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Biomedical subjects

A Jimenez

Publications and source records attributed to A Jimenez.

At least 91 records · Page 5Linked to original sources
PubMed1985

Pseudoisodicentric bisatellited extra marker chromosome (tetrasomy 22pter----q11, trisomy Yqh), derived from a maternal Y/22 translocation. Association between this tetrasomy and "cat eye" phenotypical features.

A patient with multiple congenital anomalies suggestive of the "Cat eye" syndrome was found to have an extra marker bisatellited chromosome 22 derived from a maternal Y/22 translocation, identified by multiple banding patterns in cultures treated with DA. The proband's karyotype is 47,XX, + psu idic(22)(Yqter----Yq12::22p13----22q11::++ +22q11----22p13::Yq12----Yqter), t(22;Y)(p13;q12)mat., being tetrasomic for 22pter----q11, and trisomic for Yqh. Similarity between his clinical features and reported "Cat eye" cases, confirms that this region is responsible for the phenotypical expression of the syndrome.

Abnormalities, Multiple↗
PubMed1984

Gas chromatographic determination of quazepam and two major metabolites in human plasma.

Two rapid, sensitive, and specific gas chromatographic (GC) methods for the quantitative determination of quazepam (I), 7-chloro-5-(2-fluorophenyl-1,3-dihydro-1-(2,2,2-trifluoroethyl) -2H-1,4-benzodiazepine-2-thione, and its major active plasma metabolites, the 2-oxo compound (II) and the dealkylated oxo compound (III), have been developed; the first measures I and II and the second measures III. The compounds are extracted from plasma with toluene and quantitated by electron-capture detection using the internal standard method. The methods are capable of quantitating plasma levels of I and II as low as 0.75 ng/mL and plasma levels of III as low as 1.5 ng/mL. Correlation coefficients of standard curves were greater than 0.9995 for all compounds. Precision of the methods was measured at two different concentrations for each compound; the CV values were 3-6% for all three compounds. The recovery of all compounds was greater than 80%, and the ratio of recovery of each compound to that of its internal standard did not vary at different concentrations, indicating appropriate internal standards have been selected for the methods. Quazepam metabolites, other benzodiazepines, and drugs which are potential comedication do not interfere with either method. The methods were shown to be suitable for investigating the bioavailability and pharmacokinetics of quazepam at therapeutic doses.

Anti-Anxiety Agents↗
PubMed1984

A new patient with dicarboxylic aciduria suggestive of medium-chain Acyl-CoA dehydrogenase deficiency presenting as Reye's syndrome.

A new patient with medium-chain dicarboxylic aciduria and suberyl glycinuria during an attack of acute illness is reported. When, inadvertently he was given medium-chain triglycerides for 2 days, the excretion of abnormal metabolites of medium-chain fatty acids increased and hepatomegaly became more pronounced. During remission a low excretion of the metabolites were observed. After 16 h of fasting hypoglycaemia was accompanied by an increase of urinary dicarboxylic acids and psi-hydroxyacids similar to that found on admission. Interestingly this urinary organic acid pattern persisted 8 h after intravenous administration of glucose. In a blood sample obtained after 16 h of fasting there was hypoketonaemia and increased levels of total free fatty acids, octanoic, decanoic and cis-4-decenoic acids. These biochemical data suggest the existence of a deficiency at the level of medium-chain acyl-CoA dehydrogenase.

Acyl-CoA Dehydrogenases↗
PubMed1984

Quantitative relationship between light intensity and luteinizing hormone surges in ovariectomized rats treated with estrogen.

The purpose of this study was to determine if patterns of gonadotropin secretion during estrogen-induced luteinizing hormone (LH) surges are altered by abrupt changes in light exposure. When light intensity was increased approximately threefold, before the "critical period" or during the rising phase of the LH surge, serum LH increased significantly (P less than 0.01) compared to control values. Furthermore, LH surges were prolonged when exposure to light of high intensity was continued beyond the normal extent of the photophase. In contrast to the effects of increased light intensity, acute darkness did not alter the magnitude of LH surges compared with controls exposed to light of low intensity. Thus, phasic LH secretion is enhanced by abrupt increases in light intensity, and the duration of LH secretion can be extended by prolonging the photophase. Although LH surges occur in total darkness, this study suggests that light modulates the intensity of the signal for LH secretion by a stimulatory action.

Animals↗
PubMed1983

A modified enzymatic-isotopic microassay for serotonin (5HT) using 5HT-N-acetyltransferase partially purified from Drosophila.

Serotonin-N-acetyltransferase (EC 2.3.1.5), partially purified from Drosophila melanogaster (DNAT) was substituted for rat liver enzyme (RNAT) in a previously published radioenzymatic assay for serotonin (5HT). The purpose was to determine if this modification would increase the sensitivity and reliability of the original assay. Compared with RNAT, DNAT is 3-4 times more active; it lacks secondary 5HTP decarboxylase activity; and it is more stable. Under conditions of the modified assay, the only radioactive product formed from hypothalamic tissue extracts is 3H-melatonin; which can be measured from as little as 15 pg of serotonin substrate. Thus, substitution of DNAT for RNAT improves the original radioenzymatic assay allowing measurement of endogenous 5HT in hypothalamic nuclei from individual animals.

Acetyltransferases↗
PubMed1982

Chemotherapy combination with cyclophosphamide (CTX) adriamycin (ADM), vincristine (VCR), and VP16-213 in small cell carcinoma of the lung (SCCL).

Twenty-four evaluable patients with small cell carcinoma of the lung were treated with an escalating chemotherapy regimen including Cyclophosphamide, Adriamycin, Vincristine and VP16-213. The initial doses were CTX 800 mg/m2 i.v. day 1; ADR 50 mg/m2 i.v. day 1; VCR 1.4 mg/m2 day 1 weekly; and VP16-213 100 mg/m1 i.v. days 14-18 every 4 weeks, CTX and ADR were escalated by 100 and 10 mg/m2 respectively in each subsequent cycle according to blood count. Hematologic toxicity was minimal and the treatment was well tolerated. Partial responses and complete responses were 9 of 19 and 5 of 19 respectively for patients with limited disease, and 4 of 5 respectively for patients with extensive disease. The overall response rate for the whole group was 79% These results must be considered preliminary.

Adult↗
PubMed1980

Expression of a transposable antibiotic resistance element in Saccharomyces.

Some eukaryotic genes can be expressed in bacteria but there are few examples of the expression of prokaryotic genes in eukaryotes. Antibiotic G418 is a 2-deoxystreptamine antibiotic that is structurally related to gentamicin but has inhibitory activity against a much wider variety of pro- and eukaryotic organisms. In bacteria, resistance to G418 can be determined by several plasmid-encoded modifiying enzymes and, in view of the broad spectrum of activity of G418, we considered that this antibiotic might be useful as a selective agent for the introduction of these antibiotic resistance genes into a eukaryotic organism such as Saccharomyces cerevisiae. Additional impetus for these experiments came from the knowledge that certain of the G418-resistance determinants in bacteria are carried on transposable elements; a study of the properties of these elements in eukaryotes would be intriguing.

Bacteriocin Plasmids↗
PubMed1980

Quantification of antibodies against factor VIII by an immunonephelometric method in a continuous-flow system.

A new immunonephelometric method is described for the quantification of antibodies against factor VIII in sera from patients suffering from haemophilia A. We have been able to reduce the reaction time to only 16 minutes, which permits its application to emergency cases. Applying Spearman's test, we have correlated the results obtained by the immunonephelometric and Ruggieri's methods, obtaining r = 0.87, P < 0.01 for n = 11. From the reproducibility studies we obtained SD = 1.16 as maximum dispersion value. Because it is a fully automated method in a continuous-flow system, the possible manual errors are reduced to a minimum; 60 determinations can be carried out in 1 hour.

Antibodies↗
PubMed1980

A new selective agent for eukaryotic cloning vectors.

An aminoglycoside antibiotic, G418, has been shown to be an inhibitor of many pro- and eukaryotes at concentrations from 1-300 microgram/ml. A bacterial R-plasmid determinant that phosphorylates and inactivates antibiotic G418 can be introduced into yeast by transformation and expresses resistance to G418. It is suggested that this combination of antibiotic and dominant resistance mechanism may be useful in recombinant DNA studies as a cloning selection in eukaryotes.

Animals↗
PubMed1976

Competition between trichodermin and several other sesquiterpene antibiotics for binding to their receptor site(s) on eukaryotic ribosomes.

1. Of the five sesquiterpene antibiotics tested and found to inhibit protein synthesis in yeast spheroplasts, trichothecin, trichodermol or trichodermin stabilized polyribosomes whereas, in contrast, verrucarin A or T-2 toxin induced 'run off' of polyribosomes with a corresponding increase in 80S monoribosomes. The effect of fusarenon X on the system could not be determined as the drug failed to enter the cells. 2. [acetyl-14C]Trichodermin bound to yeast polyribosomes with a dissociation constant of 2.10 muM and to yeast 'run off' ribosomes with a dissociation constant of 0.72 muM. 3. Trichothecin, trichodermol, fusarenon X, T-2 toxin and verrucarin A competed with [acetyl-14C]trichodermin for binding to its receptor site on 'run off' ribosomes. The observed competition was quantitatively similar for all drugs tested. In contrast, the five drugs competed to different extents with trichodermin for binding to its receptor site on polyribosomes. Thus trichothecin competed with relative efficiency, whereas verrucarin A competed poorly, and the other drugs occupied intermediate positions between these two extremes. 4. Studies were also carried out with yeast 'run off' ribosomes prepared from both a wild-type strain and a strain resistant to trichodermin. Competition experiments between verrucarin A and [3H]anisomycin indicated that verrucarin A bound to 'run off' ribosomes from the mutant strain less efficiently than to those from the wild-type.

Anisomycin↗
PubMed1976

Specific inhibition of translocation by tubulosine in eukaryotic polysomes.

The alkaloid tubulosine inhibits the process of peptide chain elongation by eukaryotic polysomes by specifically preventing the elongation-factor-2-dependent step of translocation. Tubulosine does not affect either the elongation-factor-1-dependent binding of aminoacyl-tRNA or peptide bond formation. The site of action of tubulosine appears to be independent from the ribosomal site involved in cycloheximide action, since the alkaloid is active in blocking polymerization and enzymic translocation by polysomes from a yeast mutant resistant to cycloheximide. Furthermore tubulosine does not affect the non-enzymic translocation which takes place in the presence of high potassium ion concentrations, whereas this reaction is strongly inhibited by cyclohemimede. The different steps of translocation are discussed to explain the reactions blocked by tubulosine and cycloheximide.

Alkaloids↗
PubMed1976

Inhibitors of protein synthesis in eukarytic cells. Comparative effects of some amaryllidaceae alkaloids.

The effects of eighteen compounds obtained from bulbs of the Amaryllidaceae family were tested on (a) animal cell growth, (b) DNA, RNA and protein synthesis by intact cells and (c) protein synthesis in cell-free systems. Dihydrolycorine, haemanthamine, lycorine, narciclasine, pretazettine and pseudolycorine halted HeLa cell growth at 10(-1) mM or lower concentrations. These compounds at their growth inhibitory concentrations block protein synthesis in ascites cells and stabilize HeLa cell polysomes in vivo. Endomyocarditis virus RNA-directed cell-free polypeptide synthesis by an ascites S-30 extract and acetyl-[14C]leucyl-puromycin formation by ascites ribosomes are also inhibited by the six compounds indicated above. It is therefore concluded that they halt protein synthesis in eukaryotic cells by inhibiting the peptide bone formation step.

Alkaloids↗
PubMed1975

Simultaneous ribosomal resistance to trichodermin and anisomycin in Saccharomyces cerevisiae mutants.

A spontaneous mutant of Saccharomyces cerevisiae resistant to trichodermin has been isolated. It displays cross resistance both in vivo and in vitro to a number of sesquiterpene antibiotics (fusarenon X, trichothecin and verrucarin A) and to the chemically unrelated antibiotic anisomycin. The mutation conferring resistance to anisomycin and trichodermin is expressed in the 60-S subunit of the yeast 80-S ribosome. Mutant ribosomes bind [-14C]trichodermin much less efficiently than wild type ribosomes, suggesting that resistance may be due, at least in part, to this property. However, both types of ribosomes bind [-3H] anisomycin equally. These results suggest that anisomycin and trichodermin have different binding sites on the 60-S subunit of eukaryotic ribosomes, even though previous results have shown that both antibiotics bind to mutually exclusive sites.

Anti-Bacterial Agents↗
PubMed1975

Quantitative binding of antibiotics to ribosomes from a yeast mutant altered on the peptidyl-transferase center.

Quantitative binding studies of [G-3H]anisomycin and [acetyl-14C]trichodermin to sensitive and resistant 80-S ribosomes from yeasts are described in this work. A single mutation, most probably affecting the ribosome peptidyl transferase centre, appears to have pleiotropic effects on the ribosome leading to resistance to trichodermin and anisomycin and to an increased sensitivity to sparsomycin. Resistance to trichodermin is due to a reduced affinity of ribosomes from the mutant for the antibiotic. Ribosomes from the sensitive strain (Y 1661 bind [acetyl-14C]trichodermin with a dissociation constant of 0.99 muM while those from the resistant one (TR1) bind [acetyl-14C]trichodermin with a dissociation constant of 15.4 muM. Similar results are obtained when the binding of [acetyl-14C]trichodermin to Y 166 and TR1 60-S subunits is studied. The mutant TR1 is also resistant to anisomycin. Although trichodermin and anisomycin bind to the ribosome at mutually exclusive sites, the higher affinity binding of [G-3H]anisomycin that is responsible for the inhibition of the peptidyl transferase center is practically identical for Y 166 and TR1 ribosomes. Therefore, the mutation in the ribosome leading to resistance to trichodermin and anisomycin decreases the affinity for trichodermin but not for anisomycin. Trichodermin, trichothecin and fusarenon X inhibit the binding of [G-3H]anisomycin to TR1 ribosomes to a lower extent than to Y 166 ribosomes, suggesting that the resistance of TR1 ribosomes to the effects of trichothecin and fusarenon X is caused by a decrease in the affinity of the ribosomes for these drugs, as was seen with trichodermin. On the other hand, verrucarin A inhibits [G-3H]anisomycin binding to Y 166 and TR1 ribosomes to a similar extent and therefore its affinity for the ribosome does not appear to be affected by the mutation leading to resistance. Trichothecin, trichodermin and fusarenon X appear to have a common binding site on the 60-S ribosomal subunits, which overlaps or is closely linked to the binding sites of anisomycin and verrucarin A.

Acyltransferases↗