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R Martin

Publications and source records attributed to R Martin.

At least 271 records · Page 15Linked to original sources
PubMed1997

T cell response to myelin basic protein in the context of the multiple sclerosis-associated HLA-DR15 haplotype: peptide binding, immunodominance and effector functions of T cells.

In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.

Alleles↗
PubMed1997

Longitudinal study of myelin basic protein-specific T-cell receptors during the course of multiple sclerosis.

This study analyzed the stability of the myelin basic protein (MBP)-specific T-cell receptor (TCR) repertoire during the course of multiple sclerosis (MS) in three patients who were monitored for three years by gadolinium-enhanced magnetic resonance imaging. Bulk-culture T-cell lines (TCLs) were generated from 3-4 time points for each patient, including times of active and quiescent disease. TCR analysis of these TCLs indicated that both the V alpha and V beta usage was similar over time for each patient. Sequencing of TCRs demonstrated conserved complementarity-determining region 3 (CDR3) sequences within TCLs that expressed the same V alpha segment over time, although the J alpha usage was different for each TCR. This indicates that the population of MBP-reactive T-cells is changing during the course of MS, but that host and/or environmental factors may be selecting T-cells with particular MHC/peptide binding domains.

Adult↗
PubMed1997

Therapeutic potential of phosphodiesterase type 4 inhibition in chronic autoimmune demyelinating disease.

It was recently demonstrated that selective phosphodiesterase type 4 (PDE4) inhibition suppresses the clinical manifestations of acute experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and inhibits the production of tumor necrosis factor-alpha (TNF-alpha), a pathogenetically central cytokine. Since the most common presentation of MS in humans is a relapsing-remitting course, we investigated the therapeutic potential of PDE4 inhibition in the relapsing-remitting EAE model of the SJL mouse. Administration of rolipram, the prototypic PDE4 inhibitor, reduced the clinical signs of EAE during both the initial episode of disease and subsequent relapses. In parallel, there was marked reduction of demyelination and also less inflammation throughout the central nervous system (CNS) of rolipram-treated animals. Gene expression of proinflammatory cytokines in the CNS was reduced in most of the rolipram-treated animals. Additional experiments demonstrated that PDE4 inhibition acted principally by inhibiting the secretion of Th1 cytokines, however, the encephalitogenic potential of myelin basic protein-specific T cells was not impaired. Our findings suggest that PDE4 inhibitors are a promising cytokine-directed therapy in chronic demyelinating disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Epidemiological significance of cutaneous, pharyngeal, and digestive tract colonization by multiresistant Acinetobacter baumannii in ICU patients.

The aim of this prospective study was to assess the relative epidemiological role of digestive tract colonization by Acinetobacter baumannii, in comparison with other body site colonizations, in patients admitted to intensive care units (ICUs). From January to May 1995, axillary, pharyngeal and rectal swabs were taken together within the first 48 h of admission, and then weekly during ICU stay. Seventy-three patients were included, 48 of them (66%) had axillary, pharyngeal, or rectal colonization with A. baumannii, nine (19%) of these 48 during the first 48 h and the remaining 28 (77%) during the first week. Twenty-one (29%) had clinical samples positive for A. baumannii and axillary, pharyngeal, or rectal colonization. In 15 of these 21 (71%), colonization on body sites occurred prior to isolation from clinical samples (mean seven days, range 1-20). Throughout admission, rates of detection of A. baumannii were 75% (36/48) for axillary or pharyngeal swabs and 77% (37/48) for rectal swabs. Combination of two body site swabs yielded culture positive rates of 90% (43/48) for axillary-pharyngeal or axillary-rectal sites, and 96% (46/48) for pharyngeal-rectal. Two epidemic clones were defined by antibiotype and pulsed-field gel electrophoresis (PFGE) of SmaI DNA digests in 48 isolates from 11 patients. We conclude that body sites of patients were a major reservoir for A. baumannii infections in the outbreak. This finding cases doubt on the value of selective decontamination of the digestive tract as an additional infection control measure in this kind of outbreak. The weekly performance of pharyngeal and rectal swabs appears to detect A. baumannii colonization early among ICU patients and enables barrier methods to be applied rapidly.

Acinetobacter Infections↗
PubMed1997

Liver hemostasis using high-intensity focused ultrasound.

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86 degrees C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of "volume cauterization," offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.

Animals↗
PubMed1997

[Effects of CO2 and adrenaline on 1% lidocaine in axillary block].

OBJECTIVES: To compare lidocaine hydrocarbonate and lidocaine hydrochloride, with and without adrenaline, in the axillary block obtained with a neurostimulator. STUDY DESIGN: Prospective, randomized, double blind study. PATIENTS: Sixty-six patients undergoing surgery of the upper limb under axillary block, allocated into four groups. METHODS: The criteria for evaluation were: onset time, duration and quality of sensory and motor blockades, and blood concentrations of lidocaine in 39 patients. In all patients musculocutaneous, radial, median and ulnar nerves were stimulated and the volume of local anaesthetic administered was 25 mL per square meter of body surface. Group 1 received lidocaine hydrocarbonate 1% (n = 17), group 2, lidocaine hydrocarbonate 1% with adrenaline 1/200,000 (n = 17), group 3, lidocaine hydrochloride 1% (n = 16) and group 4, lidocaine hydrochloride 1% with adrenaline 1/200,000 (n = 16). RESULTS: No significant inter-group differences were found concerning sensory and motor blockades and onset time. The duration of analgesia was longer in groups CO2 + A and HCL + A. The lidocaine blood concentrations were globally lower in group HCL + A. CONCLUSIONS: Considering the cost/benefit ratio and the absence of clinical benefits of lidocaine hydrocarbonate, lidocaine hydrochloride should be preferred.

Adult↗
PubMed1997

Genetic relatedness of Burkholderia (Pseudomonas) cepacia isolates from five cystic fibrosis centers in Michigan.

Burkholderia cepacia isolates from patients with cystic fibrosis (CF) attending five CF centers were studied for relatedness by cellular fatty acid methyl esters (FAME) and by chromosomal DNA restriction analysis. Twenty-eight of 32 (87.5%) isolates tested were grouped in cluster group 1 based on their FAME profiles. DNA analysis revealed that 29 of 32 (90.6%) B. cepacia isolates from five CF centers had one closely related DNA pattern. To examine strain variation over a time period, FAME profiles and DNA patterns of isolates from serial cultures on seven patients from center D were studied. For four patients, all serial B. cepacia isolates belonged to a single FAME cluster group; for the remaining three patients, all serial isolates belonged to any two of the four cluster groups. On serial culture isolates, a single DNA pattern (pattern A) was found in 31 of 32 isolates demonstrating a close genetic relatedness. These data corroborate the observations that the majority of patients colonised with B. cepacia in a CF center harbor strains genetically closely related as determined by FAME profiles and DNA patterns.

Burkholderia cepacia↗
PubMed1997

Differential roles of neuroticism, extraversion, and event desirability for mood in daily life: an integrative model of top-down and bottom-up influences.

Top-down and bottom-up approaches were combined to assess the relative impact of extraversion, neuroticism, and daily events on daily mood. Ninety-six community-residing men completed diaries for 8 consecutive nights. Extraversion predicted positive mood, whereas neuroticism predicted positive and negative mood. Undesirable events predicted negative mood and, more modestly, positive mood. Desirable events predicted positive mood. Negative dispositional and situational factors play a larger role in daily positive affect than positive factors do in daily negative affect.

Adult↗
PubMed1997

Videodensitometric analysis of electron spectroscopic micrographs--a tool for detection of biologically relevant elements with high resolution.

Electron energy-loss spectroscopic imaging (ESI) yields high-resolution, element-sensitive images. However, ESI suffers from difficulties in distinguishing element-specific and background contributions. New methods have therefore been introduced which use grey-level measurements in micrographic images for a more accurate detection of element distributions. A videodensitometric method allowed the detection of low phosphorus levels in axoplasmic neurofilaments of squid giant axons. Here we further verify these results by investigating the relationship of videodensitometry and electron energy-loss spectroscopy (EELS), particularly considering the peculiarities of these methods in terms of automatic background correction and representation of the results. Six biological specimens and two nonbiological specimens were examined both by EELS and by videodensitometry. In all cases comparable results were obtained. The overlapping PL2,3 and SL2,3 ionization edges could clearly be recognized individually by both methods, and controls showed that mass density variations within the specimens did not impair elemental analysis. Additional evidence supporting the detection of phosphorylation sites in squid neurofilaments was obtained in both EELS and videodensitometric measurements of neurofilament-enriched pellets and of aggregated axoplasmic particles. Thus, video-densitometry appears to be a useful tool for an improved exploration of the full imaging capabilities of energy filtering electron microscopy.

Animals↗
PubMed1997

Detection of low phosphorus contents in neurofilaments of squid axons by Image-EELS contrast spectroscopy.

We show that Image-EELS is suitable for detecting relatively low phosphorus concentrations in very small axoplasmic structures of squid axons. Imaging plates and a CCD camera were used as electron sensors. From image series spanning a certain energy-loss range EELS (electron energy-loss spectra) were derived by averaging read-outs from many axoplasmic particles (APs). The ratio of these spectra to spectra of the background was plotted, showing the contrast modulation as a function of the energy loss. This new approach is called EELC (electron energy-loss-dependent contrast spectroscopy). A distinct phosphorus signal was found in APs of presynaptic terminals of the squid giant synapse, in the peripheral giant axon and, as controls, in ribosomes. Biochemical experiments supported this result. In neurofilament-enriched pellets a phosphorus signal could be directly detected by serial EELS and in electron spectroscopic micrographs. After dephosphorylation of either the pellets or the extruded axoplasm with alkaline phosphatase, phosphorus signals in electron spectroscopic micrographs were absent or much reduced in size and intensity. With Image-EELS inherent limitations of traditional element detection modes in energy filtering transmission electron microscopy can be overcome. Compared with serial EELS, the selective analysis of small areas with irregular shape is possible with greatly improved signal-to-noise ratio. The identification of the element-peak in Image-EEL spectra directly proves the presence of the element within the region of interest. For small peaks, the visualization is facilitated by the contrast presentation (EELC). However, the background subtraction modes used for elemental mapping in electron spectroscopic imaging are subject to uncertainties when elemental ionization edges like the P1,2,3 edge are examined. Imaging plates are very sensitive electron sensors with a wide dynamic range. Unlike photographic emulsions, they allow acquisition of image series covering a large energy-loss range without normalization of exposure times, and direct extraction of EEL spectra. Thus, the combination of Image-EELS and imaging plates is proposed as an efficient new tool for analytical electron microscopy.

Animals↗
PubMed1997

CT-guided core-needle biopsy in omental pathology.

PURPOSE: To assess the accuracy and clinical usefulness of CT-guided core-needle biopsy in the diagnosis of omental pathology. MATERIAL AND METHODS: We retrospectively reviewed the results of CT-guided percutaneous core biopsies in 25 patients with focal (n = 2) or diffuse (n = 23) omental pathology. These results were compared to the final diagnoses as determined by laparotomy (n = 15), laparoscopic biopsy (n = 3), endoscopic biopsy (n = 1), or by the results of percutaneous biopsy and clinical-radiological and bacteriological modalities (n = 6). The final diagnoses showed 4 patients with isolated omental pathology and 21 with widespread peritoneal involvement. The CT-guided biopsies were performed with 1.0-1.8-mm Surecut core-needles. RESULTS: In 16 patients, the final diagnosis was metastatic adenocarcinoma--with the primary tumor sites in the ovary (n = 3), stomach (n = 1), appendix (n = 2), and unknown (n = 10). In the remaining 9 patients, the final diagnosis was hepatocellular carcinoma, lymphoma, and mesothelioma in 1 patient each; tuberculosis in 5; and actinomycosis in 1. Sufficient histological (n = 16) or cytological (n = 8) material was obtained by CT biopsy in 24/25 (96%) cases; the specimen was insufficient for diagnosis in 1 case. In differentiating benign from malignant disease, CT-guided biopsy showed a sensitivity, specificity and accuracy of respectively 89.5%, 100% and 92%. It gave a specific diagnosis in 78.9% (15/19) of patients with malignant conditions and in 50% (3/6) of patients with benign disorders. There were no biopsy-related complications. CONCLUSION: CT-guided percutaneous core-needle biopsy of the omentum is a safe, useful and highly accurate procedure for diagnosing malignant omental pathology.

Actinomycosis↗
PubMed1997

Reliability of estimates of diploid human spermatozoa using multicolour fluorescence in-situ hybridization.

Multicolour fluorescence in-situ hybridization (FISH) analysis permits distinction between disomic and diploid spermatozoa. Thus estimates of the frequency of diploid spermatozoa can be obtained for human semen samples. The issue of the accuracy and reliability of these diploidy estimates has been addressed by analysing diploidy frequencies in 10 men using the same sperm sample to estimate diploidy twice-once during two-colour FISH analysis of disomy for chromosomes 1 and 12 and a second independent analysis of three-colour FISH for disomy estimates for chromosomes X and Y (with chromosome 1 used as the autosomal control). A minimum of 10,000 spermatozoa per hybridization per male was counted for a total of over 200,000 spermatozoa analysed. The mean frequency of diploid spermatozoa was 0.13% for the autosomal study and 0.14% for the sex chromosomal study, which were not significantly different. One donor had extremely divergent values of diploidy in the two studies. Analysis of values in the other nine donors demonstrated no significant difference in the two diploidy estimates. These results indicate that the FISH technique is an accurate and reliable method for determining diploid frequencies in human spermatozoa.

Cell Nucleus↗
PubMed1997

Difficulty in removal of certain intramedullary nails.

Intramedullary nailing is the most common treatment for displaced diaphyseal fractures of the femur and tibia. Gerhard Küntscher introduced the technique of intramedullary nailing to clinical practice in the 1940s, and this method has been the focus of many authors with regard to indications, technique, complications, and outcome. The five cases presented here represent a complication not often reported in recent years: the difficulty in removing an intact intramedullary nail. Inspection of the interlocking nails in four of the cases presented reveals a specific design characteristic: the cross sectional design of the nail prevents the distal, unslotted end of the nail from being extracted from the medullary cavity. This problem is preventable by a change in nail design or the development of absorbable implants.

Adolescent↗
PubMed1997

Childhood hearing impairment: processing dependencies in multidimensional speech perception for an auditory level of analysis.

OBJECTIVE: Our purpose was to determine whether the influence of childhood hearing impairment (HI) on multidimensional speech processing is a purely linguistic effect or whether childhood HI also affects the processing of speech dimensions representing an auditory level of analysis. DESIGN: The processing dependencies characterizing the two dimensions of talker-gender and spatial location were studied in 40 children with HI and in two normal-hearing (NH) comparison groups representing similar chronological ages (N = 30) or similar vocabulary skills (N = 70). The processing interactions were assessed with a speeded selective-attention task requiring listeners to attend selectively to the gender of the talker and to ignore the spatial location and vice versa. The logic is that performance for the target dimension will not be affected by what is happening on the nontarget dimension if the dimensions are processed independently. On the other hand, if the dimensions are not processed independently, listeners will not be able to attend selectively and performance for the relevant dimension will be affected by what is happening on the irrelevant dimension. In the latter case, results may be analyzed in terms of Garner interference (the effect on performance of irrelevant variability in the to-be-ignored dimension) (Garner, 1974a) and Simon interference (the effect on performance of an irrelevant spatial source) (Simon, 1990). RESULTS: Overall results in all listeners, those with NH or HI, showed significant interference when the participants were attending to the gender of the talker and ignoring spatial location and vice versa. The talker-gender and spatial-location dimensions of speech were not processed independently by these children. When the processing interactions were compared between the NH and HI groups, the presence of childhood HI as a general rule significantly diminished the degree of interference from spatial location. The degree of interference from the gender of the talker, on the other hand, remained normal in the presence of childhood HI. All listeners seemed stimulus bound by the gender of the talker. The degree of Garner interference did not show age-related or degree of loss-related change. The degree of Simon interference showed significant change as a function of age in the children with mild-moderate HI, but not in the children with severe HI. The developmental function for Simon interference in the children with mild-moderate HI was delayed to a degree that corresponded to the duration of the auditory deprivation. CONCLUSIONS: The overall pattern of results indicates that the influence of childhood HI on multidimensional speech processing is not a purely linguistic effect.

Age Factors↗
PubMed1997

Nitric oxide production in burns: plasma nitrate levels are not increased in patients with minor thermal injuries.

BACKGROUND: Recent studies have suggested that adults who sustain burns of less than 15% total body surface area display elevated plasma nitrate levels, indicating increased production of nitric oxide. The present study was initiated to confirm whether plasma nitrate is elevated in minor burn injury and, if so, whether it heralds the onset of a systemic inflammatory response to that injury. METHODS: Plasma samples were taken from 98 control and 10 burns patients. RESULTS: The mean plasma nitrate level for nine burns patients with a mean total body surface area burnt of 7.65% (range, 4-15%) was 42.83 micromol/L on day 1. This was not significantly different from that of a control population of 98 preoperative plastic surgery patients: 36.91 micromol/L (p = 0.162). Eight of 10 burns patients showed a decrease in plasma nitrate to 27.47 micromol/L by day 3 (p = 0.046). Elevated nitrate levels were seen in 2 of 10 burns patients. One had concurrent smoke-inhalation injury preceding multiple organ dysfunction, and one was treated with a cream containing cerium nitrate (Flammacerium, Duphar Laboratories, Southhampton, United Kingdom). CONCLUSIONS: For patients who sustain minor burns, plasma levels of nitrate decrease from those of mean normal controls with time unless there is multiple organ dysfunction or the patient receives extraneous nitrate.

Adult↗
PubMed1997

Retroviral marking identifies grafted autologous keratinocytes in porcine wounds receiving cultured epithelium.

Cultured epithelial autografts are often applied to wounds with a capacity for regeneration from dermal appendages. It is unclear in these circumstances whether the cultured autografts act merely as a biologic dressing or whether they become incorporated into the new epithelium. We have used retroviral gene transfer techniques to identify autologous keratinocytes in an established porcine model of cultured epidermal (CE) grafting. Porcine keratinocytes were transduced with an MFG-lacZ nls vector produced by the amphotropic packaging line GP+EnvAm12. Transduction rates of 15.1%, in the absence of selection, were achieved by a single passage on gamma-irradiated retroviral producers as a feeder layer. Full-thickness wounds were created on Large White pigs and isolated from the surrounding skin by a polytetrafluoroethylene chamber. Wounds were grafted initially with autologous de-epidermized dermis (DED), followed 7 d later by sheets of retrovirally marked or unmarked CE autografts. Two weeks after grafting, the mean area of epithelium was 48.4% in wounds that received CE grafts and 32.3% in wounds that were left as DED alone. The epithelium on DED represents regeneration from dermal appendages. The contribution made by the autograft cells to the new epidermis was demonstrated unequivocally, however, by lacZ-positive areas visible macroscopically on the surface of the excised wound. In cryostat sections through the lacZ-positive areas, retrovirally marked cells were present at both superficial and basal positions in the new epithelium.

Animals↗