patients with a ventriculoperitoneal shunt are presented. Both patients experienced shunt malfunction early in the third trimester which was apparently related to anatomic changes in the abdomen associated with pregnancy. All symptoms resolved with conservative management. The obstetric and neurologic management of such patients is discussed.

Adult↗
PubMed1982

Inactivation of DNA-binding metabolites of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by glutathione and glutathione S-transferases.

The binding to DNA of reactive metabolites of trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-diol) was studied following the incubation of tritiated benzo[a]pyrene (BP) and BP-7,8-diol with nuclei from livers of 3-methylcholanthrene-treated rats. Binding was inhibited to a small extent by glutathione (GSH) alone and to a much greater extent by GSH and cytosol or purified GSH-transferases B and E. In this respect GSH-transferases A and C were also active, but less so. Inhibition of binding of BP-7,8-diol metabolites to DNA mediated by GSH-transferases was associated with the formation of GSH conjugates. The extent of inhibition of binding was similar in incubations of nuclei alone, nuclei and rat liver microsomes, and calf thymus DNA and rat liver microsomes. This indicates that reactive metabolites of BP-7,8-diol, formed either by nuclei or microsomes, are readily accessible to soluble GSH-transferases. GSH and cytosol were also active in inhibiting DNA-binding of reactive metabolites from 9-hydroxybenzo[a]pyrene (9-OH-BP). Thus, in the rat hepatocyte GSH and GSH-transferases may be important in protecting DNA from electrophilic attack by reactive BP-7,8-diol and 9-OH-BP species.

Animals↗
PubMed1981

Pharmacokinetic study of 2-(2'-methyl-3'-chloro-anilino)-lysine nicotinate (L-104).

The pharmacokinetic study of a new analgesic-antiinflammatory agent, 2-(2'-methyl-3'-chloro-anilino)lysine nicotinate (L-104), was preformed in the rat and the dog. When administered p.o. in rats at a dose of 40 mg/kg, the serum peak was 131.3 microgram/ml +/- 10.3 at 15 min post application, and the elimination t 1/2 was 1.20 h. For the same dose, given i.v., the biological t 1/2 was 1.38 h, the AUC 337.18 microgram/ml/h and the Vdss 0.232 l/kg. When administered i.v. in dogs of 10 mg/kg, the biological t 1/2 was 0.96 h +/- 0.14, the AUC 73,066 microgram/ml/h and the Vdss 0.178 l/kg. In the rat, for a dose of 40 mg/kg given p.o., 79.1% of tritium-labelled L-104 were excreted within 72 h, 56.0% of them through the kidneys. In the dog, at an i.v. dose of 10 mg/kg, the whole of the drug was excreted at the end of 72 h, corresponding 52.6% urinary excretion. The main metabolite in the rat was 2-(2'-methyl-3'-chloro-4'-hydroxy-anilino)-nicotinic acid (72.2%), whereas in the dog it was 2-(2'-methyl-3'-chloro-anilino)-5-hydroxy-nicotinic acid (35.2%).

Administration, Oral↗
PubMed1981

Keratotic lesions of the oral epithelium.

Glycogen in the epithelium is interpreted as a sign of cell activity; its accumulation seems to take place gradually during cell migration. The oxido-reductase and hydrolytic enzyme-groups represent a sensitive indicator of changes in cell metabolism. The occurrence and intensity of glycogen, lactic and succinic dehydrogenases, NAD-cytochrome-c-reductase, alkaline and acid phosphatases were studied in 20 biopsy materials obtained from patients with keratotic buccal lesions. The results were compared with 20 biopsies from healthy oral mucosa. Variations were found in the localization and amount of glycogen, but no significant difference could be observed in the intensity of the oxido-reductase enzymes and alkaline phosphatase reactions. Acid phosphatase showed increased reactivity in most superficial layers of the keratinized epithelium.

Acid Phosphatase↗
PubMed1980

Siphon suction for vitrectomy.

An intravenous container placed below the level of the surgical field can provide a gentle, safe level of suction (+/- 76 mm Hg). This is particularly useful in performing a delicate open-sky anterior vitrectomy.

Corneal Transplantation↗
PubMed1979

Evaluation of delayed auditory feedback (DAF) effect: comparison between subjective judgments and objective measures.

The effect of Delayed Auditory Feedback (DAF) on speech duration was evaluated subjectively and measured objectively in 30 subjects (10 normals, 10 nonfluent aphasics and 10 fluent aphasia). The average correlation coefficient between the subjective and objective data was .52 for 180 msec. delay and .46 for 360 msec. delay. Analysis of variance of data derived from the two methods showed the same highly significant differences among groups, delay and tasks. We conclude from these results that both objective and subjective procedures are equally useful in evaluating DAF effect on speech duration, and that both may also be valuable in assessing other types of behavior.

Aphasia↗