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Biomedical subjects

T Gómez

Publications and source records attributed to T Gómez.

At least 19 recordsLinked to original sources

Membrane mechanisms for electrogenic Na(+)-independent L-alanine transport in the lizard duodenal mucosa.

The active Na(+)-independent transport of L-alanine across the duodenal mucosa of the lizard Gallotia galloti was studied in Ussing-type chambers using a computer-controlled voltage clamp. Addition of L-alanine to the Na(+)-free bathing solutions resulted in a significant L-alanine absorption (J(net)) that was paralleled by an increase in transepithelial short-circuit current (I(sc)) and potential difference (PD) without apparent changes in the tissue conductance. The concentration dependence of J(net), PD, and I(sc) displayed Michaelis-Menten kinetics. L-alanine-induced electrical changes were completely inhibited by external alkaline pH or by the H(+)-ionophore carbonyl cyanide m-chlorophenyl-hydrazone in the bathing solution. The alanine-induced electrogenicity was dependent on the presence of extracellular K(+) and could be blocked by serosal Ba(2+) or mucosal orthovanadate. These results suggest the existence of an H(+)-coupled L-alanine cotransport at the apical membrane of enterocytes. The favorable H(+) driving force is likely to be maintained by an apical vanadate-sensitive H(+)-K(+)-ATPase, allowing the extrusion of H(+) in an exchange with K(+). Potassium exit through a basolateral barium-sensitive conductance provides the key step for the electrogenicity of L-alanine absorption.

Alanine↗

Relevance of presenting white blood cell count and kinetics of molecular remission in the prognosis of acute myeloid leukemia with CBFbeta/MYH11 rearrangement.

BACKGROUND AND OBJECTIVES: The detection of CBFbeta/MYH11 transcripts by RT-PCR has became a valuable and widely used technique in the accurate cytogenetic and molecular classification of acute myeloid leukemia (AML), but the clinical value of RT-PCR for monitoring minimal residual disease (MRD) during follow-up remains unclear. DESIGN AND METHODS: We analyzed the factors predicting relapse and the value of MRD monitoring by RT-PCR in a series of 16 patients with CBFb/MYH11-positive AML (15 M4Eo; 1 M4). Fifteen were newly diagnosed cases (CR1) and one was studied after first relapse (CR2). Eight patients had clinical relapse at 6 to 19 months from the achievement of CR. RESULTS: Presenting WBC count had a significant prognostic influence on disease-free survival (p=0.001). All four patients with a WBC count >100x10(9)/L relapsed, while only four additional relapses occurred among the eleven patients who had an initial WBC count below 100x10(9)/L. With regards to molecular monitoring, all relapses but one occurred in patients who showed persistent RT-PCR positivity during hematologic remission. By contrast, conversion to a repeatedly PCR-negative status was observed in the seven patients who remained in CR1 after a median follow-up of 48 months (range 31-79 months), as well as in the transplanted patient who was monitored in CR2. In these patients a PCR-positivity could be detected up to 24 months after diagnosis (median time to conversion to PCR-negative: 8 months). INTERPRETATION AND CONCLUSIONS: In conclusion, marked hyperleukocytosis (>100x10(9)/L) confers poor prognosis to the patient with CBFbeta/MYH11-positive AML. In addition, slow kinetics of molecular remission was observed in this subset of AML, but the CBFb/MYH11 fusion transcript is no longer detectable in long-term survivors, indicating that molecular remission is an important therapeutic goal.

Acute Disease↗

A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group.

The Spanish PETHEMA group designed a protocol for newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia (APL) in which induction and consolidation followed the original AIDA regimen, except for the omission of cytarabine and etoposide from consolidation. Induction consisted of 45 mg/m(2) all-trans retinoic acid (ATRA) daily until complete remission (CR) and 12 mg/m(2) idarubicin on days 2, 4, 6, and 8. Patients in CR received 3 monthly chemotherapy courses: idarubicin 5 mg/m(2)/d x 4 (course no. 1), mitoxantrone 10 mg/m(2)/d x 5 (course no. 2), and idarubicin 12 mg/m(2)/d x 1 (course no. 3). Maintenance therapy consisted of 90 mg/m(2)/d mercaptopurine orally, 15 mg/m(2)/wk methotrexate intramuscularly, and, intermittently, 45 mg/m(2)/d ATRA for 15 days every 3 months. Between November 1996 and December 1998, 123 patients with newly diagnosed PML/RARalpha-positive APL from 39 centers were enrolled. A total of 109 patients achieved CR (89%; 95% confidence interval [CI], 83 to 95), 12 died of early complications, and the remaining 2 were resistant. Consolidation treatment was associated with very low toxicity and no deaths in remission were recorded. Molecular assessment of response by reverse transcriptase-polymerase chain reaction (RT-PCR) showed conversion to PCR-negative in 48 of 99 (51%) and 82 of 88 patients (93%) after induction and consolidation, respectively. The 2-year Kaplan-Meier estimates of overall survival and event-free survival were 82% +/- 4% and 79% +/- 4%, respectively. For patients who achieved CR, the 2-year disease-free survival (DFS) was 92% +/- 3%. These data indicate that a significant reduction in toxicity might be obtained in APL using a less intensive consolidation without apparently compromising the antileukemic effect. These results also suggest a minor role for cytarabine and etoposide in the treatment of newly diagnosed PML/RARalpha-positive APL patients.

Adolescent↗

Evaluation of a predictive kinetic procedure for the enzymatic measurement of creatinine in serum.

We have evaluated the analytical performance of a predictive kinetic procedure for the enzymatic measurement of serum creatinine in comparison with equilibrium and kinetic fixed-time procedures. The procedure uses commercially available reagents and is based on calculating the total change in absorbance expected if the reaction were to proceed to equilibrium by fitting the initial part of the absorbance-time curve to a three-parameter function by non-linear regression. Total imprecision for different concentrations of creatinine ranges from 1.47 to 1.86% and is significantly better than that obtained for the fixed-time procedure. The results with the predictive procedure are less dependent on creatinine amidohydrolase activity in the reagent, pH of the reagent and temperature of analysis than are the results with the fixed-time procedure. All the procedures are interfered with by bilirubin and ascorbic acid to about the same extent. Recovery and linearity are quite acceptable, and the estimated accuracy is below 2.1%. However, in comparison with the equilibrium procedure, the predictive procedure tends to underestimate creatinine concentrations at values below 100 micromol/l, and the results obtained by the two procedures are not transferable. In conclusion, the predictive approach substantially improves the imprecision but not the specificity of the enzymatic assay of serum creatinine.

Artifacts↗

Effect of morphine and abstinence syndrome on [3H]bromoxidine binding to alpha 2-adrenoceptors in rat brain.

At 4 days after the implantation of two subcutaneous 75 mg morphine pellets in the back skin, rats were morphine-dependent. In the three layers studied in the occipital cortex we found that the values of the alpha 2-adrenergic agonist [3H]bromoxidine binding increased with respect to animals implanted with placebo pellets. Typical behavioral and physiological symptoms of the abstinence syndrome appeared 30 minutes after administration of naloxone, [3H]bromoxidine binding values being similar to those obtained in animals implanted with placebo pellets. The pattern of response of the [3H]bromoxidine binding was similar in the hippocampus and the superficial gray layer of the superior colliculus of the mesencephalon, but the differences were not statistically significant in these areas. This paper concludes that exist brain regional differences in the alpha 2-adrenoceptors response under morphine-treatment and possibly under naloxone-induced morphine abstinence syndrome.

Adrenergic alpha-Agonists↗

Late cardiac toxicity of doxorubicin, epirubicin, and mitoxantrone therapy for Hodgkin's disease in adults.

Cardiotoxicity is a well recognized side effect of anthracyclines (doxorubicin and epirubicin) or antracenadiones (mitoxantrone) at cumulative or high doses. However the side effects have not been evaluated in adults with Hodgkin's disease who received therapeutic doses of these drugs. We analyzed the cardiac function studying the left ventricular ejection fraction (LVEF) at rest in 136 patients with Hodgkin's disease treated with doxorubicin, epirubicin or mitoxantrone used in combination with vinblastine, bleomycin and decarbazine. No other risk factors, such as radiation therapy to the mediastinum, were considered. The follow-up is 5 to 8 years for patients in complete remission. Forty-five patients received doxorubicin (from 325 to 685 mg/m2, median 475 mg/m2), 51 patients received epirubicin (from 310 to 610 mg/m2, median 510 mg/m2) and 40 patients were treated with mitoxantrone (from 70 to 165, median 125 mg/m2). The median time between the end of treatment and the evaluation was 6.7 years. Thirty seven percent of the patients (similar rates in the three groups) showed abnormalities in the LVEF with decreased rates independent of the drug dosage. These were compared with two control groups, 46 patients treated with the MOPP combination (mechlorethamine, vincristine, prednisone and procarbazine) or LOPP (chlorambucil, for mechlorethamine) and 35 healthy volunteers. We believe that the use of anthracyclines or antracenadione will produce late cardiac effects in a fraction of patients independently of the doses used and that the indications for these drugs be carefully monitoring so as to evaluate the development of late side effects.

Adult↗

Autoradiographic localization of alpha 2-adrenoceptors in chick brain.

alpha 2-Adrenoceptors were localized in the chick brain by 'in vitro' receptor autoradiography using [3H]UK 14304 as a ligand. High or very high densities of binding sites were found in the hyperstriatum, tuberculum olfactorium, hypothalamic nuclei, tectum opticum and some medullary nuclei. Comparatively, intermediate densities were observed over the thalamic nuclei and locus ceruleus, among others. Low densities of alpha 2-adrenoceptors were detected in the paleostriatum, hippocampus and cerebellum. Our data indicate that alpha 2-adrenoceptors in the chick brain present similar properties and homologous anatomical distribution to those reported in mammalian brain.

Adrenergic alpha-Agonists↗

Electrical properties and fluxes of Na+ and Cl- across lizard intestine.

Electrical parameters and unidirectional Na+ and Cl- fluxes were determined in vitro across the duodenum, ileum and colon of lizard (Gallotia galloti). Electrical potential difference (PD) and short circuit current (Isc) were low in the three segments studied, whilst tissue conductance (Gt) was high. A net active transport of Na+ and Cl- was observed in the three segments. Net Na+ absorption was higher across duodenum and ileum than across the colon, while net Cl- absorption was similar in duodenum, ileum and colon. Ouabain virtually abolished Isc, PD and net Na+ and Cl- fluxes in all the segments. Amiloride abolished net Cl- flux in duodenum, ileum and colon, whereas net Na+ flux was abolished in colon but decreased in duodenum and ileum. PD and Isc were not affected by the presence of the diuretic.

Amiloride↗

Mechanisms of transport of Na+ and Cl- in the lizard colon.

1. Ionic fluxes of sodium and chloride across lizard colon mucosa were measured and compared with the electrical characteristics of the tissue under voltage-clamped conditions. 2. In a Ringer-bicarbonate solution there was both a net sodium flux (JNanet) and a net chloride flux (JClnet) from mucosa to serosa. The net flux residual (JR) was near zero, indicating that net sodium and chloride transport is the result of an electrically neutral transport mechanism. 3. In the presence of sodium, the net chloride flux was abolished and the short-circuit current (Isc) and the electrical potential difference (PD) were unchanged. In the absence of chloride the net sodium flux was abolished and the short-circuit current and electrical potential difference were not modified. 4. From an analysis of the effects of the inhibitors, furosemide, amiloride and disulfonic stilbene (DIDS), a plausible model was developed to explain the characteristics of sodium and chloride absorption.

Animals↗

Effect of theophylline on ion transport in the lizard colon.

1. The effect of theophylline on ion transport was examined using an in vitro short-circuited preparation of lizard colon. 2. Theophylline increased short circuit current (Isc) and transmural potential difference (PD). This increase caused by theophylline was accompanied by a small increase in transmural conductance (Gt). 3. Theophylline did not inhibit the absorption of Na+ but reversed Cl- absorption to secretion. This latter effect was due to an increase of the serosal-to-mucosal flux of Cl-. 4. Ion substitution experiments revealed that the effect of theophylline was Na+- and HCO3(-)-dependent and that these ions were required in the bathing solution. 5. These results with lizard colon are compared with those reported for mammalian colon and the mechanism of theophylline-induced Cl- secretion in these epithelia is discussed.

Animals↗

Intestinal glucose and galactose transport in the cultured gilthead bream (Sparus aurata).

1. Electrical parameters and transepithelial glucose and galactose transport were determined in vitro across anterior and posterior intestine of the culture fish Sparus aurata. 2. Electrical potential difference (PD) and short-circuit current (Isc) were serosa-positive in anterior intestine, while they were serosa-negative or near zero in posterior intestine. 3. Tissue conductance (Gt) was higher in posterior than in anterior intestine. In both parts it was decreased when the Na ion was omitted in mucosal and serosal reservoirs. 4. Addition of glucose or galactose to the mucosal side of intestine caused an increase in PD and Isc in posterior intestine but did not significantly change PD and Isc in anterior intestine. 5. Isotopic flux of glucose and galactose measurements in short-circuit conditions showed a net active glucose and galactose absorption in posterior intestine, while in anterior intestine active transport of glucose or galactose was not observed. 6. The net transport of glucose and galactose in posterior intestine was decreased to zero in the absence of Na in mucosal and serosal reservoirs or in the presence of ouabain (1 mM) in serosal solution.

Animals↗

Transport of galactose and sodium across lizard duodenum.

Electrical parameters and transepithelial Na+ and galactose transport were determined in vitro across isolated duodenum of Lacerta galloti lizard. Electrical potential difference (PD) and short-circuit current (Isc) were dependent on the presence of Na+ in the bathing solutions. PD and Isc were affected by addition of galactose to the mucosal solution. Isotopic flux of Na+ measurements across short-circuited duodenum showed a net active Na+ absorption. The net flux of Na+ (JNa+net) accounted for the observed Isc. Both (JNa+net) and Isc were increased by the addition of galactose 5 mM to the mucosal solution. Isotopic flux galactose measurements in open-circuit conditions showed a net active galactose absorption. The net transport of galactose was decreased to zero in the absence of Na+ in mucosal and serosal reservoirs. Galactose has been used to induce changes in short-circuit current (delta Isc) across intestine. delta Isc was a hyperbolic function of galactose concentration characterized by the parameters Vmax (maximum change in delta Isc) and Km (concentration needed to attain a velocity equal to half the Vmax).

Animals↗

Bioelectric parameters and sodium and chloride fluxes across the intestine of Blennius parvicornis.

Simultaneous measurements of the electric potential difference and the short-circuit current intensity were taken, as well as measurements of unidirectional fluxes of sodium and chloride in the posterior intestine of Blennius parvicornis fish. On incubating the tissue in standard Ringer solution, a potential difference of--0.9 mV, a mean net flux of sodium of 2.49 mu Eq/h x cm2 were obtained. In the absence of sodium (choline as substitute), the net chloride flux and the Isc were completely blocked. In the absence of chloride (isocyanate as substitute) the net sodium flux and the Isc were equally blocked. Ouabain lessened the sodium and chloride fluxes in the mucosa-serosa direction to the point of nulling the net fluxes of both ions. The values of the bioelectric parameters were also blocked in the presence of this inhibitor. Acetazolamide did not significantly affect the values of either the unidirectional fluxes or the net fluxes of sodium and chloride. Nor did it affect the values of the bioelectric parameters. A mechanism for the absorption of sodium and chloride is proposed in which these ions enter the cell in a coupled form and in 1:1 proportion, the transport being independent of the bicarbonate ion.

Acetazolamide↗

Purification and characterization of two hemolysins from Stichodactyla helianthus.

Two hemolysins, Sticholysin I (St I) and Sticholysin II (St II) were purified from the sea anemone Stichodactyla helianthus combining gel filtration and ion exchange chromatography. The amino acid composition of both cytolysins was determined revealing a high proportion of glycine, lysine, tyrosine and non-polar amino acids (alanine, leucine and valine). Cysteine was not found in either polypeptide. Molecular masses of St I and St II were 19401 and 19290 Da, respectively. N-terminal sequence analysis of St I and St II showed a high homology between them suggesting they are isoforms of the same cytolysin. Compared with other sea anemone cytolysins, St I and St II contain a 22 amino acid insertion fragment also present in Eq T II/Tn C and probably in CaT I and Hm T and absent in C III, the major hemolysin previously reported in this anemone.

Amino Acid Sequence↗

[Cutaneous response to 2 and 10 units of tuberculin in infants].

A study was done in 322 healthy, well nourished infants, 3 to 18 months old from day care centers of metropolitan Santiago, Chile, that were given BCG immunization in their neonatal period: 304 (94.4%) of them showed BCG scars and were included in a double blind open study, to determine the cutaneous responses to 2 TU and 10 TU tuberculin (PPD). There were no differences in the mean size of cutaneous reactions nor in percent positive responses (greater than or equal to 10 mm), but cutaneous reactions greater than or equal to 15 mm were more frequent in infants tested with PPD 10 TU. In 184 out of 304 infants (60.5%) tuberculin reactions were negative (less than or equal to 10 mm). Eighteen out of 322 infants (5.6%) that didn't show BCG scars were injected with PPD 2 TU: tuberculin reactions sized 6 to 9 mm were recorded in 3/18 of these infants but none of them attained 10 mm. Fifty five infants whose tuberculin reactions were 5 mm or less were retested: a booster effect was likely from the appearance of enhanced dermal response after a second tuberculin test done with the same or higher tuberculin strength than the first one in 12/47 of these infants with BCG scar (25%) and in only 1/8 such subjects without BCG scar.

Analysis of Variance↗