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Biomedical subjects

C Perez

Publications and source records attributed to C Perez.

At least 73 records · Page 4Linked to original sources
PubMed1999

Chlorophenylmethyl benzothiadiazine dioxides derivatives: potent human cytomegalovirus inhibitors.

Modifications of our previously reported lead compounds, acyclonucleosides derived from 2,1,3-benzothiadiazine dioxides, in the search for inhibitors of human cytomegalovirus (HCMV), lead us to identify the chlorophenylmethyl benzothiadiazine dioxides derivatives as potent HCMV inhibitors. The synthesis and antiviral data of this second-generation of benzothiadiazine dioxide compounds are reported.

Anti-Infective Agents↗
PubMed1999

Genomic organization and promoter characterization of two human UHS keratin genes.

TTD is a rare human genetic disease caused by mutations in XPB and XPD, two subunits of the transcription/repair factor TFIIH, and whose outstanding clinical characteristic is a lack of most human UHS proteins resulting in sulfur-deficient brittle hair. In an attempt to understand this transcription defect, we report here the genomic cloning of two highly related UHS keratin genes specifically expressed in follicular and epidermal cells. In addition to a high degree of nucleotide homology (87%), both genes also have a similar 90-nt promoter sequence. In-vivo and in-vitro studies allowed us to specify the position of the start sites, the TATA-boxes and some regulatory regions. Results indicate that both genes present common features in the regulation of their transcription and suggest that control of their expression might be affected by mutations in TFIIH subunits.

Amino Acid Sequence↗
PubMed1999

Current aspects of biology, risk assessment, and treatment of neuroblastoma.

Neuroblastoma is one of the most intensely studied solid malignancies that affect the pediatric age groups; its clinical presentation, treatment strategies and ultimate prognosis vary greatly. The biologic and genetic character of each tumor has an important impact on disease behavior, and clinical staging now incorporates these factors to generate an overall therapy plan. The clinical presentation of neuroblastoma is related to primary tumor location, production of metabolically active substances, and the presence of metastatic disease. There are also prognostically important associated syndromes including opsoclonus-myoclonus, Horner's syndrome, neurofibromatosis, and a variety of other neurocristopathies. The histologic features of the tumor are of prognostic significance and are utilized in treatment stratification. The International Neuroblastoma Staging System (INSS) has unified classic clinical staging. Features at diagnosis and those determined by initial operation are combined with biologic prognostic factors to achieve risk group assignment for virtually all patients. There are groups of children in which limited therapy is curative and intermediate-risk situations where standard multimodality treatment provides favorable outcomes. Unfortunately, there are many patients with high-risk disease that require intensive strategies, but success is still limited. It is in these most resistant patients that innovative approaches are being undertaken and novel strategies are being investigated.

Adolescent↗
PubMed1999

Nocardia thyroiditis: unusual location of infection.

Nocardia asteroides complex is an important opportunistic agent in immunocompromised hosts. Usually, primary pulmonary infection occurs and is followed by dissemination of the pathogen to the central nervous system and soft tissues. As described in the literature, almost every organ can be infected, but to our knowledge, Nocardia has been described as a pathogen responsible for thyroid abscess in only one report, which was published in 1993. The present report is the second case report of Nocardia thyroiditis. The patient was under immunosuppressor treatment following a combined liver-kidney transplant and presented with a preexisting nodular goiter which was probably a predisposing factor to the start and development of the thyroid infection.

Abscess↗
PubMed1998

Molecular defects of the RHCE gene in Rh-deficient individuals of the amorph type.

The deficiency of Rh proteins on the red blood cells from individuals of the Rhnull amorph type may be the result of homozygosity for a silent allele at the RH locus. This phenotype is also associated with the lack or reduced expression of glycoproteins (Rh50, CD47, LW, and glycophorin B), which interact with Rh polypeptides to form the multisubunit Rh membrane complex. In this study, we describe two molecular alterations affecting the RHCE gene in two unrelated Rhnull amorph individuals bearing Rh50 and CD47 normal transcripts. The first type of mutation, located at the donor splice-site in intron 4, induced the activation of two cryptic splice-sites within this intron and one such site in exon 4 that all generated aberrant transcripts. The second type of mutation affected the coding region and introduced a frameshift and a premature stop codon resulting in a shorter predicted protein (398 v 417 residues), including a completely different C-terminus of 76 amino acids. This suggests that protein folding and/or protein-protein interaction mediated by the C-terminal domain of the Rh proteins may play a role in the routing and/or stability of the Rh membrane complex.

Alleles↗
PubMed1998

Genomic organization and promoter characterization of the mouse and human genes encoding p62 subunit of the transcription/DNA repair factor TFIIH.

TFIIH, a multisubunit complex was shown to be involved in several biological fundamental mechanisms of the cell: transcription, nucleotide excision repair and cell cycle regulation. p62 is one of the six subunits that constitutes the core of TFIIH versus the holoenzyme, which contains, in addition, the ternary kinase CAK complex. To gain an insight into the regulation of the expression of the various subunits of the core, we report here the cDNA cloning and the genomic organization of the mouse p62 gene. A promoter analysis of both mouse and human genes allow us to localize two start sites and the regulatory regions, thus demonstrating a significative conservation among both species. Both promoters lack classical elements such as CCAAT and TATA boxes. Analysis of the expression of the p62 gene reveals an overexpression in testis tissue for both species.

3T3 Cells↗
PubMed1998

Orienting asymmetries in rhesus monkeys: the effect of time-domain changes on acoustic perception.

Humans exhibit left-hemisphere dominance for processing spoken language, a species-specific acoustic signal characterized by a suite of spectro-temporal parameters. Some nonhuman primates (genus Macaca) also exhibit left-hemisphere dominance for processing their species-specific vocalizations, as evidenced by right-ear biases in orienting and reaction-time studies, and more damaging effects from left- than right-hemisphere lesions. Little, however, is known about the acoustic features underlying such biases. We conducted field playback experiments on adult rhesus monkeys, Macaca mulatta, to determine whether asymmetries in perception (measured as an orienting bias) are sensitive to changes in the temporal characteristics of their calls. If the observed right-ear bias for perceiving conspecific calls (Hauser & Andersson 1994, Proceedings of the National Academy of Sciences, U.S.A., 91, 3946-3948) depends upon particular acoustic parameters, then experimental manipulations beyond the species-typical range of signal variation will cause a change in perceptual asymmetry, either reversing the pattern (i.e. right to left ear ) or wiping it out (i.e. no asymmetry). We presented manipulated and unmanipulated exemplars of three pulsatile call types within the rhesus repertoire: an affiliative signal 'grunt', an alarm signal 'shrill bark', and a mating signal 'copulation scream'. Signal manipulations involved either (1) a reduction of the interpulse interval to zero or the population minimum or (2) an expansion of the interpulse interval to the population maximum, or two times the maximum. For the grunt and shrill bark, manipulations of interpulse interval outside the range of natural variation either eliminated the orienting bias or caused a shift from right- to left-ear bias. For the copulation scream, however, a right-ear bias was observed in response to all stimuli, manipulated and unmanipulated. Results show that for some call types within the repertoire, temporal properties such as interpulse interval provide significant information to listeners about whether the signal is from a conspecific or not. We interpret the orienting bias as evidence that hemispheric asymmetries underly this perceptual effect.Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1998

Different modes of sialyl-Tn expression during malignant transformation of human colonic mucosa.

Monoclonal antibodies TKH2 and B72.3, which react with the mucin-associated sialyl-Tn(STn) antigen, preferentially bind to cancerous but not normal colonic tissues. If O-acetyl groups are removed by saponification of tissues, MAb TKH2 will react with normal colonocytes, whereas MAb B72.3 remains non-reactive. To explain this difference in binding specificity, we tested both MAbs against synthetic constructs of single (monomeric) or clustered (trimeric) STn epitopes by enzyme immunoassay. Both MAb TKH2 and MAb B72.3 reacted with trimeric STn, but MAb TKH2 demonstrated greater binding than MAb B72.3 to monomeric STn. This suggests that normal colonic mucosa expresses monomeric STn epitopes, but that with transformation to malignancy, clustered STn epitopes appear. The appearance of clustered STn epitopes during colonic carcinogenesis represents a novel pattern of carbohydrate antigen expression and implicates alterations at the level of apomucins and/or glycosyltransferases responsible for cluster epitope formation.

Antibodies, Monoclonal↗
PubMed1998

A single VH family and long CDR3s are the targets for hypermutation in bovine immunoglobulin heavy chains.

Bovine immunoglobulins are made from genes belonging to a small family of closely related VH genes. In this respect cattle resemble all species of domesticated mammals, which also use one VH family. The family, named BoVH1, is homologous to the mouse Q52 family, and there are no more than 20 genes of this family in the bovine genome. Another feature of bovine heavy chains is the use of long CDR3s, which have an average of 21 codons. It seems that there are several families of long, closely related D genes rich in glycine and tyrosine responsible for this length. Sequences described as targets for mutations in other species can be found in CDR1, CDR2, and the putative D genes. The mutation mechanism starts at some point between late fetal stage and birth and seems to be antigen independent. Diversity seems to be generated by hypermutation, although other mechanisms cannot be discounted at this time. Contrary to humans and mice, which have several VH gene families comprising more than 100 genes, cattle use only a few genes and long CDR3s followed by somatic mutation to generate the necessary diversity to recognize the universe of antigens they will encounter during their life.

Amino Acid Sequence↗
PubMed1998

Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children's Cancer Group study.

PURPOSE: To identify a biologically favorable and unfavorable subset of patients with Evans stage III neuroblastoma and to determine whether treatment stratification would improve the event-free survival (EFS) for high-risk patients and maintain excellent EFS for the lower-risk patients. PATIENTS AND METHODS: Risk stratification was performed by age, MYCN gene copy number, Shimada histopathologic classification, and serum ferritin level. Lower-risk patients were treated on the less intensive Children's Cancer Group (CCG)-3881, whereas high-risk patients were treated on CCG-3891, which included more intensive multimodality therapy and, in some cases, autologous bone marrow transplantation (ABMT). RESULTS: Of 228 Evans stage III patients entered onto the study, 92% also met the definition of International Neuroblastoma Staging System (INSS) stage 3. One hundred forty-three patients met the lower-risk criteria, which included 89 patients less than 1 year of age and 54 patients 1 year of age or greater, and favorable biology, whereas 85 patients were 1 year of age or greater and biologically unfavorable. Biologically unfavorable patients 1 year of age or greater who underwent gross surgical resection had improved survival, whereas the outcome of infants or biologically favorable older patients did not change according to resection. The EFS rate at 4 years was 100% for the patients with favorable biology of any age, 90% for those less than 1 year of age but with at least one unfavorable characteristic, and 54% for Evans stage III patients 1 year of age or greater with unfavorable biology. Age, ferritin level, MYCN copy number, Shimada histopathology, primary site, and intraspinal extension were significant univariate prognostic factors for all patients, but only MYCN copy number and age were independent factors in multivariate analyses. CONCLUSION: The excellent survival of the biologically favorable group and the historically improved EFS of the biologically unfavorable group suggest that biologic staging should be used to define the prognosis and treatment of stage III neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[In vitro fertilization and sperm intracytoplasmic injection: psychological repercussions for the couple].

The aim of the study was to assess the psychological repercussions of IVF + ICSI on the male partner of infertile couples and on the couples and on the couple itself. The preliminary work has been done on the 23 couples in the waiting list of an ICSI cycle in A. Beclere hospital in Clamart. All couples respond to the same questionnaire. The two members of the couples were present in a semi-structured interview by 2 clinical psychologists. This ICSI scheme requires a complete change about the biological paternity. For infertile men, getting embryos work as a real reparation of their wounded ego, and the guilt goes from the man to the women when embryos are obtained. This study shows that infertile couples involved in IVF + ICSI have not the same concerns that doctors. Genetic abnormality transmission is not mentioned. On the opposite the male patients are strongly concerned by obtention of embryos which restore their fertility power. At this stage, female patients have to prove by carry out a pregnancy that they are as "good" as their partner.

Adult↗
PubMed1997

Detection of apolipoprotein E/dimeric soluble amyloid beta complexes in Alzheimer's disease brain supernatants.

The inheritance of the apolipoprotein (apo) E4 allele is an important risk factor for late-onset Alzheimer's disease (AD). A major component of the Alzheimer's disease neuritic plaques is amyloid beta (A beta). We previously identified apoE/A beta complexes within neuritic plaques (1). It was not known if this interaction takes place before or after A beta peptides become incorporated into neuritic plaques. To address this question we sought evidence of apoE complexes with brain soluble A beta peptides in AD and control patients. In addition, numerous proteins have been shown to bind A beta peptides in vitro. It is not know if any of these bind brain sA beta in vivo. We found evidence for the presence of apoE/dimeric sA beta complexes in the AD brain and could not detect complexes with other A beta peptide binding proteins. The binding of sA beta to apoE may be one factor influencing its clearance from the brain and/or its conformational state.

Alzheimer Disease↗
PubMed1997

Modulation of heat-shock protein 70 (HSP70) gene expression by sodium butyrate in U-937 promonocytic cells: relationships with differentiation and apoptosis.

The administration of sodium butyrate at 0.75 mM induced the functional differentiation of U-937 human promonocytic leukemia cells with negligible cell mortality. However, the drug rapidly caused cell death with characteristics of apoptosis when used at concentrations of 5 mM and above. In addition, butyrate stimulated the expression of the stress-responsive heat-shock protein 70 (HSP70) gene when applied at both differentiation-inducing and apoptosis-inducing concentrations. The induction of HSP70 by butyrate was inhibited by the simultaneous addition of cAMP-increasing agents (dibutyryl cAMP or the combination of forskolin plus theophylline). However, these agents did not prevent differentiation and only partially reduced apoptosis. Moreover, the DNA topoisomerase II inhibitor etoposide, which provoked U-937 cell differentiation and apoptosis with the same or greater efficiency than butyrate, failed to stimulate HSP70 expression. Finally, it was observed that cAMP-increasing agents also abrogated the induction of HSP70 and reduced the apoptosis caused by cadmium chloride, a typical inducer of the stress response. Taken together, these results indicate that HSP70 expression is not required for differentiation of promonocytic cells, as earlier proposed, and that butyrate probably triggers the stress response in these cells.

Antineoplastic Agents, Phytogenic↗