Search PubMed⌕ Search

Biomedical subjects

C Schmitt

Publications and source records attributed to C Schmitt.

At least 37 records · Page 2Linked to original sources

Cloning and sequencing of Duck circovirus (DuCV).

The genome of Duck circovirus (DuCV) is circular and 1996 nts in size. Two major open reading frames were identified, encoding the replicase (V1) and the capsid protein (C1). A stem-loop structure comprising the nonamer 5'-TATTATTAC, conserved in all circo-, nano- and geminiviruses, was found. Unique to DuCV, the region between the 3'-ends of the rep and cap gene contains four repeats of a 44-bp sequence. Phylogenetic analysis shows close relation of DuCV with Goose circovirus and suggests classification of DuCV as a new member of the genus Circovirus of the virus family Circoviridae.

Amino Acid Sequence↗

Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.

Adolescent↗

Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects.

Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined by impaired immunoglobulin production. The functional classification of CVID patients on the basis of in vitro immunoglobulin production is time consuming and has never shown any predictive value. We propose a classification based on the quantitative repartition of naive/memory B cells according to the dual expression of IgD and CD27. Fifty-seven patients were categorized into three groups: Group MB2 (11 patients, 19%) with normal memory B cells; Group MB1 (19 patients, 33%) with defective switched memory (IgD-CD27+) but normal nonswitched memory B cells (IgD+CD27+); Group MB0 (27 patients, 47%) with almost no memory B cells. In addition, a downexpression of activation markers (CD25, CD21, CD80, CD86) on B cells characterized the group MB1 patients and was associated with an upexpression of activation markers (HLA-DR, CD95, CD57) on T cells. This classification correlates with some clinical aspects showing a higher prevalence of splenomegaly (16/27, 59%), lymphoid proliferation (13/27, 48%) and granulomatous disease (12/27, 44%) in group MB0. Splenomegaly was also frequent in group MB1 (8/19, 42%). In contrast, autoimmunity was observed with similar prevalence in all three groups. Moreover, by analyzing B cell phenotype, immunoglobulin transcript expression, and somatic mutations, we propose different putative mechanisms responsible for impaired B cell activation and memory differentiation in this syndrome.

Adult↗

Nanometer resolution and coherent optical dipole coupling of two individual molecules.

By performing cryogenic laser spectroscopy under a scanning probe electrode that induces a local electric field, we have resolved two individual fluorescent molecules separated by 12 nanometers in an organic crystal. The two molecules undergo a strong coherent dipole-dipole coupling that produces entangled sub- and superradiant states. Under intense laser illumination, both molecules are excited via a two-photon transition, and the fluorescence from this doubly excited system displays photon bunching. Our experimental scheme can be used to optically resolve molecules at the nanometer scale and to manipulate the degree of entanglement among them.

Journal Article↗

Biopolymeric colloidal carriers for encapsulation or controlled release applications.

Biopolymers represent an interesting alternative to synthetic polymers in order to be used as structured carriers for controlled release and encapsulation applications. In particular, the ability of these carriers to entrap both hydrophilic and hydrophobic drugs may be very promising for many applications. In addition, the absence of chemical compounds and organic solvents used to produce biopolymeric matrices could be very interesting for some industrial applications. Simple or complex coacervation methods involving proteins or protein and polysaccharide mixtures were used to create new matrices dedicated to controlled release applications. Controlled release experiments with model compounds were conducted in order to evaluate the performance of such matrices. An alternative and promising research field deals with particles obtained from hydrogel systems. Totally transparent solid matrices resulting from the dehydration of new protein gels were formed and swelling capacities of these matrices were studied.

Biopolymers↗

Granulocyte colony-stimulating factor in induction treatment of children with non-Hodgkin's lymphoma: a randomized study of the French Society of Pediatric Oncology.

PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF; lenograstim) decreases the incidence of febrile neutropenia after induction courses in treatment of childhood non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients were randomized to receive (G-CSF+) or not receive (G-CSF-) prophylactic G-CSF, 5 microg/kg/d, from day 7 until an absolute neutrophil count > or = 500/microL was sustained over 48 hours, after two consecutive induction courses of cyclophosphamide 1.5 or 3 g/m(2), vincristine 2 mg/m(2), prednisone 60 mg/m(2)/d x 5, doxorubicin 60 mg/m(2), high-dose methotrexate 3 or 8 g/m(2), and intrathecal injections (COPAD[M]) on protocols LMB89, LMT89, and HM91 of the French Society of Pediatric Oncology. RESULTS: One hundred forty-eight patients were assessable, 75 G-CSF+ and 73 G-CSF-. Although duration of neutropenia less than 500/microL was 3 days shorter in G-CSF+ patients (P = 10(-4)), incidence of febrile neutropenia (89% v. 93% in the first course, 88% v. 88% in the second course), durations of hospitalization and antimicrobial therapy, percentages of infections, mucositis, and transfusions were not significantly different. Although the percentage of G-CSF+ patients commencing the following course on day 21 was significantly higher (84% v 68% after the first and 57% v. 38% after the second course; P <.05), the median delay between the two courses was only 1 day less in G-CSF+ patients (median delay after first COPAD(M), 19 v. 20 days, P =.01; after second, 21 v. 22 days, P = not significant). Remission and survival rates were similar in both arms. CONCLUSION: This study demonstrates that G-CSF did not decrease treatment-related morbidity, nor increase the dose-intensity in children undergoing COPAD(M) induction chemotherapy for NHL.

Antineoplastic Combined Chemotherapy Protocols↗

[Comparison between dissociated and associated heterophoria].

BACKGROUND: Since Ogle (1949) dissociated heterophoria is distinguished from associated heterophoria. Dissociated heterophoria is defined as a deviation from the orthovergence position that occurs when no fusional contours are provided. Associated heterophoria is a deviation that occurs under prism correction of fixation disparity, i.e. under a viewing condition in which fusional contours are absent only in the centre of the visual field. Both dissociated and associated heterophoria have been used as indications for prismatic correction. It has been controversially discussed to what extent dissociated and associated heterophoria are comparable. METHODS: A total of 43 subjects were investigated using the white Maddox rod test for horizontal dissociated heterophoria and the cross test of Hans-Joachim Haase (a test similar to the fixation disparity test described by Ogle 1949) for horizontal associated heterophoria. In both tests subjects were asked to continually correct any deviation using Herschel prisms. Readings were taken after 1 min. RESULTS: The correlation between the results obtained with the white Maddox rod test and the cross test was r = 0.89 (p < 0.0001) and the slope of the regression line was 0.92 (95% confidence interval from 0.77 to 1.07). One subject was unable to reach a match in the cross test because she had an "obligate" fixation disparity due to a staphyloma posticum. CONCLUSIONS: Our study revealed a high correlation between dissociated and associated heterophoria. This result appears plausible since the feedback loop for fusion is disconnected in both cases, although in a different manner: When dissociated heterophoria is measured, fusionable contours are absent. When associated heterophoria is measured, any disparity of peripheral contours that could serve as an error signal is nullified by instantaneous prism correction. The high concordance of dissociated and associated heterophoria suggests that both measures are of equal value as an indication for prismatic spectacle correction. In rare cases of an "obligate" fixation disparity, however, associated heterophoria cannot be determined so that dissociated heterophoria remains as the only indication.

Adult↗

Dissimilar atrial rhythms: coexistence of reentrant atrial tachycardia, atrioventricular nodal reentrant tachycardia and interatrial conduction block.

We report a patient in whom mapping of the right atrium with multipolar catheters and electroanatomic mapping revealed the presence of three dissimilar rhythms: a reentrant atrial tachycardia in the antero-lateral wall of the right atrium and an atrioventricular nodal reentrant tachycardia (AVNRT) isolated from each other and a conduction disturbance at the interatrial septum resulting in a rate-related interatrial block and a slow left atrial rhythm. The AVNRT was stopped with intravenous adenosine (6 mg) and induced repeatedly by atrial extrastimuli associated with a critical atrioventricular delay and dual atrioventricular nodal pathways. Electroanatomic mapping disclosed extensive fibrosis isolating viable myocardium of the antero-lateral wall from the rest of the right atrium. The viable myocardium in the antero-lateral wall was activated by a reentrant rhythm circulating around an islet of fibrosis located in the middle of the viable tissue. The AVNRT was ablated by a standard approach and the reentrant atrial tachycardia by producing a linear lesion bridging the central islet of fibrosis with the anterior tricuspid annulus. This case highlights the complicated nature of some dissimilar atrial rhythms and the power of electroanatomic mapping tools to reveal the exact mechanism and guide radiofrequency ablation.

Adrenergic beta-Antagonists↗

Aiolos and Ikaros: regulators of lymphocyte development, homeostasis and lymphoproliferation.

Aiolos and Ikaros encode hemopoietic-specific zinc finger transcription factors that are important regulators of lymphocyte differentiation. Aiolos and Ikaros play a critical role in regulating B and T cell development. Gene targeting studies in mice have shown that inactivation of Ikaros family proteins leads to a complete absence of T, B, NK and dendritic cells, whereas a reduction of Ikaros activity induce hyperproliferation and lymphomas. Aiolos knock-out mice have quantitatively normal lymphoid cells but have chronically activated B cells producing autoantibodies and develop lymphomas with increased frequency. These proteins are involved in the control of gene expression and, associated to nuclear complexes, participate in nucleosome remodeling. This protein family governs cell fate decisions and regulates homeostasis through complex isoforms expression and dimerization. Changes in this regulatory network may reflect differentiation and proliferation adjustments made in lymphoid progenitors and precursors. The direct involvement of aberrant Ikaros protein expression in human hematological oncogenesis, although suggested by several studies, remains to be settled at the genomic level. These points will be discussed in the present review.

Amino Acid Sequence↗

Grapevine fanleaf virus replication occurs on endoplasmic reticulum-derived membranes.

Infection by Grapevine fanleaf nepovirus (GFLV), a bipartite RNA virus of positive polarity belonging to the Comoviridae family, causes extensive cytopathic modifications of the host endomembrane system that eventually culminate in the formation of a perinuclear "viral compartment." We identified by immunoconfocal microscopy this compartment as the site of virus replication since it contained the RNA1-encoded proteins necessary for replication, newly synthesized viral RNA, and double-stranded replicative forms. In addition, by using transgenic T-BY2 protoplasts expressing green fluorescent protein in the endoplasmic reticulum (ER) or in the Golgi apparatus (GA), we could directly show that GFLV replication induced a depletion of the cortical ER, together with a condensation and redistribution of ER-derived membranes, to generate the viral compartment. Brefeldin A, a drug known to inhibit vesicle trafficking between the GA and the ER, was found to inhibit GFLV replication. Cerulenin, a drug inhibiting de novo synthesis of phospholipids, also inhibited GFLV replication. These observations imply that GFLV replication depends both on ER-derived membrane recruitment and on de novo lipid synthesis. In contrast to proteins involved in viral replication, the 2B movement protein and, to a lesser extent, the 2C coat protein were not confined to the viral compartment but were transported toward the cell periphery, a finding consistent with their role in cell-to-cell movement of virus particles.

Cell Line↗

Involvement of RNA2-encoded proteins in the specific transmission of Grapevine fanleaf virus by its nematode vector Xiphinema index.

The nepovirus Grapevine fanleaf virus (GFLV) is specifically transmitted by the nematode Xiphinema index. To identify the RNA2-encoded proteins involved in X. index-mediated spread of GFLV, chimeric RNA2 constructs were engineered by replacing the 2A, 2B(MP), and/or 2C(CP) sequences of GFLV with their counterparts in Arabis mosaic virus (ArMV), a closely related nepovirus which is transmitted by Xiphinema diversicaudatum but not by X. index. Among the recombinant viruses obtained from transcripts of GFLV RNA1 and chimeric RNA2, only those which contained the 2C(CP) gene (504 aa) and 2B(MP) contiguous 9 C-terminal residues of GFLV were transmitted by X. index as efficiently as natural and synthetic wild-type GFLV, regardless of the origin of the 2A and 2B(MP) genes. As expected, ArMV was not transmitted probably because it is not retained by X. index. These results indicate that the determinants responsible for the specific spread of GFLV by X. index are located within the 513 C-terminal residues of the polyprotein encoded by RNA2.

Animals↗

Prognostic factors in localized Ewing's tumours and peripheral neuroectodermal tumours: the third study of the French Society of Paediatric Oncology (EW88 study).

PURPOSE: (1) To improve survival rates in patients with Ewing's sarcoma (ES) or peripheral neuroectodermal tumours (PNET) using semi-continuous chemotherapy and aiming to perform surgery in all; (2) To identify early prognostic factors to tailor therapy for future studies. PATIENTS AND METHODS: One hundred and forty-one patients were entered onto the trial between January 1988 and December 1991. Induction therapy consisted of five courses of Cytoxan, 150 mg/m(2) x 7 days, followed by Doxorubicin, 35 mg/m(2) i.v on day 8 given at short intervals. Surgery was recommended whenever possible. The delivery of radiation therapy was based on the quality of resection and the histological response to CT. Maintenance chemotherapy consisted of vincristine + actinomycin and cytoxan + doxorubicin. The total duration of therapy was 10 months. RESULTS: After a median follow-up of 8.5 years, the projected overall survival at 5 years was 66% and disease-free survival (DFS) was 58%. In patients treated by surgery, only the histological response to CT had an influence on survival: 75% DFS for patients with a good histological response (less than 5% of cells), 48% for intermediate responders and only 20% for poor responders (> or = 30% of cells), P < 0.0001. The initial tumor volume by itself had no influence on DFS in these patients. In contrast, the tumour volume had a strong impact on DFS in patients treated by radiation therapy alone. Age had no impact on outcome. CONCLUSION: Therapeutic trials for localized Ewing's sarcoma should be based on the histological response to chemotherapy or on the tumour volume according to the modality used for local therapy.

Adolescent↗

[Problems of electrocardiographic diagnosis of occlusion of the left circumflex coronary artery].

BACKGROUND AND OBJECTIVE: The electrocardiographic diagnosis of posterior myocardial infarction is difficult. It was the objective of the present study to evaluate ST-segment changes in angiographically documented occlusion of the left RCX in the setting of an acute myocardial infarction and to analyse the value of the posterior chest leads V(7)-V(9). PATIENTS AND METHODS: Data of 120 patients (88 males, on average 61+/-13 years old) with an acute myocardial infarction and angiographically proven occlusion of the left circumflex artery were included in the study. Mean time of pain onset to ECG recording was 5.5 +/- 2.8 hours. The ECGs were analysed for ST-segment changes of > or = 1 mm in two contiguous leads in surface leads I-aVF, > or = 2 mm in the precordial leads V(1)-V(6), and > or = 1 mm in right precordial (V(3)R-V(6)R) and posterior (V(7)-V(9)) leads. These additional leads were recorded only in a subgroup of 36 patients. Maximal creatine kinase activity was determined as a measure of infarct size. RESULTS: Standard leads I-V(6) showed ST-segment elevation in 55 of 120 patients (46 %). In the subgroup of patients with extended chest leads 61 % (11/36) had significant ST-segment elevation, whereas isolated ST-segment elevation in the posterior leads occurred in 8 % (3/36). ST-segment depression in the standard leads was observed in 73 of the 120 patients (54 %), and isolated ST-segment depression was seen in 31 patients (26 %). No significant ST-segment changes in the standard leads were found in 34 patients (28 %). Maximum CK values were not significantly different among the three groups (1107 +/- 815 IU/l vs 953 +/- 651 IU/l vs 816 +/- 553 IU/l; (P = 0.447). CONCLUSION: These findings confirm that the sensitivity of the standard ECG leads is less than 50 % in angiographically documented occlusion of the left RCX. The extended posterior chest leads (V(7)-V(9)) improve sensitivity only marginally (by 8 %). Isolated ST-segment depression or no significant ST-segment depression in the standard leads was observed in 26 % and 28 % respectively. The infarct size - as measured by maximum CK-values - did not differ among the respective groups.

Aged↗

Forced expression of the Ikaros 6 isoform in human placental blood CD34(+) cells impairs their ability to differentiate toward the B-lymphoid lineage.

Studies in mice suggest that the Ikaros (Ik) gene encodes several isoforms and is a critical regulator of hematolymphoid differentiation. Little is known on the role of Ikaros in human stem cell differentiation. Herein, the biological consequences of the forced expression of Ikaros 6 (Ik6) in human placental blood CD34(+) progenitors are evaluated. Ik6 is one of the isoforms produced from the Ikaros premessenger RNA by alternative splicing and is thought to behave as a dominant negative isoform of the gene product because it lacks the DNA binding domain present in transcriptionally active isoforms. The results demonstrate that human cord blood CD34(+) cells that express high levels of Ik6 as a result of retrovirally mediated gene transfer have a reduced capacity to produce lymphoid B cells in 2 independent assays: (1) in vitro reinitiation of human hematopoiesis during coculture with the MS-5 murine stromal cell line and (2) xenotransplantation in nonobese diabetic-severe combined immunodeficient mice. These results suggest that Ikaros plays an important role in stem cell commitment in humans and that the balance between the different isoforms is a key element of this regulatory system; they support the hypothesis that posttranscriptional events can participate in the control of human hematopoietic differentiation.

Animals↗

The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila.

Dbp5 is the only member of the DExH/D box family of RNA helicases that is directly implicated in the export of messenger RNAs from the nucleus of yeast and vertebrate cells. Dbp5 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore complex (NPC). In an attempt to identify proteins present in a highly enriched NPC fraction, two other helicases were detected: RNA helicase A (RHA) and UAP56. This suggested a role for these proteins in nuclear transport. Contrary to expectation, we show that the Drosophila homolog of Dbp5 is not essential for mRNA export in cultured Schneider cells. In contrast, depletion of HEL, the Drosophila homolog of UAP56, inhibits growth and results in a robust accumulation of polyadenylated RNAs within the nucleus. Consequently, incorporation of [35S]methionine into newly synthesized proteins is inhibited. This inhibition affects the expression of both heat-shock and non-heat-shock mRNAs, as well as intron-containing and intronless mRNAs. In HeLa nuclear extracts, UAP56 preferentially, but not exclusively, associates with spliced mRNAs carrying the exon junction complex (EJC). We conclude that HEL is essential for the export of bulk mRNA in Drosophila. The association of human UAP56 with spliced mRNAs suggests that this protein might provide a functional link between splicing and export.

Active Transport, Cell Nucleus↗