PubMed Health⌕ Search

Biomedical subjects

M López

Publications and source records attributed to M López.

At least 145 records · Page 8Linked to original sources

Uptake and distribution of 2',3'-dideoxyinosine and its derivatives in a human monocytoid cell line.

The dideoxynucleoside analogue 2',3'-dideoxyinosine (ddI) has been used in the clinic as an alternative drug to zidovudine (AZT) in the treatment of patients with the acquired immunodeficiency syndrome (AIDS). However, it shows significant and variable toxicity in patients. It is known that various dideoxynucleoside analogues can cause the termination of the DNA chain following incorporation of the corresponding triphosphate metabolite by the polymerases. In the case of ddI, the presumed active metabolite is 2',3'-dideoxyadenosine 5'-triphosphate (ddATP). In order to understand the molecular basis for the toxicity of ddI, we evaluated the relationship between the intracellular formation of ddATP, its incorporation into cellular DNA and the effects on the growth of U937 cells, a human monocytoid cell line. Dideoxyinosine was not significantly toxic to U937 cells at concentrations as high as 500 microM in a 72 hrs. growth inhibition assay. The results of the uptake of 3HddI in this cell line showed a proportional increase in total metabolites with increasing concentrations of the drug (1-20 microM) after a 24 hrs. exposure. Incubation with 10 microM 3HddI resulted in the formation of low levels of ddATP within a period of 2 hrs. A significant amount of ddI-derived radioactivity was found in both DNA and RNA after exposure to 10 microM 3HddI for 24 to 72 hrs. However, no evidence of incorporation of ddATP into the cellular DNA fraction was obtained in these experimental conditions. Therefore, the lack of significant toxicity of ddI to U937 cells can be explained, at least in part, by its inability to incorporate ddATP into its cellular DNA at the doses studied.

Biological Transport↗

Production in Escherichia coli of a rat chimeric proinsulin polypeptide carrying human A and B chains and its preparative chromatography.

A pseudohuman proinsulin coding DNA sequence (MMRPI) carrying human A and B chains, was constructed via directed mutagenesis of a previously modified rat proinsulin cDNA (MRPI) and expressed as a tryptophan (Trp)LE-proinsulin fusion protein in Escherichia coli W3110. Expression of the hybrid gene was achieved by depletion of tryptophan from the medium. The heterologous fusion protein, accumulated as insoluble inclusion bodies within the cell, was obtained by differential centrifugation and then solubilized using formic acid. At the junction of the two peptides, a methionine residue allowed proinsulin to be released from the carrier protein by cyanogen bromide treatment. The sulfonated form of this proinsulin polypeptide was easily purified, at a preparative level, using ion exchange chromatography.

Amino Acid Sequence↗

Molecular cloning and nucleotide sequence of the coat protein gene of a Cuban isolate of potato leafroll virus and its expression in Escherichia coli.

Total RNA from infected Physalis floridana was isolated to generate complementary DNA corresponding to the coat protein (GP) gene of a Cuban isolate of potato leaf roll virus (PLRV). This cDNA was amplified by the polymerase chain reaction (PCR) and cloned into the bacterial expression vectors pEX(1-3) for fusion protein expression in E. coli. The product was detected by antibodies specific for the PLRV CP. The coding sequence of the CP gene was determined, and the predicted length of the CP was 208 amino acids (23 kD). The nucleotide sequences and deduced amino acid sequences were compared with the other PLRV isolates and found to be 97-99.5% identical at both the nucleotide and amino acid sequence level of other isolates. Comparison of the deduced amino acid sequences of the PLRVcub CP revealed considerable homology to other luteoviruses. We believe that the protocol described could be applicable to other plant viruses of low abundance or of cumbersome isolation, since this method is less time consuming than the traditional methods of cloning coat protein genes of plant viruses with known sequences.

Amino Acid Sequence↗

Acute ethanol administration in diestrus-2 in the rat on pulsatile prolactin and LH release.

Exposure to ethanol is followed by changes in reproductive function in man and animals, characterized by modifications in the secretion patterns of prolactin and luteinizing hormone (LH). As both hormones are secreted in an episodic fashion, the present work was undertaken to study the effects of acute ethanol administration on pulsatile prolactin and LH secretion patterns in adult female rats. Rats were previously cannulated to allow a continuous blood withdrawal to study the pulsatile patterns of prolactin and LH. The mean values of prolactin during the bleeding period and the absolute pulse amplitude of prolactin peaks were significantly increased by acute ethanol administration, whereas a significant decrease of relative pulse amplitude and frequency of this hormone was observed. On the other hand, ethanol administration increased the mean serum LH levels and the absolute and relative amplitudes of LH peaks. Ethanol treatment did not modify either frequency or duration of LH peaks. These data suggest that acute ethanol administration in adult female rats is followed by changes in the pulsatile prolactin and LH secretory patterns, which might be part of the mechanism to explain ethanol effects on the endocrine system.

Animals↗

Development and clinical assay of the BCM ventricular assist device.

The development of a ventricular assist device is depicted. The seven subprograms that make up the project are described briefly. Results obtained during the clinical assay showed that the new design of the input cannula working as a false auricle provides better efficiency, as well as a certain level of autoregulation for the device.

Aged↗

Modification of concentration-response curves to inhaled methacholine after the pollen season in subjects with pollen induced rhinitis.

BACKGROUND: The effect of cessation of exposure to pollen on the concentration-response curves to inhaled methacholine was investigated. METHODS: Methacholine inhalation challenges (up to 200 mg/ml) were performed in 13 non-asthmatic patients with grass and/or Parietaria pollen-induced rhinitis during the pollen season, and one and four months after it. Concentration-response curves were characterised by their PC20, position, and plateau. RESULTS: Geometric mean methacholine PC20 increased from 6.4 mg/ml during the pollen season to 28.2 mg/ml and 54.9 mg/ml one and four months after the end of season, respectively. The mean (SE) level of the plateau decreased from 30.5 (4.3%) in the pollen season to 23.3 (3.7)% and 20.1 (3.3)% one and four months after the end of pollen season, respectively. Although the methacholine concentration that produced 50% of the maximal response increased from 2.9 mg/ml to 4.3 mg/ml and 6.0 mg/ml, the differences were not significant. CONCLUSIONS: In non-asthmatic patients with pollen-induced rhinitis cessation of exposure to pollen is associated with significant modifications in the methacholine threshold value and level of plateau, and with a small shift in the concentration-response curves to the right.

Adult↗

Depressed immune response in malnourished rats correlates with increased thymic noradrenaline level.

Depressed immune response is well documented in protein-calorie malnutrition (PCM). Also, central and peripheral noradrenaline (NA) activities have been reported to be increased in malnourished animals. Since increases in central and peripheral NA may inhibit immune function, it is possible that malnutrition-induced immunodepression could be mediated by noradrenergic hyperactivity. To address this hypothesis the effect of malnutrition on cell-mediated immune response, as well as on NA levels of the median eminence, spleen and thymus was studied in PCM rats. Decreased lymphoproliferative response and IL-1 production by mononuclear macrophages was observed in PCM. Besides, increased NA concentration was detected in thymuses of PCM rats, while unchanged levels of this neurotransmitter were observed in median eminence and spleen. These data suggest a positive correlation between malnutrition-induced immunodepression and sympathetic noradrenergic activity in thymus, an organ implicated in immune cell differentiation during early development.

Animals↗

[Diabetes in Mexico: what does the National Health Survey tell us?].

The purpose of this monograph is to describe the sociodemographic and health characteristics of individuals who identified themselves as diabetics (through self-notification) in a national health survey that was conducted in Mexico in 1988 and in which information about more than 200,000 persons was collected by interviewing an adult member of each household. Of the population surveyed, 1.2% stated being diabetic, and it was noted that the frequency of the disease increased with age and socioeconomic status and that it was 30% higher in women than in men. Diabetics had higher notification rates for hypertension, heart disease, and blindness than the rest of the population. Twenty percent of diabetic patients and 12% of nondiabetic individuals smoked. People with diabetes consulted physicians twice as often as nondiabetics and their chances of being hospitalized were four times higher. At the end we discuss the limitations and possible biases of self-notification as a method for detecting diabetics. Finally we conclude that diabetes is an important health problem in Mexico and that it warrants more attention from epidemiologists and other public health specialists.

Adolescent↗

[Thrombocytopenia associated with human immunodeficiency virus infection. Immunologic study of 60 patients addicted to parenteral drugs].

BACKGROUND: The immunologic study of 60 intravenous drug addict patients who were seropositive for the human immunodeficiency virus (HIV) and who developed thrombocytopenia (TP) is reported with the aim of establishing the relation of possible pathogenic factors which may trigger this complication. METHODS: In all the patients the presence of antiplatelet antibodies was studied by direct and indirect immunofluorescence together with crypto-antibodies, immune complexes, lymphocytotoxic antibodies, antiphospholipid antibodies, immunoglobulins, lymphocytic populations and subpopulations and serology against different infectious agents. RESULTS: Antiplatelet antibodies were detected in 71% of the patients of which 50% corresponded to immunoglobulins of IgG class, 12% to IgM, 21% to IgG plus IgM, 7% IgM plus IgA, 5% to IgG plus IgA and 5% IgG plus IgM plus IgA. In these patients a characteristic membrane fluorescence pattern was observed in which the fluorescein is distributed forming a thick, hard point. In 3 patients EDTA dependent crypto-antibodies were detected which in one case determined pseudothrombocytopenia. The immune complexes were demonstrated in 50% of the cases. Other findings were: hypergammaglobulinemia (86%), decrease in the CD4 population (47%), CD4/CD8 ratio < 1 (71%), lymphocytotoxic antibodies (70%), antiphospholipid antibodies (60%), and seropositivity for cytomegalovirus (62%), Epstein-Barr virus (10%) and hepatitis B virus (anti-HBc 75%, HBsAg 33%). CONCLUSIONS: Thrombocytopenia associated to infection by the human immunodeficiency virus in intravenous drug addict patients is due to the concurrence of multiple factors. The relevance of each may vary according to the risk practice of the collective analysed and even within the same group of some individuals or others. The numerous serologic findings in these patients fundamentally express the existence of a chronic polyclonal stimulation of B cells which may be initiated by the action of the drug itself and which becomes aggravated during the course of the multiple acquired infections among which that due to the human immunodeficiency virus is of note.

Adult↗

[The usefulness of the bcr/abl rearrangement in the diagnosis and evolution of chronic myeloid leukemia].

BACKGROUND: The rearrangement of the bcr/abl gene constitutes the molecular substrate of the Philadelphia chromosome (Ph'). The aim of this study was to analyze the usefulness of bcr/abl rearrangement in the diagnosis and evolution of chronic myeloid leukemia (CML). METHODS: The rearrangement of the bcr/abl gene was studied in 81 cases of which 34 corresponded to patients with CML (29 Ph' positive chromosome, 2 Ph' negative chromosome and 3 without karyotype), 2 patients with Ph' positive acute lymphoblastic leukemia, 15 patients with chronic myeloproliferative syndromes different from CML and 30 controls. Of the patients with CML, 6 were reevaluated when a blastic crisis was developed, 2 after receiving interferon treatment and 1 following allogeneic bone marrow transplantation. The technique used was that of Southern blotting using the restriction enzymes Bgl II and BamHI and the transprobe. RESULTS: Rearrangement of the bcr/abl gene was observed in all the patients with CML except in one with Ph' negative chromosome. In the remaining cases bcr/abl rearrangement was not observed. CONCLUSIONS: The Southern blotting technique for the study of the bcr/abl gene rearrangement is a sensitive and specific method in the diagnosis of chronic myeloid leukemia constituting a valid alternative to chromosomic study when this cannot be carried out or is not conclusive. It may also be used for the control of treatment in chronic myeloid leukemia.

Adult↗

QSAR and conformational analysis of the antiinflammatory agent amfenac and analogues.

The new nonsteroidal antiinflammatory drug (NSAID) arylacetic amfenac (2-amino-3-benzoylphenylacetic acid) and 19 substituted derivatives were studied in order to correlate the biological activities with the structure-related parameters. The geometry of amfenac in neutral and anionic form was totally optimized, starting from standard geometries and crystallographic data, using semiempirical AM1 and MNDO quantum-mechanical methods. Conformational analysis shows the existence of a rigid structure for rotations of the acetic acid chain (alpha degrees) and the central carbonyl group (gamma degrees) around the bonds with the phenylamine ring, whereas the carboxyl group (beta degrees) and the phenyl ring of the benzoyl group (delta degrees) can rotate almost freely. Electrostatic potential maps were analyzed and showed that the electrostatic orientation effect seems to make an important contribution to the binding of the active compounds to prostaglandin synthase. An electrostatic orientation model of the binding site is proposed. The frontier orbital charge distribution was also described for each compound. On the other hand, steric, electronic and hydrophobic (log P) parameters were calculated and QSAR analysis showed that the most significant parameter for the antiinflammatory activity was the pi-electron density of the HOMO orbital in the second aromatic ring. These results suggest a possible electronic charge transfer between the aromatic fragments and the receptor.

Anti-Inflammatory Agents, Non-Steroidal↗

Community health worker competency in managing acute respiratory infections of childhood in Bolivia.

A competency-based training and evaluation method was developed to improve and assess the management of acute respiratory infections (ARI) in young children by community health workers (CHWs) in Bolivia. This method was used to evaluate three groups of Bolivian CHWs, provide them with a one-day refresher course in ARI management, and assess the effects of the course. The results showed the CHWs capable of acquiring the skills needed to effectively manage ARI cases in accordance with the World Health Organization's ARI case management strategy. It was found important, however, that their training emphasize how to count the respirations of children with tachypnea and how to identify chest indrawing. In general, the competency-based methods appeared to be effective in training and evaluating CHWs in the area of ARI case management; it is expected that these methods will prove useful in other community-based health interventions.

Acute Disease↗

[Visceral leishmaniasis located in the intestines in patients with human immunodeficiency virus infection: a report of 2 cases].

We discuss two cases of visceral leishmaniasis (VL) with intestinal invasion in patients diagnosed of infection due to human immunodeficiency virus (HIV). The onset was as diarrheic manifestation associated to a constitutional syndrome, with no fever. One of the patients responded to treatment with antimonials, while the other died. References on this subject are scarce, being found on a literature search two similar cases as the ones described by us. We think that with every diarrheic process in HIV+ patients, VL diagnosis should be considered, and an intestinal biopsy should be performed.

AIDS-Related Opportunistic Infections↗

[Anticardiolipin antibodies and their association with the brain].

With the aim of establishing whether there is a relationship between anticardiolipin antibodies and migraine a prospective single blind study was performed. One hundred patients were analyzed, 50 without migraine [22 men (44%) and 28 women (56%)] and 50 with migraine 20 men (40%) and 30 women (60%). The mean age of the control group was 28.3 years (range 15 to 39) and that of the group with migraine was 26.5 years (range 14 to 40). The anticardiolipin antibodies were positive in two cases of each group. This study demonstrates that no association exists between migraine and the presence of anticardiolipin antibodies. Patients with migraine have the same incidence of anticardiolipin antibodies as the general population (4%).

Adolescent↗

Polarographic study of the photodecomposition of nimodipine.

Nimodipine, a calcium antagonist belonging to the dihydropyridine family, produces a well-defined polarographic peak due to the four-electron reduction of the nitro group. This peak was used to track the photodecomposition of nimodipine induced by UV light and daylight. Nimodipine was modified by UV irradiation with degradation following first-order kinetics. A degradation rate constant of 0.099 min-1, with a half-life of 7.78 min, for UV irradiation without a filter was obtained. Furthermore, a quantum yield of 1.32 x 10(-3) molecules/quantum absorbed was measured with a chemical actinometer. The UV degradation product, which was isolated and identified, showed that irradiation of nimodipine causes oxidation of the dihydropyridine ring and transmutation of the nitro group in the nitrobenzene moiety.

Nimodipine↗