Search PubMed⌕ Search

Biomedical subjects

P Sanchez

Publications and source records attributed to P Sanchez.

At least 55 records · Page 3Linked to original sources
PubMed1996

Mediastinal mass following chemotherapy in patients with Ewing sarcoma and osteosarcoma.

Thymic hyperplasia following combination chemotherapy for malignant disease is very uncommon in adolescents and adults. Our experience includes a thymic enlargement noted on the sequential computed tomography (CT) in three patients who were disease-free after chemotherapy for Ewing sarcoma (2) and osteosarcoma (1). The development of an anterior mediastinal mass after successful chemotherapy does not always imply relapse of malignant disease. To prevent inappropriate treatment, the possibility of benign aetiology must be considered.

Adolescent↗
PubMed1996

Regulation by gonadotropins of the messenger ribonucleic acid for P450 side-chain cleavage, P450(17) alpha-hydroxylase/C17,20-lyase, and 3 beta-hydroxysteroid dehydrogenase in cultured pig Leydig cells.

The Leydig cell from the immature pig provides a good model for studying testicular steroidogenesis. Regulation of the enzymes involved, which has been well studied in rodents, has not been characterized in the pig. The objectives of this study were to examine the regulation of three steroidogenic enzymes in pig Leydig cells by LH/hCG and testosterone. The mRNA for P450 side-chain cleavage and P450(17) alpha-hydroxylase/C17-20-lyase, although constitutively expressed, decreased over time in culture, while that for 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) remained relatively constant. The mRNA for all three enzymes was increased in a dose- and time-dependent manner by treatment with hCG. Run-on experiments demonstrated that the main effect of the hormone was at the level of transcription. Treatment with hydroxyflutamide, either alone or in combination with hCG, had no effect on the mRNA for these enzymes. Treatment with hCG plus aminoglutethimide, an inhibitor of steroidogenesis, had no effect on the mRNA for the two P450 enzymes, but resulted in an increase in mRNA for 3 beta HSD when compared to treatment with hCG alone. However, exogenous testosterone could not block the effect of aminoglutethimide. Therefore, the steroidal regulation of 3 beta HSD in pig Leydig cells may act through a mechanism separate from the androgen receptor. While aspects of the regulation of these enzymes are similar to those seen in rodents, some significant differences exist. Our results support the concept that regulation of steroidogenic enzymes in Leydig cells is species-specific.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo.

The members of the atypical subfamily of protein kinase C (PKC) show dramatic structural and functional differences from other PKC isotypes. Thus, in contrast to the classical or novel PKCs, they are not activated by diacylglycerol or phorbol esters. However, the atypical PKCs are the target of important lipid second messengers such as ceramide, phosphatidic acid, and 3'-phosphoinositides. The catalytic and pseudosubstrate sequences in the two atypical PKCs (lambda/iota PKC and zeta PKC) are identical but are significantly different from those of conventional or novel PKCs. It has been shown that microinjection of a peptide with the sequence of the pseudosubstrate of the atypical PKC isotypes but not of alpha PKC or epsilon PKC dramatically inhibited maturation and NF-kappa B activation in Xenopus oocytes, as well as reinitiation of DNA synthesis in quiescent mouse fibroblasts. This indicates that either or both atypical isoforms are important in cell signalling. Besides the pseudosubstrate, the major differences in the sequence between lambda/iota PKC and zeta PKC are located in the regulatory domain. Therefore, any functional divergence between the two types of atypical PKCs will presumably reside in that region. We report here the molecular characterization of lambda-interacting protein (LIP), a novel protein that specifically interacts with the zinc finger of lambda/iota PKC but not zeta PKC. We show in this paper that this interaction is detected not only in vitro but also in vivo, that LIP activates lambda/iota PKC but not zeta PKC in vitro and in vivo, and that this interaction is functionally relevant. Thus, expression of LIP leads to the transactivation of a kappa B-dependent promoter in a manner that is dependent on lambda/iota PKC. To our knowledge, this is the first report on the cloning and characterization of a protein activator of a PKC that binds to the zinc finger domain, which has so far been considered a site for binding of lipid modulators. The fact that LIP binds to lambda/iota PKC but not to the highly related zeta PKC isoform suggests that the specificity of the activation of the members of the different PKC subfamilies will most probably be accounted for by proteins like LIP rather than by lipid activators.

Amino Acid Sequence↗
PubMed1996

The lambda B cell repertoire of kappa-deficient mice.

Analysis of the B cell repertoire is complicated by the huge diversity inherent in the germ line determined combinatory. Making use of knockout technology, kappa-deficient mice have been obtained. They constitute a shrewd model to follow the expression of an Ig minilocus, such as the lambda one, in the normal condition compared with classical transgenic models. Indeed, in contrast to wild type mice, in which only 5% of lambda B cells are produced, these mutant mice exclusively produce lambda positive B cells. Although, the lambda locus is well characterized and has a relatively simple organization, the mechanistic and selective pressures that govern its utilization are still poorly understood. The analysis of the lambda B cell repertoire in kappa-deficient mice, should therefore bring more conclusive informations. Here we present the lambda subtype distribution in the various cellular compartments of the kappa-deficient mice, and discuss the rules that can be responsible for this distribution. Our recent data indicate that the lambda subtype proportions in the bone marrow and the spleen result, for the major part, from mechanistic processes (i.e., recombinase accessibility, production of V-J functional joint and H/L pairings) while the lambda proportions found in the peritoneal cavity ensue from selective processes. Finally, the capacity to respond to various antigens is discussed from such a generated lambda B cell repertoire.

Animals↗
PubMed1995

Various V-J rearrangement efficiencies shape the mouse lambda B cell repertoire.

The diversity of the B cell repertoire of C kappa knockout mice is limited by the expression of four lambda light chain types. Among the spleen B cells, lambda 1 is expressed by the majority (58%) of cells, and lambda 3 by the minority (8%), while lambda 2 (V2) and lambda 2 (Vx) are expressed in intermediate quantities (18% and 16%, respectively). To assess the influence of mechanistic pressures on the lambda subtype distribution, the proportions of the different lambda rearrangements were determined in various B cell subpopulations divided on the basis of the lambda subtype expressed, and the V lambda J lambda junction sequences were studied at different steps of B cell differentiation (pre-B, immature and mature B cells). The data show that (1) the ratio of productive/non-productive VJ junctions is determined by the nature of the lambda segments that are rearranged as can be observed in the pre-B cells, (2) V1-J1 non-productive rearrangements are often found in the lambda 1-negative B cells in the periphery, and (3) V1J3 junctions are often non-productive regardless of the nature of the cells analyzed. Our results, therefore, suggest that a strong probability of initiating a V1-J1 rearrangement and a weak probability of giving a productive V1J3 junction are responsible for the lambda 1 dominance and the lambda 3 under-expression, respectively. The intermediate proportion of lambda 2(V2) subtype is most likely due to a probability of obtaining a productive joint that is better than that for V1J3 and a probability of initiating a rearrangement that is lower than that for V1J1. However, the lambda 2(Vx) cell proportion cannot be determined only by these parameters.

Animals↗
PubMed1995

Emergence in C kappa knockout mice of a diverse cytotoxic T lymphocyte repertoire that recognizes a single peptide from the immunoglobulin constant kappa light chain region.

Allotype- or idiotype-specific CD4+ T cells have been reported to recognize immunoglobulin (Ig) peptides presented by class II molecules. In contrast, few data are available concerning the generation of Ig peptide-specific CD8+ T cells. We have therefore investigated whether T-depleted spleen cells from Ig kappa light chain-expressing 129/Sv mice (129 kappa +/+) could induce, in C kappa knockout mice (129 kappa -/-), the generation of Ig constant kappa light chain region (C kappa)-specific cytotoxic T lymphocytes (CTL). The determination of TCR beta chain expressed by nine CTL clones, together with the use of a library of overlapping peptides spanning the whole C kappa sequence, show that the B cells from kappa +/+ mice are able to elicit in C kappa knockout mice, the emergence of a diverse CTL repertoire that recognizes one single C kappa peptide presented by the H-2Kb class I molecule. In addition, these data support the notion that B cells are able to process and present on their class I molecules, peptides generated from their own kappa light chains.

Amino Acid Sequence↗
PubMed1995

Biochemically active sesquiterpene lactones from Ratibida mexicana.

Bioactivity-directed fractionation of the methanol extract of the roots of Ratibida mexicana resulted in the isolation of two bioactive sesquiterpene lactones, isoalloalantolactone and elema-1,3,11-trien-8,12-olide. Both compounds caused a significant inhibition of the radicle growth of Amaranthus hypochondriacus and Echinochloa crus-galli, exerted moderate cytotoxic activity against three different solid tumour cell lines and inhibited significantly the radial growth of three phytopathogenic fungi. Isoalloalantolactone also caused the inhibition of ATP synthesis, proton uptake and electron transport (basal, phosphorylating and uncoupled) from water to methylviologen, therefore acting as a Hill's reaction inhibitor. The lactone did not affect photosystem I but inhibited photosystem II. The site of inhibition of isoalloalantolactone is located in the span of P680 to QA redox enzymes because the uncoupled electron transport from water to silicomolybdate and, from DPC to DCIP are inhibited approximately to the same extent.

Antifungal Agents↗
PubMed1995

Involvement of renal dopaminergic system in experimental neurogenic arterial hypertension.

The effect of chronic salt loading (10 g of NaCl for a period of 7 days) on urinary dopamine release has been investigated in 3 groups of beagle dogs: normotensive dogs (group 1: n = 7), and 2 groups of dogs made hypertensive by chronic sinoaortic denervation [group 2: (n = 6) during the first 4 months after sinoaortic denervation i.e. a model of arterial hypertension with high levels of plasma catecholamines and group 3: (n = 6) one year after denervation i.e. a model of arterial hypertension with normal sympathetic tone]. In normal dogs (group 1), salt loading induced an increase in urinary dopamine excretion during the two first days after salt loading. The rise in urinary dopamine was blunted in group 2. It was not observed in group 3. Salt loading failed to change arterial pressure and heart rate in the three groups of animals. These data show an alteration of the renal dopaminergic system in hypertensive sinoaortic denervated dogs suggesting that a dopaminergic impairment can appear during the development of arterial neurogenic hypertension.

Animals↗
PubMed1995

Four days' continuous infusion of cisplatin-5-fluorouracil and short daily infusion of high-dose leucovorin as induction chemotherapy for locally advanced head and neck cancer.

Cisplatin-fluorouracil (PF) is the most frequently used combination as induction chemotherapy (CT) for the treatment of locally advanced squamous cell head and neck cancer. This study was designed to evaluate the role of leucovorin (L) in the modulation of the therapeutic activity of PF continuously infused for 4 days. Between June 1990 and June 1992, stage III and IV previously untreated patients received PFL induction chemotherapy followed by surgery, radiotherapy, or both. The chemotherapy consisted of P 25 mg/m2, F 1000 mg/m2 both continuously infused for 4 days and L 250 mg/m2 infused for 2 hours before each daily infusion of PF. PFL was administered every 3 weeks for 4 cycles. The overall response rate at the completion of PFL was 91%, with 54% CR and 37% PR. Locoregional treatment was performed on 68 patients, 11 (16%) underwent surgery, 20 (29%) surgery plus radiotherapy, and 37 (54%) radiotherapy. Complete response status after both induction and locoregional therapy was 71%. Biopsies of the primary tumor or definitive resection specimens immediately after PFL therapy were available in 25 patients in CR. Pathological CR was found in 11 (44%). With a maximum follow-up of 44 months, the overall survival rate is 51% and the median survival has not been reached. PFL is highly active as induction chemotherapy. A randomized comparison between PF and PFL is necessary to define the place of leucovorin modulation in the treatment of head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Mechanistic and selective constraints act on the establishment of V lambda J lambda junctions in the B cell repertoire.

Only four different subtypes of lambda Ig chains have been described in the mouse: lambda 1, lambda 2(V2), lambda 2(Vx), and lambda 3. These chains are encoded by gene segments all sequenced and well localized in chromosome 16. Although the lambda Ig system is both simple and well characterized, no exhaustive analysis has been done concerning V lambda J lambda junctions in nonintentionally stimulated B cells. To get an insight into the lambda B cell repertoire, we analyzed a large number of V lambda J lambda rearrangements isolated from spleen mRNA or genomic DNA of unimmunized adult BALB/c mice. By PCR amplification, more than 160 clones were obtained covering all V lambda J lambda recombinations. Simple recombinations of trimmed gene segments explain most sequences. Certain junctions have been found to be prevalent in each subtype, and an analysis of V lambda J lambda recombination sites shows that the splenic lambda repertoire can result from both differential efficiencies of rearrangement and selective processes.

Amino Acid Sequence↗
PubMed1994

Conserved distribution of lambda subtypes from rearranged gene segments to immunoglobulin synthesis in the mouse B cell repertoire.

The immunoglobulin lambda light chain system displays a limited diversity in inbred mice. Indeed, the lambda locus is organized in two recombination units: V lambda 2-V lambda x-J lambda 2-C lambda 2-psi J lambda 4-psi C lambda 4, which can produce either lambda 2(V2) or lambda 2(Vx) chains; and V lambda 1-J lambda 3-C lambda 3-J lambda 1-C lambda 1, which can produce either lambda 1 or lambda 3 chains. Each of these units is associated with an enhancer, E lambda 2-4 or E lambda 1-3, at the 3' side. The expression of each lambda chain is, therefore, controlled by distinct promoter and/or enhancer regions. To clarify the basis of these controls, we measured, by quantitative polymerase chain reaction, the proportions of each lambda subtype in BALB/c spleen mRNA and among genomic rearrangements. It appears that these distributions are similar to and consistent with the relative cellular frequencies in the spleen, as evaluated by flow cytometry. These results suggest that, in resting cells, the transcription rates are identical, regardless of the lambda subtype. After lipopolysaccharide (LPS) stimulation, the transcription rates per cell remain similar for all lambda subtypes despite different regulatory sequences. To detect eventual post-transcriptional regulations, we estimated the lambda light chain distribution in IgM secreted by LPS-stimulated B cells and in serum IgG. These distributions are still similar to those of lambda-expressing cells, lambda mRNA or genomic rearrangements. We conclude that the lambda subtype distribution is conserved from productive V-J rearranged genes to secreted lambda immunoglobulins, despite different regulatory sequences.

Animals↗
PubMed1994

Compartmentalization of lambda subtype expression in the B cell repertoire of mice with a disrupted or normal C kappa gene segment.

The establishment of the B cell repertoire depends on two major parameters. The first is determined by mechanistic processes that give rise to a great diversity of B cell receptors from a combination of multiple gene segments. The second is dominated by selective processes that recruit B cell clones via their immunoglobulin receptors. To assess the impact of these parameters on the composition of B cell repertoire, we constructed a mouse model displaying a B cell repertoire limited in its diversity. To this end, we disrupted the C kappa segment by gene targeting. B cells from such mutant mice do not express the kappa light chain. Their light chain repertoire is therefore limited by the expression of only four main lambda light chains: lambda 1, lambda 2(V2), lambda 2(Vx) and lambda 3. In this study we described the proportions of each lambda subtype in various lymphoid compartments. Our results show that the lambda 1 subtype is dominant in the spleen and the bone marrow. Moreover, lambda 1 prevalence is independent of the wild or mutant C kappa genotype. These results suggest that the mechanistic processes are mainly responsible for the bias in lambda subtype expression. On the other hand, the lambda 2(V2) and/or lambda 3 subtypes are expressed at higher levels in the peritoneal cavity. Their prevalence is again observed regardless of the C kappa genotype and seems to be due to B1 cells. These results suggest that different mechanistic processes could control lambda subtype expression in B1 and B2 cell lineages.

Animals↗
PubMed1994

Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, both in continuous 96-hour infusion, in the treatment of locally advanced head and neck cancer.

In this study, 79 patients with locally advanced head and neck cancer were treated with induction chemotherapy. Cisplatin, 25 mg/m2, and 5-fluorouracil (5-FU), 1000 mg/m2, were employed, both of them in 24-hour continuous infusion over 96 hours, four cycles. The patients later underwent surgery and/or radiation therapy. The response to chemotherapy was 49%: of the complete responses (CR), 56% were histological; 29% were partial responses (PR). With the administration of the fourth cycle, CR increased from 30% to 49%. Once the complete treatment had been finished, 75% of CR and 5% PR were achieved. With a maximum follow-up period of 44 months, overall survival stands at 50%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Linguistic influences on the auditory processing of speech by children with normal hearing or hearing impairment.

OBJECTIVE: The accurate perception of speech requires the processing of multidimensional information. The aim of this research was to examine linguistic influences on the auditory processing of speech in the presence of childhood hearing impairment. DESIGN: The processing interactions characterizing the linguistic and auditory dimensions were assessed with a pediatric auditory analog of the Pomerantz task (Pomerantz, Pristach, & Carson, 1989). The task yields measures of Stroop interference, the effect of irrelevant semantic content, and of Garner interference, the effect of irrelevant linguistic variability (Stroop, 1935; Garner, 1974a). Subjects were 100 normal-hearing children and 60 hearing-impaired children. Subjects were required to attend selectively to the auditory (voice-gender) dimension and to ignore the linguistic dimension. The logic of the task is that performance for the voice-gender dimension will be unaffected by what is happening on the irrelevant dimension if the dimensions are processed independently. On the other hand, if the dimensions are not processed independently, subjects will not be able to attend selectively and performance for the relevant dimension will be affected by what is happening on the to-be-ignored dimension. RESULTS: Both the normal-hearing and hearing-impaired children showed auditory Stroop and Garner interference effects, indicating that the auditory and linguistic dimensions were not processed independently by either group. However, the linguistic dimension exerted significantly less influence on auditory processing in the presence of childhood hearing impairment. Whereas normal-hearing children had remarkable difficulty ignoring irrelevant word input and focusing exclusively on voice-gender, hearing-impaired children were relatively successful at ignoring the linguistic dimension and attending selectively to the auditory dimension of speech. This result implies that the linguistic dimension of auditory speech input may have a different weight or processing value in the presence of childhood hearing impairment. It may be the case that hearing-impaired children encode spoken speech disproportionately in terms of the auditory dimensions, which offer important supplementary aids to speechreading. Further research is being carried out to address these possibilities. CONCLUSIONS: Both Stroop and Garner interference were significantly reduced in the presence of childhood hearing impairment. This pattern of results suggests that multidimensional speech processing is carried out in a less stimulus-bound manner in the presence of childhood hearing impairment.

Acoustic Stimulation↗
PubMed1994

Detection of Bm86 antigen in different strains of Boophilus microplus and effectiveness of immunization with recombinant Bm86.

The control of tick populations by using conventional strategies poses several problems, including the appearance of organophosphate resistant strains, among others. The possibility of using alternative strategies such as vaccination with tick antigens has been suggested by several authors. One particular antigen (Bm86) has been described and shown to be able to induce a protective immunity against the cattle tick Boophilus microplus. In this paper we demonstrate by means of immunohistochemical staining that this antigen is conserved among several strains of this species. These results correlate with those showing that animals vaccinated with a preparation of recombinant Bm86 were protected against challenge with the four different strains tested, including one resistant to organophosphates. These results favour the immunization with recombinant Bm86 for the control of the cattle tick B. microplus.

Animals↗
PubMed1993

Available lambda B cell repertoire in the mouse: evidence of positive selection by environmental factors.

We have recently shown that, from two BALB/c mice treated with rabbit anti-C lambda 2/C lambda 3 antibodies coupled to lipopolysaccharide, variable heavy chain (VH) family repertoires associated with lambda 2 or lambda 3 light chains can differ from one lambda subtype to another and from one individual mouse to another. Indeed, 4 out of 6 lambda 2 (VxJ2) hybridomas from one mouse preferentially expressed the VH10 family while 3 out of 8 lambda 2 (V2J2) and 5 out of 8 lambda 2 (VxJ2) hybridomas from a second mouse preferentially expressed the S107 and VGAM3.8 VH families, respectively. In this report, we describe the structural basis of such preferential pairings by sequence analysis of the 12 lambda 2 hybridomas. The sequence comparison of their VH regions show that each preferential association of a VH family to one V lambda region is restricted to the use of a single member or very closely related members inside a VH family and that a great variability of CDR3 of heavy chain is observed. We, therefore, suggest that environmental factors can modify the available lambda B cell repertoire through a positive selection of particular VH/V lambda pairings. Moreover, our data support that this selection does not require clonal expansion and punctual somatic mutation.

Amino Acid Sequence↗