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A Grande

Publications and source records attributed to A Grande.

At least 19 recordsLinked to original sources

Abundance of the primary transcript and its processed product of growth-related genes in normal and leukemic cells during proliferation and differentiation.

The relative abundance of primary transcript and mature mRNA of the c-myc, calcyclin, S14 ribosomal protein, and rRNA genes was determined densitometrically after reverse transcriptase-polymerase chain reaction and Northern blotting analysis in resting and mitogen-stimulated lymphocytes, proliferating and terminally differentiated HL-60 cells, and leukemic blast cells. Transcription and processing of c-myc and rRNA gene transcripts increased proportionally after mitogen stimulation, whereas these processes were independent of cell cycling status in the case of the S14 gene. Normal lymphocytes showed an unexpectedly large amount of primary transcript of the calcyclin gene, whereas the corresponding mRNA was undetectable. The abundance of c-myc, calcyclin, and S14 mRNA in terminally differentiated HL-60 cells decreased sharply, compared to their proliferating counterparts. This decrease reflected post-transcriptional modulation, since the abundance of precursor remained essentially unchanged. After HL-60 differentiation, the 32S rRNA levels remained relatively high, whereas the 45S primary transcript almost disappeared. Leukemic blast cells displayed highly variable precursor/mRNA ratios of c-myc, calcyclin, and S14 genes but consistently high ratios of 32S to 45S RNA, suggesting that the cleavage rate of the 32S rRNA was sharply reduced in these cells, resulting in an accumulation of this molecule. These results suggest the importance of efficient processing of primary transcript to generate adequate functional mRNA, thus regulating gene expression. Furthermore, in terminally differentiated cells and leukemic blast cells a stabilization of the primary transcript without efficient processing can be observed. The role of the stabilization of the primary transcript in terminal differentiation is further supported by the results of run-off transcription, indicating a sharp decrease of c-myc and calcyclin transcription rate in retinoic acid/dimethyl sulfoxide-treated HL-60 cells.

Acute Disease

The use of the alkaline phosphatase-antialkaline phosphatase technique for immunophenotyping acute myeloid leukemia.

The leukemic cells from 31 cases of acute myeloid leukemia were immunophenotyped by the alkaline phosphatase-antialkaline phosphatase (APAAP) technique, using 7 monoclonal antibodies reactive with cells of myeloid origin. We found a good correlation between the results obtained using the APAAP method and indirect immunofluorescence. In most cases, we observed a slight degree of variation in the percentages of reacting cells when comparing the two methods. Nevertheless, taking 20% of cells being immunolabeled as a threshold for defining a case as positive, we found no discrepancies in the final classification of each case. The main advantages of the APAAP method are: (1) its use with routinely prepared peripheral or blood marrow samples, and (2) the possibility of correlating immunological characterization with morphology. Since the results with the APAAP method were comparable with those obtained using indirect immunofluorescence, we suggest that this former technique can complement, and sometimes substitute, other methods of immunological evaluation.

Alkaline Phosphatase

Arrhythmogenic effects of antiarrhythmic drugs in patients with an old myocardial infarction and asymptomatic ventricular ectopic activity as studied by programmed electrical stimulation.

In 22 patients with a previous myocardial infarction and documented Lown class II to IV asymptomatic ventricular arrhythmias, the arrhythmogenic effect of mexiletine (18 patients) and propafenone (10 patients) has been assessed by programmed electrical stimulation. Ventricular arrhythmias induced during the basal study were: repetitive ventricular responses (RVR) (11/22, 50%), nonsustained ventricular tachycardia (VT) (3/22, 14%), sustained VT (7/22, 32%) and ventricular fibrillation (VF) (1/22, 4%). The induction of sustained VT or VF increased to 50% after mexiletine and to 80% following propafenone. An arrhythmogenic effect was found in 7/11 patients (64%) without VT at the control study (P = 0.004). One patient of this group spontaneously developed sustained VT both after mexiletine and propafenone. Only 1/8 patients (13%) with sustained VT/VF at the basal study had RVR after drug administration. The R-R interval of sustained VT at the basal state tended to be faster than that after the drugs (260 +/- 60 ms vs 293 +/- 56 and 332 +/- 77 ms for mexiletine and propafenone, respectively) (P = 0.052). Statistical significance was only reached in the propafenone group (P = 0.03). Facilitation of VT induction after antiarrhythmic drugs is most likely due to a modest lengthening of refractoriness in contrast with a more evident reduction in conduction velocity within the reentry pathway. Our study illustrates that treating asymptomatic ventricular ectopic activity in patients with an old myocardial infarction may be dangerous and that antiarrhythmic drugs show a significant arrhythmogenic potential at least in the laboratory setting.

Adult