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Biomedical subjects

M Alcalay

Publications and source records attributed to M Alcalay.

At least 37 records · Page 2Linked to original sources
PubMed1997

A PMLRARalpha transgene initiates murine acute promyelocytic leukemia.

The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha). To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice. PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.

Animals↗
PubMed1997

Open synovectomy for the prevention of recurrent hemarthrosis of the ankle in patients with hemophilia. A report of five cases with magnetic resonance imaging documentation.

Hemophilic arthropathy is an incapacitating complication of severe hemophilia resulting from recurrent bleeding in the same joint. Open synovectomy has been used since 1969 to prevent recurrent hemarthrosis of target joints. Between 1988 and 1993 we performed open synovectomy of the ankle in five hemophiliacs aged 6 to 9 years with early-stage hemophilic arthropathy. Magnetic resonance imaging proved very useful for evaluating the severity of joint damage, usually underestimated on plain radiographs; for determining the degree of synovial membrane hypertrophy, which is a critical factor in the decision to perform synovectomy; for planning the surgical procedure and for explaining treatment failures. A decrease in the frequency of hemarthrosis episodes occurred in all five ankles. A repeat synovectomy was needed in one case and in another patient the frequency of hemarthrosis episodes increased somewhat after the fourth year. There was no loss of range of motion. Our data suggest that open synovectomy is effective and safe for reducing the frequency of hemarthrosis and that magnetic resonance imaging should be routinely performed before the procedure.

Ankle↗
PubMed1996

Prelabour rupture of membranes at term: early induction of labour versus expectant management.

OBJECTIVES: To compare expectant management with early induction of labour in pregnant patients with prelabour rupture of membranes at term and unfavourable cervix. STUDY DESIGN: A prospective, randomised study of 154 women with prelabour rupture of membranes at term of whom 80 had been managed expectantly, and 74 had undergone oxytocin induction at a rate of 2.5 mU/min. Digital examination was not performed before oxytocin infusion, and the first was delayed until 4 h (nulliparae), or 2 h (multiparae) of regular uterine contractions. RESULTS: The mean period from rupture of membranes to delivery was significantly shorter in the induction group. The mean duration of labour was significantly shorter in the expectant group. Operative vaginal deliveries were more common in the induction group, and fetal distress was the most common cause of operative vaginal deliveries. The caesarean rates were low and similar in both groups. Maternal and neonatal infectious morbidity was similar and no difference was found in the length of hospitalisation. CONCLUSIONS: Expectant management in patients with ruptured membranes at term is safe and reduces the frequency of operative vaginal deliveries.

Adult↗
PubMed1996

Effects on differentiation by the promyelocytic leukemia PML/RARalpha protein depend on the fusion of the PML protein dimerization and RARalpha DNA binding domains.

The block of terminal differentiation is a prominent feature of acute promyelocytic leukemia (APL) and its release by retinoic acid correlates with disease remission. Expression of the APL-specific PML/RARalpha fusion protein in hematopoietic precursor cell lines blocks terminal differentiation, suggesting that PML/ RARalpha may have the same activity in APL blasts. We expressed different PML/RARalpha mutants in U937 and TF-1 cells and demonstrated that the integrity of the PML protein dimerization and RARalpha DNA binding domains is crucial for the differentiation block induced by PML/RARalpha, and that these domains exert their functions only within the context of the fusion protein. Analysis of the in vivo dimerization and cell localization properties of the PML/RARalpha mutants revealed that PML/RARalpha--PML and PML/RARalpha--RXR heterodimers are not necessary for PML/RARalpha activity on differentiation. We propose that a crucial mechanism underlying PML/RARalpha oncogenic activity is the deregulation of a transcription factor, RARalpha, through its fusion with the dimerization interface of another nuclear protein, PML.

Binding Sites↗
PubMed1996

A prospective study of high- versus low-dose oxytocin for induction of labor.

BACKGROUND: To assess the efficacy and safety of a high-dosage oxytocin induction regimen. METHODS: A randomized prospective study of 179 patients who received an initial dose of either 2.5 (n = 98) or 1.25 (n = 81) mU/minute of oxytocin, with increments of 2.5 mU/minute or 1.25 at 30-minute intervals. RESULTS: Failure rates (15.3% versus 19.8%), time to delivery, the number of assisted vaginal deliveries, cesarean sections, and maternal and fetal complications were not significantly different in the two protocols. However, the use of a high oxytocin dose resulted in significantly higher mean peak doses and increased total cumulative amounts. These were associated with a significant need to modify the oxytocin infusion protocol for hyperstimulation and fetal heart rate changes (65.1% versus 46.2%). CONCLUSIONS: Induction with higher dose oxytocin increments did not shorten time to delivery, but was associated with an increase in uterine hyperstimulation. Low-dose oxytocin was found to be appropriate and safe for labor induction.

Adult↗
PubMed1996

Variant and masked translocations in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by a unique hemorrhagic syndrome, disseminated intravascular coagulation, and the association with the specific (15;17 chi q22-23:q12-21) translocation, which disrupts the retinoic acid receptor alpha (RARA) and the promyelocytic leukemia (PML) genes. The t(15;17) leads to the formation of two reciprocal fusion genes, PML/RARA on chromosome 15 and RARA/PML on chromosome 17; it is responsible for the unique response of the disease to retinoic acid (ATRA) treatment. As was described for chronic myeloid leukemia and its associated t(9;22) [Philadelphia chromosome], variant translocations have been reported in APL, which are either complex translocations involving additional chromosome(s), or simple variant translocations involving only either one chromosome 15 or 17 and any of several chromosomes. Rearrangements of RARA and PML were documented in some of these variant translocations. In contrast, recent molecular analysis of APL cases with cytogenetically normal chromosomes 15 and 17 revealed the occurrence of submicroscopic translocations, leading to the formation of non reciprocal fusion genes, either PML/RARA or RARA/PML only. Detailed analysis of such cases may shed light on the mechanisms of translocation, on the selection of oncogenic products, and on the respective role(s) of the products of the translocation. Demonstration of the existence, in some APL-like leukemias, of masked translocations with involvement of PML and RARA, thus allows to (i) confirm the diagnosis of APL, (ii) adapt the treatment and (iii) monitor the residual disease. Finally APL-like leukemias were recently reported, with either a t(11;17) or t(5;17), resulting in the fusion of RARA to genes other than PML; these patients do not appear to respond to ATRA treatment. Altogether, these results emphasize the usefulness of a molecular definition of APL.

Humans↗
PubMed1996

Posterior rounded high-intensity zone on magnetic resonance images as a sign of painful disk. Report of a case.

In 1992, Aprill and Bogduk reported that a rounded high-intensity zone was seen in the posterior part of the annulus fibrosus on T2-weighted images of at least one of the last intervertebral disks in 29% of 500 patients with low back pain. This image was correlated with Dallas stage 4 disk disease and with reproduction of the spontaneous pain during discography coupled with computed tomography. We report a case and discuss the value of this image.

Adult↗
PubMed1995

Acute promyelocytic leukemia cases with nonreciprocal PML/RARa or RARa/PML fusion genes.

Tumor-associated chromosome translocations usually lead to the formation of two reciprocal fusion genes: one thought to be involved in the transformation process, the other the mechanical consequence of the translocation event. In the case of acute promyelocytic leukemia (APL) blasts, the 15;17 chromosome translocation generates the putatively transforming PML/RARa fusion gene and its reciprocal RARa/PML. We report APL cases with submicroscopic 15;17 recombinations leading to the formation of nonreciprocal PML/RARa or RARa/PML fusion genes. Therefore, each of the two reciprocal translocation products may be independently formed and selected by the leukemic phenotype, implying that both are involved in tumorigenesis.

Base Sequence↗
PubMed1995

Intrauterine growth of triplets as estimated from liveborn birth weight data.

This study was conducted to estimate intrauterine growth of triplet pregnancies from liveborn birth weights. During the years 1975-92, 109 sets of triplets were born at our hospital. Ten sets were excluded because of either major fetal anomalies or fetal death of one or more of the fetuses. The remaining 99 sets of triplets consisted of 297 newborns that were weighted immediately after birth. The mean birth weight was plotted against gestational week. The estimated intrauterine growth of triplets, in contrast to singletons, exhibited neither an acceleration phase during the third trimester, nor a flattening of the growth curve during the last few weeks of the third trimester. The mean birth weight of triplets was slightly below the 10th centile for singletons at 38 weeks' gestation or later. We conclude that the growth of triplet fetuses as estimated from liveborn birth weights is slower than that of singletons. The diagnosis of intrauterine growth retardation in triplet pregnancies should be based on growth curves to be devised for triplet pregnancies.

Bias↗
PubMed1995

Burch colposuspension: a 10-20 year follow up.

OBJECTIVE: To review the outcome of women who underwent Burch colposuspension 10 to 20 years ago and to assess factors which affect long term success. DESIGN: Longitudinal retrospective study. SETTING: Urogynaecology Unit, St George's Hospital, London. SUBJECTS: One hundred and nine women with genuine stress incontinence. MAIN OUTCOME MEASURES: Survival analysis of subjective and objective cure of stress incontinence. RESULTS: Cure of incontinence following Burch colposuspension is time-dependent, with a decline for 10 to 12 years when a plateau of 69% is reached. Factors adversely affecting cure are previous bladder neck surgery (logrank test P = 0.02), pre-operative weight greater than 80 kg, intra-operative blood loss more than 1000 ml and the development of post-operative detrusor instability. Post-operative complications included de novo detrusor instability (14.7%), long term complaints of voiding difficulty with objective recovery at the final follow up (22%) and recurrent urinary tract infection (4.6%). CONCLUSIONS: Long term follow up after colposuspension is necessary to assess sequelae. We suggest that new continence procedures should be followed up for 5 to 10 years.

Adult↗
PubMed1995

Polycystic ovarian syndrome: pregnancy outcome following in vitro fertilization-embryo transfer.

A retrospective study of a series of pregnant patients with polycystic ovarian syndrome following in vitro fertilization-embryo transfer was conducted to assess the outcome after ovarian stimulation by different protocols. Forty-one pregnancies were evaluated in patients with polycystic ovarian syndrome who conceived during in vitro fertilization-embryo transfer using human menopausal gonadotropin alone (17 pregnancies), or combined with gonadotropin releasing hormone analog (24 pregnancies). The demographic data of in vitro fertilization-embryo transfer cycles and pregnancy outcome were compared with the use of Student's t-test, the Mann-Whitney U test and Fisher's exact test, where appropriate. Among the pregnancies that were initiated following treatment, the protocol of the combination of the two was not associated with a higher rate of deliveries. The rate of first-trimester abortions was not statistically different between the two groups. These results suggest that the combined use of gonadotropin releasing hormone agonist and human menopausal gonadotropin in an in vitro fertilization program may not have beneficial effects on pregnancy outcome in patients with polycystic ovarian syndrome.

Adult↗
PubMed1995

Twin pregnancies complicated by the death of one fetus.

The death of one fetus in a twin pregnancy can affect both the mother and the cotwin. Thirty women with twin pregnancies in whom the death of one fetus was diagnosed during the second half of pregnancy and a matched group of 30 women with uncomplicated twin pregnancies were investigated. The mean gestational age at delivery for the study and control groups was 32.0 +/- 5.0 (mean +/- SD) weeks and 32.8 +/- 3.9, respectively. Twelve pregnancies (40%) were monochorionic. In 15 (50%) the diagnosis was made during active labor. The cesarean delivery rate was higher in the study group than in the control group (18 vs. 11, chi 2 = 5.43, P < .02). The mean neonatal weight was similar in both groups (1,586 +/- 725 g vs. 1,543 +/- 691 g). The subgroup of neonates (n = 15) whose cotwins were diagnosed as dead during labor had higher birth weight as compared to the neonates (n = 15) in whom the diagnosis was made prior to delivery and were managed expectantly (1,829 +/- 859 vs. 1,346 +/- 474 g, P < .01). The week of delivery was similar in both subgroups. Neonatal mortality was 30% and 26.6%, while neonatal morbidity was 26.6% and 21.7%, respectively (NS). All the cases of neonatal mortality were in the subgroup of twins in which the diagnosis of in utero death was made before 32 weeks' gestation. The death of one fetus from a twin pregnancy did not significantly jeopardize maternal health, and the neonatal outcome in the remaining twins was primarily a function of gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1995

Strategy for identifying primary malignancies with inaugural bone metastases.

The diagnosis of primary tumors with inaugural bone metastases is a serious and difficult problem commonly encountered in rheumatology. Helpful information can be derived from the radiologic appearance of the metastases, history of the patient, clinical findings, chest film, standard laboratory tests, imaging studies, serum marker assays, and histologic findings. Based on our personal experience and on previously published data, we have developed a decision tree aimed at enhancing the efficacy of the diagnostic process while ensuring optimal patient comfort and containing costs.

Adult↗
PubMed1994

PML/RAR alpha+ U937 mutant and NB4 cell lines: retinoic acid restores the monocytic differentiation response to vitamin D3.

We have analyzed the differentiation program of a U937 promonocytic leukemia clone transduced with the acute promyelocytic leukemia specific PML/RAR alpha fusion gene, the expression of which is under the control of the inducible metallothionine (MT) I promoter (MTPR9 clone). MTPR9 cells treated with Zn2+ hence exhibit levels of PML-RAR alpha protein as high as fresh acute promyelocytic leukemia blasts. In the absence of Zn2+, i.e., upon low level PML/RAR alpha expression, 1,25-dihydroxyvitamin D3 (D3) and particularly D3 plus transforming growth factor beta 1 (TGF-beta 1) induced terminal differentiation of MTPR9 cells (as observed in "wild-type" U937 cells), on the basis of morphology, membrane antigen pattern, and functional criteria. Conversely, in the presence of Zn2+, D3 and D3 plus TGF-beta 1 failed to induce terminal differentiation, as evaluated by the above parameters. Interestingly, retinoic acid (RA) treatment suppresses the differentiation blockade induced by high level PML-RAR alpha protein; indeed, Zn(2+)-treated MTPR9 cells incubated with RA plus D3 exhibited significant terminal monocytic maturation, comparable to that of cells treated with D3 alone or combined with RA in absence of Zn2+. Similar observations were made in NB4, a PML-RAR+ human acute leukemic line. As expected RA treatment of NB4 cells causes granulocytic differentiation. Interestingly, the cell line is only scarcely induced to mature monocytic cells by D3 or D3 plus TGF-beta 1 treatment, whereas it is effectively induced to monocytic maturation by combined treatment with D3 and RA. Accordingly, the rate of NB4 cell proliferation is only slightly affected by D3 or D3 plus TGF-beta 1 treatment, mildly inhibited by RA, and markedly decreased by D3 plus RA. These results indicate that in both U937 and NB4 cells high level PML/RAR alpha expression inhibits the monocytic terminal differentiation program triggered by D3 or D3 plus TGF-beta 1, whereas RA treatment effectively antagonizes this inhibitory PML-RAR alpha action and restores the D3 differentiative effect.

Antigens, CD↗
PubMed1994

[Lyme disease].

Lyme disease is an infectious disease due to Borrelia burgdorferi, which is transmitted by a tick bite. Bearing ticks belong to the "Ixodes" type. Germ reservoirs include rodents, birds, deers... The disease onset usually takes place in summer or in autumn. Its early stage is characterized by erythema chronicum migrans. The secondary stage, initiated by a virus-like syndrome indicating the hematogenous and lymphatic dissemination may include neurologic symptoms and signs--the most frequent ones in France and Europe (meningoradiculitis, meningitis, palsy of one or several cranial nerves), cardiac symptoms (conduction dysfunction), a relapsing oligoarthritis, and sometimes ocular signs. In some cases, joint and/or nervous system symptoms may become chronic: it's the tertiary (late) stage, which may include, too, acrodermatitis chronica atrophicans. Any of these symptoms may initiate the disease or be its only manifestation. When erythema chronicum migrans is missing, diagnosis lays upon serology which may turn positive only lately, or remain negative; the possibility of false positivity must also be noticed. Antibiotherapy must be initiated as soon as possible; even when started lately, it may prove beneficial. It consists essentially of beta lactamins or doxycyclin. Studies are progressing in view of the elaboration of a vaccine.

Anti-Bacterial Agents↗
PubMed1994

Increased incidence of high-order and singleton conceptions after ovulation induction in winter.

The possible relationship between the season of conception after ovulation induction and high-order multifetal pregnancies, was investigated. From 1975 to 1989, 111 high-order multiple births after ovulation induction were recorded at the Chaim Sheba Medical Center. This group was compared with 142 singleton pregnancies that resulted from induction of ovulation during 1989. Composite monthly cohorts of high-order multifetal pregnancies were constructed for each month of the year, and the probability of such pregnancies was estimated. The period of ovulation induction and the day of presumed conception were noted. A statistically-significant increase in the probability of high-order and singleton conceptions occurred during the winter. Our observation indicates a seasonal pattern in high order and singleton conceptions after ovulation induction.

Adolescent↗
PubMed1994

Successful pregnancy in a woman with cyanotic congenital heart disease after a palliative pulmonary-systemic shunt. A case report.

A 20-year-old woman with cyanotic congenital heart disease composed of corrected transposition of the great vessels, severe pulmonic stenosis, atresia of the left pulmonary artery and a large ventricular septal defect, had a successful pregnancy following a pulmonary-systemic shunt (Blalock-Taussig). The hemoglobin decreased from 21 to 16 g/dL following the operation. The antepartum course was complicated by intrauterine growth retardation and pregnancy-induced hypertension. A normal fetal nonstress test and biophysical profile permitted continuation of the pregnancy until 38 weeks' gestation, with delivery of a healthy infant.

Abnormalities, Multiple↗