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V Morales

Publications and source records attributed to V Morales.

At least 19 recordsLinked to original sources
PubMed2003

Risk factors in neuroleptic malignant syndrome. A case-control study.

OBJECTIVE: To determine whether environmental temperature, agitation, neuroleptic use, mental retardation, and affective disorders were risk factors for neuroleptic malignant syndrome (NMS). METHOD: Cases and age- and sex-matched psychiatric controls admitted to a regional acute psychiatric unit over a 10-year period. RESULTS: Both uni- and multivariate analysis revealed statistically significant differences between patients with NMS (n=15) and controls (n=45) with regard to the presence of mental retardation, psychomotor agitation, and a number of variables relating to neuroleptic use (newly introduced or increased, intramuscular administration, and dosage). We found no differences between NMS patients and psychiatric controls in respect of changes in environmental temperature. CONCLUSION: Our study supports the need for caution when using intramuscularly administered, abruptly increasing, high-dose neuroleptics, particularly in mentally retarded or agitated patients, regardless of environmental temperature.

Adult↗
PubMed2003

The inducible isoform of CREM (inducible cAMP early repressor, ICER) is a repressor of CYP19 rat ovarian promoter.

The synthesis of estradiol by the granulosa cells is a prominent event in ovarian physiology and depends on the expression of P450(AROM). FSH induces the expression of P450(AROM) in granulosa cells as a result of the presence in the ovarian promoter of a CRE (cAMP response element)-like sequence (CLS). In rodents, LH downregulates aromatase expression during luteinization by an as yet undescribed mechanism. In granulosa cells, LH increases the expression of the inducible cAMP early repressor (ICER), an isoform of CREM (cAMP-responsive element modulator) that represses cAMP-induced transcription. The possibility that ICER represses the activity of the aromatase ovarian promoter, thus being part of the mechanism underlying the effects of LH was investigated. We have found that: (1) nuclear proteins from forskolin-stimulated granulosa cells were specifically bound to an oligonucleotide containing the CLS sequence of the CYP19 ovarian promoter and one out of the two protein-DNA complexes formed was supershifted by an anti-CREM antibody; (2) in granulosa cells, forskolin-induced increases in P450(AROM) promoter luciferase reporter gene activity were prevented by the transient overexpression of ICER; (3) similar results were obtained in 8-Br-cAMP-stimulated R2C cells, a Leydig tumor cell line routinely used for the study of P450(AROM) promoter activity; (4) both ICER mRNA levels and P450(AROM) promoter-driven luciferase activity were elevated 6 and 12 h after stimulation of R2C cells with 8-Br-cAMP and were decreased 24 and 48 h later; (5) in an R2C polyclonal line overexpressing ICER, the promoter activity at early stages of stimulation was completely attenuated, while 24 and 48 h downregulation was prevented in another R2C line stably transfected with an antisense ICER construct. These results suggest that ICER represses CYP19 ovarian promoter and that LH-induced expression of ICER may serve to downregulate P450(AROM) transcription in granulosa cells during luteinization.

Animals↗
PubMed2001

Protein tyrosine kinase regulates FAS-mediated apoptosis in human BCG-infected monocytes.

Apoptosis of monocytes/macrophages has emerged as a central regulatory event in the defense against mycobacterial infections. The involvement of protein tyrosine kinases (PTK) in Fas-mediated apoptosis in T cells is well established, but the possible role of PTK in Fas-dependent death of human bacillus Calmette-Guerin (BCG)-infected monocytes remains unclear. Here, we first examined the expression and function of Fas on BCG-infected human monocytes by flow cytometry. The results demonstrated that BCG-infected monocytes expressed significant Fas protein levels. In addition, engagement of the Fas antigen with its agonistic antibody (Ab) resulted in apoptosis of monocytes, as monitored by DNA analysis and fluorescence-activated cell sorter (FACS) analysis. The apoptotic action of Fas was suppressed significantly by genistein, indicating a role for PTK in this death process. Consistent with this observation, herbimycin A and tyrphostin, two selective tyrosine kinase inhibitors with different mechanisms of action, effectively inhibited Fas-mediated apoptosis of BCG-infected monocytes, as demonstrated by DNA content analysis. Moreover, we confirmed the effect of genistein, herbimycin A, and tyrphostin by examining apoptosis with the terminal transferase dUTP nick endlabeling (TUNEL) assay. Collectively, these data demonstrate that Fas-induced apoptosis may represent an important mechanism for eliminating BCG-activated human monocytes and that this apoptosis is due, at least in part, to signaling via a PTK pathway.

Apoptosis↗
PubMed2000

RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein.

The retinoblastoma susceptibility gene product, the Rb protein, is a key regulator of mammalian cell proliferation. One of the major targets of Rb is the S phase inducing E2F transcription factor. Once bound to E2F, Rb represses the expression of E2F-regulated genes. Transcriptional repression by Rb is believed to be crucial for the proper control of cell growth. Recently, we and others showed that Rb represses transcription through the recruitment of a histone deacetylase. Interestingly, we show here that the Rb-associated histone deacetylase complex could deacetylate polynucleosomal substrates, indicating that other proteins could be present within this complex. The Rb-associated protein RbAp48 belongs to many histone deacetylase complexes. We show here that the histone deacetylase HDAC1 is able to mediate the formation of a ternary complex containing Rb and RbAp48. Moreover, less deacetylase activity was found associated with Rb in cell extracts depleted for RbAp48 containing complexes, demonstrating that Rb, histone deacetylase, and RbAp48 are physically associated in live cells. Taken together, these data indicate that RbAp48 is a component of the histone deacetylase complex recruited by Rb. Finally, we found that E2F1 and RbAp48 are physically associated in the presence of Rb and HDAC1, suggesting that RbAp48 could be involved in transcriptional repression of E2F-responsive genes.

Amino Acid Sequence↗
PubMed2000

Response

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Journal Article↗
PubMed2000

Clinical management of functional ovarian cysts: a prospective and randomized study.

Most ovarian cysts in women of reproductive age are physiological (functional) and patients have been treated for years with oral contraceptives to obtain the resolution of these cysts. Expectant management has been suggested to have the same effectiveness as hormonal treatment but such suggestions come from studies including all kinds of cysts. The objective of the present study was to assess the resolution of functional ovarian cysts, observed after ovulation induction, with expectant management and hormonal treatment and also to determine the period of time necessary for the resolution of the cysts. For this purpose, 53 patients with ovarian cysts, observed by transvaginal ultrasound within the first 5 days of a cycle after ovulation induction, were randomized to have expectant management (group A) or to receive oral contraception (group B) for one cycle. If the cyst persisted, the patient was followed for another cycle, without any treatment. Within the 50 women who completed the trial, a complete resolution of the cysts was observed in 19/25 (76%) and 18/25 (72%) in groups A and B respectively. On the other hand, all the persistent cysts disappeared after a second cycle without any treatment. In conclusion, expectant management is as effective as oral contraceptives for the resolution of functional ovarian cysts induced by ovarian stimulation. However, studies with a larger number of cases are needed to increase the power of the results and to obtain a firm conclusion.

Adult↗
PubMed2000

Role of histone N-terminal tails and their acetylation in nucleosome dynamics.

Histone N-terminal tails are central to the processes that modulate nucleosome structure and function. We have studied the contribution of core histone tails to the structure of a single nucleosome and to a histone (H3-H4)(2) tetrameric particle assembled on a topologically constrained DNA minicircle. The effect of histone tail cleavage and histone tail acetylation on the structure of the nucleoprotein particle was investigated by analyzing the DNA topoisomer equilibrium after relaxation of DNA torsional stress by topoisomerase I. Removal of the H3 and H4 N-terminal tails, as well as their acetylation, provoked a dramatic change in the linking-number difference of the (H3-H4)(2) tetrameric particle, with a release of up to 70% of the negative supercoiling previously constrained by this structure. The (H3-H4)(2) tetramers containing tailless or hyperacetylated histones showed a striking preference for relaxed DNA over negatively supercoiled DNA. This argues in favor of a change in tetramer structure that constrains less DNA and adopts a relaxed flat conformation instead of its left-handed conformation within the nucleosome. In contrast neither removal or hyperacetylation of H3 and H4 tails nor removal or hyperacetylation of H2A and H2B N-terminal tails affected the nucleosome structure. This indicates that the globular domain of H2A and H2B is sufficient to stabilize the tailless or the hyperacetylated (H3-H4)(2) tetramer in a left-handed superhelix conformation. These results suggest that the effect of histone tail acetylation that facilitates transcription may be mediated via transient formation of an (H3-H4)(2) tetrameric particle that could adopt an open structure only when H3 and/or H4 tails are hyperacetylated.

Acetylation↗
PubMed2000

[Chromatin remodeling in estrogen-dependent and independent human breast cancer cell lines].

Chromatin restricts the accessibility of DNA to regulatory factors; its remodeling over the regulatory regions contributes to the control of gene expression. An increasing number of evidence links defects in chromatin remodeling machinery and cancer. Our aim is to elucidate the role of chromatin structure in the control of the expression of hormone-induced genes in breast cell lines estrogen-dependent or -independent for growth. Mammary tumor growth is controlled by steroid hormones via their nuclear receptor and by growth factors via tyrosine kinase receptors. 50 % of these tumors elude to hormonal control. This limits the anti-estrogen therapy. As a model, we have analyzed in several cell lines the chromatin organization of the regulatory regions of two genes, pS2 that is associated with a good prognostic, and cathepsin D (catD) that is a bad prognostic marker. The expression of the two genes is estrogen-regulated in estrogen-dependent cell line MCF7. In contrast in the hormone-independent cell line MDA MB 231, pS2 is not expressed and catD is constitutively expressed. Within the regulatory regions of pS2 gene, we have localized two regions that undergo a hormone-dependent change in chromatin structure in MCF7 cells but not in MDA MB 231. The lack of chromatin remodeling in MDA MB 231 cells is not due to the absence of expression of the estrogen receptor in the cell line. The expression of pS2 gene can be correlated with chromatin remodeling over the regulatory regions of pS2 gene. In contrast catD regulatory regions did not display hormone-dependent changes in chromatin structure, suggesting that hormone regulation takes place within regions with a constitutively open chromatin structure.

Breast Neoplasms↗
PubMed1999

Sacro-coccigeal teratoma: antenatal diagnosis and management.

We report a case of sacro-coccygeal teratoma (ScT) in a 29 years old primigravida at 19 weeks of gestation. Ultrasonographic evaluation in antenatal management of these abnormalities is discussed. The main sonographic criteria appear to be two: dimension and rapid growth of the tumour. Cariotype must be performed to exclude aneuploidy, frequently associated.

Abortion, Induced↗
PubMed1999

Graft versus host disease in autologous stem cell transplantation.

Relapse remains the major cause of mortality in haematological malignancies treated with autologous stem cell transplantation (ASCT). Graft versus tumour reaction (GVT) associated to autologous graft versus host disease (GVDH) may contribute to eliminate minimal residual disease (MRD) after ASCT. Eighty patients with several diagnostics were submitted to ASCT. After stem cell infusion, patients randomised in 4 groups. Groups were treated as follows: Group A received either a IFN (alpha Interferon--1,000,000 U/d), Cyclosporine A (CSA--1 mg/-kg/d intravencus) for 28 days, and granulocyte-macrophage colony stimulating factor (GM-CSF-250/m2/d) until engraftment; B: CSA (same dose and way) and GM-CSF; C: CSA (1 mg/kg/d orally) and GM-CSF and D: only GM-CSF. Patients were inspected daily and if skin rash was detected, a skin biopsy was obtained at that moment, otherwise biopsies were obtained at day 21 after ASCT. GVHD was positive in 23 patients (13 from group A and 10 from group B). All cases were grades I and II. A majority of CD4+ T lymphocytes was seen in skin infiltrates. No significant differences were seen in WBC and platelets engraftment times, antibiotic administration or hospitalisation days required among the four groups. With a median follow up of 18 months, there were no differences in disease free survival (DFS) or overall survival (OS) between the patients who developed GVHD and the others. However, considering that myeloma cells do not express antigen MCH II, which is necessary for GVT effect, we excluded patients with multiple myeloma (MM) from survival analysis, thus obtaining a significant difference in OS results between patients who developed GVHD and those in whom this reaction was not observed (81% vs 58% p:0.05). We conclude that pharmacological induction of GVHD in ASCT is possible with CSA administration (1 mg/kg/d i.v.). Development of GVHD showed a better outcome for patients in our study except for those patients with MM. This results must be confirmed by a longer follow up of our patients and further studies.

Adolescent↗
PubMed1998

Complete response in severe thrombotic microangiopathy post bone marrow transplantation (BMT-TM) after multiple plasmaphereses.

A 44-year-old male with Ph+ chronic myeloid leukaemia (CML) underwent histoidentical allogeneic bone marrow transplantation 18 months after initial diagnosis. He received pretransplant conditioning with busulphan and cyclophosphamide (Bucy). GVHD prophylaxis consisted of methotrexate, cyclosporine (CsA) and methylprednisolone. On day +50, he developed a microangiopathic haemolytic anaemia with indirect bilirubinaemia, 10% fragmented red cells (FC) and an elevated LDH (1213 U/l: normal range 100-185 U/l). Clinical symptoms consisted of edema and hypertension. The patient was not febrile and had no neurological changes. A clinical diagnosis of severe (grade 4) multifactorial (acute GVHD, CMV infection and cyclosporine) BMT-TM was made. He responded following 19 plasma exchanges with replacement with fresh frozen plasma.

Adult↗
PubMed1998

Antenatal molecular diagnosis of X-linked ichthyosis by maternal serum screening for Down's syndrome.

A case of X-linked ichthyosis diagnosed antenatally by molecular analysis of fetal DNA is described. The diagnosis was made at 16 weeks gestation, following the finding of a maternal serum unconjugated estriol level lower than 0.1 MoM when performing a triple test. Fetal DNA was obtained from cultured amniocytes; two specific regions were amplified by polymerase chain reaction at 5' and 3' ends of the steroid sulfatase (STS) gene on Xp22.3 region. Analysis showed complete deletion of the STS gene on the distal tip of the X-chromosome short arm.

Amniocentesis↗
PubMed1998

Risk for spontaneous preterm delivery by combined body mass index and gestational weight gain patterns.

BACKGROUND: To investigate whether maternal anthropometric factors interact with one another or with other risk factors, thus modifying the risk of spontaneous preterm delivery. METHODS: We carried out a case-control study of 230 spontaneous preterm births with intact membranes between 24 and 35 weeks gestation and 460 control term births. All the patients had prenatal care at the same institution. Logistic regression analysis was used to test for possible interactions adjusting for potential confounders. RESULTS: A pre-pregnancy body mass index < or = 19.5 Kg/m2 (odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.20-2.38) and a rate of weight gain < or = 0.37 Kg/week during the second and third trimesters (OR = 2.4, 95% CI = 1.69-3.42) were associated with an increased risk of spontaneous preterm delivery. The risk of spontaneous preterm delivery associated with a low second/third trimester weight gain was greater among patients with a body mass index < or = 19.5 (OR = 5.63, 95% CI = 2.35-13.8) compared to those with a body mass index > 19.5 (OR = 2.45, 95% CI = 1.60-3.75, adjusted p value for interaction = 0.05). The risk of spontaneous premature delivery associated with a maternal pre-pregnancy weight < or = 48 Kg was higher among smokers (OR = 5.81, 95% CI = 1.60-22.9) than among non-smokers (OR = 2.4, 95% CI = 1.53-3.74, adjusted p value for interaction = 0.05). CONCLUSIONS: The risk of spontaneous preterm delivery associated with a low pre-pregnancy body mass index is greater among patients with low rate of gestational weight gain during the second and third trimesters compared to those with a higher rate. The results of this study support the recommendation for increased rates of weight gain to patients with low body mass index compared to those with a higher body mass index.

Adult↗
PubMed1993

A protein required for secretion of cholera toxin through the outer membrane of Vibrio cholerae.

A gene essential for the secretion of cholera toxin from the periplasm of Vibrio cholerae into the extracellular medium has been isolated and its nucleotide sequence determined. It encodes a cytoplasmic protein of 56 kDa that exhibits a high degree of similarity to gene products required for extracellular protein secretion in several other Gram- organisms. Sequence similarities in its potential ATP-binding site suggest that the protein may act as an energy provider or signal transducer in the process of extracellular secretion.

Amino Acid Sequence↗