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Biomedical subjects

A Herrera

Publications and source records attributed to A Herrera.

At least 19 recordsLinked to original sources

A dynamical model for a co-operative enzyme.

Proteins partially immersed in the hydrophobic portion of a lipid bilayer interact by means of London-van der Waals non-bonding dispersion forces. Moreover, in certain organelles, enzymes are structured in a lattice or ordered matrix. These conditions may facilitate the establishment of long-range correlations between proteins. We studied the dynamical properties of a model for an enzyme endowed with a highly co-operative conformational transition between two reactive states. Two cases were considered, a closed system and an open system. In the closed system for different degrees of interaction among the proteins, it was found that for a substrate concentration greater than a certain threshold an abrupt change of enzymatic activity occurs. This biphasic behavior has been observed in the enzymatic activity of crystalline mitochondrial aspartate aminotransferase and for some other crystalline enzymes. In the analysis of the open system, for a specific input rate of the substrate, two different dynamics were found depending on the selected degree of interaction. For a certain value of a parameter phi, representing the degree of interaction among the reacting units, three steady states co-exist. This multiplicity confers excitable properties to the model. For larger values of phi, limit cycle type solutions were obtained. Thus, a sustained oscillatory product formation of the enzymatic reaction is observed. These results are compared with experimental observations of enzyme extracts detected by NMR.

Enzyme Activation

Analysis of cytogenetic damage induced in CHO cells by the pyrethroid insecticide fenvalerate.

A synthetic pyrethroid insecticide, fenvalerate, was tested for its ability to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in CHO cells. Fenvalerate was assayed both in the presence and in the absence of a rat liver activation system (S9-mix). Our results indicate that fenvalerate in the presence of S9-mix is able significantly to increase the frequency of CA, while in the SCE test this increase occurred both in the presence and in the absence of S9-mix. In addition, fenvalerate affected the cell cycle, causing a decrease in the mitotic index (MI) and in the proliferative rate index (PRI).

Animals

Cytogenetic effects of permethrin in cultured human lymphocytes.

The pyrethroid insecticide permethrin was tested for its ability to induce sister chromatid exchanges (SCE), micronuclei (MN) and structural chromosome aberrations (CA) in cultured human peripheral blood lymphocytes. Permethrin was tested in the range of 5-500 micrograms/ml in the absence and in the presence of a rat liver activation system (S9 mix). Small elevations in the SCE frequencies were found and even though statistically significant may have no biological meaning, the more so since there was no dose-effect relationship. Permethrin induced both MN and CA when it was evaluated in the absence of a metabolic activation system. Nevertheless, it cannot be said that S9 mix suppressed the activity in itself. The effect of permethrin seemed to be time of exposure dependent. Permethrin could be characterized as a S-phase independent agent with greater potential for inducing chromosomal damage than sister chromatid exchanges.

Animals

Mutagenic evaluation of trichlorfon using different assay methods with Salmonella typhimurium.

Evaluation of the mutagenicity of trichlorfon pesticide was carried out with strains TA1535, TA100, TA97, TA98 and TA104 of Salmonella typhimurium by means of several assay methods: (i) spot test; (ii) standard plate incorporation test; (iii) plate incorporation test with preincubation; (iv) fluctuation test and (v) fluctuation test with preincubation, with and without post-mitochondrial liver fraction (S9) from Wistar rats pretreated with phenobarbital and 5,6-benzoflavone as a metabolic activation system. Trichlorfon induced base-pair substitution mutations, and its mutagenic activity was decreased by the addition of S9 mix. The fluctuation test and fluctuation test with preincubation were the most sensitive assay methods for detecting the mutagenicity of trichlorfon.

Animals

[Wegener's granulomatosis. Apropos of a new case and review of the literature].

A case of Wegener's granulomatosis (WG) is presented, high-lighting the long-term evolution of affliction of the upper airways without diagnosis, as well as the rapid evolution after detection of the rest of the compounds of the syndrome. We show the difficulties in making a differential diagnosis and the clinical improvement with immunosuppressor treatment.

Adult

[Treatment of aggressive non-Hodgkin's lymphoma in aged patients with a combination of methyl-GAG, etoposide and prednimustine].

The authors report the results of a chemotherapy regimen of methyl-GAG, etoposide and prednimustine in 21 elderly patients (median age = 78 years) with aggressive non-Hodgkin's lymphoma. Sixteen patients responded (11 complete remissions, 5 partial remissions) with minor toxic side-effects. This regimen could be proposed for patients whose age and/or cardiovascular status prohibit treatment with usual anthracycline-containing chemotherapy programs.

Aged

Clinical and pharmacokinetic study of 96-h infusions of doxorubicin in advanced cancer patients.

A phase I and a pharmacokinetic study of 96-h infusions of doxorubicin were performed in order to evaluate the maximum tolerated dose with this schedule of administration. Seventeen patients suffering from a digestive carcinoma were included in the study and a total of 71 courses of treatment were performed. The starting dose was 15 mg/m2/day and was increased in 2.5 mg/m2/day increments. The main toxicities observed were neutropenia and mucositis, which became limiting from 22.5 mg/m2/day (90 mg/m2 over a 96-h period); this dose was therefore defined as the maximal tolerated dose. No objective response to treatment was observed. For further studies, the recommended dose should not exceed 20 mg/m2/day. A plasma plateau concentration of doxorubicin was reached within 24 h. Despite a constant infusion rate, the plasma concentration of doxorubicin showed transient variations in several patients. However, an average plasma concentration could be evaluated for 33 courses of treatment, and this was linearly related to the dose. Doxorubicinol was the only detected metabolite of doxorubicin and its plasma concentration progressively increased throughout infusion. A detailed pharmacokinetic study was performed in 13 courses of treatment. The mean plasma clearance of doxorubicin was 25.2 l/h/m2 and the mean terminal half-lives of doxorubicin and doxorubicinol were respectively 43.6 and 66.2 h. Urinary excretion of doxorubicin plus metabolite was regular from the 24th to the 96th hour of infusion; however, the proportion of doxorubicinol progressively increased in urine. The protracted half-life of this metabolite probably explains its accumulation during infusion.

Adult

[Is it possible to relate reflux esophagitis to epidermoid carcinoma of the esophagus?].

The authors present a retrospective study of 120 cases of epidermoid carcinoma of the esophagus, in which they proposed to investigate the etiopathogenic relation between gastroesophageal reflux and noplastic development. A statistically significant relation was found between esophagitis and cancer of the distal esophageal third, indicating the need for vigilance of patients with reflux and for randomized prospective studies to clarify the problem definitively.

Adult

Mutagenic activity in synthetic pyrethroids in Salmonella typhimurium.

Four pyrethroids, allethrin, resmethrin, permethrin and fenvalerate, were tested for mutagenicity in bacterial reversion assay systems with seven strains (TA1535, TA100, TA1538, TA98, TA1537, TA97 and TA104) of Salmonella typhimurium. Our results show that three pyrethroids, namely resmethrin, permethrin and fenvalerate, were not found to be mutagenic in S. typhimurium in the presence or absence of a rat liver activation system. Allethrin was found to be mutagenic with TA100, TA104 and TA97 strains and required metabolic activation (S9 mix) in order to show its activity, mainly with TA100 and TA104 strains.

Allethrins

[New anthracyclines].

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Antibiotics, Antineoplastic

Theoretical model for the post-transcriptional regulation of the human c-myc gene expression, involving double-stranded RNA processing.

We propose that the human c-myc gene expression is regulated by a post-transcriptional mechanism based on the formation of a hairpin structure between c-myc mRNA exons 1 and 2. This structure could be rapidly processed by a hypothetical double stranded RNAse, removing the 5' end segment of the c-myc mRNA having the cap site. Removal of cap should propitiate exonucleolytic degradation of transcript.

Gene Amplification

Identification of macrophages and smooth muscle cells with monoclonal antibodies in the human atherosclerotic plaque.

Sections of human atherosclerotic plaques, obtained from 21 autopsy cases with various degrees of atherosclerosis, were stained with the indirect immunoperoxidase technique using specific monoclonal antibodies against macrophages and smooth muscle cells. Distinctive results were found in differing stages: Single blood monocytes were observed in diffuse intimal thickening and the foam cells seen in fatty streaks were mostly identified as mature tissue macrophages, while only very few blood monocytes were present. The spindle cells observed in fibroelastic plaques showed positive reactions to antibodies against desmin, which points to their derivation from smooth muscle cells, whereas only a few macrophage-derived foam cells were seen in these lesions. In the complicated lesions the majority of foam cells were macrophage-derived, but there was also a small number of foam cells positive to antibodies against desmin, suggesting a smooth muscle cell derivation. Our results confirm that in human atherosclerotic plaques the majority of the foam cells are obviously macrophage-derived, which emphasizes the important role of macrophages in the morphogenesis of these lesions.

Adolescent

Age as the main prognostic factor in adult aggressive non-Hodgkin's lymphoma.

From 1975 to 1983, 73 patients with aggressive non-Hodgkin's lymphoma were treated with a first-generation program including Adriamycin, VM 26, cyclophosphamide, and prednisone. Thirty-nine patients were under 60 years of age, and 34 were 60 years or older. The clinical and histologic characteristics of the two groups were similar. Using either univariate or multivariate analysis, age appeared as the only prognostic factor. Patients under 60 had a median survival of 48 months, with a five-year survival rate of 47 percent and a five-year disease-free survival rate for complete-remission patients of 72 percent. Patients 60 years or older had a median survival of 18 months with a five-year survival rate of 18 percent and a five-year disease-free survival rate for complete-remission patients of 24 percent. These highly significant differences were related to a non-significantly decreased complete-remission rate and a significantly higher relapse rate in elderly patients. Since patient selection according to age could play a role in the results achieved with intensive chemotherapy programs, randomized trials comparing the various chemotherapy programs for aggressive non-Hodgkin's lymphoma are warranted.

Adolescent

Umbilical polyps.

We report three patients, ages 5 years, 3 years, and 4 days, with umbilical polyps. In the third child the polyp was associated with an umbilical enteric fistula. An umbilical polyp is the result of incomplete closure of the omphalomesenteric duct and becomes apparent after the umbilical cord is detached. It is a reddish tumor of a few millimeters; it seldom bleeds or is exudative. We consider it important to study every case in detail in order to exclude possible underlying embryologic anomalies such as Meckel's diverticulum and umbilical enteric fistula.

Abdominal Neoplasms