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Biomedical subjects

F Martin

Publications and source records attributed to F Martin.

At least 55 records · Page 3Linked to original sources
PubMed1999

CD21high IgMhigh splenic B cells enriched in the marginal zone: distinct phenotypes and functions.

Collectively, these findings suggest that MZ B cells have unique signaling and subsequent differentiative capabilities that permit them to react much more vigorously than the majority of splenic B cells (FO) in the earliest stages of an in vivo immune response. This is particularly evident with limiting T cell help, low concentration of thymus-independent mitogens or low amounts of particulate blood-borne antigen in the spleen (Fig. 4). They are uniquely situated adjacent to the marginal sinuses and a rich array of antigen trapping macrophages. Because of this location the MZ B cells are ideally positioned for immediate exposure to blood-borne antigens. In contrast, the FO B cells are in juxtaposition to the PALS which may expedite the interactions of FO B cells with T cells and antigen presenting cells. Collectively these properties point to a role for FO B cells in antibody responses to T dependent antigens generated in germinal centers. These responses occur temporally later in immune responses and may be involved principally in the response to protein antigens. [figure: see text].

Animals↗
PubMed1999

Laparoscopic treatment vs open surgery in the solution of major incisional and abdominal wall hernias with mesh.

BACKGROUND: Despite being one of the most exact indications, laparoscopic treatment of eventrations and ventral hernias is barely known among the array of laparoscopic techniques. METHODS: A total of 60 patients were assigned at random over a 3-year period to two homogeneous groups to be operated on for major ventral hernias with mesh. Half of them were operated upon laparoscopically and the rest with open surgery. Early and longer-term complications were analyzed, as were operative time and postoperative hospital stays. RESULTS: The two groups were homogeneous in terms of demographic and clinical characteristics. The group that was operated on laparoscopically presented a lower rate of postoperative and longer-term complications; similarly, surgery time was significantly lower (p < 0.05). Hospitalization time was also significantly lower than in the group undergoing conventional open surgery (p < 0.05). CONCLUSIONS: Laparoscopic treatment of postoperative eventration and primary ventral hernia reduces complications and relapse rates, eliminates reintervention through mesh infection, reduces operative time, and considerably shortens the hospital stay.

Female↗
PubMed1999

High genetic diversity in a population of the ectomycorrhizal basidiomycete laccaria amethystina in a 150-year-old beech forest

The genetic structure of a population of the ectomycorrhizal basidiomycete Laccaria amethystina (Bolt. ex Hooker) Murr. was assessed in a closed 150-year-old beech (Fagus sylvatica L.) forest in the Vosges Mountains in northeastern France. During the autumn of 1994 and 1997, sporophores were collected from three 100-m2 sampling plots located along a 120-m transect crossing the beech stand. The genetic variation of 676 sporophores was initially estimated using heteroduplex analysis of the ribosomal DNA intergenic spacer (IGS1). Ten unique IGS1 heteroduplex/homoduplex patterns were identified, although three types represented most of the sporophores analysed. Each group of IGS1 type was then analysed using random amplified microsatellite analysis (RAMS). RAMS resolved 388 different genotypes amongst the 634 sporophores analysed from the three plots during the autumn of 1994 and 1997. Density as high as 130 genets per 100 m2 was observed during the autumn of 1994. The largest clone covered approximately 1 m2, but most genets covered a few cm2 and produced only one to three sporophores. Only eight genotypes identified in 1994 were found in 1997. Although L. amethystina has the capacity for vegetative persistence, the present study indicates that its populations maintain a genetic structure more consistent with a high frequency of sexual reproduction. This suggests that beech trees could be recolonized by new genotypes each year. Alternatively, this spatial distribution may also arise from erratic fruiting of underground persistent genets. These features (i.e. numerous genets of small size), typical of ruderal species, contrast with studies carried out on other ectomycorrhizal basidiomycetes occurring in mature closed forests.

Journal Article↗
PubMed1999

A loop-mimetic inhibitor of the HCV-NS3 protease derived from a minibody.

We have been interested for some time in establishing a strategy for deriving lead compounds from macromolecule ligands such as minibody variants. A minibody is a minimized antibody variable domain whose two loops are amenable to combinatorial mutagenesis. This approach can be especially useful when dealing with 'difficult' targets. One such target is the NS3 protease of hepatitis C virus (HCV), a human pathogen that is believed to infect about 100 million individuals worldwide and for which an effective therapy is not yet available. Based on known inhibitor specificity (residues P6-P1) of NS3 protease, we screened a number of minibodies from our collection and we were able to identify a competitive inhibitor of this enzyme. We thus validated an aspect of recognition by HCV NS3 protease, namely that an acid anchor is necessary for inhibitor activity. In addition, the characterization of the minibody inhibitor led to the synthesis of a constrained hexapeptide mimicking the bioactive loop of the parent macromolecule. The cyclic peptide is a lead compound prone to rapid optimization through solid phase combinatorial chemistry. We therefore confirmed that the potential of turning a protein ligand into a low molecular weight active compound for lead discovery is achievable and can complement more traditional drug discovery approaches.

Binding Sites↗
PubMed1999

A novel class of ectomycorrhiza-regulated cell wall polypeptides in Pisolithus tinctorius.

Development of the ectomycorrhizal symbiosis leads to the aggregation of fungal hyphae to form the mantle. To identify cell surface proteins involved in this developmental step, changes in the biosynthesis of fungal cell wall proteins were examined in Eucalyptus globulus-Pisolithus tinctorius ectomycorrhizas by two-dimensional polyacrylamide gel electrophoresis. Enhanced synthesis of several immunologically related fungal 31- and 32-kDa polypeptides, so-called symbiosis-regulated acidic polypeptides (SRAPs), was observed. Peptide sequences of SRAP32d were obtained after trypsin digestion. These peptides were found in the predicted sequence of six closely related fungal cDNAs coding for ectomycorrhiza up-regulated transcripts. The PtSRAP32 cDNAs represented about 10% of the differentially expressed cDNAs in ectomycorrhiza and are predicted to encode alanine-rich proteins of 28.2 kDa. There are no sequence homologies between SRAPs and previously identified proteins, but they contain the Arg-Gly-Asp (RGD) motif found in cell-adhesion proteins. SRAPs were observed on the hyphal surface by immunoelectron microscopy. They were also found in the host cell wall when P. tinctorius attached to the root surface. RNA blot analysis showed that the steady-state level of PtSRAP32 transcripts exhibited a drastic up-regulation when fungal hyphae form the mantle. These results suggest that SRAPs may form part of a cell-cell adhesion system needed for aggregation of hyphae in ectomycorrhizas.

Amino Acid Sequence↗
PubMed1999

Structure and dynamics of experimentally introduced and naturally occurring laccaria sp. Discrete genotypes in a douglas fir plantation

Ectomycorrhizal fungi have been introduced in forest nurseries to improve seedling growth. Outplanting of inoculated seedlings to forest plantations raises the questions about inoculant persistence and its effects on indigenous fungal populations. We previously showed (M.-A. Selosse et al. Mol. Ecol. 7:561-573, 1998) that the American strain Laccaria bicolor S238N persisted 10 years after outplanting in a French Douglas fir plantation, without introgression or selfing and without fruiting on uninoculated adjacent plots. In the present study, the relevance of those results to sympatric strains was assessed for another part of the plantation, planted in 1985 with seedlings inoculated with the French strain L. bicolor 81306 or left uninoculated. About 720 Laccaria sp. sporophores, collected from 1994 to 1997, were typed by using randomly amplified polymorphic DNA markers and PCR amplification of the mitochondrial and nuclear ribosomal DNAs. All plots were colonized by small spontaneous discrete genotypes (genets). The inoculant strain 81306 abundantly fruited beneath inoculated trees, with possible introgression in indigenous Laccaria populations but without selfing. In contrast to our previous survey of L. bicolor S238N, L. bicolor 81306 colonized a plot of uninoculated trees. Meiotic segregation analysis verified that the invading genet was strain 81306 (P < 0.00058), implying a vegetative growth of 1.1 m. year-1. This plot was also invaded in 1998 by strain S238N used to inoculate other trees of the plantation. Five other uninoculated plots were free of these inoculant strains. The fate of inoculant strains thus depends less on their geographic origin than on unknown local factors.

Journal Article↗
PubMed1999

Retrovirus targeting by tropism restriction to melanoma cells.

Targeted vectors will be necessary for many gene therapy applications. To target retroviruses to melanomas, we fused a single-chain variable fragment antibody (scFv) directed against the surface glycoprotein high-molecular-weight melanoma-associated antigen (HMW-MAA) to the amphotropic murine leukemia virus envelope. A proline-rich hinge and matrix metalloprotease (MMP) cleavage site linked the two proteins. The modified viruses bound only to HMW-MAA-expressing cells, as inclusion of the proline-rich hinge prevented viral binding to the amphotropic viral receptor. Following attachment to HMW-MAA, MMP cleavage of the envelope at the melanoma cell surface removed the scFv and proline-rich hinge, allowing infection. Complexing of targeted retroviruses with 2, 3-dioleoyloxy-N-[2(spermine-carboxamido)ethyl]N, N-dimethyl-1-propanaminium trifluoroacetate-dioleoyl phosphatidylethanolamine liposomes greatly increased their efficiency without affecting their target cell specificity. In a cell mixture, 40% of HMW-MAA-positive cells but less than 0.01% of HMW-MAA-negative cells were infected. This approach can therefore produce efficient, targeted retroviruses suitable for in vivo gene delivery and should allow specific gene delivery to many human cell types by inclusion of different scFv and protease combinations.

Antibodies, Neoplasm↗
PubMed1999

[Dysphagia due to tracheotomy].

FUNDAMENTALS: Dysphagia is a common appearance after tracheostomy especially in patients with neurologic diseases of the following reasons: 1. fixation of trachea and larynx to the scin leads to lack of laryngeal elevation in a forward and upward direction, 2. pressure in the upper esophagus may be increased following high cuff pressure, 3. reduction of hypopharyngeal and laryngeal sensitivity and alteration of the coughing mechanism, 4. loss of olfactorial and gustatorial stimulation of the swallowing process. CONCLUSION: Consequently noninvasive ventilation modes are recommended alternatively in patients with respiratory insufficiency.

Deglutition Disorders↗
PubMed1999

[Role of surgery in treatment of hyperthyroidism].

Hyperthyroidism is treated with antithyroid drugs, radioactive iodine or surgery. The aim of surgery is to obtain long-lasting euthyroidism with a minimal risk of recurrence, secondary hypothyroidism, and complications involving the recurrent nerve or the parathyroids. Depending on the etiology, total or partial resection is indicated in light of these objectives. According to the literature, surgery is not used as first intention treatment for Grave's disease, its role and indications remaining a question of debate. However, surgery is the treatment of choice for toxic nodules, current consensus favoring extracapsular total lobectomy. For multinodular toxic goiter, three are several surgical indications: failure of medical treatment, relapse after drug withdrawal, specific clinical or socioeconomic situations requiring rapid efficacy. Total lobectomy associated with subtotal contralateral hemithyroidectomy appears to be the most appropriate procedure. Surgery may also be indicated for treatment of pregnancy-, diabetes-, or amiodarone-induced hyperthyroidism.

Female↗
PubMed1998

Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins [see comment].

The mitochondrial outer membrane contains machinery for the import of preproteins encoded by nuclear genes. Eight different Tom (translocase of outer membrane) proteins have been identified that function as receptors and/or are related to a hypothetical general import pore. Many mitochondrial membrane channel activities have been described, including one related to Tim23 of the inner-membrane protein-import system; however, the pore-forming subunit(s) of the Tom machinery have not been identified until now. Here we describe the expression and functional reconstitution of Tom40, an integral membrane protein with mainly beta-sheet structure. Tom40 forms a cation-selective high-conductance channel that specifically binds to and transports mitochondrial-targeting sequences added to the cis side of the membrane. We conclude that Tom40 is the pore-forming subunit of the mitochondrial general import pore and that it constitutes a hydrophilic, approximately 22 A wide channel for the import of preproteins.

Amino Acid Sequence↗
PubMed1998

Design of selective eglin inhibitors of HCV NS3 proteinase.

Hepatitis C virus (HCV) infection is a major health problem that leads to cirrhosis and hepatocellular carcinoma in a substantial number of infected individuals, estimated to be 100-200 million worldwide. Unfortunately, immunotherapy or other effective treatments for HCV infection are not yet available, and interferon administration has limited efficacy. Different approaches to HCV therapy are being explored, and these include inhibition of the viral proteinase, helicase, and RNA-dependent RNA polymerase and development of a vaccine. Here we present the design of selective inhibitors with nanomolar potencies of HCV NS3 proteinase based on eglin c. These eglin c mutants were generated by reshaping the inhibitor active site-binding loop, and the results emphasize the role played by residues P5-P4' in enzyme recognition. In addition, alanine scanning experiments provide evidence that the N terminus of eglin c also contributes to NS3 binding. These eglin inhibitors offer a unique tool for accurately assessing the requirements for effective inhibition of the enzymatic activity of NS3 and at the same time can be considered lead compounds for the identification of other NS3 inhibitors in targeted design efforts.

Animals↗
PubMed1998

Separation of structural and dynamic functions of the mitochondrial translocase: Tim44 is crucial for the inner membrane import sites in translocation of tightly folded domains, but not of loosely folded preproteins.

The essential gene TIM44 encodes a subunit of the inner mitochondrial membrane preprotein translocase that forms a complex with the matrix heat-shock protein Hsp70. The specific role of Tim44 in protein import has not yet been defined because of the lack of means to block its function. Here we report on a Saccharomyces cerevisiae mutant allele of TIM44 that allows selective and efficient inactivation of Tim44 in organello. Surprisingly, the mutant mitochondria are still able to import preproteins. The import rate is only reduced by approximately 30% compared with wild-type as long as the preproteins do not carry stably folded domains. Moreover, the number of import sites is not reduced. However, the mutant mitochondria are strongly impaired in pulling folded domains of preproteins close to the outer membrane and in promoting their unfolding. Our results demonstrate that Tim44 is not an essential structural component of the import channel, but is crucial for import of folded domains. We suggest that the concerted action of Tim44 and mtHsp70 drives unfolding of preproteins and accelerates translocation of loosely folded preproteins. While mtHsp70 is essential for import of both tightly and loosly folded preproteins, Tim44 plays a more specialized role in translocation of tightly folded domains.

Adenosine Triphosphatases↗
PubMed1998

Bcl-2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors.

Tumor cell clones from a rat colon carcinoma differ in their tumorigenicity and immunogenicity. The PRO clones give rise to progressive tumors, whereas the REG clones yield tumors that regress in a few weeks through a specific immune response. REG cells were more sensitive than PRO cells to apoptosis triggered by serum withdrawal in vitro. Furthermore, a fraction of REG cells, but no PRO cells, underwent apoptosis in the hours following injection into syngeneic rats. To further analyze the role of apoptosis, we overexpressed the antiapoptotic protein Bcl-2 in REG cells. Unlike parental or fake-transfected REG cells, Bcl-2-overexpressing REG cells resisted serum withdrawal-induced apoptosis, did not undergo apoptosis at 48 h postinjection into naive syngeneic rats, and gave rise to progressive, metastatic, and lethal tumors. Interestingly, REG-bcl2 cells were rejected by syngeneic hosts that had been preimmunized by an injection of parental REG cells, indicating that Bcl-2 overexpression did not alter tumor cell sensitivity to the effector cells of the immune response. Taken together, these observations indicate that tumor cell apoptosis may contribute to immunogenicity.

Adenocarcinoma↗