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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 37 records · Page 2Linked to original sources
PubMed2006

The infective larva of Litomosoides yutajensis Guerrero et al., 2003 (Nematoda: Onchocercidae), a Wolbachia-free filaria from bat.

The infective larva of Litomosoides yutajensis Guerrero et al., 2003, a parasite of the bat Pteronotus pamellii, is described; it is distinct from congeneric infective larvae by the absence of caudal lappets. The life cycles of five other species of Litomosoides are known; three are parasites of rodents, one of a marsupial and one of a bat. As with these species, the experimental vector of L. yutoajensis used was the macronyssid mite Ornithonyssus bacoti. In nature, the main vectors are probably other macronyssids but transmission by O. bacoti, with its large host-range, could account for the characteristic host-switchings in the evolution of Litomosoides. Unlike the murine model L. sigmodontis Chandler, 1931, L. yutajensis is devoid of the endosymbiontic bacteria Wolbachia and may be of great interest.

Animals↗
PubMed2006

Oxygen uptake kinetics during heavy submaximal exercise: Effect of sickle cell trait with or without alpha-thalassemia.

Sickle cell trait (SCT) is a genetic disease affecting the synthesis of normal hemoglobin (Hb) marked by the heterozygous presence of HbA and HbS. It is thought that exercise tolerance and aerobic capacity could be limited in SCT carriers, but that the co-existence of alpha-thalassemia with SCT (SCTAT) could improve exercise response. To examine these issues, we compared the characteristics of VO2 kinetics during a constant heavy exercise among athletes carrying either the SCT (n = 6), the SCTAT (n = 9), or the normal Hb (control group; n = 10). After determination of maximal power output (Ppeak), all subjects underwent a constant heavy cycling exercise lasting 9 min at approximately 70 % Ppeak. Pulmonary VO2 and cardio-respiratory parameters were measured breath-by-breath and the VO2 response was modelled using non-linear regression techniques. The time constant of the VO2 primary component and oxygen deficit were not significantly different among the three groups. The VO2 slow component was 28 % and 33 % higher (p < 0.05) in SCT and SCTAT than in the control groups, respectively. Altogether, athletes with the SCT and the SCTAT had higher heart rate at the beginning (+ 5.2 %) and the end (+ 7.4 %) of the slow component compared to the control group (p < 0.05). These results suggest that SCT and SCTAT subjects are not limited during the first exercise minutes, but are prone to exercise intolerance and to lower aerobic capacity thereafter, due to a higher VO2 slow component, and that alpha-thalassemia does not improve exercise response. The finding of a higher slow component in SCT and SCTAT athletes was possibly due to the loss of O2 availability to muscles, additional fiber recruitment and/or higher cardiac load with time.

Adult↗
PubMed2006

Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice.

BACKGROUND: The surfactant protein SP-D has been reported to reduce bronchial hyper-responsiveness, blood eosinophilia, and T-helper type 2 cytokines in models of allergic asthma. However, little is known about the functional effect of SP-D on the early airway response upon allergen inhalation, which is an important feature of this disease. OBJECTIVE: We investigated whether SP-D is able to reduce the immediate allergen-induced mediator release and the early bronchial obstruction in addition to its effects on airway inflammation and bronchial hyperresponsiveness in an Aspergillus fumigatus mouse asthma model. METHODS: A. fumigatus-sensitized mice were treated with a recombinant fragment of human SP-D or placebo. Lung functions were measured in orotracheally intubated, spontaneously breathing animals using body plethysmography. In addition, passively sensitized precision-cut lung slices (PCLS) were used to determine the effect of SP-D on allergen-induced histamine release. RESULTS: SP-D inhibited the allergen-induced early airway response and reduced airway hyperresponsiveness compared with placebo. Eosinophilia in bronchoalveolar lavage and lung tissue was reduced after SP-D treatment, possibly by reducing eotaxin levels in the lung. Furthermore, SP-D treatment reduced the allergen-induced histamine release from PCLS. CONCLUSION: These data suggest that SP-D not only reduces allergen-induced eosinophilic inflammation and airway hyperresponsiveness but also provides protection against early airway obstruction by inhibition of early mediator release.

Administration, Inhalation↗
PubMed2006

Decreased expression of VEGF-A in rat experimental autoimmune encephalomyelitis and in cerebrospinal fluid mononuclear cells from patients with multiple sclerosis.

Vascular endothelial growth factor A (VEGF-A) stimulates angiogenesis, but is also pro-inflammatory and plays an important role in the development of neurological disease, where it can have both attenuating and exacerbating effects. VEGF-B, a related molecule, is highly expressed in the central nervous system and seems to be important in neurological injury. A few studies have indicated that VEGF-A may play a role in the pathogenesis of multiple sclerosis (MS), but the role of VEGF-B has not been studied. We have studied the expression of VEGF-A, -B and their receptors by mRNA in situ hybridization, immunohistochemistry and real-time PCR in spinal cord from LEW rats with experimental autoimmune encephalomyelitis (EAE) and in cerebrospinal fluid (CSF) and blood samples from MS patients. Whereas VEGF-A is downregulated in glia in EAE, the infiltrating inflammatory cells are positive for VEGF-A. Expression of VEGF-B and the VEGF receptors is unaltered. In addition, the levels of VEGF-A mRNA in mononuclear cells [corrected] in CSF are lower in MS patients compared with controls. These results demonstrate a complex regulation of VEGF-A during neuroinflammation and suggest that VEGF-B is not involved in the pathogenesis of MS.

Adolescent↗
PubMed2006

The interaction of von Willebrand factor-A1 domain with collagen: mutation G1324S (type 2M von Willebrand disease) impairs the conformational change in A1 domain induced by collagen.

BACKGROUND: It is established that the A3 domain in von Willebrand factor (VWF) contains the major collagen-binding site. However, there are conflicting reports describing the capacity of the A1 domain to interact with collagen types I and III. METHODS: In this study, we have used recombinant VWF-A1 polypeptides, as well as conformation-specific monoclonal antibodies (mAb), to analyze the A1-collagen interaction. RESULTS: The A1 domain bound to collagen with K(d) approximately 8.0 nm and this binding was blocked by the mAb 6G1, which blocks the interaction between ristocetin and VWF. In addition, collagen-bound A1 protein was able to support flow-dependent adhesion of platelets, demonstrating that the binding sites for collagen and glycoprotein (GP)Ib are different. Analysis with two conformation-specific mAb demonstrated that the structure of the A1 domain changed as a result of the binding to collagen. In contrast, the antibodies failed to detect conformational change in the G1324S mutant (type 2M von Willebrand disease). Thus, direct binding to collagen induces a change in the structural conformation within the VWF-A1 domain, and the G1324S substitution prevents this conformational change. CONCLUSION: This study has shown that the isolated A1 domain can simultaneously bind to collagen and platelet GPIb, supporting platelet adhesion under high-flow conditions. In addition, this study has used mAb to demonstrate that the binding of the isolated A1 domain or full-length VWF to collagen is accompanied by a conformational change in A1 domain.

Amino Acid Substitution↗
PubMed2005

Identification of isomeric 4-nonylphenol structures by gas chromatography-tandem mass spectrometry combined with cluster analysis.

The endocrine-disrupting effect of 4-nonylphenols (NP) formed from industrial detergents such as nonylphenol polyethoxylates is well known today. The technical mixture contains a great variety of 4-iso-nonylphenol isomers having different endocrine-disrupting activities. Currently used gas chromatography-mass spectrometry (GC-MS) protocols allow the detection of about 20 peaks, mostly co-eluting isomers. In the present study, Product Ion mass spectrometry obtained by ion trap technology enhanced the selectivity in NP detection resulting in improved gas chromatographic resolution as well as structure assignment of the isomers. The structure proposals of 4-nonylphenol isomers given were derived from GC-MS-MS data processed by multivariate statistics. The cluster analysis allowed the classification of NP due to common structural features that were reflected in the mass spectra. The fragmentation pathways of three reference NP isomers, 4-(1-ethyl-1,4-dimethylpentyl)phenol (NP1), 4-(1,1,5-trimethylhexyl)phenol (NP2) and 4-(1-ethyl-1,3-dimethylpentyl)phenol (NP3), were investigated in more detail. They served as model compounds to aid the interpretation of spectra from unknown NP isomers. Structures of two groups of isomers, characterized by alpha-ethyl as well as alpha-propyl substituents, could be proposed.

Cluster Analysis↗
PubMed2005

Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome.

Li-Fraumeni syndrome, resulting from p53 (TP53) germline mutations, represents one of the most devastating genetic predispositions to cancer. Recently, the MDM2 SNP309 (T-->G variation) was shown to be associated with accelerated tumour formation in p53 mutation carriers. The impact of the common p53 codon 72 polymorphism on cancer risk remains controversial. We therefore investigated the effect of these two polymorphisms in 61 French carriers of the p53 germline mutation. The mean age of tumour onset in MDMD2 SNP309 G allele carriers (19.6 years) was significantly different from that observed in patients homozygous for the T allele (29.9 years, p<0.05). For the p53 codon 72 polymorphism, the mean age of tumour onset in Arg allele carriers (21.8 years) was also different from that of Pro/Pro patients (34.4 years, p<0.05). We observed a cumulative effect of both polymorphisms because the mean ages of tumour onset in carriers of the MDM2G and p53Arg alleles (16.9 years) and those with the MDM2T/T and p53Pro/Pro genotypes (43 years) were clearly different (p<0.02). Therefore, our results confirm the impact of the MDM2 SNP309 G allele on the age of tumour onset in germline p53 mutation carriers, and suggest that this effect may be amplified by the p53 72Arg allele. Polymorphisms affecting p53 degradation therefore represent one of the rare examples of modifier genetic factors identified to date in mendelian predispositions to cancer.

Adolescent↗
PubMed2005

[A case of type A botulism].

The neurotoxin produced by Clostridium botulinum, is responsible for botulism. The clinical signs are digestive disorders, pupillar alterations, and peripheral muscular weakness. The failure of thoracic muscles is responsible for the severity of botulism. We describe a case of a 74 year old woman who presented a severe form of botulism, requiring a prolonged intensive care unit stay.

Aged↗
PubMed2005

Predictive perioperative factors for developing severe sepsis after major surgery.

BACKGROUND: Early identification of high-risk patients undergoing major surgery can result in an aggressive management affecting the outcome. METHODS: We designed a prospective cohort study of 93 adult patients undergoing major oncological surgery to identify the predictive risk factors for developing postoperative severe sepsis. RESULTS: Nineteen of 93 patients developed a severe sepsis after surgery; seven of the septic patients died in intensive care unit. Multivariate analysis discriminated preoperative and postoperative (first and second day after surgery) predictive risk factors. The postoperative severe sepsis was independently associated with preoperative factors like male gender (OR 4.7, 95% CI between 1.5 and 15.5, P<0.01) and Charlson co-morbidity index (OR 1.3, 95% CI between 1.07 and 1.6, P<0.01). After the surgery, the presence of systemic inflammatory response syndrome (OR 4.0, 95% CI between 1.02 and 15.7, P<0.05) and a logistic organ dysfunction score on day 2 (OR 3.3, 95% CI between 1.9 and 5.7, P<0.001) were found as independent predictive factors. CONCLUSION: We have shown that some of the markers that can be easily collected in the preoperative or postoperative visits can be used to screen the patients at high risk for developing severe sepsis after major surgery.

Adult↗
PubMed2005

Cholesterol-bile salt vesicles as potential delivery vehicles for drug and vaccine delivery.

The aim of this study was to further investigate the interactions between cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium deoxycholate) and their suitability for drug and vaccine delivery. Insulin was used as a model protein to assess the ability of CH:BS vesicles to entrap a therapeutically relevant macromolecule. The association of protein (FITC-insulin) with the CH:BS structure was confirmed with fluorescence microscopy, and the overall morphology of the vesicles was examined with atomic force microscopy (AFM). Results demonstrate that the nature of the vesicles formed between CH and BS is dependent not only on the concentration of BS but also on the increasing CH concentration leading to CH crystal formation.

Bile Acids and Salts↗
PubMed2005

Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update.

BACKGROUND: Autosomal dominant early onset Alzheimer's disease (ADEOAD) is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes have been identified. OBJECTIVE: To further clarify the respective contribution of these genes to ADEOAD. METHODS: 31 novel families were investigated. They were ascertained using stringent criteria (the occurrence of probable or definite cases of Alzheimer's disease with onset before 60 years of age in three generations). All cases fulfilled the NINCDS-ADRDA criteria for probable or definite Alzheimer's disease. The entire coding regions of PSEN1 and PSEN2 genes and exons 16 and 17 of APP gene were sequenced from genomic DNA RESULTS: PSEN1 mutations, including eight previously unreported mutations, were detected in 24 of the 31 families, and APP mutations were found in five families. In this sample, the mean ages of disease onset in PSEN1 and APP mutation carriers were 41.7 and 51.2 years, respectively. CONCLUSIONS: Combining these data with previously published data, yielding 65 ADEOAD families, 66% of the cases were attributable to PSEN1 mutations and 16% to APP mutations, while 18% remained unexplained.

Adult↗
PubMed2005

A phase II trial of raltitrexed (Tomudex) in advanced pancreatic and biliary carcinoma.

PURPOSE: To evaluate the impact of raltitrexed (Tomudex) on the quality of life in a multicenter, phase II study in advanced pancreatic and biliary carcinomas. PATIENTS AND METHODS: Forty-six patients with advanced, histologically proven pancreatic (n = 37, 80.4%) or biliary (n = 9, 19.6%) carcinoma received 3 mg/m2 raltitrexed intravenously once every 3 weeks. For the quality of life assessments, EORTC QLQ-C30 was used, and the evaluation of the clinical benefit was performed according to the 4 criteria of the clinical benefit response. All patients were assessed for safety, and 41 patients were evaluable for objective response. RESULTS: Patients (63% male/37% female) had a mean age of 61.2 years, 71.7% had a PS of 0-1, 78.3% had metastatic disease, and 63% had at least 2 tumoral sites. A total of 176 cycles were administered with a mean of 4 cycles per patient (range 1-12). Three out of 43 patients evaluable for EORTC QLQ-C30 (7.0%; CI(95%) 1.4-19.0%) had a quality of life improvement. Thirty-two patients fulfilled the 4 criteria required to evaluate the clinical benefit response; 5 were responders (15.6%; CI(95%) 5.3-32.8%); 1 patient was a good responder based on both the EORTC questionnaire and the clinical benefit response. Forty-one patients were assessable for response, 3 responded to treatment (response rate: 6.5 %; CI(95%) 1.3-17.9%). Median survival was 4.6 months (CI(95%) 2.9-8.2 months), the 1-year survival rate was 21.8%. The most common grade 3-4 toxicities were neutropenia (8%), leukopenia (8%), thrombopenia (6%), anemia (6%), liver enzyme elevations (11%), asthenia (9%), vomiting (9%), abdominal pain (7%), and phlebitis (6%). One treatment-related death occurred (neutropenic sepsis). CONCLUSION: Raltitrexed appeared to be generally well tolerated and showed a clinical benefit response and/or quality of life improvement in a limited number of patients.

Antimetabolites, Antineoplastic↗
PubMed2005

Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801).

BACKGROUND: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy after resection for gastric cancer in a randomized controlled trial. PATIENTS AND METHODS: After curative resection, stage II-III-IVM0 gastric cancer patients were randomly assigned to postoperative chemotherapy or surgery alone. 5-Fluorouracil (5-FU) 800 mg/m(2) daily (5-day continuous infusion) was initiated before day 14 after resection. One month later, four 5-day cycles of 5-FU (1 g/m(2) per day) plus cisplatin (100 mg/m(2) on day 2) were administered every 4 weeks. RESULTS: The study was closed prematurely after enrollment of 260 patients (79.7% N+), owing to poor accrual. At 97.8 months median follow-up, 5- and 7-year overall survival were 41.9% and 34.9% in the control group versus 46.6% and 44.6% in the chemotherapy group (P=0.22). Cox model hazard ratios were 0.74 [95% confidence interval (CI) 0.54-1.02; P=0.063] for death and 0.70 (95% CI 0.51-0.97; P=0.032) for recurrence. An invaded/removed lymph nodes ratio >0.3 was the main independent poor prognostic factor identified by multivariate analysis (P=0.0001). Because of toxicity, only 48.8% of patients received more than 80% of the planned dose. CONCLUSION: There was no statistically significant survival benefit with this toxic cisplatin-based adjuvant chemotherapy, but a risk reduction in recurrence was observed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer.

We report the association of CDH1/E-cadherin mutations with cleft lip, with or without cleft palate (CLP), in two families with hereditary diffuse gastric cancer (HDGC). In each family, the CDH1 mutation was a splicing mutation generating aberrant transcripts with an in-frame deletion, removing the extracellular cadherin repeat domains involved in cell-cell adhesion. Such transcripts might encode mutant proteins with trans-dominant negative effects. We found that CDH1 is highly expressed at 4 and 5 weeks in the frontonasal prominence, and at 6 weeks in the lateral and medial nasal prominences of human embryos, and is therefore expressed during the critical stages of lip and palate development. These findings suggest that alteration of the E-cadherin pathway can contribute to human clefting.

Adult↗
PubMed2005

Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans.

A key challenge of functional genomics today is to generate well-annotated data sets that can be interpreted across different platforms and technologies. Large-scale functional genomics data often fail to connect to standard experimental approaches of gene characterization in individual laboratories. Furthermore, a lack of universal annotation standards for phenotypic data sets makes it difficult to compare different screening approaches. Here we address this problem in a screen designed to identify all genes required for the first two rounds of cell division in the Caenorhabditis elegans embryo. We used RNA-mediated interference to target 98% of all genes predicted in the C. elegans genome in combination with differential interference contrast time-lapse microscopy. Through systematic annotation of the resulting movies, we developed a phenotypic profiling system, which shows high correlation with cellular processes and biochemical pathways, thus enabling us to predict new functions for previously uncharacterized genes.

Animals↗