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Biomedical subjects

M C Alonso

Publications and source records attributed to M C Alonso.

At least 55 records · Page 3Linked to original sources

Regulation of scute function by extramacrochaete in vitro and in vivo.

The pattern of adult sensilla in Drosophila is established by the dosage-sensitive interaction of two antagonistic groups of genes. Sensilla development is promoted by members of the achaete-scute complex and the daughterless gene whereas it is suppressed by whereas extramacrochaete (emc) and hairy. All these genes encode helix-loop-helix proteins. The products of the achaete-scute complex and daughterless interact to form heterodimers able to activate transcription. In this report, we show that (1) extra-macrochaete forms heterodimers with the achaete, scute, lethal of scute and daughterless products; (2) extramacrochaete inhibits DNA-binding of Achaete, Scute and Lethal of Scute/Daughterless heterodimers and Daughterless homodimers and (3) extramacrochaete inhibits transcription activation by heterodimers in a yeast assay system. In addition, we have studied the expression patterns of scute in wild-type and extramacrochaete mutant imaginal discs. Expression of scute RNA during imaginal development occurs in groups of cells, but high levels of protein accumulate in the nuclei of only a subset of the RNA-expressing cells. The pattern is dynamic and results in a small number of protein-containing cells that correspond to sensillum precursors. extramacrochaete loss-of-function alleles develop extra sensilla and correspondingly display a larger number of cells with scute protein. These cells appear to arise from those that in the wild type already express scute RNA; hence, extramacrochaete is a repressor of scute function whose action may take place post-transcriptionally.

Amino Acid Sequence↗

A direct membrane filter method for enumerating somatic coliphages in drinking water.

The application of a simple membrane filter method to enumerate specific somatic bacteriophages of Escherichia coli, using E. coli C as host strain, from drinking water samples was studied. The efficiency of the method using cellulosic membrane filters, samples pretreated with magnesium ions and Tween 80 added to agar medium-host cell lawns ranged from 68.9 to over 112%, depending on the phage content of the sample. To avoid the pre-treatment of the sample with magnesium salts, electropositive-charged filters of cellulosic ester (HA-PEI and HA-Nalco) and Virosorb-1MDS filters were tested in conjunction with the simple membrane filter method. The electropositive filters showed wide bacteriophage recovery rate intervals depending on the sample treatment, ranging between 31.4 and 96.2% for ester-type filters, and a mean recovery lower than 2.2% for Virosorb filters. On the other hand, it was proved that the use of Tween 80 as an eluent improved somatic coliphage recovery rates for all the filters tested. In short, this methodology provides a rapid analysis (6-8 h) of the somatic coliphages from drinking water using the membrane filtration technique.

Adsorption↗

Direct effect of deferoxamine on hemoglobin synthesis in patients on hemodialysis treated with recombinant human erythropoietin.

We have studied the response of hemoglobin (Hb), hematocrit, reticulocytes, mean corpuscular volume, ferritin, serum iron, total iron-binding capacity (TIBC) and the transferrin saturation index in 9 patients on chronic hemodialysis (HD) with minimal aluminum overload who were treated with recombinant human erythropoietin (rHuEPO) when a single dose of deferoxamine (DFO; 40 mg/kg b.w.) was administered. Analytical determinations were performed basally and 48 h, 7 days and 14 days after a DFO test. Hb increased from a basal value of 10 +/- 0.28 to 10.7 +/- 0.33 (p < 0.05), 10.4 +/- 0.33 (p < 0.05) and 10.1 +/- 0.31 g/dl (NS), respectively, and similar increases were seen with the hematocrit. Serum iron increased from 52 +/- 7.62 to 89.2 +/- 14.48 (p < 0.01), 94 +/- 18.73 (p < 0.01) and 85 +/- 14.01 micrograms/dl (p < 0.01), respectively. TIBC and ferritin did not change but the transferrin saturation index increased significantly. DFO produces an immediate improvement of the anemia in HD patients treated with rHuEPO and who have minimal aluminium accumulation: it should be related to an increased iron availability to erythroid precursors either releasing stored iron or decreasing aluminum-bound transferrin.

Aged↗

[Usefulness of IgG and IgM detection against antigen 60 in the diagnosis of thoracic tuberculosis].

We conducted a prospective study in order to assess the use of the "ELISA" method (Anda-Tb) for the detection of antibodies IgG and IgM against antigen 60 in mycobacterias for the initial diagnosis of thoracic tuberculosis. 215 serum samples from 44 patients with tuberculosis and 171 control cases were studied. The threshold value for IgG in our environment is 200 U, resulting in a specificity of 98% and a sensitivity of 34%. The IgM test has a low sensitivity, although when combined with the IgG, the sensitivity of the test increases while its specificity is reduced. This method is not useful in patients with HIV infection and immunodepression (AIDS). We have not observed any relationship between the serology and the response to PPD intradermorreaction. We conclude that this method could be used in our environment as a supplementary test, but in any case as a substitute of the traditional microbiological diagnosis.

Adolescent↗

Mechanisms involved in NK resistance induced by interferon-gamma.

Human tumor cell lines were treated with interferon-gamma (IFN-gamma) and then used as target cells in NK assays to measure their ability to form conjugates and stimulate the production of NK cytotoxic factors (NKCF) and to determine their susceptibility to NKCF lysis. K562 and cell lines RS1, RS3, RS7, CAC, and CAP2, obtained from solid brain tumors, were used as targets, and peripheral blood lymphocytes (PBL) from normal donors were used as effector cells. IFN-gamma-treated cell lines had a decreased susceptibility to NKCF lysis and a decreased ability to induce the release of these factors without affecting target-effector cell binding. These results were not due to changes in HLA class I antigen expression, given that the level of HLA class I antigens on the tumor cell lines was not affected, the only exception being K562. In an attempt to further clarify the possible influence of HLA class I expression on K562, IFN-gamma-pretreated K562 cells were separated into HLA class I positive and HLA class I negative subsets for the NK assays. The results showed that both populations behaved similarly upon target-effector conjugate formation, whereas the HLA class I positive population showed a reduced susceptibility to lysis by NK cells and NKCF. Thus, these results establish that NK resistance induced by IFN-gamma is mediated by blocking the target cell's ability to activate NK cell triggering and release of NKCF and by blocking its susceptibility to lysis by these factors. This analysis helps to clarify not only the NK process but also the controversial regulatory effect of IFN in NK lysis.

Cell Adhesion↗

Ovarian carcinoma preceded by cerebral metastasis: review of the literature.

A patient with an asymptomatic primary ovarian carcinoma preceded several months before by a solitary intracranial metastasis is reported. The rarity of this phenomenon, the therapeutic experience in this patient, and the possible mechanism of spread are discussed. Also, a review of the literature is made.

Brain Neoplasms↗

Transcriptional activation by heterodimers of the achaete-scute and daughterless gene products of Drosophila.

The achaete-scute complex (AS-C) and the daughterless (da) genes encode helix-loop-helix proteins which have been shown to interact in vivo and to be required for neurogenesis. We show in vitro that heterodimers of three AS-C products with DA bind DNA strongly, whereas DA homodimers bind weakly and homo or heterocombinations of AS-C products not at all. Proteins unable to dimerize did not bind DNA. Target sequences for the heterodimers were found in the promoters of the hunchback and the achaete genes. Using sequences of the former we show that the DNA binding results obtained in vitro fully correlate with the ability of different combinations to activate the expression of a reporter gene in yeast. Embryos deficient for the lethal of scute gene fail to activate hunchback in some neural lineages in a pattern consistent with the lack of a member of a multigene family.

Animals↗

Alternating sequential endocrine therapy: tamoxifen and medroxyprogesterone acetate versus tamoxifen in postmenopausal advanced breast cancer patients.

The effects of tamoxifen (TAM) versus the alternating sequential combination of TAM plus medroxy-progesterone acetate (MPA) has been evaluated in 20 postmenopausal patients with advanced breast cancer in a randomized controlled trial. In the TAM arm, patients received 20 mg b.i.d. of TAM. In the TAM-MPA arm, patients received only 20 mg b.i.d. of TAM for 7 days and, on the following 7 days. TAM plus an oral daily dose of 500 mg of MPA, in alternating sequence. Objective tumor reduction was achieved in 22 (41%) of the 54 patients in the TAM arm and in 25 (43%) of the 58 patients in the TAM-MPA arm. With regard to the stabilization of disease, a significant difference was observed between patients treated with the TAM-MPA combination and those treated with TAM alone (47% vs 22%). The percentage of nonresponders was also significantly higher in the TAM group (37%) than in the TAM-MPA group (10%). The time to progression was significantly shorter for the TAM arm than for the TAM-MPA arm (median, 7 vs 15 months), but the duration of remission was not significantly different for either treatment.

Aged↗

Macrophage and lymphocyte antibody-dependent cellular cytotoxicity in spontaneous leukemogenesis of AKR/J mice.

Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by peritoneal macrophages and splenic lymphocytes was studied in young (15 weeks) and old (45 +/- 5 weeks) preleukemic AKR/J mice and leukemic (55 +/- 5 weeks) AKR/J mice. This strain spontaneously develops a virally induced T cell leukemia-lymphoma between the ages of 32 and 48 weeks. The peritoneal macrophages from the AKR/J leukemic and old preleukemic mice showed an impaired ADCC when compared with their respective age and tumor-free BALB/c controls and with young preleukemic AKR/J mice. Young and old preleukemic AKR/J mice and their respective controls had similar ADCC values with respect to splenic lymphocytes, whereas an impaired ADCC was observed by the splenic cells from leukemic AKR/J mice. The possibility of using ADCC mediated by macrophages as a test to detect the onset of the leukemic process is discussed.

Animals↗

The achaete-scute gene complex of Drosophila melanogaster comprises four homologous genes.

We have determined the nucleotide sequence of two genes of the achaete - scute complex (AS-C) and show that they are homologous to two previously sequenced members of the same locus. These four genes are interspersed with other transcription units of unknown function. We also study the expression of one of these genes by in situ hybridization and compare it with the other three genes. We suggest that the complete function ascribed to the AS-C by genetic experiments is carried out by the four homologous genes. We discuss the possible biochemical function of the AS-C in neurogenesis in the light of the homologies of the four genes with the mammalian myc family.

Animals↗

Phenocopies induced with antisense RNA identify the wingless gene.

Earlier work suggested that the wingless gene of Drosophila is required for cooperation within discrete groups of cells during development. We show that antisense RNA made from a 3 kb transcript produces wingless mutant phenocopies when injected into wild-type eggs, proving that this transcript executes the wingless function. In the accompanying paper, Rijsewijk et al. report cloning of a Drosophila homolog (Dint-1) of the mouse int-1 gene and show that this gene is identical to wingless+. The partial sequence of the wingless cDNA that we have isolated is identical to part of the complete Dint-1 sequence described by Rijsewijk et al.

Animals↗

Follow-up of breast cancer stages I and II. An analysis of some common methods.

A retrospective analysis of the follow-up methodology was done in 343 cases of breast cancer Stages I and II, in order to ascertain the effectiveness of the explorations performed and the usefulness of the follow-up program. The actuarial probability of relapse at 6 years was 35% for the 237 patients with negative axillary nodes and 46% for the 106 patients with nodal involvement. Fifty-eight per cent of the relapses were detected by the patients themselves, 24% of relapses were found by physical examination and 9% of relapses were discovered in chest radiographs, leading to 91% of relapses diagnosed by combination of these explorations. The authors conclude that follow-up methodology for these patients could be limited to the above-mentioned methods, without significant reduction of curability or survival possibilities after relapse.

Breast Neoplasms↗

Ontogenic and functional implications of the differential expression of HLA-DQ antigens on leukemic cells.

We have examined the HLA class II antigenic profiles on different types of leukemic cells and have attempted to relate these findings to the normal differentiation pathways of the cells from which they have arisen. Monoclonal antibodies reacting with the different HLA class II determinants, HLA-DR, DRw52(MT), and DQ, were used to study the expression of these antigens on Epstein-Barr virus transformed cell lines, chronic lymphocytic leukemic cells, acute lymphoblastic leukemic blasts, acute myeloblastic leukemic blasts, and established leukemic cell lines by indirect immunofluorescence binding and immunoprecipitations. The results showed that whereas the HLA-DR and HLA-DRw52(MT2) antigens are normally expressed on the majority of the cells tested, there is a different expression of the HLA-DQ antigens on acute leukemic blasts, chronic lymphocytic leukemic cells, and leukemic cell lines indicating that the DQ molecules may be differentiation antigens preferentially expressed on mature cells. Furthermore, when the pre-B cell leukemic line NALM 6 was induced to differentiate with phorbol ester (TPA), normal expression of the HLA-DQ antigen was obtained after 5 days of culture. The absence of HLA-DQ antigens from the acute leukemic blasts suggests that these immature cells "froze" in the early stages of cell differentiation. We discuss these findings in relation to the role of these HLA class II antigens in cell differentiation and the immune response.

Antibodies, Monoclonal↗

Locally advanced breast cancer with inflammatory component: a clinical entity with a poor prognosis.

Locally advanced and inflammatory carcinomas of the breast are two distinct entities, with widely accepted differential clinical criteria. We describe a particular type of locally advanced cancer which acquires during its evolution inflammatory characteristics, although limited to a small area of skin and thus not accomplishing the common diagnostic criteria of inflammatory carcinoma. When comparing this type of tumors, named locally advanced cancer with inflammatory component, to other locally advanced cancers, some remarkable differences are found: there is a preponderance of younger patients, premenopausal or perimenopausal, with a greater percentage of poorly differentiated tumors and negative estrogen receptors. Their evolution and survival are similar to that of inflammatory carcinomas; thus, we conclude they should be considered and treated as inflammatory carcinomas. Finally, the prognostic limitations of the TNM classification are discussed and some adjustments for future classifications are suggested.

Adult↗

Chemotherapy versus chemotherapy plus hormonotherapy in postmenopausal advanced breast cancer patients. A randomized trial.

One hundred seventeen postmenopausal advanced breast cancer patients previously untreated with chemotherapy were randomized to receive: cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), CMF and tamoxifen (TMX), and CMF and medroxyprogesterone (MAP). Treatments B and C induced a greater proportion of responses than treatment A. No effect was identified on the number of complete responses. After treatment failure, patients from groups A and C received Adriamycin (doxorubicin) (ADX) vincristine (VCR), and TMX and patients from group B received ADM, VCR, and MAP. No differences were found between the branches in the response rates to the second protocol. Responders to both treatments had a longer survival experience than nonresponders or responders to only one of the treatments. Survival was independent of the treatment group.

Antineoplastic Combined Chemotherapy Protocols↗

No influence of number of donor CFU-GM on granulocyte recovery in bone marrow transplantation for acute leukemia.

The possible interrelation between infused bone marrow CFU-GM and peripheral granulocyte recovery was studied in 16 patients transplanted for acute leukemia. The influence of several clinical events that could modify the graft fate were also analysed. Our results show that: 1) There was no correlation between the number of infused nucleated cells and granulocyte recovery. 2) There was no correlation between the number of infused CFU-GM and granulocyte regeneration. 3) There were significant differences between the day of engraftment in patients with clinically documented HSV infection compared to patients without infection.

Acute Disease↗