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Biomedical subjects

A Favre

Publications and source records attributed to A Favre.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Constipation and chronic intestinal pseudoobstruction as a clinical expression of intestinal neuronal dysplasia (IND)].

BACKGROUND: Intestinal neuronal dysplasia (IND) belongs to the group of dysganglionosis. It may occur as part of a syndrome of early chronic constipation, neonatal intestinal occlusion, chronic intestinal pseudo obstruction. The aim of this study was to report the cases examined by the Istituto G. Gaslini in Genoa and to discuss the numerous aspects of this disease which are still unclear. METHODS: 787 children were included in the study and underwent biopsy between 1984 and 1997. Rectal biopsies were obtained by suction or in some cases during surgery and were treated using enzymohistochemical techniques, such as acetylcholinesterase, rapid acetylcholinesterase and alpha-naphthylesterase. RESULTS: 574 children were found to be suffering from innervative alterations: 348 (60.6%) presented isolated Hirschsprung's disease, IND was found in 83 (14.5%), in 8 of the latter in association with other dysganglionosis. IND was accompanied by other diseases in 40 cases (48.2%). Over the past three years (since October 1994) a total of 164 dysganglionosis have been diagnosed, including 55 cases of aganglia. During this period IND was the most frequently observed alteration and affected 61 children. CONCLUSIONS: Rectal biopsy is the essential diagnostic test for the diagnosis of intestinal dysganglionosis. Biopsies are performed in outpatient clinics without sedation, and do not represent an invasive procedure for the young patients. Radiological and manometric examinations cannot provide reliable data for the diagnosis of IND. In our experience, the incidence of IND over the past few years has increased and its diagnosis is essential for correct treatment which is not surgical in the majority of cases. The real incidence of IND and its pathogenesis still need to be clarified.

English Abstract↗
PubMed1998

Affinity modification of phenylalanyl-tRNA synthetase from Thermus thermophilus by tRNAPhe transcripts containing 4-thiouridine.

Photoreactive derivatives of tRNAPhe containing residues of 4-thiouridine (s4U) were synthesized by the transcription system of T7 RNA polymerase. Complete substitution of s4U for 16 uridine residues ([16s4U]-tRNAPhe) caused a 14-fold decrease in the catalytic efficiency of aminoacylation of the tRNAPhe transcript by phenylalanyl-tRNA synthetase from T. thermophilus. [1s4U]-tRNAPhe obtained by random incorporation of s4U residues with further isolation of s4U-monosubstituted RNA molecules on an affinity gel has the same kinetic parameters in aminoacylation as the tRNAPhe transcript. The s4U-containing tRNAPhe transcripts were shown to bind covalently to phenylalanyl-tRNA synthetase, and the specificity of modification was demonstrated. The modification stoichiometry determined in this work suggests that the enzyme is a functional dimer. The modification labels both alpha- and beta-subunits of the enzyme, which has an oligomeric structure of alpha2beta2, and forms "cross-linking" products of subunits upon modification with [16s4U]-tRNAPhe. The prevalence of modification of the alpha-subunit suggests that tRNA has contacts with the enzyme, which have not been deciphered previously by X-ray analysis.

Base Sequence↗
PubMed1998

Localization of the binding site for the 3'-terminal sequence of tRNAPhe in subunits of phenylalanyl-tRNA synthetase from Thermus thermophilus.

A photoreactive tRNAPhe derivative containing a 4-thiouridine residue at the 3'-end (tRNAPhe-s4U-75) was prepared by tRNA nucleotidyltransferase-mediated incorporation of s4UMP into a tRNAPhe transcript lacking the 3'-terminal dinucleotide. The resulting tRNAPhe-s4U-75 was covalently bound to phenylalanyl-tRNA synthetase from Thermus thermophilus, and all criteria of an affinity modification were met. The main products of modification displaying various electrophoretic mobilities were formed by binding tRNAPhe-s4U-75 to the beta-subunit (major) of the enzyme. These data suggest that the nucleotide found at position 75 of tRNAPhe interacts with the beta-subunit of phenylalanyl-tRNA synthetase.

Base Sequence↗
PubMed1997

[Does stopping of oral feeding favour the occurrence of auriculoventricular block in premature infants treated with diphemanil?].

BACKGROUND: Bradycardia in preterm infants may require anticholinergic therapy (diphemanil methylsulphate). Such treatment may cause prolongation of QT interval and auriculoventricular block. CASE REPORTS: Three premature infants born before 34 weeks of gestational age were given 6-8 mg/kg/d diphemanil because they suffered from bradycardiac episodes. Aggravation and/or persistence of bradycardia required withdrawal of gavage feeding: heart block occurred within a few hours which subsided after cessation of diphemanil and oral refeeding. Diphemanil at progressive dosage was later introduced safely in two of these infants. CONCLUSION: The short interval of time between the oral feeding withdrawal and occurrence of heart block justified therapy be stopped or transiently reduced whenever oral feeding must be interrupted.

Administration, Oral↗
PubMed1997

Immunohistochemical study of skin lesions in acute and chronic graft versus host disease following bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) is the therapy of choice for a variety of malignant and nonmalignant disorders; however, a major constraint to successful BMT is graft versus host disease (GVHD). Skin lesions are the earliest presentation of GVHD. Donor-derived cytotoxic T lymphocytes are the effector cells responsible for lesions in the skin and other tissues. Here we show that most skin-infiltrating lymphocytes, in all forms of GVHD, are memory T cells with a predominance of CD4+ cells in the dermis and CD8+ cells in the epidermis. Relatively little attention has been focused on the adhesive phenotype of keratinocytes in GVHD. In this study, immunohistochemical analyses of skin biopsies from BMT patients with acute or chronic GVHD were conducted, with particular emphasis on antigen-presenting cells (APCs) and on keratinocytes. The distribution of APCs in the epidermis (Langerhans' cells) was investigated. Keratinocytes were analyzed for the expression of human leukocyte antigen DR locus (HLA-DR) and of a novel integrin, alpha10.1.2 beta1, which is detected in the basal layer of normal epidermis. Langerhans' cells were decreased in all grades of acute GVHD, but the epidermal APC network was reconstituted in chronic GVHD. HLA-DR was expressed by keratinocytes in grade 2 and 3 acute GVHD lesions, but not in two of three chronic GVHD cases, and in the regression phase of acute GVHD. Integrin chains alpha10.1.2 and beta1 were detected in the epidermal basal cell layer of most GVHD cases but they were also expressed in suprabasal keratinocytes of both acute and chronic GVHD. This latter finding indicates that a proliferative response uncoupled from differentiation occurs in keratinocytes in the course of GVHD.

Acute Disease↗
PubMed1997

HIV is trapped and masked in the cytoplasm of lymph node follicular dendritic cells.

To gain further insight into the pathogenesis of human immunodeficiency virus (HIV) infection, lymph nodes from seven asymptomatic HIV+ subjects were analyzed during the latent phase of disease. Both ultrastructural and immunohistochemical analyses revealed that, in all of the cases, plasma cells producing IgM/gamma were present in germinal centers. Secreted immunoglobulins formed extracellular deposits mimicking the follicular dendritic cell network. Immunoglobulin produced by germinal center plasma cells are specific for HIV because they bind the HIV env protein gp 120. Plasma cells producing antibodies with the same specificity were also abundant in the extrafollicular regions of lymph nodes. During the latent phase of infection, the virus largely accumulates within the germinal centers. Therefore, extracellular immunoglobulin may form immune complexes, as shown by the presence of HIV-specific antibodies, HIV particles, and complement components C3c, C3d, and C1q in the interdendritic spaces. When the ultrastructural localization of HIV in germinal centers was analyzed, abundant virus particles were found in the interdendritic spaces. In addition to this extracellular localization of HIV, receptor-mediated endocytosis of viral particles by follicular dendritic cells was observed. Complete HIV particles were found within the endosomal compartment of the follicular dendritic cells and, as complete viral particles, free in the cytoplasm, indicating that the virus may escape from the endocytic compartment. As the virus is abundant in the cytoplasm, this event leads to formation of a hidden reservoir within follicular dendritic cells. In this location, HIV escapes recognition by cytotoxic T lymphocytes. In contrast, virus budding indicating a productive infection of follicular dendritic cells that would render them susceptible to T-cell-mediated lysis has been seldom observed.

Antigen-Antibody Complex↗
PubMed1996

Apoptosis of Burkitt's lymphoma cells induced by specific interaction of surface IgM with a self-antigen: implications for lymphomagenesis in acquired immunodeficiency syndrome.

In a previous study, we described a cell line (BRG-P) derived from a woman with Burkitt's lymphoma (BL) and acquired immunodeficiency syndrome that shared the same characteristic cytogenetic abnormalities as the patient's malignant cells. This cell line contained subclones that displayed an isotype switch from IgM to IgA1 and an accumulation of point mutations in the Vh region genes. Because these two features suggested an antigen-driven process, we began a search for the antigen responsible for the stimulation of the malignant B cells. Specifically, we hypothesized that because the patient's tumor had presented as a lymphomatous infiltration of the breast, the malignant B cells were recruited to this site because of the reactivity of their surface lg with breast tissue. A hybridoma (BRG-H) was obtained by fusing BRG-M cells (an IgM producing subclone of the BRG-P cell) with an appropriate cellular partner. The monoclonal antibody (BRG MoAb) produced by this hybridoma reacted strongly with two of five breast cancer cell lines and stained normal and malignant ductal epithelial cells on breast tissue sections. The antigen recognized by the BRG MoAb consisted of a single, minimally glycosylated polypeptide chain of 45 kD (p45). The BRG MoAb failed to react with a panel of human cell lines from different tissues, except for one cell line from a uterine cervical carcinoma. No reactivity was detected for a panel of exogenous antigens from various pathogens, including human immunodeficiency virus and self-antigens frequently recognized by polyspecific antibodies. Experiments were performed to investigate the functional consequences of the interaction of surface IgM with its specific ligand. Coculture of BRG-M cells with p45+, but not with p45-, breast cells caused apoptosis of BRG-M cells. The specificity of the interaction was shown by the observation that apoptosis was prevented by pretreatment of BRG-M cells with a monovalent F(ab') fragment of rabbit IgG antibody to human mu chains. Moreover, only BRG-M cells, but not other BL cells, underwent apoptosis after exposure to p45+ breast cells. The interaction between the CD40 molecule expressed by BRG-M cells and its specific ligand (CD40L) prevented p45-induced cell apoptosis. Because this interaction mimics that occurring in vivo between T and B cells during immune responses, our data suggest that various events contributed to the emergence of the BL, in this particular patient, including antigenic stimulation possibly assisted by T-cell help.

Adult↗
PubMed1996

Folding of the HDV antigenomic ribozyme pseudoknot structure deduced from long-range photocrosslinks.

A trans-acting system has been designed in order to explore the three-dimensional structure of the anti-genomic HDV ribozyme. In this system, the substrate (SANT) is associated by base-pairing to the catalytic RNA (RzANT) forming helix H1. RzANT is able to cleave specifically the RNA substrate as well as a deoxysubstrate analogue containing a single ribocytidine at the cleavage site (position -1). This demonstrates that such deoxysubstrate analogues are valuable tools for structural studies of this ribozyme domain. They form however weak complexes with RzANT which is due in part to their ability to fold as stable hairpins unlike the RNA substrate. Using a set of full deoxy or of mixed deoxy-ribo substrate analogues site-specific substituted with the photoaffinity probe deoxy-4-thiouridine, ds4U, at a defined position, we were able to determine a number of long range contacts between the substrate and the ribozyme core. In particular, crosslinks between substrate position -1 and position -2 with residues C15, G19 and C67, thought to be involved in the ribozyme catalytic site, were detected. A three dimensional model of the antigenomic ribozyme system, derived from the structure proposed by Tanner et al. [Current Biol (1994) 4, 488-498] for the genomic system was constructed. Apart from residue deletion or insertion, only minor accommodations were needed to account for all photocrosslinks but one which is attributed to an alternative hybridization of the substrate with the ribozyme. This study therefore further supports the structure proposed by Tanner et al. for the pseudoknot model.

Base Sequence↗
PubMed1996

Subepithelial B cells in the human palatine tonsil. I. Morphologic, cytochemical and phenotypic characterization.

This study describes the purification of a subset of tonsillar B cells which share phenotypic, morphologic and cytochemical features with subepithelial (SE) B cells. These cells, which represented the 5-10% of the total tonsillar B cells, were found in the Percoll gradient fraction of highest density, together with resting follicular mantle (FM) B cells. The latter B cells, however, expressed surface CD5 and could be removed by an immune rosetting procedure. The remaining small CD5- B cells had a surface phenotype (IgM+, IgD+, CD23-, CD38+/-, CD10-, CD44+) that was different from that of FM (IgM+, IgD+, CD23+, CD39+, CD38-, CD10-, CD44+2) and of germinal center (GC) (CD23-, CD39-, CD38+, CD10+, CD44+/-, IgG+) B cells isolated from the same cell suspensions. Furthermore, the absence of surface activation markers (CD71 and CD69) and of surface IgG allowed us to distinguish small CD5- B cells from activated and memory cells migrating within Percoll fractions of lower density. In situ immunohistochemical studies revealed that B cells with an identical phenotype as that of small CD5- B cells could be detected predominantly in the SE region (lamina propria) of the tonsil, and also within the epithelium lining the cryptae. This area was also comprised of a relatively minor proportion of activated B cells, not found in the small CD5- B cell fraction owing to the separation procedure used. Consistent with the notion that the SE area could be a site of B cell activation was also the presence of activated macrophages and of plasma cells. Thirty to forty percent of small CD5- B cells isolated in suspension were positive for the endogeneous alkaline phosphatase (ALP) activity. In contrast, only a few FM B cells were ALP+, while GC cells were consistently ALP-. In situ studies also demonstrated a prevalent expression of ALP activity by the B cells in the SE area. At the ultrastructural level, small CD5- B cells were clearly different from both FM and GC B cells. They displayed a cytoplasm more extended than that of FM B cells with abundant endosomes and plasma membrane projections, and a speckled pattern of nuclear heterochromatin distribution. When fixed tissue sections were examined, cells with identical ultrastructural features could be demonstrated in the tonsillar lamina propria. Collectively, the above data demonstrate an identity of features between the small CD5- B cells isolated in suspension and SE B cells analyzed in situ. Since tonsillar SE B cells are generally thought to represent the homolog of the extrafollicular B cells (including those of the splenic marginal zone), these studies may provide new opportunities for functional studies on this so far incompletely characterized B cell subset.

Alkaline Phosphatase↗
PubMed1996

Establishment and characterization of three new cell lines derived from the ascites of human ovarian carcinomas.

Three human cancer cell lines (OC 314, OC 315, and OC 316) were newly established in permanent culture from the ascites of patients with serous adenocarcinoma of the ovary. OC 314 was derived from an untreated tumor presenting with ascites at diagnosis; OC 315 was isolated from a neoplasm progressing after cisplatin-containing regimen; and OC 316 was collected from a patient with pleural metastasis at diagnosis, resistant to different chemotherapeutic treatments including Taxol. These cell lines were repetitively subcultured once to twice a week through 75-80 passage generations. Tumor cells grew as monolayers and displayed epithelial-like morphology, consistent with a feature of adenocarcinoma, which was then confirmed by the expressions of cytokeratins and vimentin. The cell lines proved highly tumorigenic when transplanted into nude mice, both subcutaneously and intraperitoneally. In addition, the mice inoculated with subcutaneous OC 316 developed extremely aggressive tumor, also invading the peritoneum, which correlated with the malignant behavior of the original tumor. Drug sensitivity, evaluated by the MTT assay, showed that the three cell lines expressed similar sensitivity to doxorubicin. Responses to cisplatin essentially reported low sensitivity of OC 314 and OC 315 and resistance of OC 316, thus reflecting the original sensitivity at the clinical level.

Animals↗
PubMed1996

Neutrontherapy in soft tissue sarcomas: a review of European results.

The purpose of this publication is to review the data on European neutrontherapy facilities in the treatment of soft tissue sarcoma. Data on 1171 patients treated at 11 centers were analyzed. Neutrontherapy was of advantage especially for patients with primary radiotherapy of inoperable tumors, and those with macroscopic disease after surgery. Local control was about 50% in these groups. Results for postoperative neutrontherapy after R0 and R1 resection were similar to those for photon therapy. The incidence of late side effects was considerable. This was influenced by the fact that most patients were treated with first-generation machines.

Disease-Free Survival↗
PubMed1996

European results in neutron therapy of malignant salivary gland tumors.

In Europe to date, 501 patients with salivary gland tumors have been treated with neutrons alone or with combined modalities. The most common histological types are adenoid cystic carcinomas, mucoepidermoid carcinomas and malignant mixed tumors. The results of conventional radiotherapy are suboptimal in inoperable or incompletely resected salivary gland tumors and in recurrent disease. The pooled data of some international series for low linear energy transfer radiation show a local control of 28%. Especially in advanced tumors neutron therapy can improve local control and should be the treatment of choice. The clinical data from different therapy centers in Europe show local control of 67% in gross disease.

Carcinoma, Adenoid Cystic↗
PubMed1996

Fast neutrons in the treatment of grade IV astrocytomas.

In 1981, the Hôpital Tenon group and the Orléans neutron therapy team initiated a collaborative study for the treatment of grade IV astrocytomas using a combination of photons and neutrons. Neutrons were used as boost in a reduced volume. Doses were progressively increased from 6 to 7 Gy and later up to 8 Gy. Since October 1994, a neutron boost of 7.5 Gy has been delivered. At the time of evaluation, 294 patients had a minimum follow-up of 12 months. Univariate analysis indicated that clinical status, tumor location and photon fractionation scheme had no significant influence on survival. In contrast, age, surgical procedure and neutron dose were found to be prognostic factors. In a multivariate analysis, the prognostic value of the surgical procedure disappeared and the only remaining independent prognostic factors up to 11 months after treatment (P = 0.001) were age and the neutron dose. As far as neutron dose was concerned, survival increased with dose from 6 to 7 Gy up to 15 months. However, after 15 months, there was no longer any benefit in survival for the patients treated with 8 Gy, and complications related to overdosage began to appear. There was a long-term survival group: 55 patients were alive 18 months after treatment (18%). The median survival was 26.7 months. The best survival was observed for patients treated with a neutron boost of 7 Gy in eight fractions over 11 days (25 vs 18%). The present study demonstrates the feasibility of a combination of photons (30 Gy total brain) followed by a neutron boost (7 Gy) in the treatment of high-grade astrocytomas. The results are in good agreement with the published data. In the literature, age and surgical procedure are currently considered as the most important prognostic factors. The prevalence of neutron dose over these two other prognostic factors, as shown in this study, is an important additional argument in favor of the use of neutrontherapy in the management of these tumors. A possible benefit when combining external fast neutrontherapy with boron neutron capture therapy (BNCT) could reasonably be expected.

Astrocytoma↗
PubMed1996

Fast neutron therapy for inoperable or recurrent sacrococcygeal chordomas.

Between 1981 and 1994, 13 patients were referred to the Orleans neutrontherapy department with inoperable or recurrent pelvic chordomas. One patient who had already been irradiated refused the treatment, fearing complications. Among the 12 patients suitable for evaluation, ten had undergone one to five previous surgical operations. The time lapse between the last surgical operation and neutrontherapy was 13 months. Neutrons were used alone or as a boost depending on the tumor volume or treatment purpose. At four years, crude survival and local control probability (Kaplan-Meier) were 61 and 54% respectively. This small series suggests that fast neutrontherapy can provide a good alternative for the treatment of inoperable sacral chordomas.

Adolescent↗
PubMed1996

[Cardio-respirography in neonatal medicine: value, interpretation, indications].

The development of cardiorespirography with data processing enables to perform polygraphic recordings. However the standardized results supplied by this new generation of equipment cannot be used directly and need to be validated and analized by the clinician. The confrontation of the cardiac and respiratory curves allows a semiological analysis of the cardiac and respiratory functions and of their relationships in the various syndromic contexts encountered in the neonate (bradycardia and other cardiac arythmia, central or obstructive apnea, thoracic hypoampliation, periodic breathing).

Apnea↗