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Biomedical subjects

A Macías

Publications and source records attributed to A Macías.

At least 37 records · Page 2Linked to original sources
PubMed1992

Autocatalysis and phenotypic expression of Drosophila homeotic gene Deformed: its dependence on polarity and homeotic gene function.

Previously published experiments have shown that the endogenous Dfd gene can be ectopically activated by its own (heat-shock-driven) product in a subset of cells of different segments. This results in the differentiation of maxillary structures like cirri and mouth hooks in places where they normally do not appear, and represents a phenomenon of autocatalysis of homeotic gene function that differs from the normal activation process. We show that this out-of-context activation occurs in cells belonging to the anterior compartments of the three thoracic and the A1 to A8 abdominal segments and that it requires the normal function of the polarity genes wingless (wg) and engrailed (en). The wg product, in addition to that of Dfd, appears to be sufficient to activate the endogenous Dfd gene in many embryonic cells. We have studied the effect of several homeotic genes on Dfd activation and phenotypic expression: Scr, Antp, Ubx and Abd-B repress Dfd both transcriptionally and at the phenotypic level, if their products are in sufficient amounts. The endogenous abd-A gene does not have a noticeable effect, but when it is replaced by an hsp70-abd-A gene, which produces a high and uniform level of expression, the phenotypic expression of Dfd is suppressed. Our results also suggest that the differentiation of cirri is induced by Dfd-expressing cells in non-expressing neighboring cells, and that this interaction occurs across the parasegmental border.

Animals↗
PubMed1990

Specific amplification of rearranged immunoglobulin variable region genes from mouse hybridoma cells.

In this article we show how the polymerase chain reaction (PCR) and primers designed for conserved sequences of leader (L), framework one (FR1) and constant (CONST) regions of immunoglobulin light and heavy chain genes can be used for the cloning and sequencing of rearranged antibody variable regions from mouse hybridoma cells. RNA was extracted from the mouse hybridoma cells secreting MAbs: IOR-T3a (anti-CD3), C6 (anti-P1 of N. meningitidis B385), IOR-T1 (anti-CD6), CB-CEA.1 (anti-carcinoembryonic antigen), and CB-Fib.1 (anti-human fibrin). First strand cDNA was synthesized and amplified using PCR. The newly designed primers are superior to others reported recently in the literature. Isolated PCR DNA fragments of C6 and IOR-T3a were sequenced after asymmetric amplification, or M13 cloning. The FR1/CONST primer combinations selectively amplified mouse lights chain of groups kappa II, V, and VI, and heavy chains of groups IIa and IIc. The L/CONST primers for light chains amplified light chains from all four hybridomas. These methods greatly facilitate structural and functional studies of antibodies by reducing the efforts required to clone and sequence their variable regions.

Amino Acid Sequence↗
PubMed1990

Homoeotic genes.

Region specific differentiation in Drosophila, (and possibly in many other higher organisms), is controlled by the activity of families of transcription factors encoded by the homoeotic genes. In Drosophila these genes are clustered in two complexes: the Antennapedia complex is responsible for directing the differentiation of the head and thoracic body segments whereas the bithorax complex controls the differentiation of the thorax and abdomen. The precise way in which these genes work is still a mystery but both the levels and combinations of gene activities play an important role in directing the development of individual segments.

Animals↗
PubMed1989

Intravenous ciprofloxacin and ceftazidime in serious infections. A prospective, controlled clinical trial with third-party blinding.

Oral ciprofloxacin has been shown to be effective in the treatment of infections due to gram-positive cocci and gram-negative rods. The efficacy and safety of intravenous ciprofloxacin was compared with that of intravenous ceftazidime in the treatment of 59 patients with well-documented serious infections in a prospective, controlled, randomized study with a third-party blinding. Thirty-three patients were treated with intravenous ciprofloxacin (200 mg every 12 hours, plus a daily extra placebo dose); 26 patients were treated with ceftazidime (1 g every eight hours). The severity of the infections, underlying diseases, and demographic features were comparable in both groups, although there were more men in the ciprofloxacin group. For ciprofloxacin/ceftazidime treatments, respectively, the evaluated infections were: pyelonephritis (16 patients/nine patients), pneumonia (three/five), soft-tissue infections (four/zero), spontaneous peritonitis (five/two), primary bacteremia (three/eight), and other (two/two). Isolated pathogens included: Escherichia coli (22/12), Klebsiella sp. (five/four), Pseudomonas aeruginosa (two/three), Haemophilus influenzae (one/one), Proteus mirabilis (two/zero), Proteus vulgaris (one/zero), Salmonella sp. (zero/two), Plesiomonas shigelloides (one/zero), and others (one/four). The clinical responses were cure or improvement in 31 ciprofloxacin cases/21 ceftazidime cases; failure, zero/four; and indeterminate, two/one. The bacteriologic responses were eradication in 28 ciprofloxacin cases/22 ceftazidime cases; persistence, one/three; and indeterminate, four/one. Mild intolerance occurred in three ciprofloxacin cases and two ceftazidime cases. A mild increase in serum hepatic enzymes was observed in two patients in each group. Superinfections occurred in five patients: enterococcal septicemia (zero/two) and urinary tract infections (one/two). The results presented suggest that intravenous ciprofloxacin is an effective and safe antimicrobial agent for the treatment of serious infections, with an efficacy comparable with that of ceftazidime, a broad-spectrum cephalosporin. An additional advantage seems to be a lower rate of superinfections.

Adolescent↗
PubMed1987

Factors associated with prognosis in human breast cancer. VII. A comparison between a Cuban and a Swedish study.

Prognosis in human breast cancer is important since therapeutic plans can be adjusted to individual probability of relapse. Comparative studies are not very frequent in literature. Prognostic factors are not assessed in the same way in different countries, thus contradictory results can be obtained. This paper summarizes the studies performed in two different populations of Swedish and Cuban patients. A group of prognostic factors was compared: age, tumor size, lymph node status, hormone receptors and DNA distribution. Some differences were obtained in these parameters and in short-term relapses. Lymph node status was more important in Swedish series, whereas ER content and DNA pattern were of more predictive value in the Cuban series. Biological interpretations of the results is suggested.

Adult↗
PubMed1985

Factors associated with prognosis in human breast cancer. V. The simultaneous use of estrogen and progesterone receptor measurements for prediction of short-term relapse.

Prediction of individual fate of breast cancer patients is one of the most important subjects studied because of the heterogeneity of the disease and the possibility of establishment of new therapeutic strategies. Hormone receptors have been recognized to be a valuable tool in prognosis at least in regard to short-term relapse. We have analyzed 400 patients in which hormone receptors has been determined, through stratification techniques, in 18-month and 3-year periods of disease-free interval. Clinical stage was chosen at the most important predictor in the total number of patients, lymph node status was the first predictor, estradiol receptor (ER) automatically was the second one, and the amount of receptor content had an important role in prognosis also. Inside Stage III patients ER should be the first predictor. Remarkable and independent association of progesterone receptor (PgR) content with relapse could be established. Predictive ability of ER and PgR inside lymph node status groups of patients was clearly shown. There was a remarkable difference between polar groups (lymph node-negative, ER+PgR+6% of relapse, and lymph node-positive, ER-PgR-30% of relapse) estrogen receptor status retains its predictive value, at the third year.

Breast Neoplasms↗
PubMed1984

Epidermal growth factor receptors in human breast cancer.

The capacity for specific binding of 125I-epidermal growth factor (EGF) was studied in crude membrane fractions from 95 human breast carcinomas. About 42% of the samples showed saturable, high affinity, specific binding of EGF. In 21% of the tumors we were able to demonstrate high (above 10 fmoles/mg protein) binding capacity. Moreover, high EGF receptor values were associated with a low content of estradiol receptor. These studies are related to the definition of new biochemical markers in human breast cancer.

Animals↗
PubMed1983

Factors associated with prognosis in human breast cancer. III. Estradiol receptors and short term relapse.

Prognosis in breast cancer is one of the most important subjects currently studied because of the heterogeneity of the disease even inside the same clinical stage. Estrogen receptor determination in human breast cancer has been recognized as a prognostic factor since it is related to the long-term survival and disease-free interval. In a series of papers concerning prognosis in breast cancer this the third one which includes estrogen receptor determination in the multivariate analysis, because of the limitations of the clinical factor to conform stratification groups. We have analyzed the short term probability of relapse in a group of 136 patients treated for breast cancer. Multivariate stratification analysis was performed with the aid of Bintree computer program, which produces binary splits of the population according to the criterion of maximal reduction of variance and generates a binary stratification tree. Lymph node involvement is the most important prognostic factor in the probability of relapse. Patients without nodal involvement lacking estradiol receptor had 25% of relapse. It is therefore evident that estradiol receptor is a factor of prognostic value even inside node negative patients.

Breast Neoplasms↗
PubMed1983

Factors associated with prognosis in human breast cancer. IV. Progesterone receptors and clinical factors.

We have found no correlation between progesterone receptor PgR content in human breast tumors and clinical factors associated with the presence of estrogen receptor (ER, age, menopausal status, parity, age at first childbirth, menarche), in spite of the positive correlation between both receptors. Moreover, the association between clinical factors and the percentage of ER(-) PgR(-) tumors were identical to those of ER(-) tumors, but the association between clinical factors and the percentage of ER(+) PgR(-) tumors were inverse to those of ER(-) tumors. That implies that clinical factors associated with the presence of estrogen receptor can not distinguish ER(+) PgR(+) and ER(+) PgR(-) tumors. The stage of the disease is the most important clinical feature in breast cancer patients. In our series the pattern of hormone-receptor was different between Stages I/II and Stage III patients, while the percentage of PgR(+) tumors was constant, a decrease in ER(+) tumors occurred in Stage III patients. In addition similar percentages of ER(+) PgR(+) were found in both groups, but an increase in ER(-) PgR(-) tumors and a decrease in ER(+) PgR(-) tumors occurred in the Stage III patients. Altogether these results suggest that primary loss of progesterone receptors and primary loss of estrogen receptors could be related to different pathogenic mechanisms.

Adult↗
PubMedDate not supplied

Monoclonal anti-EGFreceptor antibody (ior-R3) pharmacokinetic study in tumor bearing nude mice: role of the receptor-mediated endocytosis on drug clearance.

With the purpose of describing the MAb ior-R3's kinetic behavior in disease state, this paper is focused on the study of this response using a human cancer (lung carcinoma cell line, H125) bearing nude mice animal model. This MAb was administered by a single 16 mg/Kg intravenous bolus dose and the blood samples were collected at several times ranging from 0 to 72 hours for serum drug quantification. The experimental data set was best fitted using a classical two-compartment mammilary pharmacokinetic (PK) model and the corresponding PK parameters were determined. Comparatively, the analysis of the more relevant physiologically-based PK parameters showed a significant enhancing of clearance as compound with the earlier reported study on healthy mice, increasing from 0.09 to 0.19 mL/h (p<0.01). However, the corresponding distribution volumes don't seem to be altered by the tumor xenograft. We conclude that all of these evidences suggest a possible mechanism of receptor-mediated endocytosis (RME) as a major cause of this increased drug clearance which also contributed to the faster decrease of the drug disposition.

Animals↗