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M Alcalay

Publications and source records attributed to M Alcalay.

At least 19 recordsLinked to original sources
PubMed1992

[Unsatisfactory results of intradiscal injection of triamcinolone hexacetonide in the treatment of sciatica caused by intervertebral disk herniation].

Sciatica caused by intervertebral disc herniation can be treated with intradiscal injection of chymopapain. A search for a cheaper and less allergizing product led to triamcinolone hexacetonide, this procedure being known as "nucleorthesis". The first results at 6 months were encouraging. In 3 centres where triamcinolone hexacetonide was tested with a more than 2 years' follow-up 92 patients could be evaluated. The results obtained were considered satisfactory in 34 patients (36.9 percent), but they were poor in 19 patients (20.6 percent), and 39 patients (42 percent) had to be operated upon within 2 years. Return to surgery took place within the 6 months following nucleorthesis in 18 patients (19.56 percent) and beyond this period in 17 patients (22.8 percent) with degradation of the results. Moreover, calcifications were found in 19 out of 38 patients; they were of varying size, sometimes detected only at computerized tomography, and some of them appeared to produce symptoms. All considered, the failure rates, the number of patients who required surgery and the occurrence of large and sometimes symptomatic calcifications make triamcinolone nucleorthesis unacceptable compared with the recognized percentages of success with papain nucleolysis and surgical operations. For these reasons, we consider that this treatment should be abandoned.

Anti-Inflammatory Agents↗
PubMed1992

Molecular monitoring of the myl/retinoic acid receptor-alpha fusion gene in acute promyelocytic leukemia by polymerase chain reaction.

The acute promyelocytic leukemia (APL) t(15;17) translocation generates a myl/retinoic acid receptor-alpha (RAR-alpha) chimeric gene that is transcribed as a fusion myl/RAR-alpha messenger RNA. Using primer sets derived from RAR-alpha and myl cDNAs, we were able to amplify the breakpoint sites of the fusion transcripts of all 35 APL RNA samples by reverse polymerase chain reaction (PCR) and nested primer approach of two rounds of amplification. DNA fragments of different size were obtained according to the chromosome 15 breakpoints (intron 3-bcr 3; exon 6-bcr 2; and intron 6-bcr 1). bcr 1 and bcr 3 represent the regions of the myl locus most frequently involved among APL (48.5 and 34.2 of cases, respectively); bcr 3 constitutes 62.5% of cases among M3V as compared with 25.9% of M3 cases. The feasibility of monitoring the APL clone by PCR analysis in five APL patients who received different treatment (chemotherapy, all-trans-retinoic acid or bone marrow transplantation) was evaluated. In five of nine bone marrow samples of patients in complete remission, t(15;17)-positive cells could be detected by PCR analysis. We conclude that PCR amplification of the myl/RAR-alpha junctions represents the easiest and rapid method for diagnosis and monitoring of the APL clone.

Adolescent↗
PubMed1992

Expression pattern of the RAR alpha-PML fusion gene in acute promyelocytic leukemia.

Two chimeric genes, PML-RAR alpha and RAR alpha-PML, are formed as a consequence of the acute promyelocytic leukemia (APL)-specific reciprocal translocation of chromosomes 15 and 17 [t(15;17)]. PML-RAR alpha is expressed as a fusion protein. We investigated the organization and expression pattern of the RAR alpha-PML gene in a series of APL patients representative of the molecular heterogeneity of the t(15;17) and found (i) two types of RAR alpha-PML mRNA junctions (RAR alpha exon 2/PML exon 4 or RAR alpha exon 2/PML exon 7) that maintain the RAR alpha and PML longest open reading frames aligned and are the result of chromosome 15 breaking at two different sites; and (ii) 10 different RAR alpha-PML fusion transcripts that differ for the assembly of their PML coding exons. A RAR alpha-PML transcript was present in most, but not all, APL patients.

Base Sequence↗
PubMed1992

Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia.

The acute promyelocytic leukaemia (APL) 15;17 translocation generates a PML/RAR alpha chimeric gene which is transcribed as a fusion PML/RAR alpha mRNA. Molecular studies on a large series of APLs revealed great heterogeneity of the PML/RAR alpha transcripts due to: (i) variable breaking of chromosome 15 within three PML breakpoint cluster regions (bcr1, bcr2 and bcr3), (ii) alternative splicings of the PML portion and (iii) alternative usage of two RAR alpha polyadenylation sites. Nucleotide sequence analysis predicted two types of proteins: multiple PML/RAR alpha and aberrant PML. The PML/RAR alpha proteins varied among bcr1, 2 and 3 APL cases and within single cases. The fusion proteins contained variable portions of the PML N terminus joined to the B-F RAR alpha domains; the only PML region retained was the putative DNA binding domain. The aberrant PML proteins lacked the C terminus, which had been replaced by from two to ten amino acid residues from the RAR alpha sequence. Multiple PML/RAR alpha isoforms and aberrant PML proteins were found to coexist in all APLs. These findings indicate that two potential oncogenic proteins are generated by the t(15;17) and suggest that the PML activation pathway is altered in APLs.

Amino Acid Sequence↗
PubMed1992

Immunoreactive circulating endothelin-1 in normal and hypertensive pregnancies.

OBJECTIVE: The purpose of this study was to measure the circulatory levels of endothelin-1 in the serum of pregnant women with hypertension. STUDY DESIGN: Endothelin-1 levels were measured by means of radioimmunoassay in the serum of 26 pregnant women with hypertension (14 with pregnancy-induced preeclamptic toxemia, 12 with chronic hypertension) and in the serum of 17 control pregnant women and 18 control nonpregnant women. The mean levels in the different groups were subject to statistical analysis with the analysis of variance. RESULTS: The mean level among the women with preeclampsia (29.9 +/- 13.2 fmol/ml) was significantly higher than those of the chronically hypertensive women (16.1 +/- 7.3 fmol/ml, p = 0.002) and of the control pregnant women (19.7 +/- 9.2 fmol/ml, p = 0.011). The mean level of the control nonpregnant women (26.9 +/- 9.3) was significantly higher than that of the control pregnant women (p = 0.029). Among the patients with preeclampsia there was no correlation between endothelin-1 levels and the mean arterial blood pressure. Six to 10 weeks after delivery the mean levels of 15 studied patients (7 with preeclampsia, 8 with chronic hypertension) were similar to the levels of the nonpregnant control women. CONCLUSION: We conclude that increased endothelin-1 production may play a role in the pathogenesis of preeclampsia.

Adult↗
PubMed1992

Successful pregnancy in a patient with polycystic kidney disease and advanced renal failure: the use of prophylactic dialysis.

Adult polycystic kidney disease is an inherited disease that is transmitted as an autosomal dominant trait. The clinical manifestations, which develop during the third or fourth decade of life, usually do not affect women during childbearing age and thus do not affect fertility or pregnancy outcome. The patient presented here had polycystic kidney disease and advanced renal failure, and was treated with meticulous fetal surveillance and prophylactic hemodialysis during pregnancy. The successful outcome strengthens the trend to perform prophylactic dialysis in pregnancies with advanced renal failure, despite the lack of controlled studies.

Adult↗
PubMed1992

Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations.

The power spectrum of instantaneous heart rate fluctuations was used to determine the optimal doses of atropine that induce a maximal vagolytic or vagomimetic effect. In a crossover placebo controlled study, eight volunteers received increasing bolus doses of intravenous atropine (0.1 to 2.3 mg per subject) or placebo, and frequency bands of the power spectrum were integrated. During atropine administration a significant bimodal dose dependence was observed for the respiratory peak (0.2 to 0.4 Hz, p = 0.0006), the midfrequency band (0.09 to 0.15 Hz, p = 0.0035), and mean heart rate (p < 0.0001). Low doses (< 0.4 mg per subject) increased the respiratory and midfrequency band power, with maximal response at 0.2 mg per subject. Larger doses of atropine, 0.5 to 2.3 mg per subject, markedly reduced the power in all frequency bands in a dose-dependent way. The corresponding changes in mean heart rate were simultaneous, but in the opposite direction. We suggest that the respiratory peak of the power spectrum can be used to optimize drug effects on cardiac parasympathetic control.

Adult↗
PubMed1992

PML/RAR-alpha rearrangement in acute promyelocytic leukaemias apparently lacking the t(15;17) translocation.

Recent investigations have clarified some of the molecular mechanisms underlying the t(15;17) translocation specific for acute promyelocytic leukaemia (APL). Together with providing new insights into the pathogenesis of the disease, the identification of breakpoints within the RAR-alpha and PML loci on chromosomes 17 and 15 has allowed a new relevant diagnostic tool for the recognition of this leukaemic form. We report the molecular characterization of 6 cases of acute myelogenous leukaemia (AML) in which a diagnosis of typical M3 by conventional morphocytochemistry (FAB criteria) was not accompanied by cytogenetic evidence of the specific t(15;17) aberration. DNA rearrangements were documented in all cases at the PML and RAR-alpha loci. Moreover, in 4 cases also analysed by Northern blot hybridization, we could detect aberrant RAR-alpha transcripts. These findings highlight the specificity of PML/RAR-alpha rearrangements in APL, whereas the lack of t(15;17) may be attributed to sub-microscopic translocations as well as to the presence of non-neoplastic cells undergoing mitosis in the samples examined for karyotype.

Adolescent↗
PubMed1992

[Infectious spondylodiscitis. Analysis of a series of 105 cases].

Among 105 cases of infectious spondylitis diagnosed and treated from 1971 through 1990, 23 were due to tuberculosis (TS) and 82 to other causes (NTS). The annual number of cases of NTS rose over the study period, partly because of an increase in iatrogenic spondylitis, whereas the number of TS cases fell. In both groups, mean age of patients was higher than in earlier studies. The leading causative agents in NTS were staphylococci, followed by streptococci, then Escherichia coli. Diagnosis of spondylitis was dependent on the imaging techniques used; among available methods, the most reliable was magnetic resonance imaging which improved diagnostic performance by detecting early, specific changes. Except in patients with positive blood cultures and in TS patients with Koch bacilli recovered from other visceral foci, bacteriologic diagnosis rested on studies of samples taken from the spinal infection site. Half the subjects underwent discovertebral needle biopsy, with a success rate of 47.5%, a figure comparable with those reported in other studies. In 30% of patients, bacteriologic documentation of the infection was not obtained and diagnosis rested on a set of clinical, biological, and radiological criteria.

Bacterial Infections↗
PubMed1992

Alternative splicing of PML transcripts predicts coexpression of several carboxy-terminally different protein isoforms.

The acute promyelocytic leukaemia (APL)-specific chromosome 15;17 translocation leads to the fusion of a newly identified putative transcription factor, PML, and the retinoic acid receptor alpha. We have characterized the structure of the PML genomic locus and preliminarily characterized its expression pattern. The PML locus spans a minimum of 35 kb and is subdivided into nine exons. The putative PML DNA binding site is encoded by exons 2 and 3. We isolated a large number of alternatively spliced PML transcripts that encode numerous PML isoforms. Two groups of isoforms were identified that differed either in their C-terminal region or in the length of their central region, but retained the putative DNA-binding and dimerization domains. RNAase protection experiments revealed that the different PML isoforms are equally expressed in established cell lines of different histological origin.

Amino Acid Sequence↗
PubMed1991

Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia.

The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short-lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor alpha (RAR alpha) locus, which has recently been shown to be rearranged in all APLs. Southern blot analysis demonstrated that the RAR alpha rearrangements persisted in the APL samples containing maturing myeloid cells 2 to 3 weeks after the start of RA treatment, but disappeared after 5 to 8 weeks, when the patients achieved CR. Our investigations provide clear evidence that CR occurs at molecular level and that there is reconstitution of an apparently normal, nonclonal hematopoiesis. Further, it shows that RA acts by triggering differentiation rather than by exerting a cytotoxic effect on the leukemic clone.

Adult↗
PubMed1991

RAR-alpha gene rearrangements as a genetic marker for diagnosis and monitoring in acute promyelocytic leukemia.

Acute promyelocytic leukemias (APLs) are characterized by a translocation that involves chromosomes 15 and 17. The translocation breakpoints have recently been identified and shown to involve the RAR-alpha gene on 17 and myl on 15. Here we report Southern blotting analysis of 26 APLs, including cases with normal karyotypes and atypical morphology, which showed RAR-alpha rearrangements in 92% cases, myl rearrangements in 73%, and either RAR-alpha or myl rearrangements in 100%. Despite a negative clinical and morphologic picture, DNA rearrangement analysis showed that neoplastic promyelocytes persisted in the bone marrow of two patients sampled after induction chemotherapy. Therefore, the RAR-alpha and myl rearrangements provide molecular markers for accurately diagnosing APLs and monitoring the course of the disease during and after chemotherapy.

Adolescent↗
PubMed1991

Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus.

Acute promyelocytic leukemias (APLs) are characterized by a reciprocal balanced translocation that involves chromosomes 15 and 17 [t(15;17)]. We report the isolation and characterization of one of the two reciprocal break sites and demonstrate that the chromosome 17 breakpoint lies within the retinoic acid receptor alpha locus. Nucleotide sequencing of the 15;17 cross-over junction on 15q+ showed that the retinoic acid receptor alpha gene is truncated within its first intron, 370 base pairs upstream from the splicing donor site of exon II. Such a recombination would be expected to generate abnormal RAR alpha mRNA and protein. Southern blot analysis of a number of APLs with chromosome 15- and 17-derived DNA probes revealed similar 15;17 recombinations in the majority of other APLs. Our data are strong evidence that the retinoic acid receptor alpha gene plays a crucial role in the leukemogenesis of APL.

Animals↗
PubMed1991

Modulation of the dose-dependent effects of atropine by low-dose pyridostigmine: quantification by spectral analysis of heart rate fluctuations in healthy human beings.

The interaction between a low-dose cholinesterase inhibitor, pyridostigmine (PYR), and atropine was investigated by spectral analysis of heart rate fluctuations in eight healthy humans. Each subject was given increasing boluses of IV atropine during treatment with PYR (30 mg.3/day) or placebo. PYR attenuated the bimodal dose-dependent changes in the respiratory peak (which respresents the parasympathetic control) in response to atropine. We suggest that spectral analysis can be used for quantifying the complex dose-dependent cholinergic agonist-antagonist interactions, and may help to disclose an asymptomatic low-dose intoxication with acetylcholinesterase inhibitors.

Adult↗
PubMed1991

Pharmacological modulation of vagal cardiac control measured by heart rate power spectrum: a possible bioequivalent probe.

The autonomic cardiac control was studied as a sensitive parameter of anticholinergic treatment in humans, using heart-rate (HR) power spectrum. A cross-over placebo controlled study was performed in 8 young volunteers who received increasing bolusdoses of IV atropine (from 1.3 micrograms/kg to 29.9 micrograms/kg) or placebo. Computing the HR power spectrum and integrating over specific frequency bands, we focused in particular on the respiratory frequency band (usually between 0.2-0.4 Hz) which is purely of vagal mediation. At small atropine doses (less than 5.2 micrograms/kg), the respiratory peak increased, relative to baseline, with maximal response at 2.6 micrograms/kg (from 1.0 to 1.9 +/- 0.9). Larger doses of atropine (greater than or equal to 6.5 micrograms/kg) reduced the power of the respiratory peak, by a few orders of magnitude, in a dose-dependent way. Corresponding changes were observed in mean HR but in the opposite direction i.e., a maximal bradycardia at 2.6 micrograms/kg and a nearly two fold increase in mean HR at 29.9 micrograms/kg. We conclude that atropine has a bimodal dose-dependent effect on parasympathetic cardiac control. Since the use of HR spectral analysis has been demonstrated in various animal species, we suggest that it can be used as a sensitive noninvasive probe for animal to man transformation studies.

Adult↗
PubMed1991

Rearrangements of the RAR-alpha gene in acute promyelocytic leukaemia: correlations with morphology and immunophenotype.

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.

Acute Disease↗