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Biomedical subjects

R Martin

Publications and source records attributed to R Martin.

At least 55 records · Page 3Linked to original sources
PubMed2003

Moraxella catarrhalis induces mast cell activation and nuclear factor kappa B-dependent cytokine synthesis.

Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-kappaB) nuclear binding activity. In some experiments, NF-kappaB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-kappaB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-kappaB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.

Cell Line, Tumor↗
PubMed2003

A model for the preliminary biological screening of potential keratoprosthetic biomaterials.

A series of in vitro screening assays for the preliminary selection of biomaterials for use in the fabrication of artificial corneas (keratoprostheses) (KPros) have been investigated. These screening assays assessed the initial binding of inflammatory and cell adhesive proteins, activation of inflammatory proteins, adhesion of keratocytes, epithelial cells and macrophages and the production of inflammatory cytokines by keratocytes contacting biomaterials. Central optic biomaterials were selected on the basis of low-inflammatory and cell adhesion potential. Peripheral skirt materials were selected on the basis of low-inflammatory potential but good cell adhesion to anchor the implant within the host cornea. Green fluorescent protein (GFP) gene transfer was used in a novel context to investigate cell invasion in the absence of external staining techniques. Confocal laser scanning microscopy and scanning electron microscopy were used to investigate GFP positive keratocyte invasion of porous materials. The results of in vitro assays were compared to a corneal organ culture system in which the biomaterials were assessed within a stromal environment. A range of polyurethane-based interpenetrating polymers with a range of water contents were screened. All materials showed low-inflammatory potential. A reduction in biomaterial water content induced an increase in complement C3 and fibronectin binding and in cell adhesion to materials, whilst differences in co-monomer formulation had little impact. The screening methods used in the current study provide a suitable preliminary assessment regime for the in vitro evaluation of potential KPro materials.

Biocompatible Materials↗
PubMed2003

Assessment of Acinetobacter baumannii susceptibility to antiseptics and disinfectants.

Disinfection and antisepsis are of primary importance in controlling outbreaks of Acinetobacter baumannii, a nosocomial pathogen that frequently shows multiple antibiotic resistance. In this study we assessed the susceptibility of nine A. baumannii strains isolated during a sustained intensive care unit outbreak, to several antiseptics and disinfectants based on European Standards. While the tested strains showed diverse antibiotic resistance patterns, they were equally sensitive to the biocides assessed in vitro. We observed neither evidence of development of resistance to biocides over time, nor a correlation between resistance to antibiotics and a decreased susceptibility to antiseptics or disinfectants.

Acinetobacter Infections↗
PubMed2003

Hydration properties of the molecular chaperone alpha-crystallin in the bovine lens.

Topographic studies of crystalline fractions from different morphological layers of the young adult bovine lens were conducted. Crystallin profiles were obtained for each lens layer, using thin-layer isoelectric focusing in polyacrylamide gel (IEF). Water soluble (WS) crystallins from the lens equator revealed a separation into HM (high molecular weight) alpha(L)-, beta(H)-, beta(L)-, beta(S)-, and gamma-crystallins. The nature of the water insoluble (WI) protein fraction in the separated lens layers reflected the aggregated state of alpha(L)-, beta(L)-, beta(S)-, and gamma-crystallins in different regions of the lens, concealed in the central cavity of the alpha-crystallin chaperone model. The IEF data demonstrate a possible chaperone-like function for alpha-crystallin in the nucleus and inner cortex of the lens, but not in the outer cortex. The water binding properties of bovine lens alpha-crystallin, calf skin collagen, and bovine serum albumin (BSA) were investigated with various techniques. The water adsorptive capacity was obtained in high vacuum desorption experiments volumetrically, and also gravimetrically in controlled atmosphere experiments. The NMR spin-echo technique was used to study the hydration of protein samples and to determine the spin-spin relaxation times (T(2)) from the protons of water adsorbed on the proteins. Isolated bovine lenses were sectioned into 11-12 morphological layers (from anterior cortex through nucleus to posterior cortex). The water content in relation to dry weight of proteins was measured in individual morphological lens layers. During water vapor uptake at relative humidity P/P(0) = 0.75, alpha-crystallin did not adsorb water suggesting that hydrophobic regions of the protein are exposed to the aqueous solvent. At relative humidity P/P(0) = 1.0, the adsorption of water by alpha-crystallin was 17% with a single component decay character of spin echo (T(2) = 3 msec). Addition of water to alpha-crystallin to about 50% of its weight/weight in the protein sample showed T(2) = 8 msec with only one single component decay of the spin-echo signal. The single component decay character of the spin echo indicates water tightly bound by alpha-crystallin. Under a relative humidity P/P(0) = 1.0, collagen and BSA adsorbed, correspondingly, 19.3 and 28% of water and showed a two-component decay curve with T(2) about 5 and 40 msec. The findings demonstrate the presence of two water fractions in collagen and BSA which are separated in space. The IEF data suggest a tight binding of water with alpha-crystallin with similar distribution patterns in the lens layers. To conclude, it was found that alpha-crystallin can immobilize water to a greater extent than other proteins such as collagen and BSA. These results shed new light on structural properties of alpha-crystallin and its superhydration properties and have important implications for understanding the mechanism of the chaperone-like action of this protein in the lens and non-ocular tissues.

Aging↗
PubMed2003

Immunological questions on hematopoietic stem cell transplantation for multiple sclerosis.

Multiple sclerosis (MS) is considered an inflammatory autoimmune disorder. Approved immunotherapies are only moderately effective in reducing disease exacerbations and brain inflammation in a subset of patients. Autologous hematopoietic stem cell transplantation (HSCT) has emerged in recent years as the first opportunity to offer to patients a radical, potentially curative treatment. Here, we will summarize key immunopathological aspects of MS and discuss important questions that need to be addressed to clarify the therapeutic role and mechanism of action of HSCT in this disorder.

Animals↗
PubMed2003

Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis.

Autoimmune diseases such as multiple sclerosis are characterized by complex genetic traits and pathomechanisms that translate into clinical heterogeneity. This wide heterogeneity of multiple sclerosis as well as different biological responses to immunomodulatory drugs can be expected to contribute to differential treatment responses. Strategies that dissect the relationship between the treatment response and the biological characteristics in individual patients are valuable not only as a clinical tool, but also in leading to a better understanding of the disease. Here we address the in vitro and ex vivo RNA expression profile under one approved therapy of multiple sclerosis, interferon-beta (IFN-beta, Betaseron), by cDNA microarrays and demonstrate that non-responder and responder phenotypes to IFN-beta as assessed by longitudinal gadolinium-enhanced MRI scans and clinical disease activity differ in their ex vivo gene expression profile. These findings will help to better elucidate the mechanism of action of IFN-beta in relation to different disease patterns and eventually lead to optimized therapy.

Follow-Up Studies↗
PubMed2003

New approaches to investigating heterogeneity in complex traits.

Great advances in the field of genetics have been made in the last few years. However, resolving the complexity that underlies the susceptibility to many polygenic human diseases remains a major challenge to researchers. The fast increase in availability of genetic data and the better understanding of the clinical and pathological heterogeneity of many autoimmune diseases such as multiple sclerosis, but also Parkinson's disease, Alzheimer's disease, and many more, have changed our views on their pathogenesis and diagnosis, and begins to influence clinical management. At the same time, more powerful methods that allow the analysis of large numbers of genes and proteins simultaneously open opportunities to examine their complex interactions. Using multiple sclerosis as a prototype, we review here how new methodologies such as gene expression profiling can be exploited to gain insight into complex trait diseases.

Base Sequence↗
PubMed2003

Intrahepatic cholangiocarcinoma. Current management.

Peripheral/Intrahepatic Cholangiocarcinoma (IHC), a malignant epithelial tumor originating from the intrahepatic bile ducts, is the second most common primary liver cancer after hepatocellular carcinoma. Unlike hepatocellular carcinoma, however, IHC is infrequently associated with chronic underlying liver disease. A recent study from the United States has demonstrated a 9% annual percentage increase and an overall 10-fold increase in mortality related to IHC since 1973. Despite this observation, however, IHC remains a rare disease in Western countries. Of the approximately 4000 patients seen at Memorial Sloan-Kettering Cancer Center with hepatic lesions since from 1995-2001, 7% had a diagnosis of cholangiocarcinoma and only 1% had IHC. As a result, progress in elucidating the pathogenesis and clinical behavior of these tumors has been slow. However, the increasing number of reports in recent years has increased awareness of IHC and provided some insight into its biology. At present, complete resection is the only therapy that offers the possibility of long-term survival. Single agent or combination chemotherapy and radiation therapy have not been shown to have a significant impact, either as primary treatment or as an adjuvant to resection. This report reviews the relevant literature pertaining to IHC with emphasis on clinical presentation, radiologic evaluation, treatment and outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

RAPD polymorphisms in spring wheat cultivars and lines with different level of Fusarium resistance.

Random amplified polymorphic DNA (RAPD) markers have been used to characterize the genetic diversity among 35 spring wheat cultivars and lines with different levels of Fusarium resistance. The objectives of this study were to determine RAPD-based genetic similarity between accessions and to derive associations between Fusarium head blight (FHB) and RAPD markers. Two bulked DNA from either highly resistant lines or susceptible lines were used to screen polymorphic primers. Out of 160 screened primers, 17 primers generated reproducible and polymorphic fragments. Genetic similarity calculated from the RAPD data ranged from 0.64 to 0.98. A dendrogram was prepared on the basis of a similarity matrix using the UPGMA algorithm, which corresponded well with the results of principal component analysis and separated the 35 genotypes into two groups. Association analysis between RAPD markers and the FHB index detected three RAPD markers, H19(1000), F2(500) and B1(2400), significantly associated with FHB-resistant genotypes. These results suggest that a collection of unrelated genotypes can be used to identify markers linked to an agronomically important quantitative trait like FHB. These markers will be useful for marker-assistant breeding and can be used as candidate markers for further gene mapping and cloning.

Fusarium↗
PubMed2002

Sustained immunological effects of Glatiramer acetate in patients with multiple sclerosis treated for over 6 years.

The availability of a group of multiple sclerosis (MS) patients at the University of Maryland, who had participated in the pivotal Copaxone trial in the early 1990s, provided an opportunity to examine the long-term immunologic effects of Glatiramer acetate (GA) treatment in MS. Forty-eight GA-reactive T-cell lines (TCL) were generated from 10 MS patients who have been receiving GA treatment for 6-9 years. Proliferative responses, cytokine production, and cross-reactivity with myelin basic protein (MBP) and the MBP immunodominant peptide 83-99 were compared to responses obtained from 10 MS patients who were tested pretreatment and after a shorter period of treatment ranging from 1 to 10 months. The results indicate that while long-term treatment with GA results in a 2.9-fold decrease in the estimated precursor frequency of GA-reactive T-cells, the sustained response to GA remains Th2-biased and in part cross-reactive with MBP and MBP (83-99) as measured by proliferation and cytokine release assays. The results indicate that despite a drop in the precursor frequency of GA-reactive T-cells with long-term treatment, the sustained response remains predominantly Th2-biased and cross-reactive with MBP, which is consistent with the anti-inflammatory effects of the drug and bystander suppression.

Biomarkers↗
PubMed2002

Neoclassical tearing physics in the spherical tokamak MAST.

Results from MAST provide a first test of neoclassical tearing mode physics in the spherical tokamak (ST). The mode accounts for the main performance limit in conventional tokamaks. Its behavior in the ST is remarkably well described by existing theoretical models, although it is more readily seeded by sawtooth events in these scenarios. Modeling confirms the significance of stabilizing field-curvature effects. This provides good grounds for optimism that with suitable control of profiles, it may be possible to avoid these modes in the ST.

Journal Article↗
PubMed2002

Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults.

BACKGROUND: Anticonvulsant drugs have multiple mechanisms of action. Recent in vivo MRS studies suggest that cerebral gamma-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans. OBJECTIVE: To investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral GABA concentrations in healthy volunteers and correlate the GABA concentrations with serum drug levels. METHODS: Seventeen healthy adults were randomly assigned to receive topiramate, gabapentin, and lamotrigine and underwent GABA measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital region. GABA concentrations and serum levels were measured at 3 and 6 hours following administration of an acute single dose of one of the drugs. Thereafter, drugs were titrated over 4 weeks to target doses, with GABA measurements performed at 2 and 4 weeks. RESULTS: Cerebral GABA concentrations rose 70% in the acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with gabapentin but not with lamotrigine. With long-term dosing and once target doses were achieved at 4 weeks, significant elevations in GABA were observed compared with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine 25%). CONCLUSION: This study demonstrates that single doses of topiramate and gabapentin increase cerebral GABA concentrations acutely (hours) in healthy individuals, but all drugs at clinically utilized doses increase cerebral GABA at 4 weeks. These results suggest that the mechanisms of action of anticonvulsant drugs are more complex and are likely to be multiple in nature.

Acetates↗
PubMed2002

L-H transition in the mega-amp spherical tokamak.

H-mode plasmas have been achieved on the MAST spherical tokamak at input power considerably higher than predicted by conventional threshold scalings. Following L- H transition, a clear improvement in energy confinement is obtained, exceeding recent international scalings even at densities approaching the Greenwald density limit. Transition is accompanied by an order-of-magnitude increase in edge-density gradient, a marked decrease in turbulence, the efficient conversion of internal electron Bernstein waves into free space waves, and the onset and saturation of edge poloidal rotation.

Journal Article↗
PubMed2002

[Age dependence of laboratory parameters in a health study--attempt at calculating a laboratory index for assessing biological aging].

The laboratory analyses of 404 participants of the health study GUNDULA, 201 men and 203 women between 30 and 80 years old, were performed to evaluate the variables for the determination of biological age. From the more than 70 laboratory variables resulting from clinical-chemical and hematologic tests and from urinalysis, less than 40 are significantly age-dependent. About half of these variables were examined by regression analysis to evaluate whether they are useful for the estimation of biological age by a laboratory index. Considerable sex differences were observed. The laboratory indexes for the participants altogether (resulting from 13 parameters) and separated for women (10 parameters) and men (8 parameters) show more variations than the biological age estimated by non-invasive parameters. In men only, there exists a significant but inverse correlation between laboratory index and relative aging rate, the difference between biological and chronological age. The results of some striking variables (e.g. dehydroepiandrosterone sulfate and others) and the results of an explorative factor analysis with regard to possible interconnections between variables and chronological age will be discussed.

Adult↗
PubMed2002

Effect of age and pedalling rate on cycling efficiency and internal power in humans.

The present study was undertaken to examine the effect of age and pedalling frequency on metabolic internal power (MPint) and delta efficiency (deltaE), defined as the ratio of the change in external work accomplished to the change in energy expended, during sub-maximal exercise on a cycle ergometer. A group of II children [mean age (SD)][10.6 (1.0) years] and 12 adults [23.6 (3.0) years], all cyclists, performed two incremental tests at 60 rpm and 90 rpm in a randomised order. External power (EP) was measured as the product of friction load and pedalling frequency. Oxygen consumption (VO2) was measured using the Douglas bag method and an energy equivalent of 20.6 kJ x lO2(-1) was used to convert VO2 into metabolic power (MP). Linear relationships were drawn between MP and EP (MP = aEP + b) to enable the calculation of deltaE (I/a) and MPint (b). All coefficients of determination were greater than 0.97. The results showed that children and adults increased their deltaE with the increase in pedalling rate [27 (6)% to 36 (5)%, P < 0.05 in children and 27 (3)% to 30 (2)%, P < 0.05 in adults]. Likewise, net MPint (MPint minus basal metabolism) expressed relative to total leg volume was higher at 90 rpm compared to 60 rpm [16.5 (5.0) W x l(-1) and 4.2 (2.0) W x l(-1), P<0.05, respectively, in children and 7.4 (3.0) W x l(-1) and 5.0 (2.5) W x l(-1), NS, respectively, in adults]. At 60 rpm, children and adults showed the same deltaE and net MPint values. At 90 rpm, children showed significantly higher deltaE and net MPint compared to adults. This study demonstrated that deltaE and net MPint are equally influenced by increasing pedalling rate in children and adults. Furthermore, it was hypothesized that differences between children and adults at 90 rpm could be related to different anthropometric characteristics.

Adult↗
PubMed2002

T cell response to 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in multiple sclerosis patients.

T cell responses targeting myelin antigens are possibly involved in the pathogenesis of demyelinating diseases, such as multiple sclerosis (MS). Little is known about human T cell responses to 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), the third most abundant myelin protein. We examined the primary peripheral T cell response to CNPase and characterized CNPase-specific CD4+ long-term T cell lines (TCL) from MS patients and healthy donors. The strongest primary responses were found in two MS patients with very active disease and were directed against CNP(343-373). We identified immunodominant epitope clusters in the regions CNP(343-373) and (356-388) that were recognized in the context of MS-associated HLA-DR2 and DR4 molecules. These data provide the immunological basis for further investigation of CNPase as a potential target self-antigen in MS.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗